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11,900 | 20,458,651 | DPN patients experienced a greater improvement in quality of life when using 5%LMP compared to pregabalin .
Adverse events were significantly fewer in patients treated with 5%LMP .
The results suggest that the effects in pain reduction of 5 % lidocaine medicated plaster are comparable to those of amitriptyline , capsaicin , gabapentin and pregabalin .
Topical agents such as 5%LMP may be associated with fewer and less clinical ly significant adverse events than is the case for systemic agents . | BACKGROUND Several pharmacological treatments are used to manage painful diabetic peripheral neuropathy ( DPN ) .
OBJECTIVE To compare 5 % lidocaine medicated plaster ( 5%LMP ) for the relief of DPN with other relevant interventions and placebo . | Background Recent consensus guidelines recommend pregabalin as a first-tier treatment for painful diabetic peripheral neuropathy ( DPN ) . We evaluated the efficacy of pregabalin 600 mg/d ( 300 mg dosed BID ) versus placebo for relieving DPN-associated neuropathic pain , and assessed its safety using objective measures of nerve conduction ( NC ) . Methods In this r and omized , double-blind , placebo-controlled trial , the primary efficacy measure was endpoint mean pain score ( MPS ) from daily pain diaries ( 11-point scale ) . NC velocity and sensory and motor amplitudes were assessed at baseline , endpoint , and end of follow-up ( 2 weeks post-treatment ) . At each timepoint , the median-motor , median-sensory , ulnar-sensory , and peroneal-motor nerves were evaluated . Secondary efficacy measures included weekly MPS and proportion of responders ( patients achieving ≥50 % reduction in MPS from baseline to endpoint ) . After 1-weeks ' dosage escalation , pregabalin-treated patients received 300 mg BID for 12 weeks . Results Eighty-two patients received pregabalin and 85 placebo . Mean duration s were 10 years for diabetes and ~5 years for painful DPN . Pregabalin-treated patients had lower MPS than controls ( mean difference , -1.28 ; p < .001 ) . For all four nerves , 95 % CIs for median differences in amplitude and velocity from baseline to endpoint and baseline to follow-up included 0 ( ie , no significant difference vs. placebo ) . Significant pain improvement among pregabalin-treated patients was evident at week 1 and sustained at every weekly timepoint . More pregabalin-treated patients ( 49 % ) than controls ( 23 % ) were responders ( p < .001 ) . Conclusion Pregabalin 600 mg/d ( 300 mg BID ) effectively reduced pain , was well tolerated , and had no statistically significant or clinical ly meaningful effect on NC in patients with painful DPN.Trial registration Clinical Trials.gov & NA ; Post‐herpetic neuralgia ( PHN ) is a common and often intractable neuropathic pain syndrome predominantly affecting the elderly . Topical local anesthetics have shown promise in both uncontrolled and controlled studies . Thirty‐five subjects with established PHN affecting the torso or extremities completed a four‐session , r and om order , double‐blind , vehicle‐controlled study of the analgesic effects of topically applied 5 % lidocaine in the form of a non‐woven polyethylene adhesive patch . All subjects had allodynia on examination . Up to 3 patches , covering a maximum of 420 cm2 , were applied to cover the area of greatest pain as fully as possible . Lidocaine containing patches were applied in two of the four 12‐h‐long sessions , in one session vehicle patches were applied , and one session was a no‐treatment observation session . Lidocaine containing patches significantly reduced pain intensity at all time points 30 min to 12 h compared to no‐treatment observation , and at all time points 4–12 h compared to vehicle patches . Lidocaine patches were superior to both no‐treatment observation and vehicle patches in averaged category pain relief scores . The highest blood Lidocaine level measured was 0.1 & mgr;g/ ml , indicating minimal systemic absorption of Lidocaine . Patch application was without systemic side effects and well tolerated when applied on allodynic skin for 12 h. This study demonstrates that topical 5 % Lidocaine in patch form is easy to use and relieves post‐herpetic neuralgia An 8-week double-blind , multicenter , parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet . Two hundred thirty-five patients were r and omized to treatment with either capsaicin cream or amitriptyline capsules . Capsaicin-treated patients received inactive capsules , and amitriptyline-treated patients applied vehicle cream . A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals . A visual analogue scale of pain relief and physicians ' global evaluation assessed changes in pain status from baseline . Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study . By the end of week 8 , 76 % of patients in each group experienced less pain , with a mean reduction in intensity of more than 40 % . By the end of the study , the interference with daily activities by pain had diminished significantly ( P = .001 ) in both groups , including improvements in sleeping and walking . No systemic side effects were observed in patients treated with topical capsaicin . Most patients receiving amitriptyline experienced at least one systemic side effect , ranging from somnolence ( 46 % ) to neuromuscular ( 23 % ) and cardiovascular ( 9 % ) adverse effects . Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy An 8-week , double-blind , vehicle-controlled study was conducted to determine the effectiveness of topical capsaicin 0.075 % cream in relieving pain associated with diabetic neuropathy . Patients were selected who experienced moderate to very severe pain , which interfered with sleep or activities on a daily basis , and who were unresponsive or intolerant to conventional therapy . The results after 8 weeks showed a statistically significant difference in favor of the capsaicin-treated patients , with 90 % of these patients improved . The results of this study indicate that topical capsaicin 0.075 % cream is safe and effective in managing painful diabetic neuropathy The objective of this study was to compare the efficacy and tolerability of gabapentin and amitriptyline monotherapy in painful diabetic neuropathy . This was a 12-week , open-label , prospect i ve , r and omized trial . Twenty-five type-II diabetic patients with pain attributed to diabetic neuropathy and a minimum score of 2 on a pain intensity scale ranging from 0 ( no pain ) to 4 ( excruciating pain ) were r and omized to receive either gabapentin , titrated from 1,200 mg/day to a maximum of 2,400 mg/day , or amitriptyline , titrated from 30 mg/day to a maximum of 90 mg/day . Both drugs were titrated over a 4-week period and maintained at the maximum tolerated dose for 8 weeks . The main outcome measures were weekly pain intensity and paresthesia intensity , measured on two categorical scales . Thirteen patients received gabapentin and 12 received amitriptyline . All 25 patients completed the trial . Gabapentin produced greater pain reductions than amitriptyline ( mean final scores were 1.9 vs. 1.3 points below baseline scores ; P = 0.026 ) . Decreases in paresthesia scores also were in favor of gabapentin ( 1.8 vs. 0.9 points ; P = 0 . 004 ) . Adverse events were more frequent in the amitriptyline group than in the gabapentin group : they were reported by 11/12 ( 92 % ) and 4/13 ( 31 % ) of patients , respectively ( P = 0.003 ) . Side effects were the main limiting factor preventing dose escalation . Gabapentin produced greater improvements than amitriptyline in pain and paresthesia associated with diabetic neuropathy . Additionally , gabapentin was better tolerated than amitriptyline . Further controlled trials are needed to confirm these preliminary results Postherpetic neuralgia ( PHN ) following herpes zoster is a common and disabling neuropathic pain syndrome . In a double‐blind , three‐session study , 5 % lidocaine gel or vehicle was applied simultaneously to both the area of pain and to the contralateral mirror‐image unaffected skin . In the local session , lidocaine gel was applied to the painful skin area . In the remote session , lidocaine gel was applied to mirror‐image skin . In the placebo session , vehicle was applied bilaterally . For cranial PHN , gel was applied without occlusion for 8 hours . For limb or torso PHN , gel was applied under occlusion for 24 hours . The 16 subjects with cranial PHN reported pain relief significantly favoring local drug application at 30 minutes , 2 , 4 , and 8 hours . The 23 subjects with torso or limb PHN reported significantly lower pain intensity with local drug application at 8 hours and both pain relief and reduced pain intensity at 24 hours . Remote lidocaine application to mirror‐image skin was no different from placebo . No systemic adverse effects were reported and blood levels did not exceed 0.6 μg/ml . Topical application of 5 % lidocaine gel relieves PHN pain by a direct drug action on painful skin ABSTRACT Objective : Neuropathic pain is often difficult to treat due to a complex pathophysiology . This study evaluated the efficacy , tolerability and safety of combination therapy with 5 % lidocaine medicated plaster and pregabalin for neuropathic pain in patients with post-herpetic neuralgia ( PHN ) or painful diabetic polyneuropathy ( DPN ) . Methods : Patients completing 4-week monotherapy with 5 % lidocaine medicated plaster or pregabalin were enrolled in an 8-week combination phase . Patients with adequate response to monotherapy ( recalled average pain intensity of 4 or less on 11-point numeric rating scale in the previous 3 days [ NRS-3 score ] ) continued their previous therapy , whereas those with insufficient response received combination therapy . Efficacy endpoints included change in NRS-3 from combination phase baseline , Patient and Clinical Global Impression of Change ( PGIC/CGIC ) , and patient 's satisfaction with treatment . Safety evaluation included adverse events ( AEs ) , drug-related AEs ( DRAEs ) , and withdrawal due to AEs . Clinical trial registration : EudraCT No. 2006 - 003132 - 29 . Results : Of 229 patients in the per- protocol set ( PPS : 68 PHN and 161 DPN ) , 71 received 5 % lidocaine medicated plaster monotherapy , 57 had pregabalin added to 5 % lidocaine medicated plaster , 57 pregabalin monotherapy and 44 received 5 % lidocaine medicated plaster in addition to continued pregabalin treatment . There were no meaningful differences in demographic data between the treatment groups . Patients continuing on monotherapy demonstrated additional decreases in NRS-3 scores . Patients receiving combination therapy achieved clinical ly relevant reduction in NRS-3 values in addition to improvement achieved during the 4 weeks of monotherapy . Improvement was similar between the two combination therapy groups . Considerable improvements in patients ’ treatment satisfaction were reported . Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well tolerated . Conclusions : In patients with PHN and painful DPN failing to respond to monotherapy , combination therapy with 5 % lidocaine medicated plaster and pregabalin provides additional clinical ly relevant pain relief and is safe and well-tolerated Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials . This EFNS Task Force aim ed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain . Studies were identified using first the Cochrane Data base then Medline . Trials were classified according to the aetiological condition . All class I and II controlled trials ( according to EFNS classification of evidence ) were assessed , but lower‐class studies were considered in conditions that had no top level studies . Only treatments feasible in an outpatient setting were evaluated . Effects on pain symptoms/signs , quality of life and comorbidities were particularly search ed for . Most of the r and omized controlled trials included patients with postherpetic neuralgia ( PHN ) and painful polyneuropathies ( PPN ) mainly caused by diabetes . These trials provide level A evidence for the efficacy of tricyclic antidepressants , gabapentin , pregabalin and opioids , with a large number of class I trials , followed by topical lidocaine ( in PHN ) and the newer antidepressants venlafaxine and duloxetine ( in PPN ) . A small number of controlled trials were performed in central pain , trigeminal neuralgia , other peripheral neuropathic pain states and multiple‐aetiology neuropathic pains . The main peripheral pain conditions respond similarly well to tricyclic antidepressants , gabapentin , and pregabalin , but some conditions , such as HIV‐associated polyneuropathy , are more refractory . There are too few studies on central pain , combination therapy , and head‐to‐head comparison . For future trials , we recommend to assess quality of life and pain symptoms or signs with st and ardized tools Neuropathic pain ( NeP ) , generated by disorders of the peripheral and central nervous system , can be particularly severe and disabling . Prevalence estimates indicate that 2 % to 3 % of the population in the developed world suffer from NeP , which suggests that up to one million Canadians have this disabling condition . Evidence -based guidelines for the pharmacological management of NeP are therefore urgently needed . R and omized , controlled trials , systematic review s and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting . Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one method ologically sound , r and omized , controlled trial showing significant benefit relative to placebo or another relevant control group . Recommendations for treatment are based on degree of evidence of analgesic efficacy , safety , ease of use and cost-effectiveness . Analgesic agents recommended for first-line treatments are certain antidepressants ( tricyclics ) and anticonvulsants ( gabapentin and pregabalin ) . Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine . Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain . Recommended fourth-line treatments include cannabinoids , methadone and anticonvulsants with lesser evidence of efficacy , such as lamotrigine , topiramate and valproic acid . Treatment must be individualized for each patient based on efficacy , side-effect profile and drug accessibility , including cost . Further studies are required to examine head-to-head comparisons among analgesics , combinations of analgesics , long-term outcomes , and treatment of pediatric and central BACKGROUND Reports of gabapentin use in diabetic peripheral neuropathy pain stimulate a need for controlled trials to determine its comparative efficacy to the therapeutic st and ard of amitriptyline hydrochloride . OBJECTIVE To determine the efficacy of gabapentin compared with amitriptyline in treating diabetic peripheral neuropathy pain . DESIGN Prospect i ve , r and omized , double-blind , double-dummy , crossover study . SETTING Veterans Affairs San Diego Healthcare System , Ambulatory Care Clinic . PATIENTS Twenty-eight veterans were referred by their primary care providers . Two patients withdrew before r and omization because of no neuropathic pain after washout ; a third withdrew for unexpected surgery that required analgesics . Three patients withdrew because of adverse effects and 1 for protocol violation . INTERVENTIONS Patients with stable glycemic control and neuropathic pain r and omized to 6 weeks of therapy with gabapentin , 900 to 1800 mg/d , or amitriptyline hydrochloride , 25 to 75 mg/d , with a 1-week washout before crossover . MAIN OUTCOME MEASURES Pain relief measured by pain scale with verbal descriptors and global pain score assessment at treatment end . RESULTS Participants and investigators were blinded throughout . Mean dosages were of gabapentin , 1565 mg/d , and of amitriptyline hydrochloride , 59 mg/d . Sixty-five percent of patients reached maximum dose with gabapentin and 54 % with amitriptyline . Mean score diary analysis showed pain relief with gabapentin and amitriptyline was not significantly different ( P = .26 ) . Global data were obtained from 21 of 25 enrolled patients who completed the study . Moderate or greater pain relief was experienced in 11 ( 52 % ) of 21 patients with gabapentin and 14 ( 67 % ) of 21 patients with amitriptyline . There were no significant period or carry-over effects ( P = .35 ) . CONCLUSIONS Although both drugs provide pain relief , mean pain score and global pain score data indicate no significant difference between gabapentin and amitriptyline . Gabapentin may be an alternative for treating diabetic peripheral neuropathy pain , yet does not appear to offer considerable advantage over amitriptyline and is more expensive . Larger trials are necessary to define gabapentin 's place in treating diabetic peripheral neuropathy pain UNLABELLED This was a 6-week , r and omized , double-blind , multicenter study evaluating the efficacy of pregabalin in the treatment of painful diabetic neuropathy . Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin ( 150 or 600 mg/day by mouth ) or placebo . The primary efficacy variable was mean pain score at the end of treatment . Efficacy results indicate that pregabalin 600 mg/day significantly decreased mean pain score to 4.3 ( vs 5.6 for placebo , P = .0002 ) and increased the proportion of patients who had a > or = 50 % decrease from baseline pain ( 39 % vs 15 % for placebo , P = .002 ) . Pregabalin also significantly reduced sleep interference , past week and present pain intensity , sensory and affective pain scores , and bodily pain and decreased by > or = 50 % the number of patients describing their pain as gnawing , sickening , fearful , and punishing-cruel . More patients receiving pregabalin 600 mg/day than placebo showed improvement , as rated on the Clinical and Patient Global Impression of Change scales , 73 % vs 45 % and 85 % vs 47 % , respectively . Pregabalin 150 mg/day was essentially no different from placebo . Dizziness was the most common side effect . These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy . PERSPECTIVE Painful diabetic peripheral neuropathy is a challenging neuropathic pain syndrome . This r and omized controlled trial demonstrates that pregabalin , a new drug that interacts with the alpha2-delta protein subunit of the voltage-gated calcium channel , is an efficacious and safe treatment for the pain of this condition In this single center , double blind and r and omized trial gabapentin as a new anticonvulsant was compared in efficacy and safety with amitriptyline which is a classic agent in neuropathic pain treatment . Fourty six patients with neuropathic pain which was burning , stabbing and shooting in quality were allocated to take gabapentin ( group GBP ) and amitriptyline ( group AMI ) monotherapy . The assesment variables were burning , stabbing , shooting pain on visual analog scale ( VAS ; 0 : no pain , 10 : worst pain imaginable ) , allodynia as present or not by lightly touching the skin with cotton . Primary efficacy variable was the degree of burning , stabbing and shooting pain improvement that was accepted as the difference of beginning and 4th week 's VAS of all pain qualities . The secondary efficacy variable was the patient satisfaction scale determined as whether possible side effects of study drugs affect the patients ' daily life . The degree of pain improvement was only seen in shooting pain and was statistically significantly high in group GBP . The patient satisfaction scale was also high in group GBP . Both gabapentin and amitriptyline provided effective pain control in peripheral neuropathic pain . Additionally gabapentin was more effective especially in paroxysmal shooting pain than other pain qualities . And also gabapentin was tolerated well Objective : Pregabalin , an alpha2-delta lig and with analgesic , anxiolytic , and anticonvulsant activity , has been evaluated for treatment of neuropathic pain . The authors assessed the efficacy and tolerability of pregabalin ( 75 , 300 , 600 mg/day ) vs placebo in patients with diabetic peripheral neuropathy ( DPN ) . Methods : Patients with a 1- to 5-year history of DPN and average weekly pain score of ≥4 on an 11-point numeric pain-rating scale were enrolled in a 5-week , double-blind , multicenter , placebo-controlled study . Patients ( n = 338 ) were r and omized to receive one of three doses of pregabalin or placebo TID . Pregabalin 600 mg/day was titrated over 6 days ; lower doses were initiated on day 1 . Results : Patients in the 300- and 600-mg/day pregabalin groups showed improvements in endpoint mean pain score ( primary efficacy measure ) vs placebo ( p = 0.0001 ) . Improvements were also seen in weekly pain score , sleep interference score , patient global impression of change , clinical global impression of change , SF-McGill Pain Question naire , and multiple domains of the SF-36 Health Survey . Improvements in pain and sleep were seen as early as week 1 and were sustained throughout the 5 weeks . Responders ( patients with ≥50 % reduction in pain compared to baseline ) were 46 % ( 300 mg/day ) , 48 % ( 600 mg/day ) , and 18 % ( placebo ) . Pregabalin was well tolerated with a low discontinuation rate . The most common adverse events were dizziness and somnolence . Conclusions : In patients with diabetic peripheral neuropathy , pregabalin demonstrated early and sustained improvement in pain and a beneficial effect on sleep , which were confirmed by positive patient global impression . Pregabalin was well tolerated at all doses Seven published , r and omized , placebo-controlled clinical trials with pregabalin have shown robust efficacy for relief of neuropathic pain from DPN and PHN . An investigation of the efficacy and safety of twice daily pregabalin enrolled 395 adults with painful DPN for > or = 1 year in a 12-week , double-blind , placebo-controlled trial . Patients were r and omized to placebo , 150 , 300 , or 600 mg/day pregabalin ( n = 96 , 99 , 99 , and 101 ) . Primary efficacy measure was change from baseline in endpoint mean pain score from patients ' daily pain diaries . Secondary efficacy measures included pain-related sleep-interference scores , Patient and Clinical Global Impressions of Change ( PGIC , CGIC ) , and the EuroQOL Health Utilities Index ( EQ-5D ) . Statistically significant reduction in pain was observed in patients receiving pregabalin 600 mg/day , and 46 % of patients treated with 600 mg/day pregabalin reported > or = 50 % improvement in mean pain scores from baseline ( vs 30 % of placebo patients , p = 0.036 ) . Number needed to treat to achieve such response was 6.3 . Pregabalin 600 mg/day was significantly superior to placebo in improving pain-related sleep-interference scores ( p = 0.003 ) , PGIC ( p = 0.021 ) , and CGIC ( p = 0.009 ) . ( Neither pregabalin 150 nor 300 mg/day separated from placebo on these measures , largely because of an atypically large placebo response in one country representing 42 % of patients . ) All pregabalin dosages were superior to placebo in improving EQ-5D utility scores ( all p > or = 0.0263 vs placebo ) . Pregabalin was well tolerated at all dosages ; adverse events were generally mild to moderate . Number needed to harm ( discontinuation because of adverse events ) was 10.3 for pregabalin 600 mg/day This study compared the efficacy of topical lidocaine patches versus vehicle ( placebo ) patches applied directly to the painful skin of subjects with postherpetic neuralgia ( PHN ) utilizing an ' enriched enrollment ' study design . All subjects had been successfully treated with topical lidocaine patches on a regular basis for at least 1 month prior to study enrollment . Subjects were enrolled in a r and omized , two-treatment period , vehicle-controlled , cross-over study . The primary efficacy variable was ' time to exit ' ; subjects were allowed to exit either treatment period if their pain relief score decreased by 2 or more categories on a 6-item Pain Relief Scale for any 2 consecutive days . The median time to exit with the lidocaine patch phase was greater than 14 days , whereas the vehicle patch exit time was 3.8 days ( P < 0.001 ) . At study completion , 25/32 ( 78.1 % ) of subjects preferred the lidocaine patch treatment phase as compared with 3/32 ( 9.4 % ) the placebo patch phase ( P < 0.001 ) . No statistical difference was noted between the active and placebo treatments with regards to side effects . Thus , topical lidocaine patch provides significantly more pain relief for PHN than does a vehicle patch . Topical lidocaine patch is a novel therapy for PHN that is effective , does not cause systemic side effects , and is simple to use Objective To evaluate the safety and efficacy of gabapentin and venlafaxine in the treatment of painful diabetic neuropathy in patients whose pain did not improve with gabapentin monotherapy . Methods ( 1 ) A r and omized , double-blind , placebo-controlled , 8-week clinical trial comparing gabapentin versus placebo to define a patient population whose pain did not improve with monotherapy ; ( 2 ) a second 8-week trial comparing gabapentin plus venlafaxine with gabapentin plus placebo ; ( 3 ) a third uncontrolled 8-week trial of patients who did not improve on gabapentin monotherapy and then received venlafaxine in addition to gabapentin . Results ( 1 ) Gabapentin-treated patients showed statistically significant improvement in pain reduction as well as improvement in quality of life and mood disturbance when compared with placebo-treated patients ; ( 2 ) patients who received gabapentin plus venlafaxine showed significant improvement in pain reduction , mood disturbance , and quality of life when compared with patients treated with gabapentin plus placebo ; ( 3 ) patients who received gabapentin plus venlafaxine showed significant improvement in pain reduction , mood disturbance , and quality of life . Conclusions ( 1 ) Gabapentin is efficacious in the treatment of painful diabetic neuropathy ; ( 2 ) and ( 3 ) in patients who do not respond to gabapentin monotherapy , the addition of venlafaxine is also efficacious Objective — To establish the effects of topically applied capsaicin on daily activities in patients with painful diabetic neuropathy . Research Design and Methods — Investigators at 12 sites enrolled 277 men and women with painful peripheral polyneuropathy and /or radiculopathy in an 8-wk double-blind vehicle-controlled study with parallel r and omized treatment assignments . Participants were unresponsive or intolerant to conventional therapy and were experiencing pain that interfered with functional activities and /or sleep . Either 0.075 % capsaicin cream or vehicle cream was applied to the painful areas 4 times/day . A visual analogue scale of pain intensity and baseline measurements of the pain 's interference with the ability to walk , work , participate in recreational activities , use shoes and socks , sleep , and eat were recorded at onset and at 2-wk intervals . A physician 's global evaluation scale assessed changes in pain status from baseline . Results — Statistically significant differences are percentage of patients with improvement in favor of capsaicin versus vehicle : 69.5 vs 53.4 % with clinical improvement in pain status ( P = 0.012 ) , 26.1 vs. 14.6 % with improvement in walking ( P = 0.029 ) , 18.3 vs. 9.2 % with improvement in working ( P = 0.019 ) , 29.5 vs. 20.3 % with improvement in sleeping ( P = 0.036 ) , and 22.8 vs. 12.1 % with improvement in participating in recreational activities ( P = 0.037 ) . Conclusions — The results from this study suggest that topical 0.075 % capsaicin is effective for reducing pain in patients with painful diabetic neuropathy with subsequent improvement in daily activities , enhancing the quality of the patient 's life ABSTRACT Objective : To compare efficacy and safety of 5 % lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia ( PHN ) or painful diabetic polyneuropathy ( DPN ) . Study design and methods : This was a two-stage adaptive , r and omized , open-label , multicentre , non-inferiority study . Data are reported from the initial 4-week comparative phase , in which adults with PHN or painful DPN received either topical 5 % lidocaine medicated plaster applied to the most painful skin area or twice-daily pregabalin capsules titrated to effect according to the Summary of Product Characteristics . The primary endpoint was response rate at 4 weeks , defined as reduction averaged over the last three days from baseline of ≥2 points or an absolute value of ≤4 points on the 11-point Numerical Rating Scale ( NRS-3 ) . Secondary endpoints included 30 % and 50 % reductions in NRS-3 scores ; change in allodynia severity rating ; quality of life ( QoL ) parameters EQ-5D , CGIC , and PGIC ; patient satisfaction with treatment ; and evaluation of safety ( laboratory parameters , vital signs , physical examinations , adverse events [ AEs ] , drug-related AEs [ DRAEs ] , and withdrawal due to AEs ) . Results : Ninety-six patients with PHN and 204 with painful DPN were analysed ( full analysis set , FAS ) . Overall , 66.4 % of patients treated with the 5 % lidocaine medicated plaster and 61.5 % receiving pregabalin were considered responders ( corresponding numbers for the per protocol set , PPS : 65.3 % vs. 62.0 % ) . In PHN more patients responded to 5 % lidocaine medicated plaster treatment than to pregabalin ( PPS : 62.2 % vs. 46.5 % ) , while response was comparable for patients with painful DPN ( PPS : 66.7 % vs 69.1 % ) . 30 % and 50 % reductions in NRS-3 scores were greater with 5 % lidocaine medicated plaster than with pregabalin . Both treatments reduced allodynia severity . 5 % lidocaine medicated plaster showed greater improvements in QoL based on EQ-5D in both PHN and DPN . PGIC and CGIC scores indicated greater improvement for 5 % lidocaine medicated plaster treated patients with PHN . Improvements were comparable between treatments in painful DPN . Fewer patients administering 5 % lidocaine medicated plaster experienced AEs ( safety set , SAF : 18.7 % vs. 46.4 % ) , DRAEs ( 5.8 % vs. 41.2 % ) and related discontinuations compared to patients taking pregabalin . Conclusion : 5 % lidocaine medicated plaster showed better efficacy compared with pregabalin in patients with PHN . Within DPN , efficacy was comparable for both treatments . 5 % lidocaine medicated plaster showed a favourable efficacy/safety profile with greater improvements in patient satisfaction and QoL compared with pregabalin for both indications , supporting its first line position in the treatment of localized neuropathic pain & NA ; A r and omized , double‐blind , placebo‐controlled , parallel‐group , multicenter , 8‐week trial ( with subsequent open‐label phase ) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy ( DPN ) . For enrollment , patients must have had at baseline : 1‐ to 5‐year history of DPN pain ; pain score ≥40 mm ( Short‐Form McGill Pain Question naire [ SF‐MPQ ] visual analogue scale ) ; average daily pain score of ≥4 ( 11‐point numerical pain rating scale [ 0=no pain , 10=worst possible pain ] ) . One hundred forty‐six ( 146 ) patients were r and omized to receive placebo ( n=70 ) or pregabalin 300 mg/day ( n=76 ) . Primary efficacy measure was endpoint mean pain score from daily patient diaries ( 11‐point numerical pain rating scale ) . Secondary measures included SF‐MPQ scores ; sleep interference scores ; Patient and Clinical Global Impression of Change ( PGIC and CGIC ) ; Short Form‐36 ( SF‐36 ) Health Survey scores ; and Profile of Mood States ( POMS ) scores . Safety assessment included incidence and intensity of adverse events , physical and neurological examinations , and laboratory evaluations . Pregabalin produced significant improvements versus placebo for mean pain scores ( P<0.0001 ) ; mean sleep interference scores ( P<0.0001 ) ; total SF‐MPQ score ( P<0.01 ) ; SF‐36 Bodily Pain subscale ( P<0.03 ) ; PGIC ( P=0.001 ) ; and Total Mood Disturbance and Tension – Anxiety components of POMS ( P<0.03 ) . Pain relief and improved sleep began during week 1 and remained significant throughout the study ( P<0.01 ) . Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo . Most adverse events were mild to moderate and did not result in withdrawal . Pregabalin was safe and effective in decreasing pain associated with DPN , and also improved mood , sleep disturbance , and quality of life Pain is the most disturbing symptom of diabetic neuropathy . Traditionally this type of pain was treated with tricyclic antidepressants which frequently have many side effects . In the study reported here , gabapentin was administered in escalating doses up to 3600 mg per day to eligible patients with moderate to severe diabetic neuropathy pain in a double blind placebo controlled fashion . Gabapentin provided superior and significant pain relief over placebo . In addition , patients taking gabapentin had improvement of sleep scores and a number of items on mood and quality of life question naires . Gabapentin was tolerated well with mild and tolerable side effects CONTEXT Postherpetic neuralgia ( PHN ) is a syndrome of often intractable neuropathic pain following herpes zoster ( shingles ) that eludes effective treatment in many patients . OBJECTIVE To determine the efficacy and safety of the anticonvulsant drug gabapentin in reducing PHN pain . DESIGN Multicenter , r and omized , double-blind , placebo-controlled , parallel design , 8-week trial conducted from August 1996 through July 1997 . SETTING Sixteen US outpatient clinical centers . PARTICIPANTS A total of 229 subjects were r and omized . INTERVENTION A 4-week titration period to a maximum dosage of 3600 mg/d of gabapentin or matching placebo . Treatment was maintained for another 4 weeks at the maximum tolerated dose . Concomitant tricyclic antidepressants and /or narcotics were continued if therapy was stabilized prior to study entry and remained constant throughout the study . MAIN OUTCOME MEASURES The primary efficacy measure was change in the average daily pain score based on an 11-point Likert scale ( 0 , no pain ; 10 , worst possible pain ) from baseline week to the final week of therapy . Secondary measures included average daily sleep scores , Short-Form McGill Pain Question naire ( SF-MPQ ) , Subject Global Impression of Change and investigator-rated Clinical Global Impression of Change , Short Form-36 ( SF-36 ) Quality of Life Question naire , and Profile of Mood States ( POMS ) . Safety measures included the frequency and severity of adverse events . RESULTS One hundred thirteen patients received gabapentin , and 89 ( 78.8 % ) completed the study ; 116 received placebo , and 95 ( 81.9 % ) completed the study . By intent-to-treat analysis , subjects receiving gabapentin had a statistically significant reduction in average daily pain score from 6.3 to 4.2 points compared with a change from 6.5 to 6.0 points in subjects r and omized to receive placebo ( P<.001 ) . Secondary measures of pain as well as changes in pain and sleep interference showed improvement with gabapentin ( P<.001 ) . Many measures within the SF-36 and POMS also significantly favored gabapentin ( P < or = .01 ) . Somnolence , dizziness , ataxia , peripheral edema , and infection were all more frequent in the gabapentin group , but withdrawals were comparable in the 2 groups ( 15 [ 13.3 % ] in the gabapentin group vs 11 [ 9.5 % ] in the placebo group ) . CONCLUSIONS Gabapentin is effective in the treatment of pain and sleep interference associated with PHN . Mood and quality of life also improve with gabapentin therapy & NA ; Pregabalin binds with high affinity to the alpha2‐delta subunit protein of voltage‐gated calcium channels and , thereby , reduces release of excitatory neurotransmitters . This 12‐week r and omised , double‐blind , multicentre , placebo‐controlled , parallel‐group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia ( PHN ) or painful diabetic peripheral neuropathy ( DPN ) . Patients were r and omised to placebo ( n=65 ) or to one of two pregabalin regimens : a flexible schedule of 150 , 300 , 450 , and 600 mg/day with weekly dose escalation based on patients ' individual responses and tolerability ( n=141 ) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks ( n=132 ) . Both flexible‐ and fixed‐dose pregabalin significantly reduced endpoint mean pain score ( primary outcome ) versus placebo ( P=0.002 , P<0.001 ) and were significantly superior to placebo in improving pain‐related sleep interference ( P<0.001 ) . The most common adverse events ( AEs ) for pregabalin‐treated patients were dizziness , peripheral oedema , weight gain ( not affecting diabetes control ) , and somnolence . These results are consistent with previous studies ' demonstrating pregabalin 's efficacy , tolerability , and safety for treatment of chronic neuropathic pain associated with DPN or PHN . Pregabalin dosing aim ed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation In a r and omized , double-blind crossover study , 29 patients with painful diabetic neuropathy received 6 weeks of amitriptyline and 6 weeks of an “ active ” placebo that mimicked amitriptyline side effects . Amitriptyline was superior to placebo in relieving pain in weeks 3 through 6 . Both steady , burning pain and lancinating pains were relieved . Patients able to tolerate higher amitriptyline doses reported greater relief , through the maximum dose of 150 mg nightly . Amitriptyline analgesia was similar in depressed and nondepressed subgroups and was not associated with mood improvement . We conclude that amitriptyline relieves pain in diabetic neuropathy ; this effect is independent of mood elevation |
11,901 | 24,106,321 | : Most of the PR programs had significant positive effects on exercise capacity and HRQOL in patients with mild COPD ; however , their effects on health-care re source use and lung function were inconclusive . | BACKGROUND : Pulmonary rehabilitation ( PR ) is effective in improving exercise capacity and health-related quality of life ( HRQOL ) in patients with moderate-to-very-severe COPD .
Quadriceps strength and HRQOL can be impaired in patients with mild COPD , therefore , patients at this grade may already benefit from PR .
However , the impact of PR in patients with mild COPD remains unestablished .
Thus , this systematic review assessed the impact of PR on exercise capacity , HRQOL , health-care re source use and lung function in patients with mild COPD . | OBJECTIVE This study attempted to determine the total direct costs derived from the management of chronic bronchitis and COPD in an ambulatory setting through a prospect i ve , 1-year , follow-up study . METHOD A total of 1,510 patients with chronic bronchitis and COPD were recruited from 268 general practice s located throughout Spain . Patients were followed up for 1 year . All direct medical costs incurred by the cohort and related to their respiratory disease were quantified . Costs were calculated for patients with confirmed COPD according to the degree of severity of airflow obstruction . RESULTS The global mean direct yearly cost of chronic bronchitis and COPD was $ 1,876 . The cost generated by patients with COPD was $ 1,760 , but the cost of severe COPD ( $ 2,911 ) was almost double that of mild COPD ( $ 1,484 ) . Hospitalization costs represented 43.8 % of costs , drug acquisition costs were 40.8 % , and clinic visits and diagnostic tests represented only 15.4 % of costs . CONCLUSION This is the first prospect i ve follow-up study on a large cohort of patients with chronic bronchitis and COPD aim ed at quantifying direct medical costs under usual clinical practice in the community . Costs of chronic bronchitis and COPD were almost twofold those reported for asthma . Patterns of COPD management in the community differ from those recommended in guidelines . COPD represents a great health-care burden in developed countries , and aging of the population and continuing smoking habits predict that it will continue to do so in the future Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Background Pulmonary rehabilitation ( PR ) is recognized as an evidence -based treatment in improving dyspnea and quality of life in patients with COPD . We evaluated the number needed to treat ( NNT ) to achieve an increase in physical capacity , as defined by a significant improvement in the six-minute walk test ( 6MWT ) in patients with COPD undergoing PR . Methods The study enrolled 284 patients aged 41 to 86 years ( mean age 69.4 years ) divided into two groups : a study group ( 222 patients ) undergoing a PR program , and a control group ( 62 patients ) treated only with drugs . The study group included patients with COPD divided in four subgroups according to GOLD stages . Results In the study group , 142 out of 222 patients ( 64 % ) had an increase of at least 54 m in the 6MWT following PR versus 8 out of 62 patients ( 13 % ) in the control group after the same time interval . The NNT in the overall study group was 2 ; the same NNT was obtained in GOLD stages 2 , 3 , and 4 , but was 8 in stage 1 . Conclusions PR is highly effective in improving the exercise capacity of patients with COPD , as demonstrated by a valuable NNT , with better results in patients with a more severe disease Background Pulmonary rehabilitation is known to be a beneficial treatment for COPD patients . To date , however , there is no agreement for how long a rehabilitation program should be implemented . In addition , current views are that pulmonary rehabilitation does not improve FEV1 or even slow its decline in COPD patients . The aim of the study was to examine the efficacy of a 3 year outpatient pulmonary rehabilitation ( PR ) program for COPD patients on pulmonary function , exercise capability , and body mass index ( BMI ) . Methods A matched controlled trial was performed with outcome assessment s evaluated at 6 , 12 , 18 , 24 , 30 , and 36 months . Eighty patients with moderate to severe COPD ( age 63 ± 7 years ; FEV1 48 % ± 14 ) were recruited . The control group received st and ard care only , while in addition , the case study group received PR for duration of three years . These groups were matched for age , sex , BMI , FEV1 % and number of pack-years smoked . Results The decline in FEV1 after the three years was significantly lower in the PR group compared to control , 74 ml versus 149 ml , respectively ( p < 0.001 ) . Maximal sustained work and endurance time improved after a short period of PR and was maintained throughout the study , in contrast to the control group ( p < 0.01 ) . A decreased BMI was noted in the control group after three years , while in the PR group a mild improvement was seen ( p < 0.05 ) . Conclusion Three years of outpatient pulmonary rehabilitation result ed in modifying the disease progression of COPD , as well as improving physical performance in these patients OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity OBJECTIVE To establish the minimal important difference ( MID ) for the six-minute walk distance ( 6MWD ) in persons with chronic obstructive pulmonary disease ( COPD ) . DESIGN Analysis of data from an observational study using distribution- and anchor-based methods to determine the MID in 6MWD . SETTING Outpatient pulmonary rehabilitation program at 2 teaching hospitals . PARTICIPANTS Seventy-five patients with COPD ( 44 men ) in a stable clinical state with mean age 70 years ( SD 9 y ) , forced expiratory volume in one second 52 % ( SD 21 % ) predicted and baseline walking distance 359 meters ( SD 104 m ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Participants completed the six-minute walk test before and after a 7-week pulmonary rehabilitation program . Participants and clinicians completed a global rating of change score while blinded to the change in 6MWD . RESULTS The mean change in 6MWD in participants who reported themselves to be unchanged was 17.7 meters , compared with 60.2 meters in those who reported small change and 78.4 meters in those who reported substantial change ( P=.004 ) . Anchor-based methods identified an MID of 25 meters ( 95 % confidence interval 20 - 61 m ) . There was excellent agreement with distribution-based methods ( 25.5 - 26.5 m , kappa=.95 ) . A change in 6MWD of 14 % compared with baseline also represented a clinical ly important effect ; this threshold was less sensitive than for absolute change ( sensitivity .70 vs .85 ) . CONCLUSIONS The MID for 6MWD in COPD is 25 meters . Absolute change in 6MWD is a more sensitive indicator than percentage change from baseline . These data support the use of 6MWD as a patient-important outcome in research and clinical practice BACKGROUND The aim of our study was to determine the effect of one year of pulmonary rehabilitation ( PR ) on functional parameters and exacerbation rates in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS A total of 100 patients were enrolled in a multidisciplinary PR program . PR included endurance , resistance and respiratory muscle training . We performed spiroergometry , a modified Bruce Test and measurements of upper and lower limb contractility as well as inspiratory muscle strength before , six and 12 months after beginning rehabilitation . Additionally , we assessed the quality of life and the number of exacerbations and exacerbation days one year before and after starting rehabilitation . RESULTS 100 patients ( 42 female/58 male ) with COPD ( COPD IV-N=36 , COPD III-N=42 , COPD II-N=22 ) , a mean age of 60.5+/-9.6 years , BMI 25.8+/-6.0 attended a rehabilitation training program over a time period of one year . Spiroergometry ( VO2max from 1.1 to 1.3 l/min , P<0.05 ) , modified Bruce Test ( from 13+/-7 Min to 18+/-9 Min ; P<0.001 ) , upper limb ( from 39.9+/-3 to 52.9+/-8 kg ; P<0.001 ) and lower limb strength increased significantly ( from 85.3+/-45 to 131.5+/-57 kg ; P<0.001 ) . The maximal inspiratory pressure rose from 81.1 mbar to 108.8 mbar ( p<0.001 ) . There was no improvement in FEV1 or FEV1/FVC but Saint Georges Respiratory Question naire ( total score ) improved from 37.2+/-3.6 to 26.5+/-2.8 ; P<0.001 . The same was true for exacerbation rates ( they dropped from 2.8 to 0.8 ; P=0.006 ) and the number of hospitalization days ( from 27.3 to 3.3 , P<0.001 ) . CONCLUSIONS One year of outpatient pulmonary rehabilitation is an effective intervention leading to a significant improvement in exercise tolerance and quality of life in patients with COPD also reducing COPD exacerbation rates and hospitalizations |
11,902 | 26,961,239 | Conclusions This study demonstrated that TCE can effectively improve physiological outcomes , biochemical outcomes , physical function , quality of life , and depression among patients with cardiovascular disease . | Background Traditional Chinese exercise ( TCE ) has widespread use for the prevention and treatment of cardiovascular disease ; however , there appears to be no consensus about the benefits of TCE for patients with cardiovascular disease .
The objective of this systematic review was to determine the effects of TCE for patients with cardiovascular disease . | Regular physical exercise is broadly recommended by current European and American hypertension guidelines . It remains elusive , however , whether exercise leads to a reduction of blood pressure in resistant hypertension as well . The present r and omized controlled trial examines the cardiovascular effects of aerobic exercise on resistant hypertension . Resistant hypertension was defined as a blood pressure ≥140/90 mm Hg in spite of 3 antihypertensive agents or a blood pressure controlled by ≥4 antihypertensive agents . Fifty subjects with resistant hypertension were r and omly assigned to participate or not to participate in an 8- to 12-week treadmill exercise program ( target lactate , 2.0±0.5 mmol/L ) . Blood pressure was assessed by 24-hour monitoring . Arterial compliance and cardiac index were measured by pulse wave analysis . The training program was well tolerated by all of the patients . Exercise significantly decreased systolic and diastolic daytime ambulatory blood pressure by 6±12 and 3±7 mm Hg , respectively ( P=0.03 each ) . Regular exercise reduced blood pressure on exertion and increased physical performance as assessed by maximal oxygen uptake and lactate curves . Arterial compliance and cardiac index remained unchanged . Physical exercise is able to decrease blood pressure even in subjects with low responsiveness to medical treatment . It should be included in the therapeutic approach to resistant hypertension BACKGROUND Preliminary evidence suggests that meditative exercise may have benefits for patients with chronic systolic heart failure ( HF ) ; this has not been rigorously tested in a large clinical sample . We sought to investigate whether tai chi , as an adjunct to st and ard care , improves functional capacity and quality of life in patients with HF . METHODS A single-blind , multisite , parallel-group , r and omized controlled trial evaluated 100 out patients with systolic HF ( New York Heart Association class I-III , left ventricular ejection fraction ≤40 % ) who were recruited between May 1 , 2005 , and September 30 , 2008 . A group-based 12-week tai chi exercise program ( n = 50 ) or time-matched education ( n = 50 , control group ) was conducted . Outcome measures included exercise capacity ( 6- minute walk test and peak oxygen uptake ) and disease-specific quality of life ( Minnesota Living With Heart Failure Question naire ) . RESULTS Mean ( SD ) age of patients was 67 ( 11 ) years ; baseline values were left ventricular ejection fraction , 29 % ( 8 % ) and peak oxygen uptake , 13.5 mL/kg/min ; the median New York Heart Association class of HF was class II . At completion of the study , there were no significant differences in change in 6-minute walk distance and peak oxygen uptake ( median change [ first quartile , third quartile ] , 35 [ -2 , 51 ] vs 2 [ -7 , 54 ] meters , P = .95 ; and 1.1 [ -1.1 , 1.5 ] vs -0.5 [ -1.2 , 1.8 ] mL/kg/min , P = .81 ) when comparing tai chi and control groups ; however , patients in the tai chi group had greater improvements in quality of life ( Minnesota Living With Heart Failure Question naire , -19 [ -23 , -3 ] vs 1 [ -16 , 3 ] , P = .02 ) . Improvements with tai chi were also seen in exercise self-efficacy ( Cardiac Exercise Self-efficacy Instrument , 0.1 [ 0.1 , 0.6 ] vs -0.3 [ -0.5 , 0.2 ] , P < .001 ) and mood ( Profile of Mood States total mood disturbance , -6 [ -17 , 1 ] vs -1 [ -13 , 10 ] , P = .01 ) . CONCLUSION Tai chi exercise may improve quality of life , mood , and exercise self-efficacy in patients with HF . Trial Registration clinical trials.gov Identifier : NCT00110227 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective : To examine the effects of a brief Tai Chi Chuan Qigong ( ` Qigong ' ) exercise intervention on individuals with traumatic brain injury . Design : A single-centre r and omized controlled trial pilot study . Setting : A registered charity day centre in the community . Subjects : Twenty individuals with traumatic brain injury . Intervention : Intervention participants attended a Qigong exercise session for one hour per week over eight weeks . Control participants engaged in non-exercise-based social and leisure activities for the same intervention period . Measures : Outcome was assessed at baseline and post intervention using the General Health Question naire-12 , the Physical Self-Description Question naire and the Social Support for Exercise Habits Scale , to measure perceived mood , self-esteem , flexibility , coordination , physical activity and social support . Results : Groups were comparable at baseline . After the intervention , mood was improved in the exercise group when compared with controls ( U = 22.0 , P = 0.02 ) . Improvements in self-esteem ( Z = 2.397 , P = 0.01 ) and mood ( Z = —2.032 , P = 0.04 ) across the study period were also evident in the exercise group only . There were no significant differences in physical functioning between groups . In view of the sample size , these findings are inconclusive . Conclusions : This study provides preliminary evidence that a brief Qigong exercise intervention programme may improve mood and self-esteem for individuals with traumatic brain injury . This needs to be tested in a large-scale r and omized trial Objectives . To evaluate the effectiveness of Baduanjin Qigong exercise on sleep , fatigue , anxiety , and depressive symptoms in chronic fatigue syndrome- ( CFS- ) like illness and to determine the dose-response relationship . Methods . One hundred fifty participants with CFS-like illness ( mean age = 39.0 , SD = 7.9 ) were r and omly assigned to Qigong and waitlist . Sixteen 1.5-hour Qigong lessons were arranged over 9 consecutive weeks . Pittsburgh Sleep Quality Index ( PSQI ) , Chalder Fatigue Scale ( ChFS ) , and Hospital Anxiety and Depression Scale ( HADS ) were assessed at baseline , immediate posttreatment , and 3-month posttreatment . The amount of Qigong self- practice was assessed by self-report . Results . Repeated measures analyses of covariance showed a marginally nonsignificant ( P = 0.064 ) group by time interaction in the PSQI total score , but it was significant for the " subjective sleep quality " and " sleep latency " items , favoring Qigong exercise . Improvement in " subjective sleep quality " was maintained at 3-month posttreatment . Significant group by time interaction was also detected for the ChFS and HADS anxiety and depression scores . The number of Qigong lessons attended and the amount of Qigong self- practice were significantly associated with sleep , fatigue , anxiety , and depressive symptom improvement . Conclusion . Baduanjin Qigong was an efficacious and acceptable treatment for sleep disturbance in CFS-like illness . This trial is registered with Hong Kong Clinical Trial Register : HKCTR-1380 OBJECTIVE To assess the effects of a 12-week Tai Chi exercise program on sleep using the sleep spectrogram , a method based on a single channel electrocardiogram (ECG)-derived estimation of cardiopulmonary coupling , previously shown to identify stable and unstable sleep states . METHODS We retrospectively analyzed 24-h continuous ECG data obtained in a clinical trial of Tai Chi exercise in patients with heart failure . Eighteen patients with chronic stable heart failure , left ventricular ejection fraction < or= 40 % ( mean [ + /-st and ard deviation ] age , 59+/-14 years , mean baseline ejection fraction 24%+/-8 % , mean ) were r and omly assigned to receive usual care ( N=10 ) , which included pharmacological therapy and dietary and exercise counseling , or 12 weeks of Tai Chi training ( N=8 ) in addition to usual care . Using the ECG-based sleep spectrogram , we compared intervention and control groups by evaluating baseline and 12-week high ( stable ) and low ( unstable ) frequency coupling ( HFC & LFC , respectively ) as a percentage of estimated total sleep time ( ETST ) . RESULTS At 12 weeks , those who participated in Tai Chi showed a significant increase in HFC ( + 0.05+/-0.10 vs. -0.06+/-0.09 % ETST , p=0.04 ) and significant reduction in LFC ( -0.09+/-0.09 vs. + 0.13+/-0.13 % ETST , p<0.01 ) , compared to patients in the control group . Correlations were seen between improved sleep stability and better disease-specific quality of life . CONCLUSIONS Tai Chi exercise may enhance sleep stability in patients with chronic heart failure . This sleep effect may have a beneficial impact on blood pressure , arrhythmogenesis and quality of life Purpose . To assess if Tai Chi added to endurance training ( ET ) is more effective than ET alone in improving exercise tolerance and quality of life ( QOL ) of elderly patients with chronic heart failure ( CHF ) . Design . Sixty CHF patients , age 73.8 ± 6 years , M/F 51/9 , were enlisted . Thirty pts were r and omized to combined training ( CT ) performing Tai Chi + ET and 30 patients to ET ( ET only ) . Methods . At baseline and after 12 weeks all patients underwent 6-minute walking test ( 6MWT ) , assessment of amino terminal probrain natriuretic peptide ( NT-pro BNP ) , quadriceps maximal voluntary contraction ( MVC ) and peak torque ( PT ) , QOL question naire ( MacNewQLMI ) , blood pressure ( BP ) , and heart rate ( HR ) . All patients performed 4 sessions of exercise/week . Results . Distance at 6mwt improved in both groups with significant between-groups differences ( P = .031 ) . Systolic BP and NT-proBNP decreased significant in the CT group compared to ET ( P = .025 ) and P = .015 ) , resp . ) . CT group had a greater significant improvement in physical perception ( P = .026 ) and a significant increase of PT compared to ET group . Conclusions . The association of Tai Chi and ET improves exercise tolerance and QOL of patients with CHF more efficiently than ET Exercise and relaxation decrease blood pressure . Qigong is a traditional Chinese exercise consisting of breathing and gentle movements . We conducted a r and omised controlled trial to study the effect of Guolin qigong on blood pressure . In all , 88 patients with mild essential hypertension were recruited from the community and r and omised to Goulin qigong or conventional exercise for 16 weeks . The main outcome measurements were blood pressure , health status ( SF-36 scores ) , Beck Anxiety and Depression Inventory scores . In the qigong group , blood pressure decreased significantly from 146.3±7.8/93.0±4.1 mmHg at baseline to 135.5±10.0/87.1±7.7 mmHg at week 16 . In the exercise group , blood pressure also decreased significantly from 140.9±10.9/93.1±3.5 mmHg to 129.7±11.1/86.0±7.0 mmHg . Heart rate , weight , BMI , waist circumference , total cholesterol , renin and 24 h urinary albumin excretion significantly decreased in both groups after 16 weeks . General health , bodily pain , social functioning and depression also improved in both groups . No significant differences between qigong and conventional exercise were found . In conclusion , Guolin qigong and conventional exercise have similar effects on blood pressure in patients with mild hypertension . While no additional benefits were identified , it is nevertheless an alternative to conventional exercise in the nondrug treatment of hypertension In this study , 126 patients ( 90 males , average age 56 years , range 39 - 80 ) were r and omised to Wu Chian-Ch'uan style Tai Chi ( 38 ) , aerobic exercise ( 41 ) or a non-exercise support group ( 47 ) following acute myocardial infa rct ion . Patients attended twice weekly for three weeks then weekly for a further five weeks . Heart rate and blood pressure were recorded before and after each session . Over the 11 sessions of exercise there was a negative trend in diastolic blood pressure only in the Tai Chi group ( Rs = 0.79 , p < 0.01 ) . Significant trends in systolic blood pressure occurred in both exercise groups ( Rs = 0.64 and 0.63 , both p < 0.05 ) . Only four ( 8 % ) patients completed the support group eight-week programme which was less than the number completing Tai Chi ( 82 % ; p < 0.001 ) and aerobic exercise groups ( 73 % ; p < 0.001 ) OBJECTIVES To evaluate the effects on blood pressure , lipid profile , and anxiety status on subjects received a 12-week Tai Chi Chuan exercise program . DESIGN R and omized controlled study of a Tai Chi Chuan group and a group of sedentary life controls . SETTING Taipei Medical University Hospitals and University campus in the Taipei , Taiwan , area . SUBJECTS Two ( 2 ) selected groups of 76 healthy subjects with blood pressure at high-normal or stage I hypertension . INTERVENTION A 12-week Tai Chi Chuan exercise training program was practice d regularly with a frequency of 3 times per week . Each session included 10-minute warm-up , 30-minute Tai Chi exercise , 10-minute cool-down . Exercise intensity was estimated to be approximately 64 % of maximal heart rate . OUTCOME MEASURES Blood pressure , lipid profile and anxiety status ( State-Trait Anxiety Inventory ; STAI ) were evaluated . RESULTS After 12-weeks of Tai Chi training , the treatment group showed significant decrease in systolic blood pressure of 15.6 mm Hg and diastolic blood pressure 8.8 mm Hg . The serum total cholesterol level decreased 15.2 mg/dL and high-density lipoprotein cholesterol increased 4.7 mg/dL. By using STAI evaluation , both trait anxiety and state anxiety were decreased . CONCLUSIONS This study shows that under well- design ed conditions , Tai Chi exercise training could decrease blood pressure and results in favorable lipid profile changes and improve subjects ' anxiety status . Therefore , Tai Chi could be used as an alternative modality in treating patients with mild hypertension , with a promising economic effect This study was design ed to measure changes in blood pressure ( BP ) , urinary catecholamines and ventilatory functions of patients with mild essential hypertension after 10 weeks of Qigong ( Shuxinpingxuegong ) . Fifty-eight patients volunteered to participate in this study and were r and omly divided into either a Qigong group ( n = 29 ) , or a control group ( n = 29 ) . Systolic blood pressure and diastolic blood pressure decreased significantly in the Qigong group such that both became significantly lower after 10 weeks in the Qigong than in the control group . Also , there was a significant reduction of norepinephrine , metanephrine and epinephrine compared to baseline values in the Qigong group . The ventilatory functions , forced vital capacity and forced expiratory volume per sec , were increased in the Qigong group but not the control . These results suggest that Qigong may stabilize the sympathetic nervous system is effective in modulating levels of urinary catecholamines and BP positively , and in improving ventilatory functions in mildly hypertensive middle-aged patients Falls among people aged 65 and older are a significant public health problem and one that is expected to increase as the population ages . R and omized controlled trials have demonstrated that Tai Ji Quan can reduce falls and associated injuries among older adults . In this paper , we describe how Tai Ji Quan community programs are being utilized by public health and aging services organizations to reduce older adult falls . We conclude that , to have a population -level impact on reducing falls and improving the health of older adults , Tai Ji Quan interventions must be translated into community programs that meet the needs and abilities of older adults . These programs must be adapted to fit into existing community structures , disseminated through multiple delivery channels , adopted and implemented broadly by organizations , and institutionalized to ensure sustainability Although exercise is an important component of heart failure management , optimal regimens , particularly in heart failure with preserved ejection fraction ( HFPEF ) , are uncertain . Tai chi ( TC ) is a mind-body exercise that may have potential benefits but has not been studied in this population . The authors r and omized 16 patients with HFPEF to either 12 weeks TC or aerobic exercise . Assessment s included peak oxygen uptake , 6-minute walk , quality of life , echocardiography , mood , and self-efficacy at baseline and at 12 weeks . Cardiorespiratory measures during exercise were obtained to characterize training intensities . Baseline characteristics were as follows : age 66±12 years , E/A ratio 1.3±0.7 , and E/e ' ratio 15.9±4.8 . Overall , adherence was excellent ( 89 % attendance ) . Change in peak oxygen uptake was similar between groups after 12 weeks , but 6-minute walk distance increased more after TC ( 69±46 m vs 10±31 m , P=.02 ) . While both groups had improved Minnesota Living With Heart Failure scores and self-efficacy , Profile of Mood States (POMS)-Depression scores improved more with TC ( -1.7±2.8 vs 1.6±3 , P=.05 ) . Cardiorespiratory assessment during TC showed lower oxygen uptake ( 4.3 mL/kg/min vs 9.4 mL/kg/min , P<.01 ) , respiratory rate , and heart rate . TC is feasible and safe in HFPEF . Therepeutic endpoints appear similar with TC relative to aerobic exercise despite a lower aerobic training workload This study investigated the effectiveness of Qigong on blood pressure and several blood lipids , such as high-density lipoprotein ( HDL ) cholesterol , Apolipoprotein A1 ( APO-A1 ) , total cholesterol ( TC ) , and triglycerides ( TG ) in hypertensive patients . Thirty-six patients were r and omly divided into either the Qigong group , or a wait-listed control group . Blood pressures decreased significantly after eight weeks of Qigong . The levels of TC , HDL , and APO-A1 were changed significantly in the Qigong group post-treatment compared with before treatment . In summary . Qigong acts as an antihypertensive and may reduce blood pressure by the modulation of lipid metabolism Objective : To study the effect of Tai Chi on exercise tolerance in patients with moderate heart failure . Design : R and omised parallel group study balanced for baseline variables . Setting : Cardiology Department , Royal Hallamshire Hospital . Patients and methods : 52 patients 42 men , mean age 68.9 years , range 4690 years , and 10 women , mean age 70.0 years , range 5882 with chronic heart failure New York Heart Association symptom class IIIII were studied . Patients were r and omised to Tai Chi Chuan twice a week for 16 weeks or to st and ard medical care without exercise rehabilitation . Main outcome measures : The primary outcome measure was the change in the distance walked in the shuttle walk test . Secondary outcome measures were changes in symptom scores and quality of life indices . Results : Objective measures of exercise tolerance did not improve significantly with Tai Chi , but patients having Tai Chi exercise had an improvement in symptom scores of heart failure measured by the Minnesota Living with Heart Failure Question naire comparison of deltas , 2.4 control vs 14.9 ; p0.01 , and depression scores measured by the SCL-90-R question naire 2.9 vs 6.8 ; p0.12 compared with those patients in the control group . Conclusion : In patients with chronic heart failure , 16 weeks of Tai Chi training was safe , with no adverse exercise related problems . It was enjoyed by all taking part and led to significant improvements in symptoms and quality of life This study was design ed to investigate the efficacy of Qigong as a non-pharmacological treatment of hypertension and evaluate the contribution of Qigong in the blood pressure ( BP ) reduction of essential hypertension patients . Fifty-eight patients volunteered to participate in this study and were r and omly divided into either a Qigong group ( n = 29 ) , or a wait list control group ( n = 29 ) . In response to 10 weeks of Qigong , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and rate pressure product ( RPP ) were decreased significantly . There was a significant reduction of norepinephrine , epinephrine , cortisol , and stress level by the Qigong . These results suggest that Qigong may reduce BP and catecholamines via stabilizing the sympathetic nervous system . Therefore , Qigong is an effective nonpharmacological modality to reduce BP in essential hypertensive BACKGROUND Cerebral vascular disorder ( CVD ) might result in a quantifiable decrease in quality of life , which is determined not only by the neurological deficits but also by impairment of cognitive functions . There are few studies that report on the cognitive effect of Tai Chi exercise ( Tai Chi ) on the elderly with CVD . The purpose of the present study was to examine the cognitive effect of Tai Chi on the elderly with CVD using P300 measurement , in addition to the General Health Question naire ( GHQ ) and Pittsburgh Sleep Quality Index ( PSQI ) . METHODS A total of 34 patients with CVD were recruited from outpatient Akistu-Kounoike Hospital and r and omly assigned to receive Tai Chi ( n= 17 ) or rehabilitation ( n= 17 ) in group sessions once a week for 12 weeks . To examine the time courses of each score ( P300 amplitude , P300 latency , GHQ score and PSQI score ) , repeated- measures analysis of variance was carried out with groups and time as factors . RESULTS For the time courses of P300 amplitudes and latencies , there were no significant effects of interaction between group and time . However , significant time-by-group interactions were found for Sleep Quality ( P= 0.006 ) , GHQ total score ( P= 0.005 ) , anxiety/insomnia score ( P= 0.034 ) , and severe depression score ( P= 0.020 ) . CONCLUSIONS Tai Chi might therefore be considered a useful non-pharmacological approach , along with rehabilitation , for the maintenance of cognitive function in the elderly with CVD and might be a more useful non-pharmacological approach for the improvement of sleep quality and depressive symptoms in the elderly with CVD than rehabilitation OBJECTIVE T'ai chi chuan ( TCC ) is a traditional Chinese exercise and is beneficial for health . Nevertheless , its effect on cardiovascular risk factors in dyslipidemic patients is not clear . The aim of this study was to evaluate the effect of TCC training on coronary heart disease ( CHD ) risk factors in patients with dyslipidemia . DESIGN This was design ed as a case-controlled study . SETTING The study was conducted in a community setting . SUBJECTS Fifty-three ( 53 ) patients ( males : 24 ; females : 29 ) with dyslipidemia completed this study . INTERVENTIONS The TCC group included 28 patients who participated in a 12-month yang TCC training program . The usual-care group included 25 patients who maintained a sedentary lifestyle during this study . OUTCOME MEASURES Exercise testing was conducted at baseline and after 1 year of training . Body composition , lipid profile , fasting glucose and insulin levels , and inflammatory markers were also measured before and after training . RESULTS After training , the TCC group showed an increase in V(.)O(2peak ) from 25.2 + /- 4.2 to 27.4 + /- 4.1 mL x kg(1 ) x min(1 ) ; while the usual-care group displayed a significant decrease from 25.6 + /- 4.9 to 24.1 + /- 4.0 mL x kg(-1 ) x min(-1 ) . The TCC group also showed a reduction in blood pressure , triglyceride , total cholesterol , low density lipoprotein cholesterol , plasma insulin , homeostasis model assessment index , and high-sensitivity C-reactive protein . Conversely , the usual-care group showed no significant improvement in these cardiovascular risk factors . CONCLUSIONS A 12-month TCC training program significantly improves aerobic capacity and CHD risk factors in patients with dyslipidemia Eighteen community-dwelling first-stroke survivors , aged 45 to 65 , underwent following examinations : Romberg 's Test , st and ing on the unaffected leg , Emory Fractional Ambulation Profile , the Berg Balance Test , the Timed ‘ Up and Go ’ Test and the Duke Health Profile . They were then r and omly divided into two matched groups of 9 subjects each . The study group ( SG ) received Tai Chi exercises and the control group ( CG ) physiotherapy exercises focused on improvement of balance , both groups for 1 h twice weekly for 12 weeks . On completion of exercises , SG subjects showed improvement in social and general functioning whereas CG subjects showed improvement in balance and speed of walking . It is concluded that there are potential and no adverse effects in Tai Chi practice in stroke survivors Objective : Examine the safety and feasibility of a 12-week Tai Chi intervention among stroke survivors . Design : Two-group , prospect i ve pilot study with r and om allocation . Setting : Outpatient rehabilitation facility . Subjects : Stroke survivors ≥50 years and at ≥three months post-stroke . Interventions : Tai Chi subjects attended group-based Yang Style classes three times/week for 12-weeks , while Usual Care subjects received weekly phone calls along with written material s/re sources for participating in community-based physical activity . Main outcome measures : Indicators of study safety and feasibility included recruitment rates , intervention adherence , falls or adverse events , study satisfaction , drop-outs , and adequacy of the outcomes measures . Results : Interested persons pre-screened by phone ( n = 69 ) were on average 68 years old , ( SD = 13 ) years old , 48 % ( n = 33 ) women , 94 % ( n = 65 ) were at least three months post-stroke . A total of 28 subjects aged 69 ( SD = 11 ) years enrolled in this pilot study . Intervention adherence rates were very high ( ≥92 % ) . There were no falls or other adverse events . The dose of Tai Chi exercise ( ≥150 minutes/week ) was well tolerated . Overall study satisfaction was high ( 8.3 ( SD = 1.9 ) ; 1 = not satisfied , 10 = most satisfied ) , while drop-outs ( n = 3 , 11 % ) were unrelated to study intervention . Score distributions for the outcome measures were approximately normal , sensitive to change , and seemed to favor the Tai Chi intervention . Conclusions : Tai Chi is a safe , community-based exercise program for stroke survivors . Our data suggest that recruitment and retention of an adequate sample is feasible , and that in a full-scale study 52 subjects/group are needed to detect statistically significant between group differences ( alpha = 0.05 , power = 0.80 ) |
11,903 | 24,746,873 | Endovascular aneurysm repair is not inferior to open repair in patients with a ruptured abdominal aortic aneurysm . | BACKGROUND There is clinical equipoise between open ( OR ) and endovascular aneurysm repair ( EVAR ) for the best treatment of ruptured abdominal aortic aneurysm ( RAAA ) .
OBJECTIVE The aim of the study was to perform a systematic review and meta- analysis to estimate the short-term ( combined 30-day or in-hospital ) survival after EVAR and OR for patients with RAAA . | The aim of the paper is to prospect ively describe early and mid-term outcomes for emergency endovascular aneurysm repair ( eEVAR ) versus open surgery in acute abdominal aortic aneurysms ( aAAAs ) , both unruptured ( symptomatic ) and ruptured . We enrolled all consecutive patients treated for aAAA at our center between April 2002 and April 2008 . The main outcome parameters were 30-day , 6- and 12-month mortality ( all-cause and aneurysm-related ) . Two hundred forty patients were enrolled in the study . In the unruptured aAAA group ( n = 111 ) , 47 ( 42 % ) underwent eEVAR . The 30-day , 6- and 12-month mortality rates were 6 , 13 and 15 % in the eEVAR group versus 11 % ( NS ) , 13 % ( NS ) and 16 % ( NS ) in the open group , respectively . In the ruptured aAAA group ( n = 129 ) , 25 ( 19 % ) underwent eEVAR ( mortality rates : 20 , 28 and 36 % , respectively ) compared with 104 ( 81 % ) patients who underwent open surgery ( mortality rates : 45 % ( P = 0.021 ) , 60 % ( P = 0.004 ) and 63 % ( P = 0.014 ) , respectively ) . In conclusion , the present study showed a reduced 30-day , 6- and 12-month mortality of eEVAR compared with open surgery in all patients with aAAA , mainly due to a lower mortality in the ruptured aAAA group . Late aneurysm-related mortality occurred only in the eEVAR group Endovascular aortic repair ( EVAR ) treatment for ruptured aortoiliac aneurysms ( rAIA ) avoids the additional surgical insult to physiology that comes with laparotomy and open repair ( OR ) . In systematic review s , the pooled mortality rate from rAIA after EVAR is around 20 % and morbidity around 40 % . The proportion of patients with rAIA treated by EVAR is steadily increasing , as most centers are adopting an EVAR as a first line therapy . However , two trials , one r and omized ( n = 32 ) and one nonr and omized , failed to demonstrate any benefit of EVAR to OR . The multicentric r and omized study named ECAR ( for Endosvasculaire vs Chirurgie dans les Anévrysmes Rompus ) was setup on 160 patients to compare the EVAR vs OR in rAIA . The primary outcome is mortality at 1 month . The study started in January 2008 and is still in progress OBJECTIVE Emergency Endovascular Aortic Aneurysm Repair ( eEVAR ) is a rapidly evolving approach to ruptured Abdominal Aortic Aneurysms ( rAAA ) . Yet longer-term outcomes following eEVAR remain unclear . This study compares mid-term outcomes of eEVAR and open rAAA . METHODS A prospect i ve data base for all patients undergoing eEVAR and open rAAA from January 2006 to April 2010 was analysed . Patients were offered eEVAR if anatomically suitable . RESULTS 52 patients ( 45 male , median age 78 years ( 62 - 92 years ) , underwent eEVAR , 50 patients ( 44 male , median age = 71 ( 62 - 95 years ) underwent open rAAA repair . In-hospital mortalities were 12 % ( 6/52 ) for eEVAR , 32 % ( 16/50 ) for open repair . There were five re- interventions ( 10 % ) in the eEVAR group . The peri-operative survival benefits of eEVAR over open rAAA repair were maintained at 1 and 2 years post-operatively with open repair demonstrating a two-fold increased risk of mortality ( Hazard ratio 2.2 , Fisher Exact test , 95 % Confidence Interval ( CI ) 1.108 - 4.62 , p = 0.0122 ) . Overall survival was 81 % at 1 year , 73 % at 2 years for eEVAR , and 62 % at 1 year and 52 % at 2 years for open rAAA repair . CONCLUSION EEVAR is associated with excellent mid-term survival in this cohort . We would recommend eEVAR as the management of choice for rAAA in anatomically suitable patients where local facilities and expertise exist OBJECTIVE Endovascular aneurysm repair ( EVAR ) decreases 30-day mortality for patients with ruptured abdominal aortic aneurysms ( r-AAAs ) compared with open surgical repair ( OSR ) . However , which patients benefit or whether there is any long-term survival advantage is uncertain . METHODS From 2002 to 2011 , 283 patients with r-AAA underwent EVAR ( n = 120 [ 42.4 % ] ) or OSR ( n = 163 [ 57.6 % ] ) at Albany Medical Center . All data were collected prospect ively . Patients were analyzed on an intention-to-treat basis , and outcomes were evaluated by a logistic regression multivariable model . Kaplan-Meier analysis was used to compare long-term survival . RESULTS The EVAR patients had a significantly lower 30-day mortality than did the OSR patients ( 29/120 [ 24.2 % ] vs 72/163 [ 44.2 % ] ; P < .005 ) and better cumulative 5-year survival ( 37 % vs 26 % ; P < .005 ) . Men benefited more from EVAR ( mortality : 20.9 % for EVAR vs 44.3 % for OSR ; P < .001 ) than did women ( mortality : 32.4 % vs 43.9 % ; P = .39 ) . Age ≥80 years was a significant predictor of death for EVAR ( odds ratio [ OR ] , 1.07 ; P = .003 ) but not for OSR ( OR , 1.04 ; P = .056 ) . Preexisting hypertension was a significant predictor of survival for both EVAR ( OR , 0.17 ; P < .001 ) and OSR ( OR , 0.48 ; P = .021 ) . Almost one fourth of EVAR patients ( 21/91 [ 23.1 % ] ) required secondary interventions . Survival advantage was maintained for EVAR patients to 5 years . CONCLUSIONS For r-AAA , EVAR reduces the 30-day mortality and improves long-term survival up to 5 years . However , whereas open survivors require few graft-related interventions , up to 23 % of EVAR patients will require reintervention for endoleaks or graft migration . Close follow-up of all EVAR survivors is m and atory AIM Several studies have shown the feasibility of endovascular repair of ruptured abdominal aortic aneurysms ( rEVAR ) . However , the role and value of rEVAR remains controversial due to selection bias and lack of long-term results . In the present study we describe our short- and long-term results of treating patients with rEVAR irrespective of hemodynamic condition and challenging anatomy . METHODS In April 2006 we started the single centre prospect i ve non-r and omised Ruptured Aneurysm Study ( RASA ) . During a four year enrolment period all consecutive patients presenting with infrarenal ruptured AAA ( rAAA , N.=117 ) were assessed for preferential rEVAR treatment . A rAAA was defined as extravasation of blood or hematoma outside the AAA due to transmural tear in the infrarenal abdominal aorta wall documented by preoperative computed tomography ( CT ) angiography examination or during open repair . Patients with challenging anatomy ( infrarenal neck length below 15 mm and neck angulation above 60 degrees ) were included as part of a damage control concept . Complication and mortality rates were studied at 30 days and yearly afterwards . RESULTS Thirty-five patients ( 33 % of all admitted rAAA ) were treated with rEVAR and 42 % of them were considered hemodynamically unstable ( systolic blood pressure < 100 mmHg ) and 30 % had challenging AAA anatomy . The mortality rate at 30 days in the rEVAR group was 17 % , in the open repair group 31 % , and in the entire rAAA group ( including abstained patients ) 36 % . During the first 30 days , 18 rEVAR patients experienced complications with nine re- interventions as a result . Long-term mortality of the rEVAR patients was 34 % after a median follow-up of 3.4 years . All deaths after one year follow-up were non-AAA related . Multivariate analysis shows that Hardman index , presence of peripheral arterial obstructive disease and lowest systolic blood pressure during surgery are independently associated with long-term survival . Challenging rAAA anatomy was not associated with impaired survival . CONCLUSION Our study shows that rEVAR is feasible irrespective of hemodynamic condition and that it is associated with relative low mortality rates . Challenging rAAA anatomy may not affect overall long-term survival , but six out of ten patients remain unsuitable for rEVAR because of inappropriate anatomy INTRODUCTION The successful application of endovascular techniques for the elective repair of abdominal aortic aneurysms ( AAAs ) has stimulated a strong interest in their possible use in dealing with a long-st and ing surgical challenge : the ruptured abdominal aortic aneurysm ( RAAA ) . The use of a conventional open procedure to repair ruptured aneurysms is associated with a high operative mortality of 45 % to 50 % . In this study , we evaluated the current frequency of endovascular repair of RAAAs in four large states and the impact of this technique on patient outcome . METHODS We examined discharge data sets from 2000 through 2003 from the four states of California , Florida , New Jersey , and New York , whose combined population represents almost a third of the United States population . Proportions and trends were analyzed by chi2 analysis and continuous variables by the Student 's t test . RESULTS We found that since the year 2000 , endovascular repair has begun to emerge as a viable treatment option for RAAAs , accounting for the repair of 6.2 % of cases in 2003 . During the same period , the use of open procedures for RAAAs declined . The overall mortality rate for the 4-year period was significantly lower for endovascular vs open repair ( 39.3 % vs. 47.7 % , P = .005 ) . Moreover , compared with open repair , endovascular repair result ed in a significantly lower rate of pulmonary , renal , and bleeding complications . Survival after endovascular repair correlated with hospital experience , as assessed by the overall volume of elective and nonelective endovascular procedures . For endovascular repairs , mortality ranged from 45.9 % for small volume hospitals to 26 % for large volume hospitals ( P = .0011 ) . Volume was also a determinant of mortality for open repairs , albeit to a much lesser extent ( 51.5 % for small volume hospitals , 44.3 % for large volume hospitals ; P < .0001 ) . CONCLUSION We observed a benefit to using endovascular procedures for RAAAs in institutions with significant endovascular experience ; however , the analysis of administrative data can not rule out selection bias as an explanation of better outcomes . These data strongly endorse the need for prospect i ve studies to clarify to what extent the improved survival in RAAA patients is to be attributed to the endovascular approach rather than the selection of low-risk patients OBJECTIVE To retrospectively compare a single center 's immediate and mid-term outcomes of ruptured abdominal aortic aneurysm open and endovascular repair ( EVAR ) for two patient groups-hemodynamically stable and unstable patients -in the same time period . METHODS Patients presenting at our center with confirmed rupture of an abdominal aortic aneurysm between December 1999 and April 2006 were considered according to an intention-to-treat model with EVAR . Patients with symptomatic or acute ( but not ruptured ) AAAs were not included in this study . Thirty-three patients underwent EVAR , and 91 underwent open repair . Seventy-two patients ( EVAR , 45 % ; open , 63 % ) were classified as hemodynamically unstable at arrival , and 52 were classified as stable ( EVAR , 55 % ; open , 37 % ) . Ninety-seven percent of EVAR procedures commenced under local anesthesia , and 100 % of open repairs occurred with general anesthesia . Overall successful graft deployment , 30-day mortality , overall reintervention rate , and complications were the study primary end points . RESULTS Overall successful graft deployment for EVAR was 91 % ; for open repair , it was 96 % . Overall 30-day mortality for EVAR was 30 % ( unstable , 53 % ; stable , 11 % ) , and the rate was 46 % for open repair ( unstable , 61 % ; stable , 21 % ) . The EVAR postoperative reintervention rate ( within 30 days ) was 15 % ( unstable , 20 % ; stable , 11 % ) , and for open repair it was 10 % ( unstable , 9 % ; stable , 15 % ) . We recorded a 27 % severe complication rate for EVAR patients ( unstable , 40 % ; stable , 17 % ) , and for patients treated with open repair , it was 33 % ( unstable , 35 % ; stable , 29 % ) . Our overall EVAR eligibility rate was 52 % , and our overall EVAR treatment rate was 27 % . CONCLUSIONS Our study 's overall results for EVAR remain encouraging when compared with those of conventional repair , but large r and omized trials are required to confirm the efficacy of the procedure BACKGROUND The study was conducted to demonstrate improved survival ( 30-day mortality ) after the introduction of an emergency endovascular therapy protocol for ruptured abdominal aortic aneurysms ( rAAA ) . Numerous authors have successfully demonstrated reduced mortality in patients with rAAA using endovascular techniques . Comparison of endovascular aneurysm repair ( EVAR ) with open repair for rAAA may be misleading , however , because EVAR can not be performed on all patients , and selection bias may explain the superior performance of any given surgical or endovascular strategy . We developed a model to predict mortality in patients before the introduction of EVAR ( pre protocol population ) , applied this model to predict 30-day mortality among prospect i ve patients ( post protocol population ) , and compared observed vs expected results . METHODS We assessed 126 patients with rAAA . Primary outcome was 30-day mortality . Potential confounding variables were age , sex , presurgical lowest recorded systolic blood pressure ( SBP ) , and glomerular filtration rate ( GFR ) . A logistic regression model incorporating significant confounders was used to evaluate changes in 30-day mortality for all patients with rAAA after introduction of the EVAR protocol . Separate logistic regressions were done to compare 30-day mortality for pre protocol vs patients receiving EVAR and pre protocol vs patients receiving post protocol open repair . Cumulative sum ( CUSUM ) analysis was used to assess shifts in the performance of the rAAA program over time . RESULTS Significant confounders were SBP , absence of SBP , and GFR . Logistic regression found evidence of lower mortality after the protocol was introduced , 17.9 % vs 30.0 % ( odds ratio [ OR ] , 0.385 ; 95 % confidence interval [ CI ] , 0.141 to 0.981 ; P = .046 ) . Comparison of all open repairs ( pre protocol and post protocol ) and EVAR demonstrated decreased risk for EVAR of 5.0 % vs 28.3 % ( OR , 0.109 ; 95 % CI , 0.013 to 0.906 ; P = .0084 ) . Unstable patients ( SBP < or=80 ) showed a trend towards improved survival with EVAR relative to open repair ( 14.3 % vs 56.0 % , P = .061 ) . Comparison of pre protocol surgery with open repair after the introduction of the protocol found no evidence of a difference between mortality rates for the open procedures -30.0 % ( pre protocol ) vs 25.0 % ( post protocol ; OR , 0.688 ; 95 % CI , 0.335 to 1.415 , P = .3031)-demonstrating that the improved performance observed with CUSUM analysis was related to the introduction of the EVAR protocol . CONCLUSION Our predictive model using " weighted " CUSUM analysis ( a measure of performance over time ) demonstrated that a predefined strategy of management of rAAA that includes EVAR is associated with improved ( P < .05 ) mortality . Unstable patients with rAAA may be particularly benefited by EVAR and should not be excluded from repair . Appropriate patients with rAAA who are undergoing treatment in experienced vascular centers should be offered EVAR as the treatment of choice OBJECTIVE Endovascular repair of ruptured abdominal aortic aneurysm ( rAAA ) is being increasingly performed despite lack of good evidence for its superiority . Other reported studies suffer from patient selection and publication bias with limited follow-up . This study is a single-center propensity score comparing early and midterm outcomes between open surgical repair ( OSR ) and endovascular repair of rAAA ( REVAR ) . METHODS A retrospective review from January 2001 to November 2010 identified 312 patients who underwent rAAA repairs . Thirty-one patients with antecedent AAA repair and three with incomplete records were excluded , leaving 37 REVARs and 241 OSRs . Propensity score-based matching for sex , age , preoperative hemodynamic status , surgeon 's annual AAA volume , and preoperative cardiopulmonary resuscitation was performed in a 1:3 ratio to compare outcomes . Thirty-seven REVARs were matched with 111 OSRs . Late survival was estimated by Kaplan-Meier methods . RESULTS Operative time and blood replacement were higher with OSR . Overall complication rates were similar ( 54 % REVAR vs 66 % OSR ; P = .23 ) , except for higher incidences of tracheostomies ( 21 % vs 3 % ; P = .015 ) , myocardial infa rct ion ( 38 % vs 18 % ; P = .036 ) , and acute tubular necrosis ( 47 % vs 21 % ; P = .009 ) with OSR . Operative mortality rates were similar ( 22 % REVAR vs 32 % OSR ) , with an odds ratio of 0.63 for REVAR ( 95 % confidence interval = [ 0.24 , 1.48 ] ; P = .40 ) . No differences in the incidences for secondary interventions for aneurysm- or graft-related complications were noted ( 22 % REVAR vs 22 % OSR ; P = .99 ) . Kaplan-Meier estimates of 1- , 2- , and 3-year survival rates were also similar ( 50 % , 50 % , 42 % REVAR vs 54 % , 52 % , 47 % OSR ; P = .66 ) . CONCLUSIONS REVAR for rAAA does not seem to conclusively confer either acute or late survival advantages . Routine use of REVAR should be deferred until prospect i ve , r and omized trial data become available |
11,904 | 26,852,170 | The use of molecular targeted agents does not translate into clinical benefit . | AIM A systematic review and meta- analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer . | Background : To evaluate the efficacy and tolerability of the urokinase plasminogen activator ( uPA ) inhibitor upamostat in combination with gemcitabine in locally advanced pancreatic adenocarcinoma ( LAPC ) . Methods : Within a prospect i ve multicenter study , LAPC patients were r and omly assigned to receive 1000 mg m−2 of gemcitabine IV weekly either alone ( arm A ) or in combination with 200 mg ( arm B ) or 400 mg ( arm C ) oral upamostat daily . Efficacy endpoints of this proof-of-concept study included response rate , time to first metastasis , progression-free and overall survival ( OS ) . Results : Of the 95 enroled patients , 85 were evaluable for response and 93 for safety . Median OS was 12.5 months ( 95 % CI 8.2–18.2 ) in arm C , 9.7 months ( 95 % CI 8.4–17.1 ) in arm B and 9.9 months ( 95 % CI 7.4–12.1 ) in arm A ; corresponding 1-year survival rates were 50.6 % , 40.7 % and 33.9 % , respectively . More patients achieved a partial remission ( confirmed responses by RECIST ) with upamostat combination therapy ( arm C : 12.9 % ; arm B : 7.1 % ; arm A : 3.8 % ) . Overall , only 12 patients progressed by developing detectable distant metastasis ( arm A : 4 , arm B : 6 , arm C : 2 ) . The most common adverse events considered to be related to upamostat were asthenia , fever and nausea . Conclusion : In this proof-of-concept study targeting the uPA system in LAPC , the addition of upamostat to gemcitabine was tolerated well ; similar survival results were observed for the three treatment arms Gemcitabine is a key drug for the treatment of pancreatic cancer ; however , with its limitation in clinical benefits , the development of another potent therapeutic is necessary . Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis , and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide ( elpamotide ) . Based on the promising results of this phase I trial , a multicenter , r and omized , placebo‐controlled , double‐blind phase II/III clinical trial has been carried out for pancreatic cancer . The eligibility criteria included locally advanced or metastatic pancreatic cancer . Patients were assigned to either the Active group ( elpamotide + gemcitabine ) or Placebo group ( placebo + gemcitabine ) in a 2:1 ratio by the dynamic allocation method . The primary endpoint was overall survival . The Harrington – Fleming test was applied to the statistical analysis in this study to evaluate the time‐lagged effect of immunotherapy appropriately . A total of 153 patients ( Active group , n = 100 ; Placebo group , n = 53 ) were included in the analysis . No statistically significant differences were found between the two groups in the prolongation of overall survival ( Harrington – Fleming P‐value , 0.918 ; log – rank P‐value , 0.897 ; hazard ratio , 0.87 , 95 % confidence interval [ CI ] , 0.486–1.557 ) . Median survival time was 8.36 months ( 95 % CI , 7.46–10.18 ) for the Active group and 8.54 months ( 95 % CI , 7.33–10.84 ) for the Placebo group . The toxicity observed in both groups was manageable . Combination therapy of elpamotide with gemcitabine was well tolerated . Despite the lack of benefit in overall survival , subgroup analysis suggested that the patients who experienced severe injection site reaction , such as ulceration and erosion , might have better survival Abstract Background Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis . A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine . The present r and omized , double-blinded , phase II trial compared the efficacy and safety of gemcitabine plus simvastatin ( GS ) with those of gemcitabine plus placebo ( GP ) in patients with locally advanced and metastatic pancreatic cancer . Methods Patients were r and omly assigned to receive a 3-week regimen with GS ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 plus simvastatin 40 mg once daily ) or GP ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 plus placebo ) . The primary end point was time to progression ( TTP ) . Results Between December 2008 and April 2012 , 114 patients were enrolled . The median TTP was not significantly different between the two arms , being 2.4 months ( 95 % CI 0.7–4.1 months ) and 3.6 months ( 95 % CI 3.1–4.1 months ) in the GS and GP arms , respectively ( P = 0.903 ) . The overall disease control rate was 39.7 % ( 95 % CI 12.2–33.8 % ) and 57.1 % ( 95 % CI 19.8–44.2 % ) in the GS and GP arms , respectively ( P = 0.09 ) . The 1-year expected survival rates were similar ( 27.7 and 31.7 % in the GS and GP arms , respectively ; P = 0.654 ) . Occurrence of grade 3 or 4 adverse events was similar in both arms , and no patients had rhabdomyolysis . Conclusions Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit , although it also does not result in increased toxicity . Given the emerging role of statins in overcoming resistance to anti-EGFR treatment , further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents , such as erlotinib or cetuximab , plus gemcitabine for treating advanced pancreatic cancer BACKGROUND Axitinib ( AG-013736 ) is a potent and selective oral inhibitor of vascular endothelial growth factor receptors 1 , 2 , and 3 , which have an important role in pancreatic cancer . The aim of this study was to assess the safety and efficacy of gemcitabine plus axitinib versus gemcitabine alone . METHODS Between January and August , 2006 , 103 patients with unresectable , locally advanced , or metastatic pancreatic cancer were r and omly assigned in a two to one ratio to receive gemcitabine ( 1000 mg/m(2 ) ) plus axitinib 5 mg twice daily ( n=69 ) or gemcitabine ( 1000 mg/m(2 ) ) alone ( n=34 ) by a central ised registration system . The primary endpoint was overall survival . Analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00219557 . FINDINGS All r and omised patients were included in the efficacy analyses . Median overall survival was longer with gemcitabine plus axitinib than with gemcitabine alone ( 6.9 [ 95 % CI 5.3 - 10.1 ] months vs 5.6 [ 3.9 - 8.8 ] months ) . The hazard ratio for survival with gemcitabine plus axitinib versus with gemcitabine alone , adjusted for stratification factors , was 0.71 ( 95 % CI 0.44 - 1.13 ) . The most common grade 3 or worse adverse events were fatigue ( 15 [ 22 % ] patients in the gemcitabine plus axitinib group vs one [ 3 % ] in the gemcitabine alone group ) , abdominal pain ( eight [ 12 % ] vs five [ 16 % ] ) , and asthenia ( eight [ 12 % ] vs one [ 3 % ] ) . INTERPRETATION Gemcitabine plus axitinib showed a similar safety profile to gemcitabine alone ; the small , non-statistically significant gain in overall survival needs to be assessed in a r and omised phase III trial BACKGROUND Axitinib is a potent , selective inhibitor of vascular endothelial growth factor ( VEGF ) receptors 1 , 2 , and 3 . A r and omised phase 2 trial of gemcitabine with or without axitinib in advanced pancreatic cancer suggested increased overall survival in axitinib-treated patients . On the basis of these results , we aim ed to assess the effect of treatment with gemcitabine plus axitinib on overall survival in a phase 3 trial . METHODS In this double-blind , placebo-controlled , phase 3 study , eligible patients had metastatic or locally advanced pancreatic adenocarcinoma , no uncontrolled hypertension or venous thrombosis , and Eastern Cooperative Oncology Group performance status 0 or 1 . Patients , stratified by disease extent ( metastatic vs locally advanced ) , were r and omly assigned ( 1:1 ) to receive gemcitabine 1000 mg/m(2 ) intravenously on days 1 , 8 , and 15 every 28 days plus either axitinib or placebo . Axitinib or placebo were administered orally with food at a starting dose of 5 mg twice a day , which could be dose-titrated up to 10 mg twice daily if well tolerated . A central ised r and omisation procedure was used to assign patients to each treatment group , with r and omised permuted blocks within strata . Patients , investigators , and the trial sponsor were masked to treatment assignments . The primary endpoint was overall survival . All efficacy analyses were done in all patients assigned to treatment groups for whom data were available ; safety and treatment administration and compliance assessment s were based on treatment received . This study is registered at Clinical Trials.gov , number NCT00471146 . FINDINGS Between July 27 , 2007 , and Oct 31 , 2008 , 632 patients were enrolled and assigned to treatment groups ( 316 axitinib , 316 placebo ) . At an interim analysis in January , 2009 , the independent data monitoring committee concluded that the futility boundary had been crossed . Median overall survival was 8·5 months ( 95 % CI 6·9 - 9·5 ) for gemcitabine plus axitinib ( n=314 , data missing for two patients ) and 8·3 months ( 6·9 - 10·3 ) for gemcitabine plus placebo ( n=316 ; hazard ratio 1·014 , 95 % CI 0·786 - 1·309 ; one-sided p=0·5436 ) . The most common grade 3 or higher adverse events for gemcitabine plus axitinib and gemcitabine plus placebo were hypertension ( 20 [ 7 % ] and 5 [ 2 % ] events , respectively ) , abdominal pain ( 20 [ 7 % ] and 17 [ 6 % ] ) , fatigue ( 27 [ 9 % ] and 21 [ 7 % ] ) , and anorexia ( 19 [ 6 % ] and 11 [ 4 % ] ) . INTERPRETATION The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer . These results add to increasing evidence that targeting of VEGF signalling is an ineffective strategy in this disease . FUNDING Pfizer BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group , as compared with 3.7 months in the gemcitabine group ( hazard ratio for disease progression or death , 0.69 ; 95 % CI , 0.58 to 0.82 ; P<0.001 ) ; the response rate according to independent review was 23 % versus 7 % in the two groups ( P<0.001 ) . The most common adverse events of grade 3 or higher were neutropenia ( 38 % in the nab-paclitaxel-gemcitabine group vs. 27 % in the gemcitabine group ) , fatigue ( 17 % vs. 7 % ) , and neuropathy ( 17 % vs. 1 % ) . Febrile neutropenia occurred in 3 % versus 1 % of the patients in the two groups . In the nab-paclitaxel-gemcitabine group , neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days . CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma , nab-paclitaxel plus gemcitabine significantly improved overall survival , progression-free survival , and response rate , but rates of peripheral neuropathy and myelosuppression were increased . ( Funded by Celgene ; Clinical Trials.gov number , NCT00844649 . ) PURPOSE The combination of gemcitabine plus bevacizumab produced a 21 % response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer . These encouraging data led Cancer and Leukemia Group B ( CALGB ) to conduct a double-blind , placebo-controlled , r and omized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients . PATIENTS AND METHODS Eligible patients had no prior therapy for advanced disease , Eastern Cooperative Oncology Group ( ECOG ) performance status 0 to 2 , no tumor invasion of adjacent organs , and no increased bleeding risk . The primary end point was overall survival . Patients were stratified by performance status , extent of disease , and prior radiotherapy . Patients received gemcitabine at 1,000 mg/m(2 ) over 30 minutes on days 1 , 8 , and 15 every 28 days and bevacizumab at 10 mg/kg or placebo on days 1 and 15 every 28 days . RESULTS Between June 2004 and April 2006 , 602 patients were enrolled onto the study and 535 were treated . Median overall survival was 5.8 months for gemcitabine/bevacizumab and 5.9 months for gemcitabine/placebo ( P = .95 ) . Median progression-free survival was 3.8 and 2.9 months , respectively ( P = .07 ) . Overall response rates were 13 % and 10 % , respectively . Patients with a performance status of 0 , 1 , and 2 survived a median of 7.9 , 4.8 , and 2.4 months , respectively . The only statistically significant differences in grade s 3 and 4 toxicity occurred for hypertension ( 10 % v 3 % ; P < .001 ) and proteinuria ( 5 % v 1 % ; P = .002 ) ; venous thrombosis grade > or = 3 was equivalent in both arms ( 14 % and 15 % , respectively ) . CONCLUSION The addition of bevacizumab to gemcitabine does not improve survival in advanced pancreatic cancer patients BACKGROUND The RAF-MEK-ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations . A phase II r and omized trial was design ed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer . METHODS Locally advanced or metastatic pancreatic adenocarcinoma patients were r and omized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400 mg bid ( arm A ) or without sorafenib ( arm B ) . RESULTS One hundred and fourteen patients were enrolled ; of these , 43 ( 74.6 % ) patients progressed in arm A and 44 ( 82.4 % ) in arm B. Median progression-free survival was 4.3 months ( 95 % CI : 2.7 - 6.5 ) and 4.5 months ( 95 % CI : 2.5 - 5.2 ) , respectively ( HR=0.92 ; 95 % CI : 0.62 - 1.35 ) . Median overall survival was 7.5 ( 95 % CI : 5.6 - 9.7 ) and 8.3 months ( 95 % CI : 6.2 - 8.7 ) , respectively ( HR=0.95 ; 95 % CI : 0.62 - 1.48 ) . Response rates were 3.4 % in arm A and 3.6 % in arm B. CONCLUSIONS Sorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancer patients , and therefore should not be assessed in phase III trials PURPOSE Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies . Pre clinical and early clinical evidence has supported targeting the epidermal growth factor receptor ( EGFR ) signaling pathway in patients with pancreas cancer . This trial was conducted to evaluate the contribution of an EGFR-targeted agent to st and ard gemcitabine therapy . Cetuximab is a monoclonal antibody against the lig and -binding domain of the receptor . PATIENTS AND METHODS Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were r and omly assigned to receive gemcitabine alone or gemcitabine plus cetuximab . The primary end point was overall survival . Secondary end points included progression-free survival , time to treatment failure , objective response , and toxicity . RESULTS A total of 745 eligible patients were accrued . No significant difference was seen between the two arms of the study with respect to the median survival time ( 6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm ; hazard ratio = 1.06 ; 95 % CI , 0.91 to 1.23 ; P = .23 , one-sided ) . Objective responses and progression-free survival were similar in both arms of the study . Although time to treatment failure was longer in patients on gemcitabine plus cetuximab ( P = .006 ) , the difference in length of treatment was only 2 weeks longer in the combination arm . Among patients who were studied for tumoral EGFR expression , 90 % were positive , with no treatment benefit detected in this patient subset . CONCLUSION In patients with advanced pancreas cancer , the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone . Alternate targets other than EGFR should be evaluated for new drug development PURPOSE Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms . To date , no treatment has had a significant impact on the disease . In early studies with gemcitabine , patients with pancreas cancer experienced an improvement in disease-related symptoms . Based on those findings , a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer . PATIENTS AND METHODS One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were r and omized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest , then weekly x 3 every 4 weeks thereafter ( 63 patients ) , or to fluorouracil ( 5-FU ) 600 mg/m2 once weekly ( 63 patients ) . The primary efficacy measure was clinical benefit response , which was a composite of measurements of pain ( analgesic consumption and pain intensity ) , Karnofsky performance status , and weight . Clinical benefit required a sustained ( > or = 4 weeks ) improvement in at least one parameter without worsening in any others . Other measures of efficacy included response rate , time to progressive disease , and survival . RESULTS Clinical benefit response was experienced by 23.8 % of gemcitabine-treated patients compared with 4.8 % of 5-FU-treated patients ( P = .0022 ) . The median survival duration s were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients , respectively ( P = .0025 ) . The survival rate at 12 months was 18 % for gemcitabine patients and 2 % for 5-FU patients . Treatment was well tolerated . CONCLUSION This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced , symptomatic pancreas cancer . Gemcitabine also confers a modest survival advantage over treatment with 5-FU BACKGROUND Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways . A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer ( APC ) patients . The BAYPAN study was a multicentric , placebo-controlled , double-blind , r and omized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC . PATIENTS AND METHODS The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma , no prior therapy for advanced disease and a performance status of zero to two . The primary end point was progression-free survival ( PFS ) . The patients received gemcitabine 1000 mg/m(2 ) i.v . , weekly seven times followed by 1 rest week , then weekly three times every 4 weeks plus sorafenib 200 mg or placebo , two tablets p.o . , twice daily continuously . RESULTS Between December 2006 and September 2009 , 104 patients were enrolled on the study ( 52 pts in each arm ) and 102 patients were treated . The median and the 6-month PFS were 5.7 months and 48 % for gemcitabine/placebo and 3.8 months and 33 % for gemcitabine/sorafenib ( P = 0.902 , stratified log-rank test ) , respectively . The median overall survivals were 9.2 and 8 months , respectively ( P = 0.231 , log-rank test ) . The overall response rates were similar ( 19 and 23 % , respectively ) . CONCLUSION The addition of sorafenib to gemcitabine does not improve PFS in APC patients In this r and omized , double-blind , placebo-controlled study comparing gemcitabine+tipifarnib ( G+t ) or gemcitabine+placebo ( G+p ) in patients with pancreatic cancer , the primary endpoint of time to deterioration ( TTD ) was based primarily on patient-reported outcomes . Deterioration was defined as death or worsening of disease-related symptoms , based on patient-reported outcomes of pain intensity and analgesic use in a daily diary , plus investigator-rated weekly performance status . Secondary endpoints included survival and safety . Two hundred and forty-four patients were treated for a total of 4780 weeks , during which the diary was completed daily . Overall , the completion of the diary was found to be feasible : patients completed approximately 95 % of scheduled diary entries . Baseline characteristics were well balanced between the two treatment arms . The primary endpoint of TTD was not significantly different between the G+t arm ( 69 days ) and the G+p arm ( 91 days , P=0.40 ) . Survival was not significantly different between the G+t arm ( 202 days ) and the G+p arm ( 221 days , P=0.66 ) . The combination of G+t had an acceptable toxicity profile , with primarily neutropenia and thrombocytopenia . Method ologically , measurement of patient-reported outcomes is feasible and useful in assessing the effect of anti-cancer therapy in pancreatic cancer if comprehensive initial and ongoing training is provided to all people involved , including not only the patients but also the study personnel BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application BACKGROUND Pancreatic ductal adenocarcinoma ( PDAC ) is one of the most common malignant tumours and is still associated with a poor prognosis in advanced disease . To improve the st and ard therapy with gemcitabine , we initiated a prospect i ve r and omised phase-II trial with gemcitabine ( GEM ) versus gemcitabine plus sunitinib ( SUNGEM ) based on data of in vitro trials and phase-I data for the combination treatment . The rational of adding sunitinib was its putative antiangiogenic mechanism of action . METHODS A total of 106 eligible patients with locally advanced , unresectable or metastatic PDAC without previous system therapy were r and omised to receive GEM at a dosage of 1.000mg/m(2 ) d1 , 8 , 15 q28 versus a combination of SUNGEM at a dosage of GEM 1.000mg/m(2 ) d1 + 8 and sunitinib 50 mg p.o . d1 - 14 , q21d . The primary end-point was progression free survival ( PFS ) , secondary end-points were overall survival ( OS ) , toxicity and overall response rate ( ORR ) . RESULTS The confirmatory analysis of PFS was based on the intend-to-treat ( ITT ) population ( N=106 ) . The median PFS was 13.3 weeks ( 95 % confidence interval ( 95%-CI ) : 10.4 - 18.1 weeks ) for GEM and 11.6 weeks for SUNGEM ( 95%-CI : 7.0 - 18.0 weeks ; p=0.78 one-sided log-rank ) . The ORR was 6.1 % ( 95%-CI : 0.7 - 20.2 % ) for GEM and for 7.1 % ( 95%-CI : 0.9 - 23.5 % ) for SUNGEM ( p=0.87 ) . The median time to progression ( TTP ) was 14.0 weeks ( 95%-CI : 12.4 - 22.3 weeks ) for GEM and 18.0 weeks ( 95%-CI : 11.3 - 19.3 weeks ) for SUNGEM ( p=0.60 ; two-sided log-rank ) . The median OS was 36.7 weeks ( 95%-CI : 20.6 - 49.0 weeks ) for the GEM arm and 30.4 weeks ( 95%-CI : 18.1 - 37.6 weeks ) for the SUNGEM ( p=0.78 , one-sided log-rank ) . In regard to toxicities , suspected SAEs were reported in 53.7 % in the GEM arm and 71.2 % in the SUNGEM arm . Grade 3 and 4 neutropenia was statistically significantly higher in the SUNGEM arm with 48.1 % versus 27.8 % in the GEM arm ( p=0.045 , two sided log-rank ) . CONCLUSIONS The combination SUNGEM was not sufficient superior in locally advanced or metastatic PDAC compared to GEM alone in regard to efficacy but was associated with more toxicity PURPOSE Patients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996 . Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 ( HER1/EGFR ) and this is associated with a worse prognosis . We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable , locally advanced , or metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned 1:1 to receive st and ard gemcitabine plus erlotinib ( 100 or 150 mg/d orally ) or gemcitabine plus placebo in a double-blind , international phase III trial . The primary end point was overall survival . RESULTS A total of 569 patients were r and omly assigned . Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio ( HR ) of 0.82 ( 95 % CI , 0.69 to 0.99 ; P = .038 , adjusted for stratification factors ; median 6.24 months v 5.91 months ) . One-year survival was also greater with erlotinib plus gemcitabine ( 23 % v 17 % ; P = .023 ) . Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 ( 95 % CI , 0.64 to 0.92 ; P = .004 ) . Objective response rates were not significantly different between the arms , although more patients on erlotinib had disease stabilization . There was a higher incidence of some adverse events with erlotinib plus gemcitabine , but most were grade 1 or 2 . CONCLUSION To our knowledge , this r and omized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine . The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d BACKGROUND A prospect i ve , r and omized phase II study , with m and atory tumor sampling at current disease stage , aim ed to identify biomarkers predictive of improved progression-free survival ( PFS ) in patients with pancreatic cancer treated with erlotinib . PATIENTS AND METHODS Patients with histologically/cytologically confirmed , unresectable , locally advanced/metastatic pancreatic cancer , who had failed on or were unsuitable for first-line chemotherapy , underwent a tumor biopsy and were then r and omized to receive once-daily erlotinib 150 mg or placebo . The primary end point was identification of biomarkers predicting improved PFS with erlotinib . Secondary end points included PFS , overall survival , response and toxicity . RESULTS At data cut-off , 207 patients were enrolled and analyzed . Prespecified biomarker analyses of EGFR protein expression , EGFR gene copy number/mutations/polymorphisms and KRAS mutations did not identify any subgroups with a detrimental effect or a strong benefit for PFS with erlotinib . In the primary analysis , the median PFS was 6.1 versus 5.9 weeks in the erlotinib and placebo arms , respectively [ hazard ratio ( HR ) 0.83 ; 95 % confidence interval ( CI ) 0.63 - 1.10 ; P = 0.1909 ] . However , observed baseline imbalances indicated worse prognosis in the erlotinib arm . After adjustment for baseline characteristics , a significant PFS benefit for erlotinib was observed ( HR 0.68 ; 95 % CI 0.50 - 0.91 ; P = 0.0102 ) . Exploratory biomarker analyses showed patients with high baseline serum amphiregulin levels might benefit from erlotinib . CONCLUSION This study in patients with inoperable pancreatic cancer did not identify any prespecified biomarkers predictive of PFS benefit with erlotinib . Exploratory analyses suggested high amphiregulin might predict PFS benefit from erlotinib . CLINICAL TRIALSGOV NUMBER NCT00674973 |
11,905 | 25,510,681 | Subgroup analysis showed the distribution of microorganisms from the six regions of China varied .
The main pathogens derived from women with PROM and their newborns were Staphylococcus and E. coli , which differs from the pathogens in Western countries . | To describe the spectrum of pathogens isolated from Chinese women experiencing premature rupture of the membranes ( PROM ) and those of their neonates , in order to provide effective management of PROM . | BACKGROUND The ORACLE I trial compared the use of erythromycin and /or amoxicillin-clavulanate ( co-amoxiclav ) with that of placebo for women with preterm rupture of the membranes without overt signs of clinical infection , by use of a factorial r and omised design . The aim of the present study --the ORACLE Children Study I -- was to determine the long-term effects on children of these interventions . METHODS We assessed children at age 7 years born to the 4148 women who had completed the ORACLE I trial and who were eligible for follow-up with a structured parental question naire to assess the child 's health status . Functional impairment was defined as the presence of any level of functional impairment ( severe , moderate , or mild ) derived from the mark III Multi-Attribute Health Status classification system . Educational outcomes were assessed with national curriculum test results for children resident in Engl and . FINDINGS Outcome was determined for 3298 ( 75 % ) eligible children . There was no difference in the proportion of children with any functional impairment after prescription of erythromycin , with or without co-amoxiclav , compared with those born to mothers who received no erythromycin ( 594 [ 38.3 % ] of 1551 children vs 655 [ 40.4 % ] of 1620 ; odds ratio 0.91 , 95 % CI 0.79 - 1.05 ) or after prescription of co-amoxiclav , with or without erythromycin , compared with those born to mothers who received no co-amoxiclav ( 645 [ 40.6 % ] of 1587 vs 604 [ 38.1 % ] of 1584 ; 1.11 , 0.96 - 1.28 ) . Neither antibiotic had a significant effect on the overall level of behavioural difficulties experienced , on specific medical conditions , or on the proportions of children achieving each level in reading , writing , or mathematics at key stage one . INTERPRETATION The prescription of antibiotics for women with preterm rupture of the membranes seems to have little effect on the health of children at 7 years of age . FUNDING UK Medical Research Council OBJECTIVE This study aims to determine the incidence of prelabor rupture of membranes ( PROM ) in a tertiary care institution , the bacterial pathogens involved in maternal and neonatal colonization , and the major bacterial pathogens of neonatal sepsis in PROM . METHODS This prospect i ve study was conducted over 2 years from March 1999 to February 2001 in Abha Maternity Hospital , Abha , Kingdom of Saudi Arabia . Consecutive admissions of infant- and -mother pairs with PROM constitute the subjects of this survey . Every mother had endocervical swab taken before delivery , and their infants had surface swabs and sepsis screening before starting antibiotic therapy . RESULTS The incidence of PROM was 12.6 per 1000 live births . Premature delivery rate was 54.6 % while , the overall prematurity rate was 7.2 % . The major microorganisms involved in genital colonization of the mothers were coagulase negative Staphylococcus ( CONS ) ( 24 % ) , Klebsiella pneumoniae ( 13 % ) , Pseudomonas aeruginosa ( 11.3 % ) and Enterococcus species ( 11.3 % ) . The infants were colonized largely with CONS ( 31 % ) , Klebsiella pneumoniae ( 18 % ) and Escherichia coli ( E.coli ) ( 17 % ) . Fourteen percent of the infants were infected but in only 6 % was septicemia documented ( Staphylococcus aureus , 3 cases and 1 case each with CONS , group B Streptococci ( GBS ) and E.coli ) . In contrast to Western experience , the incidence of GBS was uncommon in both mothers and infants . The bacterial pattern suggests vancomycin and cefotaxime or aminoglycoside combination as empirical antibiotic therapy for both infected infants and selected contaminated mothers with PROM . CONCLUSION Generally , it appears wasteful to routinely admit , screen and empirically treat all infants born after PROM ; only ill infants , febrile mothers , or either , with associated chorioamnionitis deserve antibiotic treatment Fifty-one babies with prolonged rupture of fetal membranes ( longer than 24 hours ) were studied for evidence of latent infection . Cord blood was taken from all babies for a full blood count and blood culture . Gastric aspirates were collected and vernix swabs were taken immediately after delivery . Microscopy , culture and antibiotic sensitivity tests were done on the appropriate specimens . Each baby had a thorough medical examination immediately after birth , and 3 and 7 days afterwards . After the initial investigation they were allocated to a treatment ( penicillin 50 000 U/kg/d and kanamycin 10 mg/kg/d ) or a non-treatment group by r and omised card selection . Six patients became infected , as was shown by a positive blood culture , while 4 of the 6 had clinical signs of infection as well . These infants were treated with penicillin and kanamycin , and all did well . None of the remaining babies showed any signs of infection . There were no deaths . Blood culture was found to correlate well with clinical infections , and many be used as a guide to latent infection and treatment Background : Few studies from developing countries have examined sensitivity , specificity , positive and negative predictive values of routine surface cultures . Objectives : The purpose of the study was to determine sensitivity , specificity , and positive predictive value ( PPV ) of skin cultures among preterm neonates admitted to Dhaka Shishu Hospital , Bangladesh . Methods : The study was nested within a prospect i ve , r and omized , controlled trial of emollient treatment in Dhaka Shishu Hospital , Bangladesh . A total of 497 preterm infants <33 weeks gestational age and < 72 h of chronological age were enrolled , and the sensitivity , specificity , and PPV of skin cultures were analyzed among 3,765 blood-skin culture pairs , wherein the skin culture was obtained within 13 days before the blood culture . Results : Overall sensitivity , specificity , and PPV were 16 , 38 , and 5 % , respectively . PPV during Klebsiella pneumoniae outbreaks was about 9 % , and the inguinal site had the highest PPV ( 6 % ) among the three skin sites . Acinetobacter spp.- and K. pneumoniae-specific PPVs were 28 and 23 % , respectively . PPV was < 2 % for C and ida spp . , Enterobacter spp . , and Salmonella spp . Conclusion : Routine skin culture is inefficient in predicting the pathogen responsible for sepsis among premature neonates , even in a developing country setting , where the burden of bacterial infection is relatively high . Skin cultures are also of limited utility during K. pneumoniae outbreaks , and are not recommended CONTEXT Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes ( PPROM ) . Antibiotic therapy has been shown to prolong pregnancy , but the effect on infant morbidity has been inconsistent . OBJECTIVE To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network . PATIENTS A total of 614 of 804 eligible gravidas with PPROM between 24 weeks ' and 0 days ' and 32 weeks ' and 0 days ' gestation who were considered c and i date s for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of r and omization . INTERVENTIONS Intravenous ampicillin ( 2-g dose every 6 hours ) and erythromycin ( 250-mg dose every 6 hours ) for 48 hours followed by oral amoxicillin ( 250-mg dose every 8 hours ) and erythromycin base ( 333-mg dose every 8 hours ) for 5 days vs a matching placebo regimen . Group B streptococcus ( GBS ) carriers were identified and treated . Tocolysis and corticosteroids were prohibited after r and omization . MAIN OUTCOME MEASURES The composite primary outcome included pregnancies complicated by at least one of the following : fetal or infant death , respiratory distress , severe intraventricular hemorrhage , stage 2 or 3 necrotizing enterocolitis , or sepsis within 72 hours of birth . These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed . RESULTS In the total study population , the primary outcome ( 44.1 % vs 52.9 % ; P=.04 ) , respiratory distress ( 40.5 % vs 48.7 % ; P=.04 ) , and necrotizing enterocolitis ( 2.3 % vs 5.8 % ; P=.03 ) were less frequent with antibiotics . In the GBS-negative cohort , the antibiotic group had less frequent primary outcome ( 44.5 % vs 54.5 % ; P=.03 ) , respiratory distress ( 40.8 % vs 50.6 % ; P=.03 ) , overall sepsis ( 8.4 % vs 15.6 % ; P=.01 ) , pneumonia ( 2.9 % vs 7.0 % ; P=.04 ) , and other morbidities . Among GBS-negative women , significant pregnancy prolongation was seen with antibiotics ( P<.001 ) . CONCLUSIONS We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity BACKGROUND There is paucity of information on the pattern of bacterial colonization of a new neonatal intensive care unit . OBJECTIVE To study the pattern of bacterial colonization on the environmental surfaces in a new neonatal intensive care unit ( NICU ) and correlate it with infections in the infants . METHODS Environmental cultures from the faucets and computer keyboards in the NICU were obtained prospect ively every 2 weeks for 1 year . Positive blood , cerebrospinal fluid , and respiratory cultures from the infants in the NICU were also obtained . RESULTS A total of 175 swab cultures was collected , which were sterile for initial 6-week period . Subsequently , 31 cultures grew microbes : 26 ( 83.8 % ) from the faucets and 5 ( 16.2 % ) from the computers keyboard ( P < .001 ) . Of the 48 positive blood cultures in NICU patients , 6 ( 12.5 % ) matched the organism growing from the surveillance sites , but the correlation was not significant ( P = .076 ) . None of the 31 positive respiratory cultures and 1 positive cerebrospinal fluid culture correlated to the organisms grown from the NICU environment . CONCLUSION The environment was colonized after an initial period of sterile cultures in a new NICU . Once colonized , they can persist , increasing the risk of developing resistance to antibiotics . They did not correlate with the positive cultures from the infants admitted to the NICU during the study period Summary A prospect i ve case control study that was conducted at the University of Ilorin Teaching Hospital , Ilorin , Nigeria , between 1st January and 31st December 2002 . The purpose of this study was to determine the association and the pattern of bacteria/microorganisms in the aetiology of pre-labour premature rupture of membrane ( PROM ) in this centre . A total of 108 cases of PROM and 98 control cases that presented between 37 completed weeks ' and 40 weeks ' gestation were analysed . Pathogens were isolated in 48 patients , giving a recovery rate of 44.4 % . The common pathogens include Gardnerella vaginalis ( 29.1 % ) , C and ida ( 23.0 % ) and Staphylococcus aureus ( 18.7 % ) . Others were Streps . Pyogenes ( 16.6 % ) , coagulase negative staphylococcus ( CONS ) ( 6.3 % ) and Klebsiella ( 6.3 % ) . Only C and ida and S. aureus were isolated in the controls . Ofloxacin and azithromycin were 100 % active against all the isolated pathogens , while ampicillin was the least active . G. vaginalis was the most sensitive among the isolates while CONS and Klebsiella were the least sensitive . It is evident in this study that some pathogens were associated with PROM and that G. vaginalis was the most common organism and azithromycin was the only antibiotic with 100 % sensitivity . We suggest that metronidazole should be added to azithromycin to cover for anaerobes in cases of PROM , where facilities for screening for anaerobes are not available Editor 's Note : In order to encourage dissemination of the STROBE Statement , this article is being published simultaneously in Annals of Internal Medicine , Epidemiology , and PLoS Medicine . It is freely accessible on the Annals of Internal Medicine Web site ( www.annals.org ) and will also be published on the Web sites of Epidemiology and PLoS Medicine . The authors jointly hold the copyright of this article . For details on further use , see the STROBE Web site ( www.strobe-statement.org ) . Rational health care practice s require knowledge about the etiology and pathogenesis , diagnosis , prognosis , and treatment of diseases . R and omized trials provide valuable evidence about treatments and other interventions . However , much of clinical or public health knowledge comes from observational research ( 1 ) . About 9 of 10 research papers published in clinical specialty journals describe observational research ( 2 , 3 ) . The STROBE Statement Reporting of observational research is often not detailed and clear enough to assess the strengths and weaknesses of the investigation ( 4 , 5 ) . To improve the reporting of observational research , we developed a checklist of items that should be addressed : the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) Statement ( Appendix Table ) . Items relate to the title , abstract , introduction , methods , results , and discussion sections of articles . The STROBE Statement has recently been published in several journals ( 6 ) . Our aim is to ensure clear presentation of what was planned , done , and found in an observational study . We stress that the recommendations are not prescriptions for setting up or conducting studies , nor do they dictate methodology or m and ate a uniform presentation . Appendix Table . The Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) Statement : Checklist of Items That Should Be Addressed in Reports of Observational Studies STROBE provides general reporting recommendations for descriptive observational studies and studies that investigate associations between exposures and health outcomes . STROBE addresses the 3 main types of observational studies : cohort , casecontrol , and cross-sectional studies . Authors use diverse terminology to describe these study design s. For instance , follow-up study and longitudinal study are used as synonyms for cohort study , and prevalence study as a synonym for cross-sectional study . We chose the present terminology because it is in common use . Unfortunately , terminology is often used incorrectly ( 7 ) or imprecisely ( 8) . In Box 1 , we describe the hallmarks of the 3 study design s. Box 1 . Main Study Design s Covered by STROBE The Scope of Observational Research Observational studies serve a wide range of purpose s , from reporting a first hint of a potential cause of a disease to verifying the magnitude of previously reported associations . Ideas for studies may arise from clinical observations or from biological insight . Ideas may also arise from informal looks at data that lead to further explorations . Like a clinician who has seen thous and s of patients and notes 1 that strikes her attention , the research er may note something special in the data . Adjusting for multiple looks at the data may not be possible or desirable ( 9 ) , but further studies to confirm or refute initial observations are often needed ( 10 ) . Existing data may be used to examine new ideas about potential causal factors , and may be sufficient for rejection or confirmation . In other instances , studies follow that are specifically design ed to overcome potential problems with previous reports . The latter studies will gather new data and will be planned for that purpose , in contrast to analyses of existing data . This leads to diverse viewpoints , for example , on the merits of looking at subgroups or the importance of a predetermined sample size . STROBE tries to accommo date these diverse uses of observational research from discovery to refutation or confirmation . Where necessary , we will indicate in what circumstances specific recommendations apply . How to Use this Paper This paper is linked to the shorter STROBE paper that introduced the items of the checklist in several journals ( 6 ) , and forms an integral part of the STROBE Statement . Our intention is to explain how to report research well , not how research should be done . We offer a detailed explanation for each checklist item . Each explanation is preceded by an example of what we consider transparent reporting . This does not mean that the study from which the example was taken was uniformly well reported or well done ; nor does it mean that its findings were reliable , in the sense that they were later confirmed by others : It only means that this particular item was well reported in that study . In addition to explanations and examples , we included boxes with supplementary information . These are intended for readers who want to refresh their memories about some theoretical points or be quickly informed about technical background details . A full underst and ing of these points may require study ing the textbooks or method ological papers that are cited . STROBE recommendations do not specifically address topics , such as genetic linkage studies , infectious disease modeling , or case reports and case series ( 11 , 12 ) . As many of the key elements in STROBE apply to these design s , authors who report such studies may nevertheless find our recommendations useful . For authors of observational studies that specifically address diagnostic tests , tumor markers , and genetic associations , STARD ( 13 ) , REMARK ( 14 ) , and STREGA ( 15 ) recommendations may be particularly useful . The Items in the STROBE Checklist We now discuss and explain the 22 items in the STROBE checklist ( Appendix Table ) and give published examples for each item . Some examples have been edited by removing citations or spelling out abbreviations . Eighteen items apply to all 3 study design s , whereas 4 are design -specific . Starred items ( for example , item 8) indicate that the information should be given separately for cases and controls in casecontrol studies , or exposed and unexposed groups in cohort and cross-sectional studies . We advise authors to address all items somewhere in their paper , but we do not prescribe a precise location or order . For instance , we discuss the reporting of results under a number of separate items , while recognizing that authors might address several items within a single section of text or in a table . Title and Abstract 1(a ) Indicate the study 's design with a commonly used term in the title or the abstract . Example Leukaemia incidence among workers in the shoe and boot manufacturing industry : a casecontrol study ( 18 ) . Explanation Readers should be able to easily identify the design that was used from the title or abstract . An explicit , commonly used term for the study design also helps ensure correct indexing of articles in electronic data bases ( 19 , 20 ) . 1(b ) Provide in the abstract an informative and balanced summary of what was done and what was found . Example Background : The expected survival of HIV-infected patients is of major public health interest . Objective : To estimate survival time and age-specific mortality rates of an HIV-infected population compared with that of the general population . Design : Population -based cohort study . Setting : All HIV-infected persons receiving care in Denmark from 1995 to 2005 . Patients : Each member of the nationwide Danish HIV Cohort Study was matched with as many as 99 persons from the general population according to sex , date of birth , and municipality of residence . Measurements : The authors computed KaplanMeier life tables with age as the time scale to estimate survival from age 25 years . Patients with HIV infection and corresponding persons from the general population were observed from the date of the patient 's HIV diagnosis until death , emigration , or 1 May 2005 . Results : 3990 HIV-infected patients and 379 872 persons from the general population were included in the study , yielding 22 744 ( median , 5.8 y/person ) and 2 689 287 ( median , 8.4 y/person ) person-years of observation . Three percent of participants were lost to follow-up . From age 25 years , the median survival was 19.9 years ( 95 % CI , 18.5 to 21.3 ) among patients with HIV infection and 51.1 years ( CI , 50.9 to 51.5 ) among the general population . For HIV-infected patients , survival increased to 32.5 years ( CI , 29.4 to 34.7 ) during the 2000 to 2005 period . In the subgroup that excluded persons with known hepatitis C coinfection ( 16 % ) , median survival was 38.9 years ( CI , 35.4 to 40.1 ) during this same period . The relative mortality rates for patients with HIV infection compared with those for the general population decreased with increasing age , whereas the excess mortality rate increased with increasing age . Limitations : The observed mortality rates are assumed to apply beyond the current maximum observation time of 10 years . Conclusions : The estimated median survival is more than 35 years for a young person diagnosed with HIV infection in the late highly active antiretroviral therapy era . However , an ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population ( 21 ) . Explanation The abstract provides key information that enables readers to underst and a study and decide whether to read the article . Typical components include a statement of the research question , a short description of methods and results , and a conclusion ( 22 ) . Abstract s should summarize key details of studies and should only present information that is provided in the article . We advise presenting key results in a numerical form that includes numbers of participants , estimates of associations , and appropriate measures of variability and uncertainty ( for example , odds ratios with confidence intervals ) . We regard it insufficient to state only that an exposure is or is not significantly associated with an |
11,906 | 22,071,832 | There was no significant differences in mortality or severe morbidity in any of the comparisons .
There is currently no evidence to support or refute the use of any treatment to reduce infectious complications after liver resections . | BACKGROUND Infections cause both morbidity and mortality in patients undergoing liver resection .
Various methods have been advocated to decrease the infectious complications after liver resection .
We do not know if they are of any benefit to the patient or the health-care funder .
OBJECTIVES To determine the benefits and harms of different interventions in decreasing the infectious complications and improving the outcomes after liver resection . | Objective This prospect i ve r and omized study determined the influence of closed-suction drainage on the incidence of postoperative complications after elective hepatic resection . Summary Background Data Routine drainage is no longer advocated after several intra-abdominal surgical procedures . Methods A series of 81 patients who underwent elective hepatic resection were r and omly allocated to either a nondrainage group ( n = 39 ) and a drainage group with closed-suction drainage ( n = 42 ) . Indications for resection were 42 benign lesions and 39 malignant tumors , including 19 with cirrhosis . Major hepatic resection was performed in 25 patients and minor resection , in 56 . All patients underwent ultrasonography with puncture for bacteriologic cultures of all fluid collection s within the first 5 postoperative days . Results One patient died in each group . Ultrasonography found a significantly higher rate of subphrenic collection s in the drainage group compared with the nondrainage group ( respectively , 36 % vs. 15 % , p < 0.05 ) . These collection s were more frequently infected in the drainage group ( n = 6 ) than in the nondrainage group ( n = 2 ) . After major liver resection , the rate of intra-abdominal postoperative complications ( i.e. , subphrenic fluid collection s , hematomas , and bilomas ) was similar between the two groups . Conclusion Minor liver resection is safer without drainage . Major liver resection can be performed with or without abdominal drainage OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Background and aims The clinical value of synbiotics in surgical patients remains unclear . The aim of this study was to investigate the effect of synbiotics on intestinal integrity and microflora , as well as on surgical outcome , in patients undergoing high-risk hepatectomy . Methods Fifty-four patients with biliary cancer were r and omly allocated to two groups before hepatectomy . One group received postoperative enteral feeding that included synbiotics ; the other received enteral feeding only . Lactulose/mannitol ( L/M ) ratio , serum diamine oxidase ( DAO ) activity , and fecal microflora and organic acid concentrations were determined . Postoperative infectious complications were recorded . Results Of the 54 patients , 44 completed the trial ( 21 receiving synbiotics and 23 others as controls ) . Postoperative changes in L/M ratios and serum DAO activities were identical between the two groups . Numbers of beneficial bacteria increased in the synbiotics group after surgery but decreased in controls . Numbers of harmful microorganisms decreased in the synbiotics group but increased in controls . Total organic acid concentrations increased in the synbiotics group but decreased in controls . Incidence of infectious complications was 19 % ( 4/21 ) in the synbiotics group and 52 % ( 12/23 ) in controls ( P<0.05 ) . All study patients tolerated surgery ( mortality 0 % ) . Conclusions Synbiotics , combined with early enteral nutrition , can reduce postoperative infections . This beneficial effect presumably involves correction of an intestinal microbial imbalance induced by surgical stress Introduction : Despite advances in antibiotic prophylaxis , postoperative wound infection remains a major source of morbidity after digestive surgery . Its prevention is a challenging problem , especially in high-risk patients . The authors introduced a new method to prevent surgical wound infections and evaluated its efficacy in a prospect i ve , r and omized trial in markedly high-risk patients . Methods : Patients with biliary tract carcinoma who were scheduled to undergo combined liver and extrahepatic bile duct resection with biliary reconstruction were r and omly assigned to one of two groups , well matched in terms of clinical characteristics at baseline . In one group the new treatment was employed ( sealed group , n=31 ) , and in the other the wound was treated in the usual fashion ( open group , n=28 ) . In the sealed group , povidone-iodine gel was administered to the subcutaneous tissue , and the skin and peritoneum were approximated with a continuous suture . Wound infection was registered up to 30 days after surgery . Results : Wound infection occurred in 18 patients : 5 ( 16 % ) patients in the sealed group and 13 ( 46 % ) in the open group ( P<0.05 ) . All 18 underwent preoperative percutaneous transhepatic biliary drainage and had positive bile culture findings . In 13 of these 18 patients ( 72 % ) the micro-organisms isolated from the infected wound were identical to those in the bile . Conclusions : Our results confirm the close association between infected bile and wound infection in hepatobiliary surgery . Our new method , “ direct wound sealing , ” is simple , easy to perform , virtually cost-free , and has the potential to prevent wound infections even in markedly high-risk patients Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Objective To analyze postoperative leukocyte functions in patients undergoing hemihepatectomy , and to assess the effect of treatment with the endotoxin-neutralizing agent bactericidal/permeability-increasing protein ( rBPI21 ) . Summary Background Data Extensive liver resection is associated with a high incidence of infectious complications . Because elimination of pathogenic microorganisms occurs mainly by leukocytes , this increased rate of infections is most likely due to an impaired function of these cells . Endotoxin , translocated from the gut into the systemic circulation as a result of increased gut permeability and reduced hepatic clearance function after major liver resection , may play an important role in the impairment of posthepatectomy leukocyte function . Methods To investigate whether hemihepatectomy results in impaired leukocyte functions and to determine the role of endotoxin in this process , leukocyte oxidative burst and leukocyte antigen expression were studied in three groups of patients : patients undergoing a hemihepatectomy and receiving rBPI21 treatment , patients undergoing hemihepatectomy and receiving placebo , and as an extra control group patients undergoing other major abdominal surgeries . Blood sample s were collected before surgery , 2 hours after surgery , and at days 1 , 2 , 5 , and 7 . Phorbol myristate acetate-stimulated oxidative burst was measured using dihydrorhodamine , and leukocyte surface expression of the antigens CD11b , CD16 , and CD14 was investigated by indirect immunofluorescence . Both oxidative burst and membrane surface expression were quantified by flow cytometry . An indication of the antiendotoxin effect of rBPI21 treatment was provided by assessment of plasma lipopolysaccharide binding protein ( LBP ) levels by enzyme-linked immunosorbent assay . Results The oxidative burst in the hemihepatectomized patients receiving placebo and the controls increased 2 hours after surgery , whereas it decreased in the rBPI21-treated patients , result ing in significant differences between the groups . On day 1 , neutrophil CD11b expression and monocyte CD14 expression in the rBPI21-treated patients and controls were significantly lower than in the placebo group . At 2 hours , CD16 expression in the placebo-treated patients was significantly higher than in the rBPI21-treated patients and controls . On day 5 and day 7 , plasma LBP levels were significantly higher in the placebo-treated patients compared with the rBPI21-treated patients . Conclusions The results of this study show that patients undergoing major liver resection have an increased activation of leukocytes compared with those undergoing other major abdominal surgery . This enhanced activation may contribute to the increased risk of infection in these patients . Administration of the endotoxin-neutralizing agent rBPI21 to hemihepatectomy patients was shown to reduce plasma LBP levels , to preserve leukocyte functions partially , and to reduce leukocyte activation to the level of other , nonhepatic abdominal surgery OBJECTIVES Although the usefulness of antimicrobial prophylaxis for clean-contaminated surgery has been recognized , only a few r and omized controlled studies on the duration of administration after hepatectomy have been performed . We investigated the duration of antimicrobial prophylaxis after hepatectomy . METHODS The subjects were 180 patients who underwent hepatectomy without reconstruction of the biliary or intestinal tract between April 2003 and March 2006 at our department . The patients were r and omly allocated to groups to be treated with flomoxef sodium as antimicrobial prophylaxis for 2 days ( 89 patients ) or 5 days ( 91 patients ) , including the operation day . The presence or absence of systemic inflammatory response syndrome ( SIRS ) and infections was investigated . RESULTS No significant differences were noted in patient background between the two groups . Infections occurred in seven and six patients in the 2 day and 5 day treatment groups ( 7.9 % and 6.6 % ) , respectively , showing no significant difference between the two groups . No significant difference was noted when the cases were divided into surgical site infections and remote infections . The positive rate of SIRS was significantly higher in the 2 day treatment group than in the 5 day treatment group on days 2 and 3 after surgery . The risk factors in patients who developed infections were blood loss , operation time and the complication of biliary fistula . CONCLUSIONS Two day administration of flomoxef sodium may be sufficient for antimicrobial prophylaxis after hepatectomy . However , when SIRS is positive on post-operative day 2 , and induction of liver failure is of concern , it may be safer to continue antimicrobial drug administration until SIRS is eliminated PURPOSE A prospect i ve , r and omized trial was performed to determine if intra-abdominal drainage catheters are necessary after elective liver resection . PATIENTS AND METHODS Between April 1992 and April 1994 , 120 patients subjected to liver resection , stratified by extent of resection and by surgeon , were r and omized to receive or not receive operative closed-suction drainage . Operative blood loss was not an exclusion criteria , and no patient who consented to the study was excluded . RESULTS Eighty-seven patients ( 73 % ) had resection of one hepatic lobe or more ( 27 lobectomies , 54 trisegmentectomies , and 6 bilobar atypical resections ) and 33 had less than a lobectomy ( 8 wedge resections or enucleations , 9 segmentectomies , and 16 bisegmentectomies ) . Eighty-four patients ( 70 % ) had metastatic cancer and 36 patients ( 30 % ) had primary liver pathology . There were no differences in outcome , including length of hospital stay ( no drain , 13.4 + /- 0.9 days ; drain , 13.1 + /- 0.8 days ; P = not significant [ NS ] ) , mortality ( no drain , 3.3 % ; drain , 3.3 % ) , complication rate ( no drain , 43 % ; drain , 48 % ; P = NS ) , or requirement for subsequent percutaneous drainage ( no drain , 18 % ; drain , 8 % ; P = NS ) . All infected collection s ( n = 3 ) occurred in operatively drained patients . Two other complications were directly related to the operatively placed drains . One patient developed a subcutaneous abscess at the drain site , and a second developed a subcutaneous drain tract tumor recurrence as the only current site of recurrence . CONCLUSION In the first 50 consecutive resections performed since the conclusion of this trial , only 4 patients ( 8 % ) have required subsequent percutaneous drainage . We conclude that abdominal drainage is unnecessary after elective liver resection INTRODUCTION Major hepatic resections are still associated with considerable morbidity . Gut-derived bacteria and bacterial endotoxin are considered to play a central role in the pathophysiology of complications . Experimental studies suggest that bactericidal/permeability-increasing protein ( BPI ) , which has both antibacterial and endotoxin-neutralising properties , can reduce postoperative complications . MATERIAL AND METHODS A phase II , double-blind , placebo-controlled , multicentre , dose escalation trial was conducted in patients undergoing major liver resection , and clinical outcome , infectious complications , plasma amino acid patterns , coagulation and fibrinolytic cascade systems and neutrophil functions were compared between the two treatment groups and an extra group of patients undergoing major abdominal non-hepatic surgery . RESULTS Drug administration in this patient group was safe , and result ed in a significant reduction of infectious complications . Furthermore , beneficial effects were found in the postoperative amino acid ratio and fibrinolytic cascades , and rBPI21 preserved leukocyte functions . CONCLUSION Administration of rBPI21 in patients undergoing major liver resection is well tolerated and results in improvement of both clinical and biochemical parameters Systemic antibiotics are administered frequently after hepatectomy to prevent infective complications , but their effectiveness is uncertain Summary Background Data : Use of synbiotics has been reported to benefit human health , but clinical value in surgical patients remains unclear . Objective : To investigate the effect of perioperative oral administration of synbiotics upon intestinal barrier function , immune responses , systemic inflammatory responses , microflora , and surgical outcome in patients undergoing high-risk hepatobiliary resection . Methods : Patients with biliary cancer involving the hepatic hilus ( n = 101 ) were r and omized before hepatectomy , into a group receiving postoperative enteral feeding with synbiotics ( group A ) ; or another receiving preoperative plus postoperative synbiotics ( group B ) . Lactulose-mannitol ( L/M ) ratio , serum diamine oxidase ( DAO ) activity , natural killer ( NK ) cell activity , interleukin-6 ( IL-6 ) , fecal microflora , and fecal organic acid concentrations were determined before and after hepatectomy . Postoperative infectious complications were recorded . Results : Of 101 patients , 81 completed the trial . Preoperative and postoperative changes in L/M ratio and DAO activity were similar between groups . Preoperatively in group B , NK activity , and lymphocyte counts increased , while IL-6 decreased significantly ( P < 0.05 ) . Postoperative serum IL-6 , white blood cell counts , and C-reactive protein in group B were significantly lower than in group A ( P < 0.05 ) . During the preoperative period , numbers of Bifidobacterium colonies cultured from and total organic acid concentrations measured in feces increased significantly in group B ( P < 0.05 ) . Postoperative concentrations of total organic acids and acetic acid in feces were significantly higher in group B than in group A ( P < 0.05 ) . Incidence of postoperative infectious complications was 30.0 % ( 12 of 40 ) in group A and 12.1 % ( 5 of 41 ) in group B ( P < 0.05 ) . Conclusions : Preoperative oral administration of synbiotics can enhance immune responses , attenuate systemic postoperative inflammatory responses , and improve intestinal microbial environment . These beneficial effects likely reduce postoperative infectious complications after hepatobiliary resection for biliary tract cancer |
11,907 | 27,731,533 | Current evidence shows no superiority of blastocyst compared with cleavage-stage embryo transfer in clinical practice . | OBJECTIVES Blastocyst transfer in assisted reproduction techniques could be advantageous because the timing of exposure of the embryo to the uterine environment is more analogous to a natural cycle and permits embryo self- selection after activation of the embryonic genome on day 3 .
Conversely , the in-vitro environment is likely to be inferior to that in vivo , and in-vitro culture beyond embryonic genomic activation could potentially harm the embryo .
Our objective was to identify , appraise and summarize the available evidence comparing the effectiveness of blastocyst vs cleavage-stage embryo transfer . | BACKGROUND Recently , advances in human IVF-embryo transfer ( ET ) have been reported using sequential media and blastocyst stage ET . In our previous report , using a prospect i ve , r and omized study , no advantage was found using the blastocyst stage ET compared with day 3 ET . This study was performed in order to evaluate implantation and pregnancy rates of hatching blastocyst stage ET compared with conventional day 3 ET . METHODS AND RESULTS A total of 480 patient cycles were evaluated using a prospect i ve , r and omized study . The pregnancy rate and implantation rate were compared between the day 3 ET ( n = 240 ) and hatching blastocyst stage ET ( Hat ET ; n = 240 ) . The Hat ET group had a pregnancy rate of 29.3 % ( 55 out of 188 ) and an implantation rate of 21.4 % ( 67 out of 313 ) . The day 3 ET group had a pregnancy rate of 29.2 % ( 70 out of 240 ) and an implantation rate of 19.1 % ( 93 out of 488 ) . In the Hat ET group , the pregnancy rate , implantation rate and ongoing pregnancy rate of day 5 ET and day 6 ET were all higher than the respective rates in the day 7 - 9 ET group . CONCLUSION We found that the pregnancy rate and implantation rate of ET with hatching stage blastocysts had no advantage compared with the conventional day 3 ET OBJECTIVE : To evaluate the efficacy of blastocyst transfer in comparison with cleavage stage transfer . STUDY DESIGN : A r and omized , prospect i ve study was conducted in Infertility clinic , Department of Obstetrics and Gynecology , Mahatma G and hi Hospital , Jaipur on 300 patients aged 25 - 40 years undergoing in-vitro fertilization (IVF)/intra-cytoplasmic sperm injection ( ICSI ) cycle from May 2010-April 2011 . When three or more Grade -I embryos were observed on day 2 of culture , patients were divided r and omly into two study groups , cleavage stage transfer and blastocyst transfer group having 150 patients each . Primary outcomes evaluated were , Clinical pregnancy rate and Implantation rate . The results were analyzed using proportions , st and ard deviation and Chi-square test . RESULTS : Both the groups were similar for age , indication and number of embryos transferred . Clinical pregnancies after blastocyst transfer were significantly higher 66 ( 44.0 % ) compared to cleavage stage embryo transfer 44 ( 29.33 % ) ( P < 0.01 ) . Implantation rate for blastocyst transfer group was also significantly higher ( P < 0.001 ) . CONCLUSION : Blastocyst transfer having higher implantation rate and clinical pregnancy rate lead to reduction in multiple pregnancies OBJECTIVE To compare blastocyst-stage embryo transfers ( ETs ) with day 2 - 3 ETs in patients who failed to conceive in three or more day 2 - 3 IVF/ET cycles . DESIGN Prospect i ve , r and omized . SETTING Fertility unit in a university medical center . PATIENT(S ) Fifty-four patients with an adequate ovarian response underwent oocyte retrievals . The patients were prospect ively and r and omly divided into blastocyst-stage and day 2 - 3 ET groups . INTERVENTION(S ) Ovarian down-regulation was obtained using GnRH agonist , and controlled ovarian hyperstimulation was achieved using daily administration of gonadotropins . MAIN OUTCOME MEASURE(S ) The rate of blastocyst formation , ET cancellations , pregnancies , implantation , multiple gestation , and live births . RESULT ( S ) The clinical pregnancy rates per oocyte retrieval were 21.7 % and 12.9 % per blastocyst and day 2 - 3 ETs , respectively . Although there was a significantly higher implantation rate for blastocyst embryos ( 21.2 % ) as compared with 48- to 72-hour embryos ( 6 % ) , the multiple-pregnancy rate was not significantly different between both groups . An ET cancellation rate of 26 % and 6.4 % for blastocyst and day 2 - 3 ETs , respectively , was observed . The presence of two or more 8-cell embryos on day 3 in culture carried a high probability of obtaining blastocysts for transfer . CONCLUSION ( S ) This prospect i ve r and omized study suggests that in patients with an adequate ovarian response who failed to conceive in at least three IVF/ET cycles [ 1 ] . transfer of blastocyst-stage embryos carries a significantly higher implantation rate ; [ 2 ] . the pregnancy rate per oocyte retrieval and ET are higher in the blastocyst-stage group , even if it did not reach statistical significance ; [ 3 ] . a higher ET cancellation rate was observed in the whole blastocyst-stage group ; [ 4 ] . the ET cancellation rate was reduced significantly if the decision to proceed to blastocyst transfer was made on day 3 after oocyte retrieval , which is a post hoc conclusion BACKGROUND The respective advantages of day 3 and day 5 embryo transfer are a matter of debate . Previous comparisons did not include pronuclear stage zygote scoring and cumulative success rates ( fresh and cryopreserved embryos ) . METHODS Patients were r and omized prospect ively for day 3 or day 5 embryo transfer . Day 3 embryos were selected for transfer and cryopreservation by using combined evaluation at the pronuclear and cleavage stages . RESULTS There was no difference between day 3 and day 5 fresh embryo transfers as to the rates of pregnancy ( 58 versus 62 % ) , clinical pregnancy ( 56 versus 58 % ) , delivery ( 50 versus 48 % ) , implantation ( 35 versus 38 % ) and birth ( 33 versus 36 % ) rates . The corresponding values for cryopreserved embryo transfers were also similar . However , day 3 embryo transfer compared favourably with day 5 transfer when the pregnancy ( 90 versus 66 % ) , clinical pregnancy ( 85 versus 62 % ) and delivery ( 77 versus 52 % ) rates were calculated per oocyte recovery attempt . CONCLUSIONS With a selected population of good prognosis patients and our embryo selection criteria , the implantation potential of day 3 and day 5 embryos is equal . Per oocyte recovery attempt , day 3 transfer is more clinical ly efficient than day 5 transfer , but at least one transfer of cryopreserved embryos is necessary to manifest this superiority The effectiveness of blastocyst culture and transfer in human in-vitro fertilization ( IVF ) was evaluated in a prospect i ve r and omized trial in patients having a moderate to good response to gonadotrophin stimulation . Embryos were transferred either on day 3 after culture to around the 8-cell stage in Ham 's F-10 medium supplemented with fetal cord serum , or on day 5 after culture to the blastocyst stage in the sequential serum-free media G 1.2 and G 2.2 . The pregnancy rates after transfer on day 3 or day 5 were equivalent , 66 and 71 % respectively ; however , significantly more embryos were transferred on day 3 ( 3.7 ) than on day 5 ( 2.2 ) . The number of blastocysts transferred did not affect the implantation rate , and pregnancy rates when either two or three blastocysts were transferred were 68 and 87 % respectively . The implantation rate of the blastocysts ( 50.5 % fetal heart beat ) was significantly higher compared to the cleavage stage embryos transferred on day 3 ( 30.1 % ) . The percentage of blastocyst development was not affected by the number of 2-pronuclear embryos , or by maternal age . Irrespective of the number of blastocysts formed , pregnancy rates were similar . Furthermore , the pregnancy rate following blastocyst transfer in patients with 10 or more follicles at the time of human chorionic gonadotrophin administration was not affected by patient age . More than 60 % of patients having blastocyst culture and transfer had supernumerary embryos for cryopreservation . The establishment of a pregnancy following thaw and transfer confirmed the viability of cryopreserved blastocysts cultured in the absence of serum or co-culture . The ability to transfer just two blastocysts while maintaining high pregnancy rates will therefore help to eliminate high order multiple gestations and improve the overall efficiency of human IVF Transfer of embryos at the blastocyst stage has been associated with exceptionally high implantation rates . There are , however , only a few prospect i ve r and omized studies comparing day 3 versus day 5 embryo transfer . Furthermore , the number of embryos replaced in the day 3 group transfer is often higher than the number of blastocysts replaced , thereby affecting implantation rates . A total of 118 patients undergoing st and ard IVF/intracytoplasmic sperm injection who had developed at least three 8-cell embryos showing < 20 % extracellular fragmentation on day 3 were r and omized for day 3 or day 5 transfer . A maximum of two embryos were replaced . In this prospect i ve , r and omized study the implantation and pregnancy potential of embryos transferred on day 3 or day 5 were compared . Equal numbers of embryos were replaced in the two groups . There was no statistically significant difference between day 3 and day 5 transfer regarding positive human chorionic gonadotrophin rates ( 70 versus 67 % ) , clinical pregnancy rates ( 61 versus 51 % ) , implantation rates ( 44 versus 37 % ) , twinning rates ( 42 versus 41 % ) and rates of early pregnancy loss ( 15 versus 29 % ) . Transfer of embryos on day 3 or 5 showed similar implantation rates when equal numbers of embryos were transferred . Embryo transfer at the blastocyst stage seems to have no advantage over day 3 transfer in patients with more than two 8-cell embryos showing less than 20 % fragmentation on day 3 BACKGROUND Whether extended culture allowing selection of embryos with high development potential has any advantage over cleavage-stage embryo transfer remains a matter of debate . Among the currently unsolved questions , the cumulative delivery rate result ing from fresh and frozen embryo transfers needs to be taken into account in both strategies . The aim of our study was , therefore , to compare the efficacy of single embryo transfer either on Day 2 or on Day 5/6 combining fresh and frozen embryo transfers . METHODS A prospect i ve study including 478 couples assigned on a voluntary basis to undergo elective single embryo transfer ( eSET , n = 243 ) on Day 2 or single blastocyst transfer ( SBT , n = 235 ) on Day 5/6 was performed . The primary outcome measurement was the cumulative delivery rate including fresh and frozen-thawed cycles in both groups . RESULTS The delivery rate per cycle following fresh embryo transfer was significantly higher in the SBT group compared with the eSET group ( P < 0.01 ) . Conversely , frozen embryo and /or blastocyst transfers tended to result in a higher number of deliveries in the eSET compared with the SBT group . Altogether , the cumulative delivery rate per couple , including fresh and frozen embryo transfers , was similar between the two groups ( 37.9 % versus 34.2 % in the SBT and eSET groups , respectively ) . CONCLUSIONS The observed cumulative delivery rates in this study do not allow us to take a position in favor of SBT or eSET . An improvement in blastocyst cryopreservation may change this attitude BACKGROUND This r and omized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates ( CPR ) per oocyte retrieval when compared with day 2 transfers . METHODS Blind r and omization for transfer on day 2 ( group 1 ) or day 5/6 ( group 2 ) was performed before stimulation . Oocytes and embryos were cultured in sequential media in 5.5 % CO(2 ) , 5 % O(2 ) , 89.5 % N(2 ) and 90 % humidity . A maximum of two embryos was transferred . RESULTS The two groups were similar for age , IVF indication , number of treatment cycles , rate of ICSI/IVF , number of fertilized oocytes and number of embryos transferred . The CPR/oocyte retrieval was comparable in group 1 ( 32 % ) and in group 2 ( 44 % ) , while the CPR/embryo transfer was significantly higher ( P < 0.01 ) in group 2 ( 60 % ) than in group 1 ( 35 % ) . Similarly , the implantation rate per embryo transferred was significantly higher ( P < 0.03 ) in group 2 ( 46 % ) than in group 1 ( 29 % ) . The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 ( 36.3 % ) and in group 1 ( 28.6 % ) . CONCLUSION This r and omized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers BACKGROUND The existence of a real benefit of blastocyst transfer is still a matter of debate . The aim of this study was to compare , in a prospect i ve r and omized trial , the outcome of day 2 and day 5 transfer of human embryos cultured in an ' in-house ' sequential medium . METHODS A total of 193 cycles from 171 patients with less than four previous IVF cycles , < 39 years old and with four or more zygotes on day 1 , were r and omly allocated to day 2 ( 94 cycles ) or day 5 ( 99 cycles ) transfer . Zygotes were kept in fertilization medium until 18 h post-fertilization and then placed in a ' glucose-free ' cleavage medium . Embryos allocated for day 5 transfer were placed in a blastocyst medium 66 h post-fertilization . Two or three embryos were replaced according to the morphology . RESULTS A mean ( + /- SEM ) number of 2.1 + /- 0.4 and 1.9 + /- 0.3 embryos were replaced on day 2 and day 5 ( P < 0.001 ) respectively . Delivery rates per transfer were 44.1 and 37.1 % [ P = not significant ( NS ) ] , implantation rates were 31.4 and 29.4 % ( NS ) and multiple delivery rates 22 and 36 % ( NS ) for day 2 and day 5 groups respectively . Ten patients ( 10.1 % ) had no blastocysts available for transfer . CONCLUSIONS No clear benefits were observed using blastocyst transfer for patients aged < 39 years who had had less than four previous IVF cycle attempts STUDY QUESTION How do r and omised controlled trials ( RCTs ) in reproductive medicine report maternal and neonatal outcomes , specifically singleton live birth ? SUMMARY ANSWER Despite the widespread appeal to use singleton live birth as the outcome measure in subfertility trials , 80 % of RCTs fail to do so , and fail to report on neonatal and maternal outcomes . WHAT IS KNOWN ALREADY The aim of reproductive medicine is to assist subfertile couples in their wish to have children . A decade ago it was proposed to use singleton live birth as the outcome measure . We assessed whether clinical research has followed this recommendation , and how neonatal/maternal outcomes are reported . STUDY DESIGN , SIZE , DURATION A review of the published literature from 1 January 1966 to 31 December 2012 was performed using the Cochrane data base . We compared the time periods before and after 2004 ; the year after ESHRE recommended the use of singleton live birth . PARTICIPANTS / MATERIAL S , SETTING , METHODS We search ed the Cochrane data base for RCTs in reproductive medicine , and recorded the number of studies that used singleton live birth as the outcome measure . We also recorded the reporting neonatal and maternal outcomes . MAIN RESULTS AND THE ROLE OF CHANCE We identified 910 RCTs that reported on fertility treatments , of which 182 RCTs ( 20 % ) reported on singleton live birth [ before 2004 96/518 ( 19 % ) ; after 2003 86/392 RCTs ( 22 % ) ] . Singleton live birth was the primary outcome in 68 RCTs ( 7.4 % ) . Only 44 RCTs ( 4.8 % ) reported on neonatal outcome , while 52 RCTs ( 5.7 % ) reported on maternal outcome . LIMITATIONS , REASONS FOR CAUTION We only included Cochrane review s , thus report here only on the higher quality studies . The actual reporting on maternal and neonatal outcome may even be lower when studies of lower quality are included . WIDER IMPLICATION S OF THE FINDINGS Although a decade ago singleton live birth was recommended as the outcome measure of reproductive medicine research , this has not been followed ; currently most clinical research in reproductive medicine does not report beyond the occurrence of pregnancy . STUDY FUNDING /COMPETING INTEREST(S ) No funding was received for the study . The authors have no conflicts of interest to declare BACKGROUND Single-embryo transfer has been recommended to reduce the incidence of multiple gestations when in vitro fertilization is performed in women under 36 years of age . We design ed a prospect i ve , r and omized , controlled trial to determine whether there were any differences in the rates of pregnancy and delivery between women undergoing transfer of a single cleavage-stage ( day 3 ) embryo and those undergoing transfer of a single blastocyst-stage ( day 5 ) embryo . METHODS We studied 351 infertile women under 36 years of age who were r and omly assigned to undergo transfer of either a single cleavage-stage embryo ( 176 patients ) or a single blastocyst-stage embryo ( 175 patients ) . Multifollicular ovarian stimulation was performed with a gonadotropin-releasing hormone antagonist and recombinant follicle-stimulating hormone . RESULTS The study was terminated early after a prespecified interim analysis ( which included 50 percent of the planned number of patients ) found a higher rate of pregnancy among women undergoing transfer of a single blastocyst-stage embryo ( P=0.02 ) . The rate of delivery was also significantly higher in this group than in the group undergoing transfer of a single cleavage-stage embryo ( 32.0 percent vs. 21.6 percent ; relative risk , 1.48 ; 95 percent confidence interval , 1.04 to 2.11 ) . Two multiple births occurred , both of monozygotic twins , both of which were in the group undergoing transfer of a single cleavage-stage embryo . CONCLUSIONS These findings support the transfer of a single blastocyst-stage ( day 5 ) embryo in infertile women under 36 years of age OBJECTIVES To study the potential of embryo transfer after 3 , 4 or 5 days of embryo culture under the German embryo protection law according to which only a maximum of three zygotes are allowed to be cultured for embryo transfer . STUDY DESIGN In a prospect i ve study , 273 patients with assisted reproductive treatment were r and omly allocated for transfer on days 3 , 4 or 5 . Pregnancy and implantation rates were evaluated in regard to day of transfer and results were compared by Chi-square or ANOVA test . RESULTS Out of 234 transfer cycles , 79 were performed on day 3 , 76 on day 4 and 79 on day 5 . Pregnancy and implantation rates were 41.8%/27.1 % for transfer on day 3 , 27.6%/14.1 % for day 4 transfer and 16.5%/8.8 % for transfer on day 5 . These results were significantly different for pregnancy rates on day 3 versus day 5 ( P < 0.001 ) and for implantation rates on day 3 versus day 4 ( P < 0.005 ) and day 3 versus day 5 ( P < 0.001 ) . CONCLUSIONS These findings suggest that extended embryo culture is not beneficial when the option for embryo selection at later stages of development is not available Purpose To determine if blastocyst transfer increases the ongoing and cumulative pregnancy rates , compared with day 3 embryo transfer , in women of all ages when at least 4 zygotes are obtained . Methods Prospect i ve study including patients undergoing a first IVF/ICSI treatment and assigned to cleavage stage ( n = 46 ) or blastocyst ( n = 58 ) embryo transfer . Supernumerary embryos were vitrified and patients failing to achieve an ongoing pregnancy after fresh embryo transfer would go through cryopreserved cycles . The main outcome measure was the ongoing pregnancy rate after the fresh IVF/ICSI transfer and the cumulative ongoing pregnancy rate . Results were also analyzed according to age ( under 35 and 35 or older ) . Results A majority of patients ( 96.6 % ) had a blastocyst transfer when at least 4 zygotes were obtained . The ongoing pregnancy rate was significantly higher in the day-5 group compared with the day-3 group ( 43.1 % vs. 24 % , p = 0.041 ) . The cumulative ongoing pregnancy rate was higher ( but not significantly ) with blastocyst than with cleavage stage embryos ( 56.8 % vs. 43.4 % , p = 0.174 ) . When analysed by age , patients 35 or older showed significantly higher ongoing pregnancy rate ( 48.4 % vs. 19.3 % , p = 0.016 ) and cumulative ongoing pregnancy rate ( 58 % vs. 25.8 % , p = 0.01 ) in the day-5 group compared to the day-3 group , while no such differences were observed in women under 35 . Conclusions Blastocyst transfer can be suggested whenever there are at least 4 zygotes . While there are no differences in women under 35 , the benefit of this option over cleavage stage transfer could be significant in women 35 or older INTRODUCTION In a r and omized controlled trial , we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good- quality embryos on day 3 . METHODS Multifollicular ovarian stimulation was performed with a GnRH agonist in 44 % of patients and with a GnRH antagonist in 56 % . Overall , 164 patients younger than 37 years fulfilled embryo quality criteria ( at least four having at least six cells on the morning of day 3 , maximum 20 % anucleate fragments ) on the third day of culture and were r and omized to the day 3 ( n = 84 ) or day 5 ( n = 80 ) groups . Equal numbers of embryos ( n = 2 ) were transferred in each group . RESULTS Demographics , stimulation parameters and embryological data were comparable in the two groups . Blastocyst-stage transfer result ed in a significantly higher ongoing pregnancy rate [ 51.3 versus 27.4 % ; odds ratio ( OR ) 2.78 , 95 % confidence interval ( CI ) 1.45 - 5.34 ] and live birth rate ( 47.5 versus 27.4 % ; OR 2.40 , 95 % CI 1.25 - 4.59 ) compared with day-3 embryo transfer . A high twin birth rate was observed in both groups ( 36.8 versus 30.4 % ; P > 0.05 ) . CONCLUSIONS A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer Abstract Blastocyst transfer has been introduced as an alternative for improving the chance for in vitro fertilizations ( IVF ) implantation . The present study was to evaluate pregnancy rates when embryo transfer was performed either on day 2–3 ( cleavage stage ) or on day 4–5 ( blastocyst stage ) . This r and omized clinical trial included 118 infertile women . All the study subjects underwent controlled ovarian stimulation using a long protocol and r and omized into two groups . BS group ( n = 57 ) , the culture was extended to day 5 ( blastocyst stage ) and in the CS-group ( n = 61 ) , embryo culture was continued to day 3 ( cleavage stage ) . Ongoing pregnancies , abortion , implantation rate were evaluated . No significant differences were seen in the pregnancy rate between the two groups ( 33.3 % in the BS group versus 27.9 % in the CS group ; p = 0.519 ) . Abortion , implantation rate in two groups are not significant . Despite the lack of statistical difference between the two study groups , our data suggest that blastocyst transfer may be associated with a higher pregnancy and an overall better implantation rates . However , further studies with larger sample size are m and atory to confirm these findings . Chinese abstract 囊胚移植已经作为一种提高IVF植入机会的选择方法，本研究目的是评估在2 - 3天（卵裂期）移植或4 - 5天（囊胚期）移植的妊娠率。这个临床随机试验有118例不孕妇女。所有实验对象都采用长方案进行控制性卵巢刺激并随机分为两组。BS组(n=57)胚胎培养延长至5天（囊胚期），CS组(n=61)胚胎培养持续3天（卵裂期）。评估持续妊娠率、流产率、植入率。两组间妊娠率没有显著性差异(BS组为33.3 % ， CS组为27.9%，p=0.519)。两组间流产率和植入率无显著性差异。尽管两组之间没有明显统计学差异，数据提示囊泡期移植可能有更高的妊娠率和整体更好的植入率。但是需要进一步更大样本的研究来证实这些结果 OBJECTIVE To evaluate the efficacy of blastocyst culture and transfer in human in vitro fertilization ( IVF ) as compared to day 3 embryo transfer . DESIGN Prospect i ve r and omized trial . SETTING Private assisted reproduction unit . PATIENT(S ) A total of 162 IVF patients were included in the day 3 embryo transfer ( n = 82 ) and blastocyst transfer ( n = 80 ) groups . INTERVENTION(S ) Embryo transfer on day 3 after culture in the st and ard culture media and blastocyst transfer on day 5 or 6 after culture in the sequential culture media . MAIN OUTCOME MEASURE(S ) Implantation and pregnancy rates , multiple gestation rate . RESULT ( S ) The implantation rate for embryos transferred at the blastocyst stage was significantly higher than that for embryos transferred on day 3 ( 26 % vs. 13 % ) . The viable pregnancy rate was similar in both groups ( 29 % vs. 26 % ) . Significantly fewer embryos were required for transfer at the blastocyst stage compared with day 3 embryo transfer ( 2.0 + /- 0.1 vs. 3.5 + /- 0.63 ) . The high-order multiple gestation rate was significantly less with the blastocyst transfer than with the day 3 embryo transfer ( 4 % vs. 19 % ) . CONCLUSION ( S ) With the use of blastocyst culture , a few embryos can be transferred without decreasing the overall pregnancy rate . This may reduce multiple gestations and improve human IVF outcome To determine the best day for the selection and transfer of a single embryo , a prospect i ve , r and omized study was undertaken that compared the ongoing pregnancy rate ( PR ) after single embryo transfer ( SET ) on day 3 with that after single blastocyst transfer ( SBT ) on day 5 . Our results show an overall significantly higher PR after SBT ( 32.8 % ) compared with SET ( 23.2 % ) , and a PR of 40.8 % after SBT versus 25.6 % after excellent- quality embryos became available OBJECTIVE To determine the efficacy of single blastocyst transfer . DESIGN Prospect i ve r and omized trial . SETTING Private assisted reproductive technology unit . PATIENT(S ) Forty-eight women undergoing IVF-embryo transfer with day 3 FSH < or=10 mIU/mL and at least 10 follicles > 12 mm in diameter on day of hCG administration . INTERVENTION(S ) Embryo culture to the blastocyst stage in sequential media G1/G2 followed by transfer of either one or two blastocysts . MAIN OUTCOME MEASURE(S ) Implantation rate , ongoing pregnancy rate , and twinning . RESULT ( S ) The transfer of a single blastocyst result ed in an implantation and ongoing pregnancy rate of 60.9 % with no twins . The transfer of two blastocysts result ed in an implantation rate of 56 % , an ongoing pregnancy rate of 76 % with a 47.4 % incidence of twins . CONCLUSION ( S ) Single blastocyst transfer is an effective method of eliminating multiple births while maintaining high pregnancy rates in this selected group of patients Blastocyst transfer has been suggested to improve implantation rate without affecting pregnancy rate . The aim of this study was to compare the pregnancy and implantation rates of day 3 and 5 transfers in a prospect i ve r and omized manner . Patients with four or more zygotes were r and omly allocated on day 1 to either day 3 or 5 transfers . Fertilization was achieved through regular IVF or intracytoplasmic sperm injection . Zygotes were kept in Medicult IVF medium for day 3 transfers and transferred into G1.2 and G2.2 on day 1 and 3 respectively for day 5 transfers . The morphologically best two or three embryos or blastocysts were chosen for transfer in both groups . Overall pregnancy rates per embryo transfer were the same ( 39 % ) in day 3 and 5 transfers . Implantation rates were 21 and 24 % for day 3 and 5 transfers respectively . The pregnancy and implantation rates for day 5 transfers were significantly affected by the availability of at least one blastocyst to transfer and the number of zygotes . The number of good quality embryos on day 3 also significantly affected pregnancy and implantation rates on day 5 transfers . Multiple gestation rate , number of abortions and ongoing pregnancies were similar in both groups . In conclusion , day 3 and 5 transfer had similar pregnancy , implantation and twinning rates . Currently , day 5 transfers have no advantages over day 3 transfers OBJECTIVE To compare the implantation and pregnancy rates after cleavage stage embryo transfer ( ET ) with transfer of blastocyst-stage ( days 5 - 6 ) embryos . STUDY DESIGN Prospect i ve r and omized trial at an assisted reproduction unit in a university hospital . Women with six or more follicles at the last ultrasound scan before oocyte aspiration were r and omized for transfer of a maximum of two embryos after 2 - 3 days ( n = 80 ) or after 5 - 6 days ( n = 64 ) of culture . Embryo quality , implantation and pregnancy rates were evaluated . Statistical significance was tested with the Chi-square test and Fisher 's exact test . RESULT ( S ) No significant difference was observed in implantation rates ( 21.1 % versus 20.9 % , respectively ) and clinical pregnancy rates ( 36.7 % versus 32.5 % respectively ) after blastocyst and cleavage stage transfers for the two groups . The pregnancy rate among subjects who had at least one good quality embryo transferred was 37.5 % per day 2 - 3 ET and 60 % per day 5 - 6 ET . CONCLUSION ( S ) The overall implantation and pregnancy rates after embryo transfer at cleavage stage and at blastocyst stage transfer were not statistically different . Women who had at least one good quality blastocyst ( n = 25 ) had a high pregnancy rate ( 60 % per ET ) . Blastocyst transfer is a good alternative for couples with many good quality embryos on day 2 after insemination This prospect i ve , r and omized , controlled trial tested the hypothesis that delaying embryo transfer to the blastocyst stage can increase the probability of clinical pregnancy and live birth in women with high oestradiol concentrations on the day of human chorionic gonadotrophin ( HCG ) undergoing intracytoplasmic sperm injection using the long protocol . A total of 200 women with oestradiol > 3000 pg/ml on the HCG day with four or more good- quality , day-3 embryos were r and omized in a 1:1 ratio to undergo day-3 or day-5 embryo transfer . Clinical pregnancy rates ( CPR ; 41 % versus 59 % ; relative risk 0.70 , 95 % CI 0.52–0.93 ) and ongoing pregnancy/live-birth rates ( 35 % versus 52 % ; relative risk 0.67 , 95 % CI 0.46–0.93 ) were lower in women undergoing cleavage-stage than blastocyst-stage embryo transfer . Using receiver operating characteristic curves , among women undergoing cleavage-stage embryo transfer , a detrimental cut-off value for not achieving pregnancy for oestradiol was 4200 pg/ml , with lower CPR and ongoing pregnancy/live-birth rates ( P = 0.006 and 0.02 , respectively ) . No detrimental cut-off value for oestradiol was identified among women undergoing blastocyst-stage embryo transfer . Delaying embryo transfer to the blastocyst stage can increase the probability of pregnancy in women with high oestradiol on the HCG BACKGROUND The aim of this study was to evaluate the effectiveness of the blastocyst culture method compared with the conventional day 3 transfer method using a prospect i ve trial . METHODS A total of 235 patients with 273 cycles were evaluated for a period of almost 1 year . Depending upon the sequence in which the ovum retrieval was performed , patients were prospect ively assigned ( alternate allocation ) to a culture period of 3 or 5 days duration . Embryos were transferred either on day 3 ( after culture in human tubal fluid ) or on day 5 ( after culture in sequential media ) . RESULTS The pregnancy rates after embryo transfer on days 3 and 5 were similar at 26.5 and 25.9 % respectively . Among the day 5 embryo transfer group , patients were divided into three groups corresponding to three sequential media . The pregnancy rates were 32.0 % using Irvine blastocyst medium , 6.9 % using G1.2/G2.2 and 32.4 % using Cook blastocyst medium . CONCLUSIONS The results of our study were not as successful as previous studies had been . Additionally , there may have been problems in day 5 embryo transfer , such as choosing the sequential media , quality control , contamination and so on . From the results of this study , it appears that day 5 embryo transfer has no advantages for ordinary patients of assisted reproductive technology |
11,908 | 30,154,630 | Statins were found to affect glucose control through several ways , namely , by affecting insulin production and secretion by & bgr;‐pancreatic cells , insulin resistance , insulin uptake by the muscles and adipocytes and production of adipokines .
Current evidence available shows that most of the statins give unfavorable side effects with regards to glucose control among diabetic patients .
A dose‐dependent and time‐dependent effect was also observed in some statins which may be present among other statins as well | Abstract Worldwide statins are considered to be the first‐line pharmacological treatment for dyslipidemia and reducing the risk of coronary heart disease .
However , recently various studies have shown its adverse effect on glucose control among diabetic patients and the U.S. Food and Drug Administration have revised statin drug labels to include information that increases in fasting serum glucose and glycated hemoglobin levels have been reported . | Background The US Federal and Drug Administration ( FDA ) recently revised statin drug labels to include the information that increases in fasting serum glucose and glycated haemoglobin levels have been reported with the use of statins . Yet in a survey , 87 % of the doctors stated that they had never or infrequently observed increases in glucose or HbA1c levels in patients on statin . In this study we would like to determine the association between the use of statins and glycaemic control in a retrospective cohort of patients with hypertension . Methods A retrospective review of 1060 medical records of patients with hypertension at a primary care clinic was conducted . These records were selected using systematic r and om sampling ( 1:4 ) . Data on patient socio-demographic factors ; clinical profile ; investigation results and prescribed medications were collected . Independent t-test was used for continuous variables while Pearson ’s χ 2 test was used for categorical variables . Logistic regression was done to adjust for confounders . Results 810 ( 76.4 % ) patients with hypertension were on statins , out of which 792 ( 97.8 % ) were taking simvastatin 10 mg or 20 mg daily . Analysis of the whole group regardless of diabetes status showed that the statin user group had higher HbA1c and fasting blood glucose values . The difference in HbA1c levels remained significant ( adjusted OR = 1.290 , p = 0.044 , 95 % CI 1.006 , 1.654 ) after adjustment for diabetes , diabetic medication and fasting blood glucose . In the study population who had diabetes , statin users again had significantly higher HbA1c level compared to statin non-users . This difference remained significant ( adjusted OR 1.208 , p = 0.037 , 95 % CI 1.012 , 1.441 ) after adjustment for age and diabetic medications . Conclusions Statins use is associated with increased HbA1c levels among hypertensive patients and hypertensive patients with diabetes . Clinicians managing hypertensive patients on statins should consider monitoring the HbA1c level and ensure that those with diabetes have their hyperglycaemia kept under control OBJECTIVES We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients . BACKGROUND Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein ( LDL ) cholesterol and improvement in endothelial dysfunction . METHODS A r and omized , single-blind , placebo-controlled parallel study was conducted in 44 patients taking placebo and in 42 , 44 , 43 , and 40 patients given daily atorvastatin 10 , 20 , 40 , and 80 mg , respectively , during a 2-month treatment period . RESULTS Atorvastatin 10 , 20 , 40 , and 80 mg significantly reduced LDL cholesterol ( 39 % , 47 % , 52 % , and 56 % , respectively ) and apolipoprotein B levels ( 33 % , 37 % , 42 % , and 46 % , respectively ) after 2 months of therapy when compared with either baseline ( all p < 0.001 by paired t test ) or placebo ( p < 0.001 by analysis of variance [ ANOVA ] ) . Atorvastatin 10 , 20 , 40 , and 80 mg significantly increased fasting plasma insulin ( mean changes : 25 % , 42 % , 31 % , and 45 % , respectively ) and glycated hemoglobin levels ( 2 % , 5 % , 5 % , and 5 % , respectively ) when compared with either baseline ( all p < 0.05 by paired t test ) or placebo ( p = 0.009 for insulin and p = 0.008 for glycated hemoglobin by ANOVA ) . Atorvastatin 10 , 20 , 40 , and 80 mg decreased insulin sensitivity ( 1 % , 3 % , 3 % , and 4 % , respectively ) when compared with either baseline ( p = 0.312 , p = 0.008 , p < 0.001 , and p = 0.008 , respectively , by paired t test ) or placebo ( p = 0.033 by ANOVA ) . CONCLUSIONS Despite beneficial reductions in LDL cholesterol and apolipoprotein B , atorvastatin treatment result ed in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients . ( Effects of Atorvastatin on Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients ; NCT00745836 ) OBJECTIVE This study evaluated the effect of a atorvastatin-fenofibrate combination on lipid profile , in comparison to each drug alone , in patients with type 2 diabetes and combined hyperlipidemia ( CHL ) . RESEARCH DESIGN AND METHODS A total of 120 consecutive patients , who were free of coronary artery disease ( CAD ) at entry , were studied for a period of 24 weeks . These patients were r and omly assigned to atorvastatin ( 20 mg/day , n = 40 ) , micronized fenofibrate ( 200 mg/day , n = 40 ) , or a combination of both ( atorvastatin 20 mg/day plus fenofibrate 200 mg/day , n = 40 ) . The effect of treatment on LDL cholesterol , triglycerides ( TGs ) , HDL cholesterol , apolipoprotein A-I and B , lipoprotein(a ) , and plasma fibrinogen ( PF ) was recorded . Moreover , the percentage of patients that reached the American Diabetes Association treatment goals and the estimated CAD risk status were calculated . RESULTS No patient was withdrawn from the study because of side effects . The atorvastatin-fenofibrate combination reduced total cholesterol by 37 % , LDL cholesterol by 46 % , TGs by 50 % , and PF by 20 % , whereas it increased HDL cholesterol by 22 % ( P < 0.0001 for all ) . These changes were significantly better than those of both monotherapies . Of the patients on drug combination , 97.5 % reached the LDL cholesterol treatment goal of < 100 mg/dl , 100 % reached the desirable TG levels of < 200 mg/dl , and 60 % reached the optimal HDL cholesterol levels of > 45 mg/dl . These rates were significantly higher than those of both monotherapies . Combined treatment reduced the 10-year probability for myocardial infa rct ion from 21.6 to 4.2 % . CONCLUSIONS The atorvastatin-fenofibrate combination has a highly beneficial effect on all lipid parameters and PF in patients with type 2 diabetes and CHL . It improved patients ' CAD risk status significantly more than each drug alone Objective . To investigate the effect of simvastatin on glucose homeostasis in streptozotocin induced type 2 diabetic rats . Methods . Forty male Wistar rats were r and omly divided into four groups . Normal control rats were fed with st and ard diet , others were fed with high-fat diet . Diabetic rats were induced by a single intraperitoneal injection of STZ . The simvastatin intervention rats were fed with simvastatin during the experiment process , and the simvastatin treatment rats were fed with simvastatin after diabetes rats were induced . We measured body weight , fasting plasma glucose , cholesterol , high-density lipoprotein cholesterol , and triglyceride after an overnight fast . Results . The FPG was higher in diabetic rats when compared to normal control ones ; the simvastatin intervention rats had a higher FPG compared to the diabetic rats and were more easily be induced to diabetes at the end of 4 weeks , FPG level of simvastatin treatment rats was increased compared with diabetic model rats after 12 weeks . Conclusion . These data indicate that simvastatin intervention rats may cause hyperglycemia by impairing the function of islet β cells and have an adverse effect on glucose homeostasis , especially on FPG level While a large numbers of clinical trials using various kinds of statins has been reported , a possible preventive effect on new onset of type 2 diabetes mellitus was shown only by the sub analysis of The West of Scotl and Coronary Prevention Study ( WOSCOPS ) using pravastatin . The aim of this study was to investigate whether pravastatin has a preferable effect on glucose tolerance among statins . An open-label prospect i ve cross-over trial was performed to compare the effect of pravastatin ( 10 mg/day ) or atorvastatin ( 10 mg/day ) in Japanese early-state type 2 diabetes mellitus with hypercholesterolemia . The analyzed study subjects were treated with pravastatin ( 10 mg/day , n = 12 ) or atorvastatin ( 10 mg/day , n = 12 ) for 12 weeks . After a 4-week-washout period , the drugs were switched and treatment was continued for another 12 weeks . Oral glucose tolerance test ( OGTT ) was performed to evaluate several parameters including the appropriateness of beta cell function for the individual insulin sensitivity ( disposition index : product of a vali date d secretion parameter and sensitivity ) at the end of each therapy . HbA(1c ) and 2 h-glucose levels during OGTT in the pravastatin treatment were significantly lower than atorvastatin treatment . Disposition index after pravastatin treatment was significantly higher than after atorvastatin treatment . In conclusion , our study suggests that pravastatin has a favorable effect on pancreatic beta cell function compared with atorvastatin AIM To compare the long-term efficacy and safety of pitavastatin with atorvastatin in patients with type 2 diabetes and combined ( mixed ) dyslipidaemia . METHODS R and omised , double-blind , active-controlled , multinational non-inferiority study . Patients were r and omised 2 : 1 to pitavastatin 4 mg ( n = 279 ) or atorvastatin 20 mg ( n = 139 ) daily for 12 weeks . Patients completing the core study could continue on pitavastatin 4 mg ( n = 141 ) or atorvastatin 20 mg ( n = 64 ) [ 40 mg ( n = 7 ) if lipid targets not reached by week 8 ] for a further 44 weeks ( extension study ) . The primary efficacy variable was the change in low-density lipoprotein cholesterol ( LDL-C ) . RESULTS Reductions in LDL-C were not significantly different at week 12 between the pitavastatin ( -41 % ) and atorvastatin ( -43 % ) groups . Attainment of National Cholesterol Education Program and European Atherosclerosis Society targets for LDL-C and non-high-density lipoprotein cholesterol ( non-HDL-C ) was similarly high for both treatment groups . Changes in secondary lipid variables ( e.g. HDL-C , apolipoprotein B and triglycerides ) were similar between treatments . Post hoc analysis showed that adjusted mean treatment differences for pitavastatin vs. atorvastatin were within the non-inferiority margin at weeks 16 ( + 0.11 % ; 95 % confidence interval ( CI ) , -5.23 to 5.44 ) and 44 ( -0.02 % ; 95 % CI , -5.46 to 5.41 ) of the extension study . Both treatments were well tolerated ; atorvastatin increased fasting blood glucose from baseline ( + 7.2 % ; p < 0.05 ) , whereas pitavastatin had no significant effect ( + 2.1 % ) . CONCLUSIONS Reductions in LDL-C and changes in other lipids were not significantly different in patients treated with pitavastatin 4 mg or atorvastatin 20 or 40 mg . Pitavastatin may , however , have a more favourable effect on the glycaemic status To clarify whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statin ) increases lipoprotein lipase mass in preheparin plasma ( preheparin LPL mass ) , we observed the change in preheparin LPL mass during administration of atorvastatin and pravastatin to type 2 diabetes mellitus patients with hypercholesterolemia . The subjects were r and omly divided into two groups . One group was 24 patients given atorvastatin ( 10 mg/day ) , and the other was 23 patients given pravastatin ( 20 mg/day ) for 4 months . After 4 months of administration , no significant change of HbA1c was observed . TC significantly decreased in the atorvastatin group compared to the pravastatin group . TG significantly decreased in the atorvastatin group . Low density lipoprotein cholesterol level significantly decreased in both groups ( - 36.3 % , p < 0.01 in atorvastatin , - 24.3 % , p < 0.01 in pravastatin ) . Preheparin LPL mass slightly increased in both groups after 4 months of administration . Especially in patients who showed low preheparin LPL mass ( less than 50 ng/ml ) before statin administration , preheparin LPL mass significantly increased in both groups ( + 25.8 % in the atorvastatin group , + 24.39 % in the pravastatin group ) . These results suggested that administration of atorvastatin and pravastatin to type 2 diabetic patients with hypercholesterolemia increased serum preheparin LPL mass concentration . Especially , its effect was remarkable in patients who showed low preheparin LPL mass BACKGROUND Individuals with diabetes are at increased risk of cardiovascular morbidity and mortality , although typically their plasma concentrations of LDL cholesterol are similar to those in the general population . Previous evidence about the effects of lowering cholesterol in people with diabetes has been limited , and most diabetic patients do not currently receive cholesterol-lowering therapy despite their increased risk . METHODS 5963 UK adults ( aged 40 - 80 years ) known to have diabetes , and an additional 14573 with occlusive arterial disease ( but no diagnosed diabetes ) , were r and omly allocated to receive 40 mg simvastatin daily or matching placebo . Prespecified analyses in these prior disease subcategories , and other relevant subcategories , were of first major coronary event ( ie , non-fatal myocardial infa rct ion or coronary death ) and of first major vascular event ( ie , major coronary event , stroke or revascularisation ) . Analyses were also conducted of subsequent vascular events during the scheduled treatment period . Comparisons are of all simvastatin-allocated versus all placebo-allocated participants ( ie , intention to treat ) , which yielded an average difference in LDL cholesterol of 1.0 mmol/L ( 39 mg/dL ) during the 5-year treatment period . FINDINGS Both among the participants who presented with diabetes and among those who did not , there were highly significant reductions of about a quarter in the first event rate for major coronary events , for strokes , and for revascularisations . For the first occurrence of any of these major vascular events among participants with diabetes , there was a definite 22 % ( 95 % CI 13 - 30 ) reduction in the event rate ( 601 [ 20.2 % ] simvastatin-allocated vs 748 [ 25.1 % ] placebo-allocated , p<0.0001 ) , which was similar to that among the other high-risk individuals studied . There were also highly significant reductions of 33 % ( 95 % CI 17 - 46 , p=0.0003 ) among the 2912 diabetic participants who did not have any diagnosed occlusive arterial disease at entry , and of 27 % ( 95 % CI 13 - 40 , p=0.0007 ) among the 2426 diabetic participants whose pretreatment LDL cholesterol concentration was below 3.0 mmol/L ( 116 mg/dL ) . The proportional reduction in risk was also about a quarter among various other subcategories of diabetic patient studied , including : those with different duration , type , or control of diabetes ; those aged over 65 years at entry or with hypertension ; and those with total cholesterol below 5.0 mmol/L ( 193 mg/dL ) . In addition , among participants who had a first major vascular event following r and omisation , allocation to simvastatin reduced the rate of subsequent events during the scheduled treatment period . INTERPRETATION The present study provides direct evidence that cholesterol-lowering therapy is beneficial for people with diabetes even if they do not already have manifest coronary disease or high cholesterol concentrations . Allocation to 40 mg simvastatin daily reduced the rate of first major vascular events by about a quarter in a wide range of diabetic patients studied . After making allowance for non-compliance , actual use of this statin regimen would probably reduce these rates by about a third . For example , among the type of diabetic patient studied without occlusive arterial disease , 5 years of treatment would be expected to prevent about 45 people per 1000 from having at least one major vascular event ( and , among these 45 people , to prevent about 70 first or subsequent events during this treatment period ) . Statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk of major vascular events , irrespective of their initial cholesterol concentrations AIMS To examine whether high-dose statin therapy in Dutch European patients with Type 2 diabetes and dyslipidaemia influenced variables of glycaemic control . METHODS The CORALL study , which was a 24-week , open-label , r and omized , parallel-group , phase IIIb , multi-centre study , was design ed to compare the cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with Type 2 diabetes . Fasting plasma glucose levels and HbA(1c ) levels were collected at baseline and at 6 and 18 weeks . RESULTS Treatment with the highest dose of statins , i.e. atorvastatin 80 mg and rosuvastatin 40 mg at 18 weeks from baseline , was associated with increase in HbA(1c ) levels ; baseline 57 ± 11 mmol/l ( 7.4 ± 1.0 % ) to 61 ± 14 mmol/mol ( 7.7 ± 1.3 % ) ( range 5.0 - 11.9 ) for atorvastatin ( P = 0.003 ) and from baseline 60 ± 11 mmol/mol ( 7.6 ± 1.0 % ) to 63 ± 13 mmol/mol ( 7.9 ± 1.2 % ) ( range 5.7 - 12.3 ) for rosuvastatin ( P < 0.001 ) . Mean fasting plasma glucose increased from baseline 8.7 ± 2.4 mmol/l to 9.5 ± 3.0 mmol/l upon treatment with atorvastatin 20 mg ( P = 0.002 ) and 9.0 ± 3.0 mmol/l after treatment with 80 mg ( not significant compared with baseline ) . The mean fasting plasma glucose did not change after treatment with rosuvastatin ( 9.1 ± 2.7 mmol/l at baseline , 8.9 ± 2.7 mmol/l with 10 mg , 9.4 ± 2.9 mmol/l with 40 mg ) . CONCLUSIONS Glycaemic control deteriorated in patients with diabetes following high-dose statin therapy . Future controlled studies are needed to verify these findings and , if confirmed , determine whether such changes represent a true decline in glycaemic control . Presently , it appears that , based on the overwhelming prospect i ve trial data available , the preventive effect of statin therapy supersedes that of the slight increase in HbA(1c ) Insulin resistance ( IR ) impairs vascular responses in coronary arteries , but mechanisms of dysfunction and approaches to treatment remain unclear . We examined the ability of a new 3-hydroxy-methylglutaryl coenzyme A reductase inhibitor , rosuvastatin , to reverse reduced dilator responses in rats made IR by feeding a fructose-rich diet ( FF ) . Sprague-Dawley rats were r and omized to control ( normal rat diet ) or FF . After 1 wk , rats received rosuvastatin ( 2 mg/kg ) or placebo ( saline ) subcutaneously for 5 wk . Biochemical measurements and in vitro functional studies of small coronary arteries were performed . Fasting insulin and triglyceride ( TG ) levels were markedly increased in FF-placebo rats compared with other groups . Rosuvastatin treatment of FF rats normalized TG and modestly decreased insulin levels . ACh-induced dilator responses were depressed in arteries from FF-placebo rats . This impairment was due to decreased responses via calcium-dependent K channels ( K(Ca ) ) . Rosuvastatin treatment of FF rats completely reversed the response to ACh to normal levels . Moreover , this recovery in function was due to an improvement in vasodilation via K(Ca ) . Thus rosuvastatin treatment of IR rats normalizes coronary vascular dilator responses by improving the K(Ca ) function In addition to their expected effects on lipid profile , lipid-lowering agents may reduce cardiovascular events because of effects on nonclassic risk factors such as insulin resistance and inflammation . Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol as well as plant sterols . Although it is known that an additional reduction of low-density lipoprotein cholesterol ( LDL-C ) levels can be induced by the combination of ezetimibe with statins , it is not known if this can enhance some pleiotropic effects , which may be useful in slowing the atherosclerotic process . This study assessed the effects of simvastatin and ezetimibe , in monotherapy or in combination , on markers of endothelial function and insulin sensitivity . Fifty prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia were r and omly allocated to 2 groups receiving either ezetimibe ( 10 mg/d ) or simvastatin ( 20 mg/d ) for 12 weeks , after which the drugs were combined for both groups for an additional 12-week period . Clinical and laboratory parameters were measured at baseline and after 12 and 24 weeks of therapy . Homeostasis model assessment of insulin resistance index and the area under the curve of insulin were calculated . As expected , both groups receiving drugs in isolation significantly reduced total cholesterol , LDL-C , apolipoprotein B , and triglyceride levels ; and additional reductions were found after the combination period ( P < .05 ) . After 12 weeks of monotherapy , plasminogen activator inhibitor-1 levels and urinary albumin excretion were lower in the simvastatin than in the ezetimibe group . No change in homeostasis model assessment of insulin resistance index , area under the curve of insulin , and adiponectin levels was observed after either the monotherapies or the combined therapy . However , simvastatin combined with ezetimibe provoked significant reductions in E-selectin and intravascular cellular adhesion molecule-1 levels that were independent of LDL-C changes . Our findings support cl aims that simvastatin may be beneficial in preserving endothelial function in prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia . Alternatively , a deleterious effect of ezetimibe on the endothelial function is suggested , considering the increase in intravascular cellular adhesion molecule-1 and E-selectin levels . Simvastatin and ezetimibe , in isolation or in combination , do not interfere with insulin sensitivity OBJECTIVE We evaluated the long-term effects of rosuvastatin and simvastatin on insulin sensitivity and secretion in patients with well-controlled type 2 diabetes . METHODS After a 3 weeks run-in , 27 eligible patients were r and omly assigned to receive either rosuvastatin 20 mg daily ( Group 1 ) or simvastatin 20 mg daily ( Group 2 ) for 6 months ; thereafter they were switched to the other treatment for additional 6 months . Patients were recruited among individuals attending the outpatient service of the Diabetology Unit of the " Policlinico Tor Vergata " University Hospital , Rome , Italy . Serum lipids , glucose and insulin , glycated hemoglobin , C-reactive protein , TNF-α , leptin , adiponectin , insulin sensitivity by euglycemic-hyperinsulinemic clamp , β-cells function by HOMA-β were assessed at months 0 , 6 and 12 . Additionally , endothelial function was assessed by use of the brachial artery reactivity technique . RESULTS Besides marked reduction in lipid levels , glycated hemoglobin significantly increased from baseline after 12 months in both Group 1 ( + 0.8 ± 0.2 % , p < 0.001 ) and Group 2 ( + 0.9 ± 0.3 % ; p < 0.001 ) . Similar trends were observed for fasting glucose in both groups . No changes in insulin sensitivity were detected throughout the study , whereas HOMA-β significantly decreased from baseline after 12 months in both Group 1 ( -21.9 % , p < 0.01 ) and Group 2 ( -38.9 % ; p < 0.001 ) . In addition , both treatments similarly decreased C-reactive protein and leptin , as well as improved endothelial function . No changes in anthropometric measures were observed . CONCLUSIONS In well-controlled type 2 diabetic patients both rosuvastatin and simvastatin significantly impaired glycemic control and insulin secretion , without affecting insulin sensitivity Abstract Aims /hypothesisThe aim of the study was to examine the impact of statin or omega-3-acid ethyl esters 90 ( omega-3 EE90 ; omega-3-acid ethyl esters 90 refers to a mixture of ethyl esters of n-3 fatty acids ) on estimated cardiovascular disease ( CVD ) risk in community-based people with type 2 diabetes but without known CVD and not taking lipid-lowering therapy . Methods A central computer r and omised 800 patients in 59 UK general practice s to atorvastatin ( n = 401 , 20 mg/day ) or placebo ( n = 399 ) and omega-3 EE90 ( n = 397 , 2 g/day ) or placebo ( n = 403 ) in a concealed factorial manner . Participants with LDL-cholesterol < 2.6 mmol/l , triacylglycerol < 1.5 mmol/l and estimated 10-year CVD risk < 20 % were compared at 4 months . Results Mean ( SD ) age was 63.5 ( 11.7 ) years , HbA1c 6.9 ( 1.1 ) % and known diabetes duration ( median [ interquartile range ] ) was 4 ( 2–8 ) years . Fifty-seven per cent were men , 90 % white and 74 % had an estimated 10-year CVD risk ≥20 % . Of 732 patients with 4-month data , more allocated atorvastatin ( n = 371 ) compared with placebo ( n = 361 ) achieved LDL-cholesterol < 2.6 mmol/l ( 91 % vs 24 % , p < 0.001 ) and had estimated 10-year CVD risks < 20 % ( 38 % vs 26 % , p < 0.001 ) . No differences were seen between those allocated omega-3 EE90 ( n = 371 ) compared with placebo ( n = 361 ) for participants achieving triacylglycerol < 1.5 mmol/l ( 65 % vs 60 % , p = 0.18 ) or estimated 10-year CVD risks < 20 % ( 34 % vs 30 % , p = 0.18 ) . There were no side effects of note . Conclusions /interpretationMany community-based diabetic patients without known CVD remain at high CVD risk despite statin treatment and require additional risk-reduction strategies . The impact of omega-3 EE90 on CVD risk will remain uncertain until clinical endpoint trial results are available . Trial registration : IS RCT no. 76737502 Funding : The study was funded by Pfizer BACKGROUND Statin treatment may be associated with adverse effects on glucose metabolism . Whether this is a class effect is not known . In contrast , ezetimibe monotherapy may beneficially affect insulin sensitivity . OBJECTIVE The aim of this study was to compare the effects of three different regimens of equivalent low-density lipoprotein cholesterol ( LDL-C ) lowering capacity on glucose metabolism . METHODS A total of 153 patients ( 56 men ) , who had not achieved the LDL-C goal recommended by the National Cholesterol Education Program Adult Treatment Panel III ( NCEP-ATP III ) despite a 3-month dietary and lifestyle intervention , were r and omly allocated to receive open-label simvastatin 40 mg or rosuvastatin 10 mg or simvastatin/ezetimibe 10/10 mg for 12 weeks . The primary end point was changes in homeostasis model assessment of insulin resistance ( HOMA-IR ) . Secondary endpoints consisted of changes in fasting insulin levels , fasting plasma glucose ( FPG ) , glycosylated haemoglobin ( HbA(1c ) ) , the HOMA of β-cell function ( HOMA-B ) ( a marker of basal insulin secretion by pancreatic β-cells ) , LDL-C and high sensitivity C reactive protein ( hsCRP ) . RESULTS At week 12 , all three treatment regimens were associated with significant increases in HOMA-IR and fasting insulin levels ( p < 0.05 compared with baseline ) . No significant difference was observed between groups . No change in FPG , HbA(1c ) and HOMA-B levels compared with baseline were noted in any of the three treatment groups . Changes in serum lipids and hsCRP were similar across groups . CONCLUSION To the extent that simvastatin 40 mg , rosuvastatin 10 mg and simvastatin/ezetimibe 10/10 mg are associated with adverse effects on insulin resistance , they appear to be of the same magnitude |
11,909 | 25,280,512 | We found no advantage for clobazam over carbamazepine for retention at 12 months in drug-naïve children and a slight advantage of clobazam over phenytoin for retention at six months in adolescents and adults with neurocysticercosis in a single clinical trial each . | BACKGROUND There is a need to exp and monotherapy options available to a clinician for the treatment of new partial-onset or generalized-onset seizures .
A Cochrane systematic review for clobazam monotherapy is expected to define its place in the treatment of new-onset or untreated seizures and highlight gaps in evidence .
OBJECTIVES To evaluate the efficacy , effectiveness , tolerability and safety of clobazam as monotherapy in people with new-onset partial or generalized seizures . | The Fifth Commission on Antiepileptic Drugs of the International League Against Epilepsy was asked to advise the ILAE Executive on the place of new drugs in the treatment of patients with newly diagnosed or chronic epilepsy . With the licensing of a significant number of new antiepileptic drugs ( AEDs ) in the last 5 - 10 years , there is an obvious need for these new treatments to be introduced efficiently and effectively to benefit the care and management of people with epilepsy . Implicit in this will be a determination of the comparative efficacy , tolerability , and overall effectiveness against st and ard ( existing ) AEDs and against other new drugs . Although many of the issues relating to comparative studies were addressed in Guidelines for the Clinical Evaluation of Antiepileptic Drugs , produced by the Fourth Commission , several complex ethical and method ological problems remain that would benefit from further discussion aim ed at the establishment of some form of consensus . Although determination of the relative risks of rare but potentially serious idiosyncratic adverse reactions and teratogenicity can be determined only by adequate postmarketing surveillance , other issues concerning the efficacy , tolerability , and effectiveness of new drugs can best be determined within the context of well- design ed r and omized ( or otherwise controlled ) clinical trials ( RCTs ) . It is the design , structure , and outcomes of such comparative RCTs that dem and further consideration . Many of the difficulties arise because the most meaningful and satisfactory comparative studies will essentially be those that compare monotherapy with a new agent with monotherapy with alternative agents . The Commission recognizes that several different parties have interests in comparative studies . First and foremost patients and their doctors require adequate information to guide daily practice in an “ evidence -based ” way so that patients can make fully informed decisions about their drug treatment . Individual pharmaceutical manufacturers need to know how their drug compares with other products so that a drug can be appropriately positioned in the market . Licensing authorities have traditionally ignored issues of comparative A benzodiazepine drug , clobazam , was evaluated in 14 refractory epileptic patients , nine of whom received the drug double-blind . Ten patients have been given clobazam long enough to assess results . Four showed marked benefit , four failed to respond and two showed a transient benefit which was maintained by dose changes of both clobazam and clonazepam . Side effects were minimal ; doses ranged from 15 to 60 mg per day . Clobazam may have place in the treatment of the Lennox Gastaut syndrome and other types of refractory seizures Objective To compare the effectiveness of intermittent clobazam versus diazepam therapy in preventing the recurrence of febrile seizures and assess adverse effects of each drug . Methods This prospect i ve r and omized controlled trial was performed on neurologically normal children aged from 6 months to 5 years with a history of simple febrile seizures and normal electroencephalogram without any evidence of acute central nervous system infection . The patients were r and omly prescribed with oral clobazam ( 37 cases ) or diazepam ( 35 cases ) when they developed a febrile disease . They were advised to use the medications during the first 48 h of the onset of fever . All the patients were monitored regarding developing seizure and adverse effects of the drugs . All patients were followed for 12 months . Results Overall , 243 episodes of fever occurred during the period , including 116 episodes in the clobazam group and 127 episodes in the diazepam group . Recurrence of seizures occurred in 2 ( 1.7 % ) subjects in the clobazam group , and in 4(3.1 % ) cases in the diazepam group . ( P value = 0.474 ) . Twenty cases ( 54 % ) in the diazepam group and 5 ( 14.2 % ) cases in the clobazam group developed drowsiness and sedation during the follow-up period ( P value = 0.0001 ) . Conclusions Intermittent clobazam therapy seems advantageous to diazepam due to similar efficacy but significantly lower adverse effects such as drowsiness and sedation BACKGROUND It is now agreed that the prognosis of seizure disorder due to solitary cysticercus granuloma ( SCG ) is generally good . However , the choice antiepileptic drugs ( AEDs ) remain empirical , with no comparative trials of different AEDs being available . AIMS To determine the safety and efficacy ( measured by the incidence of ' treatment failure ' ) of clobazam in comparison to st and ard treatment with phenytoin-sodium for prevention of seizures in persons with solitary cysticercus granulomas ( SCGs ) . SETTING S AND DESIGN This pilot study was conducted in a neurology department of a medical college hospital in the form of a prospect i ve , r and omized , open-labeled trial . MATERIAL S AND METHODS Forty-eight patients with seizures due to SCG were r and omized in an open-labeled trial to either , clobazam ( 1 mg/kg oral loading followed by 0.5 mg/kg/d ) ( n=21 ) or phenytoin ( 15 mg/kg , oral loading in 3 divided doses over 24 h , followed by 5 mg/kg/d ) ( n=27 ) . They were followed over 6 months with the primary outcome measure being treatment failure ( either discontinuation or modification of AEDs ) due to either adverse effects or breakthrough seizures . RESULTS Treatment failures were noted to be significantly less common ( P = 0.03 ) in the clobazam-treated group ( n=1 ; 4.7 % ) than in phenytoin-treated group ( n=9 ; 33.3 % ) . These included one patient ( 4.7 % ) in the clobazam-group who had breakthrough seizures and 3 ( 11.1 % ) who had breakthrough seizures and 6 ( 22.2 % ) in the phenytoin-treated group who had adverse effects requiring treatment discontinuation . CONCLUSIONS Clobazam was well tolerated , safe and more effective than phenytoin in the AED treatment of patients with SCG Clobazam was compared with placebo as antiepileptic adjunct medication in 129 therapy-resistant epileptic patients who were mainly suffering from complex partial seizures . The study was performed in five European countries according to a double-blind crossover design lasting 7 months . Two treatment periods of 3 months ( 1 month adjustment and 2 months maintenance medication ) were separated by one medication switch-over month . The difference in seizure reduction between clobazam and placebo was significant ( p less than 0.05 ) . Nineteen percent of patients receiving clobazam became seizure-free during the maintenance dose period . In contrast , freedom from seizures was not observed in any placebo patient . Electroencephalogram ( EEG ) signs , mood ratings , and global impressions also indicated therapeutic effects of clobazam in epilepsy . The most frequent adverse reactions to clobazam were drowsiness and dizziness . However , the sedative effects of clobazam seemed to be less pronounced in comparison with other benzodiazepines . The study gives evidence of the therapeutic value of clobazam as adjunct medication in therapy-resistant partial seizures . The use of clobazam as monotherapy and long-term treatment , as well as the particular seizure response pattern to clobazam , has to be further investigated The effect of 1,5-benzodiazepine clobazam was assessed in a double-blind add-on trial in 20 patients with chronic complex partial seizures uncontrolled by maximally tolerable daily dosage of st and ard antiepileptic drug therapy . The number of seizures was lower during the three months of active treatment . At the end of the third month , eight ( 40 % ) of the patients had a seizure reduction by more than 75 % , including four patients ( 20 % ) who had complete control . Tolerance to the antiepileptic effect of clobazam was noted in 56 % of the patients , and mild transient sedation occurred in 40 % of the patients . Despite these drawbacks , clobazam is an effective add-on drug for individual patients with refractory focal epilepsy The cyclical exacerbations of epilepsy ( catamenial epilepsy ) were used to assess the antiepileptic effect of a benzodiazepine , clobazam . Doses of 20 mg , and in some cases 30 mg , per day were compared with placebo over predetermined ten-day periods in a double-blind cross-over study . The results were evaluated by preference in a sequential procedure . In 14 of 18 patients who received both treatments clobazam was superior to placebo , and in 4 patients no preference was established . Clobazam completely prevented seizures in most of the patients , and toxic effects were of low frequency and severity Clobazam , 20 or 30 mg/day was given for 10 days around menstruation in successive menstrual cycles to 13 women who had responded favourably to this drug in an earlier short-term placebo controlled cross-over study . Three patients have been successfully treated , with complete freedom from seizures around menstruation , for 3 - 3 1/2 years and two others responded favourably until pregnancy made treatment inappropriate . A further four patients did well during a shorter period ( 6 - 13 months ) of follow-up . An increase in seizures between periods of clobazam therapy was observed in three patients , and led to the withdrawal of this drug in two of them . However , tolerance to the antiepileptic effect of clobazam was not observed in any patient , even though nine were treated for 1 year or more . In only once case was it necessary to discontinue treatment because of sedative side effects Clobazam is a benzodiazepine with special molecular structure ( its nitrogen radicals are in positions 1 and 5 , rather than 1 and 4 as in all other antiepileptic benzodiazepines ) , and it is rapidly effective -- in a matter of hours or within a few days -- against all varieties of epileptic seizures in 52 % of subjects treated with it . Its effects are relatively mild . Unfortunately , its outst and ing antiepileptic properties are exhausted after only a few weeks in one-third of all cases . The authors discuss the potential significance of this phenomenon , and stress the urgent need for intensive study of the basic mechanism governing exhaustion of the antiepileptic properties of the benzodiazepines in general and clobazam in particular Objective : To evaluate the efficacy of intermittent clobazam therapy in preventing the recurrence of febrile seizures and to assess its safety . Methods : The study was a prospect i ve , r and omized , double-blind placebo-controlled trial conducted in the Department of Child Health , Christian Medical College Hospital , Vellore between July 2001 and September 2002 . Neurologically normal children between 6 months and 3 years of age with a history of febrile seizures and no evidence of acute CNS infection or EEG abnormality were included into the study . 19 children in a clobazam group and 20 in the placebo group were r and omly allocated . Temperature reduction measures with paractamol and tepid sponging were advised to all children . In addition the dispensed medication was to be administered at the onset of fever and continued for 48 hours irrespective of the duration of fever . The children were then monitored for seizures and adverse effects of clobazam . The children were followed up for a mean period of 9.9 months . The analysis was done on the number of febrile episodes in both the groups . Results : There were a total of 110 episodes of fever during the study period . Mean number of febrile episodes in the clobazam group was 3.1 and in placebo group 2.56 . Six ( 12.5 % ) of the 48 episodes in placebo group and one ( 1.7 % ) of 60 episodes in clobazam group had seizure recurrence . This was statistically significant ( p=0.01 ) . Drowsiness and weakness were present equally in both clobazam and placebo group whereas ataxia was present only in the clobazam group , the difference being statistically significant ( p=0.04 ) . Conclusion : Intermittent clobazam therapy is an effective measure in the prevention of recurrence of febrile seizures . The ataxia due to clobazam was much lower than that reported with diazepam PURPOSE To compare the cognitive and behavioural effects of clobazam versus st and ard monotherapy in the treatment of childhood epilepsy . METHODS A r and omized , double-blind , prospect i ve design was carried out at three Canadian pediatric epilepsy centres . This study was part of a larger multi-centre study on the efficacy of clobazam . Children with newly diagnosed epilepsy were assigned r and omly to receive clobazam or carbamazepine . Children who had failed previous treatment with carbamazepine were assigned r and omly to clobazam or phenytoin . Children who had failed on any other antiepileptic drug were assigned r and omly to receive clobazam or carbamazepine . In a subset of patients neuropsychological assessment s were carried out at 6 weeks and 12 months after initiation of medication . Intelligence , memory , attention , psychomotor speed , and impulsivity were assessed . RESULTS There were no differences between the clobazam and st and ard monotherapy groups on any of the neuropsychological measures obtained at 6 weeks or 12 months . There was no evidence for a deterioration in performance for those children who remained on clobazam for the entire 12-month study period . CONCLUSION The cognitive and behavioural effects of clobazam appear to be similar to those of st and ard monotherapy |
11,910 | 29,372,930 | Despite different design s , population s and details of question ing methods , the narrative review showed that more specific question ing of participants led to more AEs detected compared to a more general enquiry .
This review supports concerns that methods to elicit participant-reported AEs influence the detection of these data .
There was a risk for under-detection of AEs in studies using a more general elicitation method compared to those using a comprehensive method .
These AEs may be important from a clinical perspective or for patients .
This under-detection could compromise ability to pool AE data . | BACKGROUND Analysis of drug safety in clinical trials involves assessing adverse events ( AEs ) individually or by aggregate statistical synthesis to provide evidence of likely adverse drug reactions ( ADR ) .
While some AEs may be ascertained from physical examinations or tests , there is great reliance on reports from participants to detect subjective symptoms , where he/she is often the only source of information .
There is no consensus on how these reports should be elicited , although it is known that question ing methods influence the extent and nature of data detected .
This leaves room for measurement error and undermines comparisons between studies and pooled analyses .
This review investigated comparisons of methods used in trials to elicit participant-reported AEs .
This should contribute to knowledge about the method ological challenges and possible solutions for achieving better , or more consistent , AE ascertainment in trials .
OBJECTIVES To systematic ally review the research that has compared methods used within clinical drug trials ( or methods that would be specific for such trials ) to elicit information about AEs defined in the protocol or in the planning for the trial . | In a clinical trial of two antirheumatic agents two methods of collection of side effects were used , one with and the other without a check list of possible symptoms . Findings suggested that the use of a check list interfered with the collection of side effects . Known side effects of aspirin — tinnitus , deafness , and gastrointestinal disturbance — were more efficiently shown and symptoms not included in the check list were more likely to be reported when a check list was not used OBJECTIVE The authors sought to identify predictors of self-harm adverse events in treatment-resistant , depressed adolescents during the first 12 weeks of treatment . METHOD Depressed adolescents ( N=334 ) who had not responded to a previous trial with an SSRI antidepressant were r and omized to a switch to either another SSRI or venlafaxine , with or without cognitive behavior therapy . Self-harm events , i.e. , suicidal and non-suicidal self-injury adverse events were assessed by spontaneous report for the first 181 participants , and by systematic weekly assessment for the last 153 participants . RESULTS Higher rates of suicidal ( 20.8 % vs. 8.8 % ) and nonsuicidal self-injury ( 17.6 % vs. 2.2 % ) , but not serious adverse events ( 8.4 % vs. 7.3 % ) were detected with systematic monitoring . Median time to a suicidal event was 3 weeks , predicted by high baseline suicidal ideation , family conflict , and drug and alcohol use . Median time to nonsuicidal self-injury was 2 weeks , predicted by previous history of nonsuicidal self-injury . While there were no main effects of treatment , venlafaxine treatment was associated with a higher rate of self-harm adverse events in those with higher suicidal ideation . Adjunctive use of benzodiazepines , while in a small number of participants ( N=10 ) was associated with higher rate of both suicidal and nonsuicidal self-injury adverse events . CONCLUSIONS Since predictors of suicidal adverse events also predict poor response to treatment , and many of these events occurred early in treatment , improving the speed of response to depression , by targeting of family conflict , suicidal ideation , and drug use may help to reduce their incidence . The relationship of venlafaxine and of benzodiazepines to self-harm events requires further study and clinical caution Summary The incidence of side-effects on administration of chloranolol ( Tobanum ® ) , a beta-adrenergic receptor blocking drug , to 2066 patients with hypertension , angina pectoris or arrhythmias was measured by three different methods . In 600 patients in an efficacy trial ( Group 1 ) both spontaneously reported complaints and objective signs were tabulated . A side effect — directed method , utilising a question naire containing a list of possible side-effects was also used , with the question naire being completed by the physician . 35 questions referred to anticipated and other side-effects . The trial was performed in two groups : in 537 patients a placebo was also given ( Group 2 ) , and in another set of 929 patients ( Group 3 ) the question naire inquiry was performed uncontrolled , without placebo . All three groups were comparable in their distribution of sexes , ages and diagnoses , the mean daily dose of chloranolol its use alone or in combination , and in a similar duration of treatment . 55 % of all patients received chloranolol therapy for a period of more than 3 months . The ratio of in- and out patients was 1:5 . The side-effect incidence was independent of the age and sex of the patients and of the dose of chloranolol . The incidence was also unaffected whether chloranolol was used alone or in combination . The number of side-effects differed markedly between the three groups , their ratio was 1:10:24 in Groups 1 , 2 and 3 . Two-thirds of the side-effects subsided spontaneously within 1 month of their onset . The duration of the side-effects varied according to their character : cardiorespiratory side-effects were of the shortest duration and those affecting the central nervous system were the most enduring . The appreciable differences in incidence could be attributed to the methods of collection of the data . It has been stated that placebo controlled trials using a detailed question naire are the most suitable for estimating the incidence of side-effects ; recording side-effects spontaneously reported by patients are insufficiently sensitive , and uncontrolled trials using a question naire have been shown to be too sensitive . The revealed incidence of side effects leading to interruption of treatment is less affected by the method chosen . In 100 patients ( 4.8 % ) therapy had to be suspended because of the side-effects of chloranolol ( Group 1 : 1 % , Group 2 : 6.20 % , Group 3 : 6.6 % ) . Comparison of the incidence of cessation of therapy due to side-effects did not show an appreciable difference between the various beta-adrenergic receptor blocking agents , including chloranolol Introduction An increasing number of generic alendronate formulations have become available . Although expected to have the same tolerability and efficacy , head-to head comparison of generic and br and alendronate was never performed . Therefore , we compared the tolerability and efficacy of generic and br and alendronate . Methods In a r and omized double-blinded single centre cross-over study in 37 postmenopausal women ( mean age 65.4±6.4 years ) with osteoporosis were treated with generic and br and ed alendronate during 24 ( 2x12 ) weeks . Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale ( GSRS ) and self-reported side effects . Efficacy was assessed by serum bone turnover markers , carboxy terminal telopeptide ( CTX ) and procollagen type I N-terminal propeptide ( PINP ) . No wash out period was allowed ( ethical reasons ) . Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models . Results There were no significant differences in overall tolerance ( GSRS ) between treatment groups . However , for subscale abdominal pain , patients using generic had a significantly higher mean GSRS score at week 4 ( estimated mean difference ( B ) : 0.40 ; 95%CI : 0.05 to 0.74 , p = 0.024 ) . The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and br and ed alendronate ( p < 0.001 ) . Mean level of CTX was significantly lower with br and ed at week 4 ( B : 121.3 ; 95%CI : 52.0 to 190.5 ) , but not at week 12 ( B : 53.6 ; 95%CI:-3.7 to 110.9 ) . No significant differences were found for PINP at week 4 or 12 . Conclusions Bone turnover markers were significantly reduced with br and ed and generic alendronate . With br and ed , CTX was significantly lower at 4 weeks . Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment . Therefore , generic alendronate may not have the same tolerability and efficacy as br and ed alendronate in the first weeks after starting treatment in patients with a recent fracture . Trial Registration Dutch Trial Register NTR number 1867 http://www.trialregister.nl/trialreg/admin/ rct Background Historically , skin toxicity has been assessed in prospect i ve clinical trials using the clinician-reported National Cancer Institute Common Terminology Criteria for Adverse Events ( CTCAE ) . The patient-reported Skindex-16 measures symptoms and perceptions of toxicity . This study was design ed to compare information provided by these two measures . Methods Data were compiled from three placebo-controlled North Central Cancer Treatment Group studies ( N06C4 , N03CB , N05C4 ) having rash prevention as the primary objective . All used the Skindex-16 and CTCAE at baseline , weekly during treatment and during a minimum 2-week follow-up period . Statistical procedures , including Pearson correlations , were utilized to determine relationships between adverse event ( AE ) grade s and Skindex-16 scores . Results Four hundred and twelve individual patients provided data ( median age , 61 ; 134 male ) . Patients ' Skindex-16 score results show a 0.9 overall mean ( range 0–6 with 6 being worse symptoms ) , a 0.4 baseline mean ( range , 0–4.3 ) and a 1.3 end-of-treatment mean ( range , 0–5.9 ) . Ninety-three , 142 and 177 patients experienced a grade 0 , 1 and 2 + CTCAE skin toxicity , respectively . Baseline Skindex-16 scores had relatively low correlation with CTCAE grade s. The correlation of rash grade with Skindex-16 scores ranged from r = 0.49 with the function subscale to r = 0.62 with the symptom subscale . The highest correlations of the maximum grade of any dermatological AE with the Skindex-16 were r = 0.48 for the total score and r = 0.55 for the symptom subscale . Conclusions The data reported support the decision to include both measures in a clinical trial to assess the patient experience , as each measure may specifically target varying symptoms and intensities Introduction Dose-limiting neurotoxicity is a major side effect of oxaliplatin treatment , producing initial acute neurotoxicity and chronic neuropathy with increasing exposure . The improvement in survival for patients with early-stage colorectal cancer treated with oxaliplatin has highlighted the need for valid and reliable assessment of peripheral neuropathy . Objectives The objective of this paper was to explore neuropathic symptoms in oxaliplatin-treated patients as assessed using different methods . Methods Consecutive symptomatic patients reporting peripheral neuropathy after oxaliplatin chemotherapy for colorectal cancer were interviewed using a semi-structured clinical interview . Neurotoxicity was also assessed using the National Cancer Institute Common Toxicity Criteria scale ( clinician-rated ) , patient ‘ self-report ’ question naires ( PNQ ) , nerve conduction and clinical assessment . Results Twenty patients were assessed , 12.6 ± 2.8 months after treatment cessation ( mean cumulative oxaliplatin dose , 789 mg/m2 ) . In 40 % of patients , neurotoxicity necessitated early cessation of treatment . Only 10 % of patients were design ated by clinicians with severe neurotoxicity , whilst , in contrast , patient interviews and self-report question naires described significant physical limitations due to neuropathic symptoms in 60 % of patients . The majority ( 85 % ) of patients had objective evidence of sensory neuropathy with nerve conduction studies . Reports from clinical interviews were strongly correlated with patient self- assessment ( Pearson coefficient = 0.790 , p < 0.0005 ) . Conclusion Given the discrepancies in symptom prevalence highlighted by these findings , the monitoring of oxaliplatin-induced neurotoxicity would benefit from more informative clinical assessment , with inclusion of patient-reported outcome measures . Such an approach would be beneficial in a clinical trial setting to monitor the efficacy of interventions and in prospect i ve studies of survivorship to determine the true burden of peripheral neuropathy in oxaliplatin-treated patients Summary 251 patients from 23 primary health care centres were recruited to a clinical trial in which either felodipine or placebo was added to baseline metoprolol treatment . Three methods of symptom reporting were used in 191 patients , namely two previously documented self-administered question naires and an adverse event monitoring system ( spontaneous reports to treating physician).Higher frequencies of symptoms were seen with the question naires compared to spontaneous reporting . However , the overlap between the methods was moderate and they were found to complement one another . The question naires were completed twice during the study and the adverse event monitoring system was applied on five occasions . The rate of application had consequences for the ability of each method to detect transient , dose-related symptoms , e.g. headache and dizziness . Regardless of method , the possibility of detecting dose-related symptoms was enhanced when symptoms were measured not only during active treatment but also during a run-in or other baseline period , and both phases were considered in the analyses BACKGROUND A relative lack of extrapyramidal symptoms ( EPS , i.e. , the syndromes of dystonia , parkinsonism , akathisia , dyskinesia ) is one criterion used to determine whether an antipsychotic is " atypical . " The extrapyramidal symptom profiles of the novel antipsychotic olanzapine and the conventional antipsychotic haloperidol were compared in a population of 2606 patients from three well-controlled prospect i ve clinical trials . METHOD Extrapyramidal symptom data were analyzed for 1796 patients treated with olanzapine ( 5 to 20 mg/day ) and 810 patients treated with haloperidol ( 5 to 20 mg/day ) for up to 6 weeks of therapy . Patients were monitored weekly by three methods of extrapyramidal symptom assessment : ( 1 ) detection of extrapyramidal adverse events ( signs and symptoms ) by casual observation , nonprobing inquiry , and spontaneous report ; ( 2 ) objective rating scale scores : and ( 3 ) use of concomitant anticholinergic medications . Emergence of EPS was assessed by ( 1 ) analysis of the incidence of extrapyramidal syndrome categories based on adverse events , ( 2 ) the incidence of extrapyramidal syndromes based on categorical analysis of rating scale scores , ( 3 ) analysis of mean maximum change in rating scale scores , and ( 4 ) categorical analysis of anticholinergic medication use . Outcome of EPS was assessed by ( 1 ) analysis of mean change in rating scale scores at endpoint and ( 2 ) mean anticholinergic use at endpoint . RESULTS Olanzapine was statistically significantly ( p = .014 , p < .001 ) superior to haloperidol in all four analyses related to emergence of EPS and in the two analyses related to outcome . Furthermore , during acute treatment , statistically significantly fewer patients treated with olanzapine ( 0.3 % ) discontinued the study because of any extrapyramidal adverse event than patients treated with haloperidol ( 2.7 % , p < .001 ) . CONCLUSION Olanzapine exhibited a statistically significantly lower extrapyramidal symptom profile than the conventional antipsychotic haloperidol at comparably effective antipsychotic doses . The lower extrapyramidal symptom profile with olanzapine was evident despite statistically significantly more frequent use of anticholinergic drugs among haloperidol-treated patients . Fewer olanzapine-treated than haloperidol-treated patients discontinued because of EPS , suggesting that olanzapine should contribute to better compliance with longer term maintenance treatment , with minimal anticholinergic-associated events The aim of the study was to compare the onset , incidence and frequency/intensity of hot flushes during and rogen-deprivation therapy with a gonadotropin-releasing hormone antagonist ( GnRH ) blocker versus an agonist using data from a r and omized Phase 3 clinical trial . In total , 610 prostate cancer patients received monthly degarelix ( s.c . , 240/80 mg , n=207 , or 240/160 mg , n=202 ) or leuprolide ( i.m . , 7.5 mg , n=201 ) for 12 months . Data on hot flushes was collected as self-reported adverse events and in a subgroup of 254 patients with electronic diaries . The onset of hot flushes was faster on degarelix versus leuprolide , and was accompanied by higher median hot flush scores during the first 3 months . However , there were no significant differences in overall incidence rates and median hot flush scores over the entire 12 months . After the third month , incidence rates dropped below 6 % , whereas prevalence rates remained constant in all the three treatment arms . In multivariate analysis , body weight and heart rate at baseline were independent predictors of hot flushes ( P<0.05 ) . Except for a more rapid onset with the GnRH antagonist , there were no major differences in the overall pattern of hot flushes between treatment options . Weight control may help to minimize the incidence of hot flushes BACKGROUND A recent study conducted in triptan-naive migraine patients showed that tolerability was the second most important attribute of an acute treatment . However , the proportion of patients reporting side effects after any acute treatment may vary with regard to the method of assessment . OBJECTIVES To contrast two methods of assessing adverse events ( prompted and unprompted ) in those with headache using triptans . METHODS This study was conducted in two sites , a headache center in the United States , and a neurology office focusing on headache in Italy . We prospect ively surveyed 415 adults with headache , who had been using the same triptan for at least 3 months . Participants were asked about their headache and treatment history . Subjects then completed a st and ardized question naire , assessing adverse events in two different ways . First , subjects were asked if they had any adverse events when using the triptan . After returning the first part of the question naire , subjects received a second form , where 49 possible adverse events were listed . We contrasted and correlated both sets of answers . RESULTS Most patients ( U.S.=74.9 % , Italy=65.5 % ) reported no side effects in the unprompted question naire . However , most of them ( U.S.=62.9 % , Italy=54.1 % ) reported at least one side effect in the prompted question naire . Most patients that reported side effects in the unprompted question naire said they had just one adverse event , while most reported two or more side effects in the prompted question naire . Both in the unprompted and in the prompted question naires , most side effects were rated as mild or moderate . Interestingly , 31 ( 7.5 % ) subjects ( pooling data from both sites together ) grade d their adverse events as severe in the prompted question naire , but had not self-reported them . CONCLUSIONS ( 1 ) When assessing adverse events , the method of data collection may dramatically influence the results . ( 2 ) From those subjects who did not self-report adverse events after using a triptan , most of them will report positively if presented with a list of side effects A prospect i ve study has been carried out in two groups of hypertensive patients ( 482 in patients followed during 2 - 3 weeks ; 120 out patients followed for 18 months ) to evaluate the prevalence of side effects ( SE ) induced by antihypertensive drugs in current use . Only SE of definite or probable type as operatively defined were taken into consideration . SE were collected in different ways for in patients and out patients . Among 120 out patients , 30 patients were r and omly selected for cross over of placebo and drugs . Definite or probable SE were recorded in 236 ( 48.9 % ) of 482 patients : the prevalence of SE was below 20 % both in single and multiple drug therapy . A prevalence greater than 20 % was recorded in the out patients . The placebo treatment demonstrated that many SE are not related to drug administration Abstract Background : The collection of adverse event data is an important component of clinical trials , but it is not clear whether solicited or unsolicited collection methods are better at distinguishing drug effects from the effects of placebo . The objective of this analysis is to compare the reporting rates and the ability to detect drug-placebo differences with spontaneous versus solicited adverse event collection methods . Methods : Adverse events were collected by spontaneous ( unsolicited ) reporting and by structured question naires in three r and omised , double-blind clinical trials . For both spontaneous and solicited adverse event collection methods , a drug/placebo ( D/P ) reporting ratio was computed by dividing the reporting rate for the experimental drug by the reporting rate for placebo for each adverse event . An index ( Sp-So index ) was calculated by dividing the spontaneous D/P ratio by the solicited D/P ratio . A number > 1.0 indicates that the spontaneous adverse event collection method is more effective in distinguishing the drug from placebo and a number < 1.0 suggests that the solicited adverse event collection method is more effective in distinguishing the drug from placebo . Results : Reporting rates were greater when events were solicited than when the spontaneous reporting approach was used . The Sp-So index was > 1.0 for 22 of the 29 ( 75.9 % ) events examined , suggesting that spontaneous collection of adverse events is more effective in distinguishing drug effect from placebo than the solicited approach . However , more statistically significant differences between drug and placebo were detected by the solicited method ( nine events ) than the spontaneous method ( five events ) . This is due , in part , to the fact that differences in the percentages of adverse events between drug and placebo ( rather than ratios of event rates ) were more often greater when the solicited approach was used . Conclusions : As expected , adverse events collected by solicitation leads to higher reporting rates . However , it is not clear that solicitation of events leads to greater ability to detect drug-placebo differences . By using a ratio to assess drug-placebo differences , spontaneous reporting provided larger drug-placebo differences more often than solicitation This study compares two methods for elicitation of treatment-emergent side effects . One is the open-ended general inquiry and the other is a specific inquiry that asks about a wide range of events thought to be treatment-related . The study goal was to determine the extent to which the specific inquiry method elicits clinical ly useful information over and above that elicited by the general inquiry method . The assessment instrument we used is SAFTEE , a structured interview schedule developed by the National Institute of Mental Health . We looked for differences between general and specific inquiry formats in terms of number of events elicited , type of event , severity , functional impairment , and clinician action taken . We found that both methods contributed to elicitation of events that , in the clinician 's opinion , required some change in management . However , events reported on the General Inquiry form were significantly more distressing , more often interfered with daily functioning , and elicited more extensive changes in clinical management . No medically serious events were elicited on the specific inquiry form alone . Based on these findings , and in view of the amount of time and effort required to administer and score it , we do not recommend the specific inquiry form of SAFTEE as a st and ard assessment tool for routine use in all clinical trials . We do consider it to be a useful method for comprehensive elicitation about treatment-emergent effects in targeted and specific research context s. We see the schedule as a comprehensive document or library of queries to be tailored to the needs of individual protocol Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms In a general practice in Derbyshire 298 patients who had been given antibiotics were question ed about possible adverse reactions to the drug prescribed . Four methods of assessing adverse effects of drugs in the community were used , and a comparison was made of the replies elicited from patients by doctor and health visitor respectively . Significant differences were shown to occur in the way in which each investigator completed the question naires . If ancillary staff are to be employed in monitoring adverse effects of drugs in the community on a large scale then they will have to use a method less reliant on the differentiation of incidental symptoms from drug side effects than is required in the present survey OBJECTIVE Substance abuse is extremely common in patients with bipolar disorders , although minimal data are available on the treatment of this important clinical population . Aripiprazole is an atypical antipsychotic that is approved for the treatment of mania and that has a novel mechanism of action , acting as a dopamine-2 receptor partial agonist , thereby increasing dopamine release in some parts of the brain and decreasing dopa-mine release in other brain regions . Dopamine release is implicated in substance use , and both dopaminergic agonists and antagonists have been examined for the treatment of substance abuse . To our knowledge , dopa-mine receptor partial agonists have not been investigated for treatment of substance abuse in humans . METHOD Twenty antipsychotic-treated patients with bipolar or schizoaffective disorder and current substance abuse were switched to open-label aripipra-zole using an overlap and taper method . At baseline , diagnoses were confirmed using the Mini-International Neuropsychiatric Interview based on DSM-IV criteria . Psychiatric symptoms , side effects , and substance use and craving were assessed over 12 weeks . Psychiatric symptoms were assessed with the Hamilton Rating Scale for Depression ( HAM-D ) , Young Mania Rating Scale ( YMRS ) , and Brief Psychiatric Rating Scale ( BPRS ) . Substance craving was assessed with visual analogue scales , and side effects were monitored using the Abnormal Involuntary Movement Scale , Simpson-Angus Scale , Barnes Akathisia Scale , and patient report . Study enrollment was from April 2003 to February 2004 . RESULTS Significant baseline-to-exit improvement in HAM-D ( p = .002 ) , YMRS ( p = .021 ) , and BPRS ( p = .000 ) scores were observed without a significant change in antipsychotic-induced side effect scales . In 17 participants with current alcohol dependence , significant reductions in dollars spent on alcohol ( p = .042 ) and alcohol craving ( p = .003 ) were found . In 9 participants with cocaine-related disorders , significant reductions in cocaine craving ( p = .014 ) , but not use , were found . CONCLUSION A change to aripiprazole was associated with symptomatic improvement . Limitations of the study include a small sample size , high attrition , and an open-label design . Controlled trials in dual-diagnosis patients are needed to confirm these findings In a double-blind double-dummy multicenter study , patients with mild to moderate essential hypertension were r and omized to receive either nifedipine ( n = 416 , 47.6 % women ) or lisinopril ( n = 412 , 50 % women ) , and side effects were registered by specific question ing , by spontaneous reports , and by use of visual analog scales . Cough was spontaneously reported to occur in 8.5 % with lisinopril compared to 3.1 % with nifedipine . Women treated with lisinopril reported cough spontaneously three times more often than men , 12.6 % v 4.4 % , whereas no differences between the sexes were observed during the placebo period or during nifedipine treatment . Similar gender differences were observed during specific question ing . Furthermore , nonsmokers reported an increase in cough more often than did smokers Summary A pilot study was conducted to compare symptoms elicited with an open-ended question versus a checklist and to measure the responsiveness of quality -of-life measures to symptom severity . The pilot study was part of a multicentre , r and omised , double-blind , placebo-controlled study of clentiazem , a calcium channel blocker , in the treatment of essential hypertension . Symptom and quality -of-life data were obtained from 88 patients at baseline and after 10 weeks of therapy by a trained telephone interviewer . Comparison of the symptom checklist and open-ended question method suggests that both methods are necessary to capture severe symptomatology . The 24-item checklist failed to elicit approximately 50 % of the severe symptoms reported on the open question list . On the other h and , only 18 % of the most severe symptoms subsequently reported on the checklist were first reported by the open question method .The responsiveness of quality -of-life measures to symptom severity was tested using a 20 % change in symptom severity obtained from the checklist as the minimal clinical ly significant difference . Using Guyatt ’s formula , a minimum sample size of approximately 428 ( α = 0.05 , β = 0.10 ) patients per treatment group is required to detect differences in measures of general health perception , anxiety , depression and limitations in social activities . A larger sample is required to show differences in leisure activities . Differences in limitations of the capability to perform house or yard work might be demonstrable with as few as 17 patients per group . This pilot study demonstrated that the severity of symptoms associated with hypertension , and the side effects of its treatment with drugs , are adequately captured by a symptom checklist preceded by an open-ended method of question ing . Responsiveness testing estimated the sample size required to show a statistically significant difference , assuming a 20 % change in symptom severity OBJECTIVE To explore participants ' underst and ings regarding treatment decisions , made within an efficacy r and omised controlled trial ( RCT ) of decision-support tools . METHODS Qualitative study : interviews ( audio-recorded ) with participants . Participants were interviewed 3 - 5 days after using a decision-support tool ( n=30 ) and again at 3 months ( n=26 ) . Transcripts were analysed using a constant comparative approach . RESULTS Participants ' underst and ings were shaped by the ways in which they made sense of their participation . Participants made attributions about their trial identity that fell on a continuum . At one end we found participants who identified as ' experienced medical volunteers ' , and at the other those who identified as ' real patients ' . In the participants ' accounts , a trial identity of ' patient ' accompanied an expectation that the decision-support tools offered a means of making treatment decisions . ' Volunteers ' , however , saw the interventions as tasks to be completed for the purpose s of the trial team . CONCLUSION In our study , trial identity shaped participants ' underst and ings regarding treatment decisions and all other aspects of the trial . PRACTICE IMPLICATION S Different underst and ings regarding the appropriate response to trial tasks may affect behaviour and therefore outcomes in some trials . Further research is required to unravel the relationship between trial identities , underst and ing and behaviour 1 . The objective of this double-blind parallel-group study was to compare the tolerability of isradipine and amlodipine , specifically , the side-effects known to be related to the use of dihydropyridine calcium antagonists . 2 . A total of 205 patients with mild-to-moderate essential hypertension were r and omized to receive either the sustained-release ( SRO ) formulation of isradipine ( n = 103 ) or amlodipine ( n = 102 ) , both at dosages of 5 mg once daily . Blood pressure measurements were taken at the end of the dosing interval to assess the antihypertensive efficacy of the two drugs . 3 . Adverse reactions were assessed in two ways : a ) spontaneously reported adverse events were recorded and investigated in depth for severity , duration , relation to the study drug , and outcome ; b ) a question naire was used to elicit specific adverse reactions known to be related to the use of dihydropyridine calcium antagonists which were evaluated for severity , duration , relation to the study drug , and outcome . 4 . After 6 weeks of active treatment , both isradipine and amlodipine reduced mean sitting systolic/diastolic blood pressure : from 165.1/100.1 to 145.2/89.7 mm Hg with isradipine ; and from 164.1/100.6 to 145.7/90.5 mm Hg with amlodipine . There was no difference in antihypertensive effect between isradipine and amlodipine ( 95 % CI : -3.73 to 4.73 and -1.89 to 3.49 for differences in systolic and diastolic blood pressure , respectively ) . 5 . The number of patients spontaneously reporting adverse events was significantly higher ( P = 0.02 ; 95 % CI : 3.1 to 26.7 % ) with amlodipine ( 33.3 % ) than with isradipine ( 18.4 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS This qualitative study explored non-specific influences on participation in , and outcomes of , a r and omised controlled trial . It was nested within a single-blind clinical trial of western acupuncture which compared real acupuncture with two types of placebo control administered to National Health Service ( NHS ) patients awaiting hip and knee replacement surgery in Engl and . Data collection ( 2004 - 2008 ) was based on narrative-style interviews and participant observation . The results indicate that trial recruitment and retention depend on a set of convictions forged largely as a result of context ual factors peripheral to the intervention , including the friendliness and helpfulness of research centre staff and status of the administering practitioner . These convictions also influence the reporting of the study outcomes , particularly if participants experience uncertainties when choosing an appropriate response . The findings suggest that participants in clinical trials are actively involved in shaping the research process , rather than passive recipients of treatment . Thus the outcomes of trials , notably those involving contact interventions , should be regarded not as matters of fact , but as products of complex environmental , social , interpretive and biological processes . In this paper , we develop and present a ' theory of active research participation ' which offers a framework for underst and ing the impact of non-specific processes in clinical trials Neuropsychiatric symptoms in human immunodeficiency virus (HIV)-infected patients may be a late complication of efavirenz treatment . This study : 1 ) assessed the level of neuropsychiatric symptoms in HIV-infected patients on long-term efavirenz therapy ; 2 ) explored the effect of a switch to non-efavirenz containing anti-retroviral treatment on neuropsychiatric symptoms . A consecutive series of 47 HIV-infected participants on long-term efavirenz treatment were included in an observational clinical trial . Participants completed three self-report question naires on neuropsychiatric symptoms . Patients switching to a non-efavirenz regimen were retested 2 weeks and 3 months after switching . Data were analyzed using repeated measures ANOVA to assess the effect of switching over time . A change in the percentage of patients scoring above norm scores after switching was analyzed using Chi square . Neuropsychiatric symptoms were common among HIV-infected patients on long-term efavirenz therapy , mainly depression , anxiety , stress , insufficiency in thinking and paranoia . After switching , these symptoms improved significantly to ( near ) normal levels . Our results show that neuropsychiatric symptoms are common among HIV-infected subjects and may be caused by long-term efavirenz use . Neuropsychiatric assessment , such as the Depression , Anxiety and Stress scale and Symptom Checklist 90 , can identify those that may benefit from the discontinuation of efavirenz The effect of a st and ardized verbal interview on the frequency of reported adverse events to an intravenous injection of a non-ionic low-osmolar magnetic resonance ( MR ) contrast medium was studied during a low noise ( low anxiety ) magnetic resonance imaging ( MRI ) examination . During a 26-month period 863 patients had an intravenous bolus ( < 10 sec. ) injection of either 0.1 mmol/kg b.wt . or 0.3 mmol/kg b.wt . gadodiamide , were examined in 0.1 Tesla ( T ) MRI unit . All patients received written information about the examination , but no specific information about possible adverse events to the contrast medium . During the first 15 months , 479 patients were asked after the examination by the same radiographer the following question " Did you feel anything in relation to or after the contrast medium injection ? " . If the answer was affirmative , the patient was asked to specify the experience . During the subsequent 11-month period , 384 patients had no interview about whether they felt anything in relation to the contrast medium injection . Only 9 out of 863 patients reported an adverse event and they all belonged to the group , which was interviewed . In 8 cases the adverse events lasted less than 5 min . The ninth patient had an attack of migraine 20 min . after the injection of the contrast medium . In one of the patients , who experienced nausea , it was necessary to postpone scanning for 2 min . Two of the 9 adverse events were considered to be unrelated to the contrast medium . None of the 121 patients receiving the triple dose reported an adverse event . The frequency of reported adverse events depends on whether this information is obtained by active question ing . All reported adverse events were clinical ly mild and no dose-response effect was observed The detection of adverse drug reactions ( ADRs ) by a traditional passive reporting system and by a method involving patient and provider interviews was studied . The study sample consisted of r and omly selected out patients seen by their primary care provider during scheduled appointments in January and February 2001 at a Veterans Affairs medical center . After ambulatory care clinic sessions , patients and providers were asked ( by telephone and in person , respectively ) to identify potential ADRs . Also obtained were demographic data , information about drug regimens , and the severity and management of each ADR . A st and ardized ADR- assessment tool was used to determine the severity of each reported reaction and its causal relationship with the medication . A total of 198 patients were included . Of these , 51 ( 26 % ) had one or more ADRs . The patient and provider interviews identified a total of 83 ADRs , compared with 1 ADR identified by the passive reporting system . When providers were made aware of the ADRs they had not identified , changes were made to the patient 's medication regimen in 34 % of cases . The risk of an ADR was not associated with age , number of medications , or provider type . Direct patient and provider interviews yielded a significantly higher rate of ADR detection in an ambulatory care setting than did a passive ADR-reporting system OBJECTIVES Qualitative research has an important part to play in investigating how complex interventions are implemented within r and omized controlled trials ( RCTs ) and what impact the RCT context has on participants , their behavior , and their outcomes . We explored these issues within a r and omized sham-acupuncture controlled trial of traditional Chinese acupuncture for people with migraine . METHOD All trial participants who consented to take part in this qualitative study were interviewed twice by a research er who was blind to all trial data . The acupuncture practitioner was interviewed once . Nineteen ( 19 ) semistructured interviews , 30 - 60 minutes long , were transcribed , coded , and analyzed both across and within cases . RESULTS The 10 participants , 6 female , age 23 - 70 years had severe migraine and conventional treatment had been of limited benefit . They were satisfied with the organization of the trial and no acupuncture was perceived as obviously " sham . " Most participants , and the practitioner , actively " played their part " in the trial , taking on research roles that differed from their usual roles of " patient " and " doctor . " The result ing changes to their normal expectations and behavior influenced how the intervention was delivered and experienced . There was a reduction in talking , explanations , and participation , and treatment was focused on the migraine and usually excluded other conditions , even if the participants considered them to be a cause or a trigger of the migraine . CONCLUSIONS We conclude that treatment in the trial differed from that described in studies of " real life " traditional acupuncture . These differences affected the needling-the characteristic or specific intervention-as well as context ual factors . This trial design limitation appears to be inevitable when a sham-controlled design is used to research an intervention that is based on a holistic and participative treatment strategy . These findings should be taken into account in the design and interpretation of RCTs of complex interventions such as acupuncture Twenty-three in patients at Hartford Hospital were selected for the pilot study of NIMH Collaborative Study III , testing the feasibility of high-dosage chlorpromazine in depressed patients . After r and om assignment to either a nonchecklist group or a checklist group , both groups were asked the following question : " Have you noticed any change in bodily function or had any physical complaints in the past week ? " The nonchecklist group was asked no further questions , and only spontaneously reported symptoms were recorded . The checklist group was also asked specific questions from a list of possible drug side effects . Statistical analysis in terms of both quantity and severity of side effects showed significantly greater numbers and greater severity of side effects reported in the checklist group . On the basis of these resuits the authors feel that unless reports of medication side effects are obtained in a uniform manner , the data collected under varying conditions of inquiry will not be comparable . Research fi Abstract The incidence of treatment-emergent sexual dysfunction in the acute and continuation phases of the prevention of recurrent episodes of depression with venlafaxine ER for two years ( PREVENT ) study was assessed . Adult out patients with recurrent major depressive disorder were r and omly assigned to receive venlafaxine extended release ( ER ; 75–300 mg/day ) or fluoxetine ( 20–60 mg/day ) . Sexual dysfunction was assessed using items from the 17-item Hamilton Rating Scale for Depression ( HAM-D17 ) and the Inventory of Depressive Symptomatology – Self-Report ( IDS-SR ) . The baseline rates of sexual dysfunction based on the HAM-D17 and IDS-SR items were 57.9 % and 48.8 % , respectively . The rates of new-onset sexual dysfunction for the venlafaxine ER – treated ( 44.8 % , HAM-D17 ; 38.4 % , IDS-SR ) and fluoxetine-treated patients ( 52.9 % , HAM-D17 ; 50.0 % , IDS-SR ) were similar ; approximately 80 % of the cases resolved during treatment . Treatment response was associated with lower rates of new-onset sexual dysfunction compared with nonresponse . The patients who remitted were the least likely to experience sexual dysfunction during antidepressant treatment The st and ard approach for documenting symptomatic adverse events ( AEs ) in cancer clinical trials involves investigator reporting using the National Cancer Institute 's ( NCI 's ) Common Terminology Criteria for Adverse Events ( CTCAE ) . Because this approach underdetects symptomatic AEs , the NCI issued two contracts to create a patient-reported outcome ( PRO ) measurement system as a companion to the CTCAE , called the PRO-CTCAE . This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties . A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting . For each of these , a PRO-CTCAE plain language term in English and one to three items characterizing the frequency , severity , and /or activity interference of the AE were created , rendering a library of 124 PRO-CTCAE items . These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational , racial , and geographic background s. Favorable measurement properties of the items , including construct validity , reliability , responsiveness , and between-mode equivalence , were determined prospect ively in a demographically diverse population of patients receiving treatments for many different tumor types . A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing . Work is ongoing to translate the PRO-CTCAE into multiple language s and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses . It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research OBJECTIVE The incidence of sexual dysfunction due to antidepressant drugs reported in pre-marketing clinical efficacy trials is often several times lower than in subsequent clinical experiences and independent reports . Although it is commonly believed that the reason for this discrepancy is that the nonleading questions employed in conventional clinical trials underestimate sexual dysfunction while the direct question ing used in independent trials provides more accurate data , few studies have actually compared these 2 methods . METHOD In this study , 119 patients with a DSM-IV-defined major depressive episode ( 82 women and 37 men ) who had been treated with but not responded to a selective serotonin reuptake inhibitor ( SSRI ; either citalopram or paroxetine ) were assessed regarding sexual functioning by means of open-ended questions and direct question ing at baseline ( after SSRI treatment only ) and after 4 weeks of SSRI treatment plus buspirone or placebo . RESULTS More patients reported sexual dysfunction in response to direct question ing ( 41 % ) as compared with spontaneous report ( 6 % ) ( p < .001 ) . Sexual dysfunction correlated with the duration of the depressive episode , but not with age , dose of SSRI , plasma level of SSRI , duration of SSRI treatment , or any measurement of depression . No statistically significant differences regarding the incidence of sexual dysfunction were found between the citalopram and the paroxetine groups . CONCLUSION Open-ended questions are an insufficient tool to estimate sexual dysfunction , and premarketing clinical trials should therefore include basic explicit assessment s. The failure to find a correlation between treatment duration and sexual dysfunction adds to the notion that sexual side effects due to SSRIs do not abate over time In a double-blind , r and omized , crossover , multicenter study performed in 227 hypertensive out patients , two antihypertensive drugs , oxprenolol and chlorthalidone , were investigated to determine unwanted effects . Three main method ologic procedures were applied : the conventional evaluation of unwanted effects by the physician and involving the whole patient population , the checklist , and the free question naire . The latter two were assigned by r and omization to the patients themselves . The study showed that unwanted effects seem to be frequently overreported when a checklist is used , whereas the free question naire gives more information about the symptoms of the disease than about the tolerance of the drug . The conventional method , when physicians are well-informed and sensitized to the problem , seems to provide more reliable information about unwanted effects of a drug Two methods of assessing adverse drug effects-an open-ended question versus a checklist-were compared in a clinical study involving 515 patients being treated with bacampicillin for gonorrhea . Results indicate that adverse reactions are reported more frequently if a checklist is used . However , it was also observed that more serious side effects are usually reported in response to an open-ended question rather than a checklist . Thus it was concluded that the optimal procedure for assessing adverse reactions is to record responses to both an open-ended question and a checklist Context Investigators use diverse methods to assess the adverse events experienced by study participants . Contribution During a 1-month placebo run-in period of a clinical trial , this single-blind sub study r and omly assigned 214 men with benign prostatic hyperplasia to 3 groups to test different methods of asking about recent medical problems . Men who completed a checklist about 53 common side effects reported many more problems than participants in the 2 groups that were given different formats of open-ended questions . For example , 77 % of the checklist group reported 1 or more medical problems , compared with 13 % and 14 % of the open-ended groups . Implication s Varying the assessment method can cause large differences in reported rates of adverse events . The Editors Currently , there is no st and ard method for identifying adverse events that occur during a clinical trial . Although regulatory agencies ( such as the U.S. Food and Drug Administration ) require that studies of new drugs report adverse events in a st and ard way , they do not specify a st and ard method for ascertaining these data ( 1 ) . Consequently , how individual studies identify adverse events varies considerably . For example , early studies of nonsteroidal anti-inflammatory druginduced gastric ulcers reported much lower frequencies of ulcers than more recent studies , mostly because research ers have recently made greater efforts to detect this side effect ( 2 ) . The implication s of this lack of consistent ascertainment methods are substantial ; comparisons of rates of reported side effects from 2 or more drugs may not be valid if the methods of collecting adverse events differ . This could impair the ability of patients and physicians to compare the riskbenefit profile of drugs . We therefore conducted a r and omized , controlled trial to determine whether different methods of identifying adverse events in a clinical trial would lead to different estimates of the frequency of these events . Methods Study Design The study protocol and all procedures were approved by the Committee on Human Research at the University of California , San Francisco . The study , which took place between April 2002 and April 2005 , was a r and omized , single-blind , controlled trial that assigned patients to 3 groups to test self-administered methods of assessing medical problems that they experienced while taking a placebo for 1 month . Participants We recruited participants from a larger study that was examining the safety and efficacy of the herb saw palmetto for treatment of benign prostatic hyperplasia ( 3 ) . The trial , known as the STEP ( Saw Palmetto Treatment for Enlarged Prostates ) study , required that participants be 50 years of age or older , have moderate to severe symptoms of benign prostatic hyperplasia , and have no serious comorbid illness . All participants in the study gave informed consent ; were told that they would be taking placebo at some point during the study ; and were assigned to a single-blind , 1-month placebo run-in period . R and omization and Intervention After taking the placebo ( referred to as the study medication ) for 1 month , patients were r and omly assigned to 3 methods of collecting adverse events . All patients were given 1 of 3 self-administered paper forms . The form given to the first group asked an open-ended question : Did you have any significant medical problem since the last study visit ? The form given to the second group asked an open-ended question that was more defined : Since the last study visit , have you limited your usual daily activities for more than 1 day because of a medical problem ? A checklist accompanied the form given to the third group , which asked a more pointed question : Since the last visit , have you experienced any of the following ( checklist attached ) ? The checklist contained 53 symptoms , grouped by anatomical region . Two of the authors developed the checklist after conducting an unpublished review of checklists that were used in earlier clinical trials performed at the same institution . The checklist did not ask patients to rate the frequency or severity of symptoms and did not ask patients to make a judgment about whether their medical problem was caused by the study medication . Patients in the open-ended question groups who answered yes were asked to identify their medical problem , which was recorded by a study assistant on the same checklist used in the third group . Outcomes and Analysis The primary outcome measure was the difference in the proportion of patients reporting 1 or more adverse events in each group . All patients in the STEP study were included in the current study ; therefore , the sample size was not calculated on the basis of the needs of this study . Participants were r and omly assigned to the 3 groups in equal proportions by using a computer-generated , r and om allocation sequence that was prepared before the study began . Study personnel were blinded to the allocation sequence but were aware of group assignments after they were made . Patients were not informed of their group assignment . Persons performing the data analysis were blinded to group assignment . Baseline characteristics of the 3 intervention groups were compared by using analysis of variance for continuous variables and chi-square tests for categorical variables . We also used chi-square tests to compare the number and specific type of adverse events that occurred among groups . All analyses were performed by using Stata , version 8.0 ( Stata Corp. , College Station , Texas ) . Role of the Funding Sources The funding organizations had no role in the design and conduct of the study ; the collection , management , analysis , and interpretation of the data ; or the preparation , review , or approval of the manuscript . Results We r and omly assigned 214 patients to 1 of 3 methods of collecting data on adverse effects . Patients were predominantly healthy , well-educated white men ( mean age , 63 years ) who were taking a mean of 2.5 medications ( Table 1 ) . Baseline characteristics of the patients were similar among the 3 groups . All patients completed the study and the outcome assessment ( Figure ) . Table 1 . Baseline Characteristics of Study Participants Figure . Flow diagram showing the distribution of participants at each stage of the study . The group that was assigned to a checklist method reported a significantly greater number of adverse events ( 238 events ) than the first and second groups , which were asked open-ended questions ( 11 and 14 adverse events , respectively ; P < 0.001 ) ( Table 2 ) . A much higher percentage of patients in the checklist group reported 1 or more adverse events ( 77 % ) compared with the patients asked each of the 2 different open-ended questions ( 14 % for the first group and 13 % for the second group ; P < 0.001 ) . For each of the 10 most commonly reported adverse events ( Table 2 ) , participants in the checklist group reported a greater number of adverse events ( P < 0.001 ) . No serious adverse events occurred during the study period . Table 2 . 10 Most Frequently Reported Adverse Events Discussion In this r and omized , controlled trial , we found that a checklist method of identifying adverse events dramatically increased the number of reported events compared with 2 types of open-ended questions . Although this finding is intuitive , the magnitude of effect has important implication s both for the conduct of clinical trials and for assessment of the riskbenefit profile of drugs and other interventions . It is common practice for physicians and patients to select drugs and other interventions on the basis of their reported rate of side effects . However , if different drugs used for the same indication are examined in clinical trials that use different methods of identifying adverse events , then it is not valid to compare the reported rate of side effects . For example , the reported rates of sexual side effects from selective serotonin reuptake inhibitors range from 2 % to 73 % ; much of this difference is probably attributable to different methods of adverse event collection ( 4 ) . Similarly , a recent systematic review found that published trials of pharmacologic treatments for rheumatoid arthritis were much more likely to report data on harm than trials of nonpharmacologic treatment ( 5 ) , highlighting the difficulty of comparing the safety of different treatments for the same condition . The 3 self-administered questions that we used to assess the frequency of adverse events in this study were , by design , limited in scope . The self-administered forms did not ask patients to describe the timing , severity , or frequency of their medical problems , nor did they ask participants or investigators to make a judgment of causality . Other techniques to assess adverse events , such as changes in vital signs , laboratory tests , physical examinations , or more detailed search es for expected adverse events , were not included . The purpose of this simplified approach was to isolate and contrast 3 different initial screening methods of identifying medical problems occurring among participants in a clinical trial . Because all patients in the current study were taking placebo , probably none of the reported adverse events were true side effects of the study medication but were merely symptoms that commonly occur in adults . For example , a previous survey of university students and hospital staff found that 81 % of respondents reported some symptom within the past 3 days when prompted by a checklist ( 6 ) . This highlights the problem that most study participants are likely to have a high prevalence of symptoms that are unrelated to a study drug or intervention , and a checklist method is therefore likely to have very low specificity for detecting true side effects . The wording of the 3 self-administered questions that we used in this study asked about 3 different thresholds of medical problems . One question asked participants if they experienced a significant medical problem , one asked if they limited their usual daily activities OBJECTIVE The study was undertaken to determine the side effects , including depression , of oral contraceptives ( OCs ) in adolescent girls . METHODS We conducted a r and omized trial of OCs for dysmenorrhea , which assessed side effects and depression . Seventy-six adolescents received an OC ( 20 microg of ethinyl estradiol/100 mg of levonorgestrel ) or a placebo in a double-blind fashion for 3 months . We ascertained OC side effects using open-ended and closed question formats . Participants self-administered the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depressive symptoms . RESULTS Fifty-seven participants ( 77 % ) reported at least one side effect ( median=2 , range=0 - 8 , interquartile range=1.0 - 3.25 ) . The number and the type of side effects reported in the OC group and in the placebo group were similar . Mean exit CES-D scores were comparable between groups [ OC group , 14.0 ( SD=9.2 ) ; placebo group , 14.4 ( SD=8.1 ) ; p=.86 ] . CONCLUSION Adolescents treated with an OC or a placebo experienced similar numbers and types of OC side effects , as well as depressive symptoms 1 Labetalol has been compared with propranolol in a double-blind , double-dummy study of 24 patients with mild or moderate essential hypertension . 2 Two patients were unable to tolerate propranolol and five labetalol , because of symptom side effects ; this difference was not significant ( P greater than 0.1 ) . 3 On a self-administered question naire , labetalol was associated with a greater number of side effects per patient than propranolol , but no individual side effect was significantly more common with either drug . 4 There was no difference in the number of spontaneously reported side effects between the two drugs . 5 Both drugs impaired pulmonary function , but propranolol caused a greater reduction than labetalol after 8 weeks of treatment . 6 We conclude that labetalol and propranolol are similarly effective and acceptable to the patient The incidence and prevalence of cough related to enalapril was assessed by spontaneous reporting and a visual analogue scale during a 6 month r and om double-blind parallel-group study comparing enalapril with nifedipine . Cough was reported spontaneously by 6.2 % of enalapril-treated patients , and by none on nifedipine ( NS ) . No patient had to discontinue enalapril because of cough . After 24 weeks treatment increases in visual analogue scale scores for cough frequency greater than or equal to 8 mm were more common for enalapril than nifedipine ( difference 21.5 % , 95 % CI 7.3 - 35.7 % ) . Increased cough frequency by visual analogue scale was present throughout the study in women , but less consistently in men . High scores for cough were not related to the dose of enalapril . Cough with enalapril was not an important problem during the 6 months of treatment . However increased cough frequency could be detected by visual analogue scale , with a frequency consistent with that observed in open clinic-based studies of longer duration . These findings suggest that ACE inhibitor-induced cough may increase in severity over time , and that even a period of 6 months treatment is too short to evaluate this side-effect adequately 1 . A double-blind , multicentre study comparing the efficacy and safety of minaprine and amitriptyline in patients with major depression was carried out . Five hundred and thirty-one patients were r and omly assigned to treatment with either minaprine 100 mg , 200 mg or 300 mg day-1 or with amitriptyline 150 mg day-1 ( 75 mg during the first week ) . The medication was administered for 6 weeks . 2 . Efficacy was assessed using the Hamilton rating scale for depression ( HDRS ) , the Montgomery-Asberg depression rating scale ( MADRS ) and visual analogue assessment s of depression carried out by both the investigators and patients . Unwanted effects were assessed by a question naire and spontaneous reporting . In a subgroup of patients cardiovascular effects were investigated by high speed ECG and systolic time intervals . 3 . Patients in each treatment group showed a significant clinical improvement ( P < 0.01 ) from baseline . The mean HDRS and MADRS scores adjusted for baseline differences , showed significantly less improvement in the minaprine 100 mg once daily ( P < 0.01 ) and the minaprine 300 mg daily ( P < 0.01 ) groups than in the amitriptyline group at both week 4 and week 6 . The MADRS score at week 4 suggested that 200 mg day-1 minaprine was less effective than amitriptyline ( P < 0.05 ) , but there was no difference between the two groups at week 6 on either the HDRS or the MADRS . 4 . Both drugs were well tolerated and there were no significant differences between treatment groups in any of the safety and tolerance assessment s. In the ECG , amitriptyline produced a significant increase in the heart rate and PR interval while minaprine had no effect on electrocardiographic measurements . Neither drug produced changes in the systolic time intervals Forty-six patients with obsessive-compulsive disorder undergoing a double-blind controlled study of clomipramine and placebo were interviewed to assess changes in sexual function . Of 33 patients with previously normal organism , nearly all of the 24 on clomipramine developed total or partial anorgasmia ; none of the 9 on placebo did so . Anorgasmia persisted with minimal tolerance over the five months that clomipramine was taken . Men and women were equally affected . Sexual side-effects are easily missed without a structured interview , and can detract from the value of drug treatment Evaluation of safety and efficacy of new drugs is based largely on data from clinical trials involving a limited number of patients . This approach does not necessarily detect the rare adverse events that may only be observed when very large numbers of patients are studied . Consequently , we design ed a double-blind 12-week trial comparing the new angiotensin-converting enzyme ( ACE ) inhibitor , quinapril ( n = 5,053 ) , with a well-established beta-adrenergic receptor blocker , metoprolol ( n = 506 ) . Essentially hypertensive patients ( diastolic blood pressure 95 - 114 mm Hg ) received either 10 mg quinapril or 50 mg metoprolol once daily , and the doses were doubled at 4-week intervals to a maximum of 40 and 200 mg , respectively , in nonresponders . Responder rates were similar under both regimens . Adverse events were assessed by interview as well as by a st and ard question naire . The overall prevalence of adverse events reported by st and ard question naire was higher than that reported spontaneously during interviews . With respect to typical ACE inhibitor adverse reactions ( e.g. cough and taste disturbances ) , there was no difference between quinapril and metoprolol independent of the mode of reporting . In summary , both drugs showed comparable overall tolerance and safety . The discrepancy between spontaneously reported and question naire-reported adverse events was noteworthy , and this finding prevailed in a volunteer group of 327 patients who were treated with quinapril for 52 weeks . Thus , a question naire is of great significance in addition to the patient history/interview in a large-scale , double-blind study design ed to learn about details of drug safety BACKGROUND Delayed-release dimethyl fumarate ( DR-DMF ) has cytoprotective and antiinflammatory properties and has recently been approved in the United States as an oral treatment for relapsing forms of multiple sclerosis . The most common adverse events associated with DR-DMF are flushing and gastrointestinal ( GI ) events , the incidences of which diminish over time . OBJECTIVE The purpose of this study was to evaluate the tolerability and pharmacokinetic ( PK ) profile of DR-DMF with or without concomitant acetylsalicylic acid ( aspirin ) , a cyclooxygenase inhibitor . METHODS Healthy volunteers ( N = 56 ) were r and omized to receive different dosing regimens of DR-DMF or matching placebo with or without pretreatment with 325 mg aspirin for 4 days . Plasma levels of the active metabolite monomethyl fumarate were assessed on days 1 and 4 . Flushing and GI events were assessed using patient-reported scales . Potential flushing mediators were explored . RESULTS DR-DMF showed a safety , tolerability , and PK profile consistent with previous clinical experience , with no evidence of accumulation . Pretreatment with aspirin had no effect on the primary PK parameters , AUC0 - 10h , or Cmax . Flushing severity , assessed by 2 subject-reported rating scales , was generally mild and was rated highest at the start of treatment . Pretreatment with aspirin reduced flushing incidence and intensity without affecting GI events or the PK profile of DR-DMF . In some DR-DMF-treated individuals , plasma concentrations of a prostagl and in D2 ( PGD2 ) metabolite were increased . CONCLUSIONS In healthy volunteers , DR-DMF was well tolerated over 4 days of dosing , with a PK profile consistent with that previously reported and no evidence of accumulation . Aspirin pretreatment reduced the incidence and intensity of flushing without affecting GI events or the DR-DMF PK profile . Elevated levels of PGD2 in some DR-DMF-treated individuals suggest that flushing may be , at least in part , prostagl and in mediated . Clinical Trials.gov identifier : ID : NCT01281111 |
11,911 | 25,909,154 | The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment .
The most widely studied cognitive domains are memory and attention .
Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD .
We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities .
The articles review ed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD . | The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself , as well as to determine the prevalence of impairment in the various cognitive domains in such patients . | BACKGROUND patients with dementia are almost invariably unable to use any form of inhaler . Some elderly patients are unable to learn to use a metered dose inhaler or Turbohaler despite a normal abbreviated mental test score . Studies have shown that in many people this is due to unrecognised cognitive impairment and /or dyspraxia . The executive domains of cognition are particularly important in planning and sequencing ; it might be expected therefore that disordered frontal ( executive ) function could be a predictor of poor inhaler technique in subjects with no overt features of dementia . OBJECTIVE to explore the relationship between cognitive , and executive , function and the ability to acquire metered dose inhaler and Turbohaler technique in old age . DESIGN a prospect i ve r and omised observational study with blinded evaluation . SUBJECTS 30 inhaler-naive in patients ( 21 female ) with a mean age of 85 ( range 75 - 94 ) and having a normal ( 8 - 10 ) abbreviated mental test score . METHODS subjects received st and ardised metered dose inhaler and Turbohaler training and were scored on an analogue scale ( for metered dose inhaler ) or for competence ( Turbohaler ) the following day . The Mini-Mental State Examination and EXIT25 ( for executive function ) were performed by separate observers . RESULTS significant correlation was found between the metered dose inhaler score and Mini-Mental State Examination ( r 0.540 , P<0.002 ) and EXIT25 ( r -0.702 , P<0.0001 ) . Threshold effects emerged for the metered dose inhaler in that 18/19 with a competent score compared to 2/11 scored as incompetent had a Mini-Mental State Examination of > 23 ( P<0.01 ) and 19/19 compared to 0/11 had an EXIT25 of < 15 ( P<0.01 ) . Similarly , for the Turbohaler 21/21 of the competent subjects had a Mini-Mental State Examination of > 23 compared with 3/9 incompetent subjects ( P<0.01 ) , with 21/21 competent compared with 0/9 incompetent having an EXIT25 < 15 ( P<0.01 ) . CONCLUSION acquisition and short-term retention of metered dose inhaler and Turbohaler techniques is unlikely to be successful in frail elderly people who have an abnormal Mini-Mental State Examination and /or EXIT25 test . The latter test , when abnormal , is probably the superior predictor of inability to learn inhaler techniques Systemic inflammation is present in chronic obstructive pulmonary disease ( COPD ) , which has been linked to cardiovascular morbidity and mortality . We determined the effects of oral and inhaled corticosteroids on serum markers of inflammation in patients with stable COPD . We recruited 41 patients with mild to moderate COPD . After 4 weeks during which inhaled corticosteroids were discontinued , patients were assigned to fluticasone ( 500 mcg twice a day ) , oral prednisone ( 30 mg/day ) , or placebo over 2 weeks , followed by 8 weeks of fluticasone at 500 mcg twice a day and another 8 weeks at 1,000 mcg twice a day . Withdrawal of inhaled corticosteroids increased baseline C-reactive protein ( CRP ) levels by 71 % ( 95 % confidence interval [ CI ] , 16 - 152 % ) . Two weeks with inhaled fluticasone reduced CRP levels by 50 % ( 95 % CI , 9 - 73 % ) ; prednisone reduced it by 63 % ( 95 % CI , 29 - 81 % ) . No significant changes were observed with the placebo . An additional 8 weeks of fluticasone were associated with CRP levels that were lower than those at baseline ( a 29 % reduction ; 95 % CI , 7 - 46 % ) . Inhaled and oral corticosteroids are effective in reducing serum CRP levels in patients with COPD and suggest their potential use for improving cardiovascular outcomes in COPD The Nocturnal Oxygen Therapy Trial ( NOTT ) showed previously that patients with hypoxemic chronic obstructive pulmonary disease ( COPD ) frequently suffered from neuropsychologic deficit and experienced disturbed mood , personality , and life quality . The present study has followed up 150 NOTT patients six months after they were r and omized to continuous oxygen treatment ( COT ) or nocturnal oxygen treatment ( NOT ) . Tested off oxygen , 42 % showed modest neuropsychologic improvement after six months of therapy , and the rates for COT and NOT were comparable . A sub sample ( n = 37 ) was examined a third time , after 12 months of treatment . At this point patients receiving COT registered better neuropsychologic performance than those receiving NOT . Concurrently , the COT group began showing improved survival . Despite mild neuropsychologic improvement , patients reported little change in emotional status or life quality . It is concluded that prolonged oxygen treatment is associated with small but definite improvement in brain functioning among patients with hypoxemic COPD , and that COT might have some advantage over NOT in enhancing neuropsychologic functioning as well as survival BACKGROUND Cognitive impairment frequently occurs in elderly COPD patients , but little is known about its prognostic implication s. We aim ed at evaluating the prognostic role of cognitive impairment in patients with severe COPD . METHODS Our series consisted of 149 stable patients ( mean [ + /- SD ] age , 68.7 + /- 8.5 years ) with COPD and a Pao(2 ) of < 57 mm Hg at rest ( n = 97 ) or at the end of the 6-min walking test ( n = 37 ) who were enrolled in a prospect i ve observational study . After a multidimensional baseline assessment , patients were followed up by telephone calls for a mean duration of 32.5 + /- 9.2 months ( minimal follow-up duration , 24 months ) ; 134 patients were successfully tracked . We used multivariable Cox proportional hazard analysis to identify predictors of death among clinical /functional variables that previously were shown to have prognostic implication s and among neuropsychological indexes selected on the basis of univariate analysis . RESULTS We observed 29 deaths over a median follow-up time of 32 months . Only the two following variables were independently associated with the outcome : an abnormal score on the copy with l and mark test ( hazard ratio [ HR ] , 2.93 ; 95 % confidence interval [ CI ] , 1.34 to 6.39 ) ; and a 6-min walk distance of < 300 m ( HR , 3.46 ; 95 % CI , 1.15 to 10.5 ) . A Pao(2 ) of < 57 mm Hg at rest ( HR , 2.19 ; 95 % CI , 0.93 to 5.18 ) and an FEV(1 ) of < 40 % predicted ( HR , 2.74 ; 95 % CI , 0.99 to 7.57 ) were nearly significantly associated with the outcome , while Paco(2 ) , body mass index , physical dependence , comorbid diseases , and the impairment of cognitive domains other than drawing impairment were unrelated to the outcome . CONCLUSIONS Drawing impairment is a risk factor for mortality and might improve the assessment of hypoxemic COPD patients The objective of the study was to evaluate the effect of multidisciplinary pulmonary rehabilitation program on cognitive function in COPD patients , adjusting for potential confounders ( gender , age , tobacco consumption , and educational level ) . In this prospect i ve study , 34 COPD patients were su bmi tted to neuropsychological testing before and after a 3-month pulmonary rehabilitation program . A control group with 18 healthy subjects of similar age , sex , and educational status was used to compare the cognitive function of COPD patients and healthy subjects at baseline . The association between the rehabilitation and change on th scores of cognitive variables , adjusted for each covariate , was estimated by means of linear r and om-intercept regression models . At baseline , the COPD patients had worse cognitive function with regard to verbal learning , memory , subjective organization , and verbal processing in comparison to the healthy volunteers . The improvement in cognitive performance by the COPD patients was evidence d even after adjusting for the sociodemographic factors that could potentially interfere on cognitive function . Male gender and age less than 65 years old were associated to higher scores in verbal learning and memory at baseline and after the rehabilitation program . The clinical approach to COPD -induced cognitive dysfunction should include participation in pulmonary rehabilitation programs . There were gender- and age-related differences in cognitive scores that persisted after rehabilitation |
11,912 | 28,250,534 | The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years .
The few studies on cost suggest that , at current vaccine and delivery costs , pre-exposure prophylaxis campaigns would not be cost-effective in most situations . | Although pre-exposure prophylaxis has been advocated for high-risk population s , only Peru and the Philippines have implemented appropriate national programmes . | OBJECTIVE To demonstrate the safety and immunogenicity of intradermal rabies pre-exposure prophylaxis with purified chick embryo cell vaccine ( PCECV ) in schoolchildren age 5 to 8 years in Thail and . STUDY DESIGN In a r and omized , open-label , phase II clinical trial , 2 or 3 intradermal doses of 0.1 mL PCECV ( Rabipur ) were administered to 703 schoolchildren on days 0 and 28 or on days 0 , 7 , and 28 . In 206 children , 2 simulated post-exposure booster doses were given 1 year after the primary vaccination series . Rabies virus- neutralizing antibody ( RVNA ) titers were determined by the rapid fluorescent focus inhibition test . RESULTS In school-age children in Thail and , a pre-exposure immunization regimen of 3 intradermal doses of PCECV produced adequate immune responses . After primary vaccination , all subjects developed RVNA titers > or = 0.5 IU/mL and demonstrated a rapid increase in RVNA titer after 2 simulated post-exposure booster immunizations 1 year after the primary vaccination series . No serious adverse drug reactions occurred . CONCLUSIONS Rabies pre-exposure immunization with PCECV is safe and immunogenic , and its implementation could save the lives of many children in rabies-endemic areas Objectives . To assess the immunogenicity of intradermal ( ID ) booster doses of Purified Chick Embryo Cell rabies vaccine ( PCECV , Rabipur ) administered to Thai schoolchildren one , three and five years after a primary ID pre-exposure ( PrEP ) vaccination series . Methods . In this follow-up study of a r and omized , open-label , phase II clinical trial , two simulated post-exposure booster doses of PCECV were administered on days 0 and 3 intradermally to 703 healthy schoolchildren , one , three or five years after primary vaccination with either two or three ID doses of 0.1 mL PCECV . Blood was drawn immediately before and 7 , 14 and 365 days after the first booster dose to determine rabies virus neutralizing antibody ( RVNA ) concentrations . Results . An anamnestic response of approximately 30-fold increase in RVNA concentrations was demonstrated within 14 days after booster . All children ( 100 % ) developed adequate RVNA concentrations above 0.5 IU/mL. No vaccine related serious adverse events were seen in any of the vaccinees . Conclusion . ID rabies PrEP with PCECV is safe and immunogenic in schoolchildren and the anamnestic response to a two booster dose vaccination series was found to be adequate one , three , and five years after a two- or three-dose primary PrEP vaccination series BACKGROUND Chikungunya is an emerging arthropod-borne disease that has spread from tropical endemic areas to more temperate climates of the USA and Europe . However , no specific treatment or preventive measure is yet available . We aim ed to investigate the immunogenicity and safety of a live recombinant measles-virus-based chikungunya vaccine . METHODS We did a r and omised , double-blind , placebo-controlled , active-comparator , phase 1 , dose-escalation study at one centre in Vienna , Austria . Healthy men and women aged 18 - 45 years with no comorbidities were r and omly assigned , by computer-generated block r and omisation ( block size of 14 ) , to receive either one of three escalating doses of the measles-virus-based c and i date vaccine ( low dose [ 1·5 × 10(4 ) median tissue culture infection doses ( TCID50 ) per 0·05 mL ] , medium dose [ 7·5 × 10(4 ) TCID50 per 0·25 mL ] , or high dose [ 3·0 × 10(5 ) TCID50 per 1·0 mL ] ) , or the active comparator-Priorix . Participants were additionally block-r and omised to receive a booster injection on either day 28 or day 90 after the first vaccination . Participants and study investigators were masked to group allocation . The primary endpoint was the presence of neutralising anti-chikungunya antibodies on day 28 , as assessed by 50 % plaque reduction neutralisation test . Analysis was by intention to treat and per protocol . This trial is registered with EudraCT , number 2013 - 001084 - 23 . FINDINGS Between Nov 22 , 2013 , and Feb 25 , 2014 , we r and omly assigned 42 participants to receive the low dose ( n=12 ) , the medium dose ( n=12 ) , or the high dose ( n=12 ) of the measles-virus-based c and i date vaccine , or Priorix ( n=6 ) , of whom 36 participants ( 86 % ; n=9 , n=12 , n=10 , n=5 , respectively ) were included in the per- protocol population . The c and i date vaccine raised neutralising antibodies in all dose cohorts after one immunisation , with seroconversion rates of 44 % ( n=4 ) in the low-dose group , 92 % ( n=11 ) in the medium-dose group , and 90 % ( n=10 ) in the high-dose group . The immunogenicity of the c and i date vaccine was not affected by pre-existing anti-measles immunity . The second vaccination result ed in a 100 % seroconversion for all participants in the c and i date vaccine groups . The c and i date vaccine had an overall good safety profile , and the rate of adverse events increased with vaccine dose and volume . No vaccination-related serious adverse events were recorded . INTERPRETATION The live recombinant measles-virus-based chikungunya vaccine had good immunogenicity , even in the presence of anti-vector immunity , was safe , and had a generally acceptable tolerability profile . This vaccine is the first promising measles-virus-based c and i date vaccine for use in human beings . FUNDING Themis Bioscience GmBH A multivariate analysis was used to identify factors influencing the immunogenicity of rabies vaccine and to assess the efficacy of booster injections in a cohort of 407 people monitored prospect ively for 10 years after primary vaccination . Rabies vaccine ( HDCV or PVRV ) was injected by intramuscular route either on days 0 and 28 or on days 0 , 7 and 28 . All the participants received a booster injection on day 365 . At the end of follow-up ( year 10 ) , 163 subjects had titers > 0.5IU/ml ( group A ) and 59 subjects had titers < 0.5IU/ml ( group B : poor responders ) . The number of injections had a significant influence ( P<0.001 ) on the magnitude of the serological response to rabies vaccine , but the type of vaccine and the potency of the batches did not ( P=0.07 and P=0.06 , respectively ) . The difference between GMTs on day 365 and day 379 was significantly lower in group B than in group A ( 13 and 50.70IU/ml , respectively ; P<0.001 ) . In conclusion , our study confirms that the rabies pre-exposure vaccination protocol of three intramuscular injections significantly decreases the proportion of poor responders at 10 years . Moreover , our findings indicate that a routine booster injection at 1 year could significantly increase the levels and duration of antibody titers BACKGROUND For individuals traveling at short notice to rabies and Japanese encephalitis ( JE ) endemic countries , concomitant administration of travel vaccines within a short period is often required . METHODS The aim of this study was to determine whether an accelerated ( one-week : Days 1 - 8 ) pre-exposure rabies ( Rabipur ( ® ) , Novartis Vaccines ) vaccination regimen administered concomitantly with a Japanese encephalitis ( JE ) vaccination ( Ixiaro ( ® ) , Valneva ) regimen , is non-inferior to the st and ard ( four-week : Days 1 , 8 , 29 ) rabies regimen administered alone or concomitantly with the JE vaccine . Healthy adults ( 18 to ≤ 65 years ) were r and omized into Rabies + JE-St and ard , Rabies + JE-Accelerated , Rabies-St and ard and JE-St and ard groups . Relative immunogenicity for rabies in each regimen was assessed using the rapid fluorescent focus inhibition test . Safety was evaluated up to and including Day 57 . RESULTS Non-inferior immunogenicity for rabies was established between the Rabies + JE-Accelerated group compared to both the Rabies-St and ard and Rabies + JE-St and ard groups ; as well as between the Rabies + JE-St and ard regimen and the Rabies-St and ard regimen . By Day 57 , adequate neutralizing levels were achieved by 97 - 100 % of subjects across all groups . Adverse events ( AEs ) were comparable for all groups . CONCLUSIONS An accelerated pre-exposure rabies and JE vaccination regimen is non-inferior to the st and ard four-week rabies regimen and may thus provide a more convenient regimen for individuals traveling to endemic countries at short notice . NCT01662440 Children have a high risk of exposure to rabies in countries where the disease is endemic . This prospect i ve , 5-year study followed two groups of children who had received diphtheria , tetanus , whole-cell pertussis and inactivated poliomyelitis vaccine ( DTP-IPV ) at 2 , 3 , 4 months and 1 year ( Group B ) or concomitant with three doses of purified Vero cell rabies vaccine ( PVRV ) , given at 2 , 4 months and 1 year ( Group A ) . Antibody determinations were made annually for 5 years . Data were available from a total of 72 subjects ; 30 in Group A and 32 in Group B. In Group A , the percentage of patients immunized against rabies ( anti-rabies > or = 0.5 IU/ml ) decreased from 100 % after the third vaccination to 63 % , 5 years later . After 5 years , 93.8 % in Group A and 96.7 % in Group B had seroprotective diphtheria antibody titers > or = 0.01 IU/ml , and all subjects had anti-polio ( type 1 , 2 and 3 ) seroprotective titers > or = 5 1:dil . We conclude that co-administration of PVRV with DTP-IPV elicited protective antibody concentrations to all antigens that persist for at least 5 years , with continued protection against rabies in over 60 % of subjects . These results are consistent with integration of pre-exposure rabies vaccination into the Exp and ed Program on Immunization ( EPI ) in countries where rabies is endemic OBJECTIVE To evaluate abbreviated preexposure rabies vaccination schedules that would reduce cost and shorten time required for completion . METHOD A r and om prospect i ve immunogenicity study , using a group of 96 volunteer pre clinical veterinary students , primary school children , and hospital-based health care workers . They were divided into six groups and administered abbreviated schedules of preexposure tissue culture rabies vaccines . Neutralizing antibodies were determined on days 0 and 360 , and following boosters on days 367 and 374 . RESULTS All subjects , including one group that received only 0.1 mL intradermally at two sites on one day , had detectable neutralizing antibody titers 1 year later and responded with an accelerated antibody response when given booster injections . CONCLUSION It might be possible to develop a 1-week and even one clinic visit preexposure vaccine schedule that would provide at least 1 year of immune memory OBJECTIVE To evaluate the humoral immune response to the pre-exposure schedule of human rabies vaccination through intradermal and intramuscular routes , as well as the need for serological monitoring . METHODS A r and omized and controlled intervention study was carried out in São Paulo , Southeastern Brazil , from 2004 - 2005 . There were 149 volunteers , of which 127 completed the vaccination schedule ( 65 intradermal and 62 intramuscular ) and underwent humoral immune response evaluation at ten , 90 and 180 days post-vaccination . Two outcomes were considered for comparing the two routes of administration : the geometric average of neutralizing antibody titers and the proportion of individuals with satisfactory titers ( > 0.5 IU/mL ) at each evaluation point . The association of the humoral immune response with anthropometric and demographic data was analyzed through a normal distribution test and a chi-square test with a Yates correction . After completion of the vaccination schedule , the proportion of seropositive results was compared by the Kruskall Wallis test , and the average titers were compared by variance analysis . RESULTS the average antibody titers were higher in patients who were vaccinated intramuscularly . The percentage of volunteers with satisfactory titers ( > 0.5 % IU/mL ) decreased over time in both groups . However , in the group vaccinated intradermally the rate of satisfactory titers on day 180 ranged from 20 % to 25 % , while the intramuscular route varied from 63 % to 65 % . An association between the humoral immune response and the demographic and anthropometric variables was not observed . CONCLUSIONS Serology after the third dose can be considered unnecessary in unexposed patients , since 97 % and 100 % of volunteers respectively vaccinated by the intradermal and intramuscular route presented satisfactory antibody levels ( > 0.5 % IU/mL ) BACKGROUND Pre-exposure vaccination against rabies generally simplifies treatment and could be especially beneficial to children in countries where the disease is enzootic . We studied the feasibility of administering to infants pre-exposure rabies vaccination with combined diphtheria , tetanus , whole-cell pertussis , and inactivated poliomyelitis vaccine ( DTP-IPV ) . METHODS 84 Vietnamese infants were r and omly assigned to groups that received three doses of DTP-IPV vaccine at 2 , 3 , and 4 months of age alone ( n = 43 ) or with two doses of purified Vero cell rabies vaccine ( PVRV ) at 2 and 4 months ( n = 41 ) . The safety and immunogenicity data of the groups were compared . FINDINGS All infants in both groups developed protective antibody concentrations against diphtheria , tetanus , pertussis , and polio . All infants who received the PVRV vaccine developed protective antibody concentrations against rabies . No serious adverse effects were reported , nor did systemic reactions differ between groups . INTERPRETATION Administration of PVRV with DTP-IPV proved safe , and elicited what are presumed to be protective antibody concentrations to all antigens in all 41 infants . Confirmation of these results could lead to integration of pre-exposure rabies vaccination into Exp and ed Programme on Immunisation ( EPI ) sessions in selected countries where rabies is enzootic We performed an abbreviated prospect i ve study of rabies pre-exposure ( PREP ) vaccination in 109 volunteers . Group 1 , the control group , received the conventional 3 intradermal injections on days 0 , 7 and 21 . Group 2 received one rabies vaccine injection ( 0.1 ml intradermally ) at 2 sites on a single day . Group 3 was given one full ampule intramuscularly . One year later , all 3 groups received booster injections ( 0.1 ml at 4 sites ) intradermally at one time or 2 injections intramuscularly on days 0 and 3 . All subjects achieved a vigorous anamnestic antibody response 7 days after the boosters . These data suggest that one time immunization of one full dose intramuscularly or 2 site injections of 0.1 intradermally on a single day are adequate to prime immune memory and obtain an accelerated immune response one year later After concomitant administration of purified chick embryo cell rabies vaccine and Japanese encephalitis vaccine to toddlers , adequate rabies and Japanese encephalitis virus neutralizing antibodies concentrations were demonstrated by day 49 , 7 days after a booster at 1 year , and in the majorly at 3 years postvaccination . The inclusion of rabies vaccine in the exp and ed program on immunization should be considered in rabies endemic countries |
11,913 | 23,982,678 | New evidence from prospect i ve cohort studies , cross-sectional studies and clinical trials supports the beneficial role of adherence to the Mediterranean dietary pattern regarding metabolic syndrome presence and progression . | The metabolic syndrome is a health condition characterized by abdominal obesity , dyslipidemia , elevated blood pressure and impaired glucose tolerance , with increasing prevalence .
Adherence to the Mediterranean diet seems to exert beneficial effects regarding the metabolic syndrome prevalence and progression .
Thus , we performed an up date d systematic review of studies which have evaluated the effect of the Mediterranean dietary pattern on the metabolic syndrome . | BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality Objective Independently of total caloric intake , a better quality of the diet ( for example , conformity to the Mediterranean diet ) is associated with lower obesity risk . It is unclear whether a brief dietary assessment tool , instead of full-length comprehensive methods , can also capture this association . In addition to reduced costs , a brief tool has the interesting advantage of allowing immediate feedback to participants in interventional studies . Another relevant question is which individual items of such a brief tool are responsible for this association . We examined these associations using a 14-item tool of adherence to the Mediterranean diet as exposure and body mass index , waist circumference and waist-to-height ratio ( WHtR ) as outcomes . Design Cross-sectional assessment of all participants in the “ PREvención con DIeta MEDiterránea ” ( PREDIMED ) trial . Subjects 7,447 participants ( 55–80 years , 57 % women ) free of cardiovascular disease , but with either type 2 diabetes or ≥3 cardiovascular risk factors . Trained dietitians used both a vali date d 14-item question naire and a full-length vali date d 137-item food frequency question naire to assess dietary habits . Trained nurses measured weight , height and waist circumference . Results Strong inverse linear associations between the 14-item tool and all adiposity indexes were found . For a two-point increment in the 14-item score , the multivariable-adjusted differences in WHtR were −0.0066 ( 95 % confidence interval , –0.0088 to −0.0049 ) for women and –0.0059 ( –0.0079 to –0.0038 ) for men . The multivariable-adjusted odds ratio for a WHtR>0.6 in participants scoring ≥10 points versus ≤7 points was 0.68 ( 0.57 to 0.80 ) for women and 0.66 ( 0.54 to 0.80 ) for men . High consumption of nuts and low consumption of sweetened/carbonated beverages presented the strongest inverse associations with abdominal obesity . Conclusions A brief 14-item tool was able to capture a strong monotonic inverse association between adherence to a good quality dietary pattern ( Mediterranean diet ) and obesity indexes in a population of adults at high cardiovascular risk |
11,914 | 27,889,869 | Conclusion Echocardiographic 2D speckle tracking can identify subtle physiological differences in adaptations to cardiac strain and twist mechanics between athletes and healthy controls .
Differences in speckle tracking echocardiography-derived parameters can be identified using suitable sporting categorizations | Background The athlete ’s heart is associated with physiological remodeling as a consequence of repetitive cardiac loading .
The effect of exercise training on left ventricular ( LV ) cardiac strain and twist mechanics are equivocal , and no meta- analysis has been conducted to date .
Objective The objective of this systematic review and meta- analysis was to review the literature pertaining to the effect of different forms of athletic training on cardiac strain and twist mechanics and determine the influence of traditional and contemporary sporting classifications on cardiac strain and twist mechanics . | BACKGROUND The aims of this study were to establish absolute ranges for right ventricular ( RV ) structural and functional parameters for endurance athletes and to establish any impact of body size . These data may help differentiate physiologic conditioning from arrhythmogenic RV cardiomyopathy . METHODS A prospect i ve observational study design was used , and st and ard two-dimensional echocardiography was performed on 102 endurance athletes , providing RV structural indices . A two-dimensional strain ( ε ) technique was used to provide indices of RV ε and strain rate . The association of RV chamber size to body surface area ( BSA ) and functional indices was examined by simple ratio scaling as well as adoption of the general , nonlinear allometric model . RESULTS The values for RV inflow , outflow , length , and diastolic area were greater than published " normal ranges " in 57 % , 40 % , 69 % , and 59 % of the population , respectively , while 28 % of the population had RV outflow tract values greater than the proposed " major criteria " for arrhythmogenic RV cardiomyopathy . Simple ratio scaling for all RV dimensions to BSA did not produce size independence , whereas scaling for BSA allometrically did . Strain and strain rate values were consistent with published normal ranges , and there is no evidence to suggest that scaling is required . CONCLUSIONS RV chamber dimensions are larger in endurance athletes than those described by " normal ranges " and frequently meet the major criteria for the diagnosis of arrhythmogenic RV cardiomyopathy . Functional assessment of RV ε may aid in this differential diagnosis . RV size is allometrically related to BSA and therefore scaling for population -specific b exponents is encouraged Deformation analysis using 2-dimensional strain echocardiography can detect early systolic function abnormalities in patients with left ventricular hypertrophy . This study was design ed to characterize global and regional myocardial deformation using 2-dimensional strain in professional soccer players ( PSPs ) compared with control subjects and patients with hypertrophic cardiomyopathy ( HC ) . Twenty nine PSPs , 26 patients with HC , and 17 controls were investigated at rest using transthoracic echocardiography with 2-dimensional strain analysis . Radial and transverse strains were significantly higher in PSPs compared with controls , whereas longitudinal strain was lower . Compared with patients with HC , athletes had higher values for transverse , radial , and circumferential strains . In pathologic hypertrophic segments , longitudinal strain was lower in patients with HC than in PSPs . In conclusion , 2-dimensional strain can identify specific patterns of myocardial deformation in PSPs , controls , and patients with HC . It has the potential to become a routinely used method for the differentiation of athlete 's heart and HC During incremental exercise , stroke volume ( SV ) plateaus at 40 - 50 % of maximal exercise capacity . In healthy individuals , left ventricular ( LV ) twist and untwisting ( " LV twist mechanics " ) contribute to the generation of SV at rest , but whether the plateau in SV during incremental exercise is related to a blunting in LV twist mechanics remains unknown . To test this hypothesis , nine healthy young males performed continuous and discontinuous incremental supine cycling exercise up to 90 % peak power in a r and omized order . During both exercise protocol s , end-diastolic volume ( EDV ) , end-systolic volume ( ESV ) , and SV reached a plateau at submaximal exercise intensities while heart rate increased continuously . Similar to LV volumes , two-dimensional speckle tracking-derived LV twist and untwisting velocity increased gradually from rest ( all P < 0.001 ) and then leveled off at submaximal intensities . During continuous exercise , LV twist mechanics were linearly related to ESV , SV , heart rate , and cardiac output ( all P < 0.01 ) while the relationship with EDV was exponential . In diastole , the increase in apical untwisting was significantly larger than that of basal untwisting ( P < 0.01 ) , emphasizing the importance of dynamic apical function . In conclusion , during incremental exercise , the plateau in LV twist mechanics and their close relationship with SV and cardiac output indicate a mechanical limitation in maximizing LV output during high exercise intensities . However , LV twist mechanics do not appear to be the sole factor limiting LV output , since EDV reaches its maximum before the plateau in LV twist mechanics , suggesting additional limitations in diastolic filling to the heart Left ventricular ( LV ) rotation occurs due to contraction of obliquely oriented myocardial fibres . Left ventricular twist ( LVT ) results from rotation of the apex and base in opposite directions . Although LVT is altered in various cardiac diseases , physiological factors that affect LVT remain incompletely understood . Isometric h and grip testing ( IHGT ) , a well-established laboratory-based technique to increase LV afterload , was performed for 3 min at 40 % maximum force generation in healthy human subjects ( n = 18 , mean age 29.7 ± 2.7 years ) . Speckle-tracking echocardiography was used to measure LV volumes , LV apical and basal rotation , peak systolic LVT and peak early diastolic untwisting rate ( UTR ) at rest and at peak IHGT . IHGT led to significant increase in systemic blood pressure ( systolic , 120.6 ± 9.7 vs. 155.6 ± 14.5 mmHg , P < 0.001 ; diastolic , 67.5 ± 6.4 vs. 94.1 ± 21.1 mmHg , P < 0.001 ) and LV end-systolic volume ( 44.2 ± 7.8 vs. 50.5 ± 10.8 ml , P = 0.005 ) , as well as a significant increase in heart rate ( 62.8 ± 11.7 vs. 84.7 ± 13.8 beats min−1 ; P < 0.001 ) . IHGT produced a significant acute reduction in LV stroke volume ( 63.9 ± 12.0 vs. 49.4 ± 7.8 ml , P < 0.001 ) . In this setting , there was a significant decrease in peak systolic apical rotation ( 11.9 ± 3.0 vs. 8.6 ± 2.2 deg , P < 0.001 ) and a result ant 25 % decrease in peak systolic LVT ( 16.6 ± 2.8 vs. 12.5 ± 2.8 deg , P < 0.001 ) . The magnitude of peak early diastolic UTR did not change ( −114.5 ± 26.4 vs. −110.6 ± 39.8 deg s−1 , P = 0.71 ) . Peak systolic apical rotation and LVT decrease during IHGT in healthy humans . This impairment of LV twist mechanics may in part underlie the LV dysfunction that can occur in the clinical context of acute increase in afterload AIMS To investigate the physiological adaptation of the right ventricle ( RV ) in response to endurance training and to define reference values for regional deformation in the RV in endurance athletes . METHODS AND RESULTS Healthy controls ( n = 61 ) , athletes ( n = 58 ) , and elite athletes ( n = 63 ) were prospect ively enrolled with a training intensity of 2.2 + /- 1.6 , 12.5 + /- 2.3 and 24.2 + /- 5.7 h/week , respectively ( P < 0.001 ) . Conventional echocardiographic parameters , tissue Doppler imaging ( TDI ) , and 2D strain echo (2DSE)-derived velocity , strain , and strain rate ( SR ) were calculated in three RV segments . Left ventricular and RV dimensions were significantly increased ( P < 0.001 ) in both groups of athletes compared with controls . Right ventricular systolic velocities and displacement were not different between the groups . Right ventricular strain and SR values were reduced in the RV basal and mid-segment in athletes . Athletes with marked RV dilatation showed lower strain and SR values in the basal ( -20.9 + /- 4.7 vs. -24.5 + /- 4.9 % , P < 0.001 and -1.23 + /- 0.31 vs. -1.50 + /- 0.33 s(-1 ) , P < 0.001 ) and mid ( -29.3 + /- 5.4 vs. -32.1 + /- 5.3 % , P = 0.017 and -1.58 + /- 0.41 vs. -1.82 + /- 0.42 s(-1 ) , P = 0.009 ) segment , whereas athletes without RV dilatation showed no significant difference compared with the controls . CONCLUSION Regional deformation and deformation rates ( TDI and 2DSE ) are reduced in the basal RV segment in athletes . This phenomenon is most pronounced in athletes with RV dilatation and should be interpreted as normal when evaluating athletes suspected for RV pathology AIMS In individuals who exercise regularly and for extended periods of time , some structural alterations in the heart , called the athlete 's heart , develop in time . These alterations vary in type , can be eccentric or concentric , depending on the nature of exercise . Speckle tracking echocardiography ( STE ) is a novel , angle-independent method that accurately and reliably measures systolic and diastolic functions of the left ventricle ( LV ) with considerably lower inter-operator variability . METHODS AND RESULTS Twenty-two marathon runners , 24 wrestlers , and 20 healthy sedentary individuals were included in the study . The average age of subjects is 17.5 ± 2.2 in marathon runners , 16.8 ± 1.9 in wrestlers , and 16.4 ± 1.8 in control group . The parameters of LV longitudinal strain ( S ) , LV longitudinal strain rate systolic ( SRS ) , LV longitudinal strain rate diastolic early filling ( SRE ) , and longitudinal strain rate diastolic late filling ( SRA ) were evaluated by apical two- , three- , and four-chamber grayscale imaging using the global longitudinal strain ( GLS ) and GLS rate ( GLSR ) . Conventional echocardiographic parameters demonstrated increased LV diameters and wall thickness in the marathon runners and increased wall thickness without increased LV diameters in the wrestlers . Systolic and diastolic functions were comparable between the marathon runners and wrestlers with conventional echocardiography . Analysis with STE , however , yielded higher systolic strain and strain rates in the athletes . Normalized GLS parameters and end-diastolic volume ( EDV ) were shown to be correlated . CONCLUSION Overall , conventional echocardiography can detect some differences between young athletes with eccentric and concentric type of athlete 's heart but it is incapable of revealing differences in intrinsic myocardial functions . However , analysis using STE demonstrated increased systolic functions in athletes commensurate with increased load , with unaltered diastolic functions Aims This study evaluated ( a ) global LV adaption to endurance versus resistance training in male athletes , ( b ) LV assessment using by modern imaging technologies and ( c ) the impact of scaling for body size on LV structural data . Methods A prospect i ve cross-sectional design assessed the LV in 18 elite endurance-trained ( ET ) , 19 elite resistance-trained ( RT ) and 17 sedentary control ( CT ) participants . St and ard 2D , tissue Doppler and speckle tracking echocardiography assessed LV structure and function . Indexing of LV structures to body surface area ( BSA ) was undertaken using ratio and allometric scaling . Results Absolute and scaled LV end-diastolic volume ( ET : 43.7±6.8 ; RT : 34.2±7.4 ; CT 32.5±8.9 mL/m1.5 ; p<0.05 ) and LV mass ( ET : 29.8±6.6 ; RT : 25.4±8.7 ; CT 25.9±6.4 g/m2.7 ; p < 0.05 ) were significantly higher in ET compared with RT and CT . LV wall thickness were not different between ET and RT . 65 % of ET and 95 % of RT had normal geometry . Stroke volume was higher in ET compared with both RT and CT ( p<0.05 ) . Whilst regional tissue velocity data were not different between groups , longitudinal and basal circumferential strain ( ε ) was reduced in RT compared with ET . Conclusions In this comprehensive evaluation of the male athlete 's heart ( AH ) , normal LV geometry was predominant in both athlete groups . In the ET , 30 % demonstrated an eccentric hypertrophy with no concentric hypertrophy in RT . Cardiac ε data in RT require further evaluation , and any interpretation of LV size should appropriately index for differences in body size BACKGROUND The aim of this study was to investigate the systolic and diastolic properties of the right cardiac chambers ( the right ventricle and right atrium ) among different subsets of athletes to unveil potential variations in right ventricular and right atrial remodeling secondary to different training modes . METHODS A cohort of Caucasian male top-level athletes ( n = 108 ; 80 endurance athletes [ EAs ] , mean age , 31.2 ± 10.4 years ; 28 strength-trained athletes [ SAs ] , mean age , 27.4 ± 5.7 years ) and untrained controls ( n = 26 ; mean age , 26.6 ± 5.6 years ) ( P = .327 ) were prospect ively enrolled . Conventional echocardiographic parameters , including transtricuspid inflow , Doppler tissue imaging , and two-dimensionally derived peak systolic longitudinal strain and strain rate indices of the right ventricle and right atrium , were calculated . RESULTS EAs had greater internal right ventricular and right atrial dimensions compared with SAs and controls . There were no significant differences concerning strain between groups ( -23.1 ± 3.7 % in EAs vs -25.1 ± 3.2 % in SAs vs -23.1 ± 3.5 % in controls , P = .052 ) , with SAs presenting higher global systolic strain rates ( -1.42 ± 0.22 sec(-1 ) in SAs vs -1.21 ± 0.21 sec(-1 ) in EAs vs -1.2 ± 0.28 sec(-1 ) in controls , P = .016 ) , as well as greater right atrial strain rate systolic and diastolic components . Training volume ( highly vs moderately trained athletes ) did not significantly influence deformation parameters . No significant differences concerning diastolic transtricuspid inflow and Doppler tissue imaging indices were also noted among different athlete groups and controls . CONCLUSIONS Despite the existence of right geometric alterations in athletes participating in different sport disciplines , few meaningful differences in deformation and diastolic function exist Objective LV longitudinal strain , a recognised marker of LV function , has been recently applied to the evaluation of the athlete 's heart . At present , little is known about the influence of training on LV global longitudinal strain ( GLS ) in athletes . The aim of this study was to prospect ively investigate the impact of training on LV longitudinal strain and twist mechanics in a cohort of competitive athletes . Methods Ninety-one competitive athletes , practising team sports and competing at national or international level , were analysed . Echocardiographic evaluation was performed at the beginning of the season ( low training ) and after 18±2 weeks of a supervised , intensive training programme ( peak training ) . Results A significant increase in LV mass ( p<0.0001 ) , LV end-diastolic and end-systolic volume ( p=0.0001 and < 0.0001 , respectively ) was found at peak training . LV basal and apical torsion ( p=0.59 and 0.43 , respectively ) and LV twisting ( p=0.78 ) did not change , and only a mild increase in LV GLS was evident after training ( p=0.044 ) . Resting heart rate was identified as the only independent predictor of LV GLS after training ( β=0.30 , p=0.005 ) . Conclusions A 18-week , intensive training programme induced only a slight increase in LV GLS despite marked changes in cardiac morphology , suggesting a physiological adaptation of the LV to exercise conditioning OBJECTIVE Exercise training has been known to cause structural and functional alterations in the heart called athletes heart . We aim ed to investigate the effects of incremental endurance exercise training ( IEET ) on the left ventricular ( LV ) mechanics in healthy subjects . METHODS This prospect i ve observational study included 34 healthy young men who participated in competitive sports . The participants were subjected to a six-month IEET program . The LV mechanics measured using two-dimensional speckle tracking echocardiography was recorded while the participants were in an inactive state before and at the end of the six months . To compare continuous variables before and after IEET , Wilcoxon or paired-t test were used . RESULTS Baseline and post training echocardiographic measurements showed that there was no significant change in LV ejection fraction ( % ) ( p=0.64 ) and there were an increase in end-systolic and end-diastolic diameters , posterior and septal wall thickness , relative wall thickness and LV mass index ( p<0.05 , for all ) . LV mechanical parameters such as global strain ( S ) ( 19.8±1.33 % vs. 20.4±1.26 % , p=0.001 ) , apical four -chamber S ( 19.4±1.96 % vs. 20.1±1.86 % , p=0.01 ) , apical two- chamber S ( 19.9±1.75 % vs. 20.7±1.75 % , p=0.003 ) , apical ( 23.0±3.1 % vs. 23.6±3.2 % , p=0.03 ) , and basal circumferential S ( 21.1±2.2 % vs. 21.6±2.5 % , p=0.03 ) , and apical rotation ( degree ) ( 7.9±0.95 vs. 8.4±0.74 , p=0.001 ) values were significantly increased by IEET . CONCLUSION We demonstrated that IEET has led to exercise related cardiac structural and functional changes such as LV dilatation and LV hypertrophy , accompanied by a significant increase in LV systolic S and LV twist measurements Background : Left ventricular hypertrophy ( LVH ) may be an adaptative remodelling process induced by physical training , or result from pathological stimuli . We hypothesized that different LVH aetiology could lead to dissimilar spatial distribution left ventricular ( LV ) contraction , and compared different components of LV contraction using 2‐dimensional ( 2‐D ) speckle tracking derived strain in subjects with adaptative hypertrophy ( endurance athletes ) , maladaptative hypertrophy ( hypertensive patients ) and healthy controls The aim of this study was to determine the normal value of left ventricular ( LV ) twist , and to examine the effects of aging on LV twist by newly developed 2-dimensional ultrasound speckle-tracking imaging . We acquired basal and apical LV short-axis second harmonic images in 118 healthy volunteers . Using commercially available 2-dimensional strain software , time-domain speckle tracking was performed , and mean value of LV rotation obtained at each plane . LV twist was defined as apical rotation relative to the base . Adequate data were obtained in 113 volunteers . During systole , the LV performs a wringing motion with a counterclockwise rotation at the apex and a clockwise rotation at the base . The mean value of peak twist was 7.7 + /- 3.5 degrees . Immediately after end systole , rapid untwisting develops . Different LV twist profiles are noted according to age . Peak LV twist was significantly higher , and the rate of LV untwisting significantly reduced and delayed , with advancing age . LV twist can be measured noninvasively by 2-dimensional ultrasound speckle-tracking imaging . The observed reduced and delayed diastolic untwisting with aging may contribute toward the tendency of diastolic dysfunction . This novel method allows the detailed study of diastolic function in various cardiovascular diseases OBJECTIVES We investigated the significance of fibrosis detected by late gadolinium enhancement cardiovascular magnetic resonance for the prediction of major clinical events in hypertrophic cardiomyopathy ( HCM ) . BACKGROUND The role of myocardial fibrosis in the prediction of sudden death and heart failure in HCM is unclear with a lack of prospect i ve data . METHODS We assessed the presence and amount of myocardial fibrosis in HCM patients and prospect ively followed them for the development of morbidity and mortality in patients over 3.1 + /- 1.7 years . RESULTS Of 217 consecutive HCM patients , 136 ( 63 % ) showed fibrosis . Thirty-four of the 136 patients ( 25 % ) in the fibrosis group but only 6 of 81 ( 7.4 % ) patients without fibrosis reached the combined primary end point of cardiovascular death , unplanned cardiovascular admission , sustained ventricular tachycardia or ventricular fibrillation , or appropriate implantable cardioverter-defibrillator discharge ( hazard ratio [ HR ] : 3.4 , p = 0.006 ) . In the fibrosis group , overall risk increased with the extent of fibrosis ( HR : 1.18/5 % increase , p = 0.008 ) . The risk of unplanned heart failure admissions , deterioration to New York Heart Association functional class III or IV , or heart failure-related death was greater in the fibrosis group ( HR : 2.5 , p = 0.021 ) , and this risk increased as the extent of fibrosis increased ( HR : 1.16/5 % increase , p = 0.017 ) . All relationships remained significant after multivariate analysis . The extent of fibrosis and nonsustained ventricular tachycardia were univariate predictors for arrhythmic end points ( sustained ventricular tachycardia or ventricular fibrillation , appropriate implantable cardioverter-defibrillator discharge , sudden cardiac death ) ( HR : 1.30 , p = 0.014 ) . Nonsustained ventricular tachycardia remained an independent predictor of arrhythmic end points after multivariate analysis , but the extent of fibrosis did not . CONCLUSIONS In patients with HCM , myocardial fibrosis as measured by late gadolinium enhancement cardiovascular magnetic resonance is an independent predictor of adverse outcome . ( The Prognostic Significance of Fibrosis Detection in Cardiomyopathy ; NCT00930735 ) BACKGROUND The aim of this study was to test the effect of endurance training on the age-related changes of left ventricular ( LV ) twist-untwist mechanics . Aging has been shown to induce a decline of diastolic function and more recently an impairment of twist-untwist mechanics , which constitutes an important factor for early diastolic suction and filling . On the other h and , endurance training has been shown to improve cardiac function . METHODS Speckle-tracking echocardiography was performed in 106 endurance-trained male athletes and 75 controls ( age range 18 - 70 years ) , divided into three groups according to age . RESULTS From the younger to older age groups , progressive increases in LV apical rotation and twist angle and a decrease in LV untwisting rate during isovolumic relaxation time were observed . Athletes had lower systolic twist angles ( P < .01 ) but higher untwist/twist ratios and LV untwisting rate during isovolumic relaxation time compared with controls , with the largest difference between senior groups ( 51 ± 24 % vs 42 ± 22 % in the young and 42 ± 29 % vs 24 ± 25 % in seniors , P < .001 , respectively ) . The normal timing of untwisting rate occurring before radial displacement was preserved in athletes with increasing age , whereas it was blunted in controls . CONCLUSIONS Endurance training does not prevent but minimizes changes in LV twist-untwist mechanics from young subjects to seniors . Athletes showed smaller increases of twist angle with age and smaller declines of LV untwisting rate during isovolumic relaxation time and untwist/twist ratio compared with controls . This training-improved preservation of LV twist-untwist mechanics is likely to play a key role for systolic-diastolic coupling and diastolic filling , particularly during exercise OBJECTIVES We sought to examine the effect of endurance exercise training ( EET ) on peak systolic left ventricular torsion ( LVT ) and peak early diastolic untwisting rate ( UTR ) . BACKGROUND Left ventricular ( LV ) structural adaptations to EET have been well characterized . LVT , a recognized marker of LV function in numerous cardiac diseases , has recently been investigated in the setting of exercise . However , longitudinal data characterizing the impact of sustained exercise training on LVT have not been reported . METHODS A prospect i ve , longitudinal study design examined the impact of a 90-day period of training on LV twist mechanics in university male rowers ( n = 15 , mean age 18.6 ± 0.5 years ) . Conventional LV structural measurements , LV apical and basal rotation , peak systolic LVT , and peak early diastolic UTR were measured by 2-dimensional and speckle tracking echocardiography before and after the EET study period . RESULTS Participants experienced LV eccentric hypertrophy , characterized by increased LV end-diastolic volume ( 80.8 ± 8.7 ml/m(2 ) vs. 91.3 ± 8.0 ml/m(2 ) , p < 0.001 ) and LV mass ( 101.3 ± 11.4 g/m(2 ) vs. 115.7 ± 12.6 g/m(2 ) , p = 0.001 ) . There was a significant increase in peak systolic apical rotation ( 8.9 ± 4.2 ° vs. 12.7 ± 3.9 ° , p = 0.002 ) but no change in basal rotation . This translated into a highly significant increase in peak systolic LVT after EET ( 14.1 ± 5.0 ° vs. 18.0 ± 3.6 ° , p = 0.002 ) . The impact of EET on LV twist mechanics was not confined to ventricular systole , as peak early diastolic UTR ( -110.6 ± 41.8 ° /s vs. -148.0 ± 29.8 ° /s , p = 0.003 ) and the percentage of untwisting that occurred by the end of isovolumic relaxation ( 31.2 ± 12.0 % vs. 39.9 ± 14.9 % , p = 0.04 ) increased . CONCLUSIONS Participation in EET was associated with significant changes in LV twist mechanics characterized by increased apical rotation , LVT , and UTR . These findings suggest that LVT and UTR augmentation may be an important and previously unrecognized component of exercise-induced cardiac remodeling |
11,915 | 26,997,574 | Likewise , the post-lip repair studies showed better results with suction methods .
CONCLUSION The studies show that prior to surgical repair , the use of alternative methods can be beneficial .
In the postoperative period following lip repair , methods with suction are more beneficial .
However , in the postoperative period of palatoplasty , there are divergences of opinion regarding the most appropriate feeding methods | INTRODUCTION Feeding difficulties in children with cleft lip and palate ( CLP ) are frequent and appear at birth due to impairment of sucking and swallowing functions .
The use of appropriate feeding methods for the different types of cleft and the period of the child 's life is of utmost importance for their full development .
OBJECTIVE Review studies comparing feeding methods for children with CLP , pre- and postoperatively . | Using a disposable syringe to feed 1 - 14-week-old babies with cleft lip and palate ( CLP ) was studied . 57 CLP babies were r and omly divided into : syringe-fed ( intervention ) and cup- and -spoon-fed groups and compared with 55 normal breast- or bottle-fed babies . Differences in weight gained from birth to 6 , 10 and 14 weeks were compared . Syringe-fed CLP babies fed breast milk had a significant difference in weight gain ( 0.7 and 0.8 kg ) compared with cup- and -spoon-fed babies ( 0.4 kg ) , at 10 and 14 weeks , respectively . Normal breast-fed babies gained 0.6 and 0.7 kg . Cup- and -spoon-fed CLP babies fed artificial and breast milk gained 0.5 and 0.6 kg ; syringe-fed CLP babies gained 0.6 and 1.2 kg . Normal babies gained 1.0 and 1.7 kg for the same age and food . Average feeding times were 10 ml/1.25 min for syringe-fed and 10 ml/2.08 min for cup- and -spoon-fed CLP babies at 6 weeks . 19 ( 100 % ) cup- and -spoon-fed babies exhibited spill and regurgitation at 6 weeks compared with 30 ( 79 % ) CLP syringe-fed babies ( P<0.05 ) . In both groups spill and regurgitation decreased with age . CLP babies fed with the modified method had a faster feeding time , less spill and regurgitation and gained the same weight as normal babies at 10 and 14 weeks It has been a tradition for plastic surgeons to withhold breast feeding from babies after cleft lip repair to prevent wound disruption . A prospect i ve , r and omised trial of 40 infants showed that early postoperative breast feeding after cleft lip repair is safe , results in more weight gain at 6 weeks after surgery ( P < 0.01 ) and is more economical than spoon feeding OBJECTIVE To compare two feeding methods advocated for infants with cleft palate : ( a ) a squeezable plastic container with a narrow , long crosscut nipple ( squeezable cleft palate nurser ) ; and ( b ) a st and ard nipple with a crosscut ( crosscut nipple ) . The effectiveness of a nutrition intervention protocol for these infants was also documented . DESIGN Thirty-one infants ( median age = 15 days ) were r and omized to one of two feeding methods ( 18 infants , squeezable cleft lip/palate nurser ; 13 infants , crosscut nipple ) within sex ( 21 boys , 10 girls ) and palatal defect ( 22 cleft lip and palate , 9 isolated cleft palate ) categories . The intervention included feeding technique instructions , nutrition counseling at each clinic visit , use of the same 20 kcal/oz st and ard formula for 12 months , and introduction of infant and soft table foods at 6 months . Four-day food records and growth data were obtained . MAIN OUTCOME MEASURES Mean energy and protein intakes at 3 and 6 months of age and growth measurements during the first 18 months of life were obtained . STATISTICAL ANALYSES A repeated measures analysis of variance for intakes was performed with time as the repeated measure and feeding method as the covariable . Similar analyses were completed for growth measures with sex and feeding method as covariates . RESULTS Mean energy intake at 3 and 6 months of age ( P = .24 ) and growth measurements during the first 18 months of life ( P values : weight gain [ grams per day ] , .73 ; weight , .21 ; length , .07 ; head circumference , .18 ; triceps and subscapular skinfolds and mid-arm circumference , .47 , .48 , and .69 , respectively ) were not significantly different . Both feeding methods were effective in supporting normal growth . APPLICATIONS With adequate instruction related to the use of either feeding technique and close nutrition follow-up early in infancy , a dietitian or other health care practitioner may advise the use of either feeding method . These data support the need for feeding and nutrition education and early nutrition intervention This prospect i ve study conducted at the Hospital for the Rehabilitation of Craniofacial Anomalies aim ed to compare the best technique - a cup or a spoon - for feeding children immediately after palatoplasty . We assessed 44 children and their caregivers during feeding every 4 hours ; this generated 176 evaluations : 88 using a cup and 88 using a spoon . The Fisher exact test and the Mann-Whitney test were used for statistical analysis , with a significance level of 5 % ( p<0.05 ) . When the spoon was used , the percentage of patients with food escaping through the labial commissure was lower ( 17 % ; p=0.024 , the portion administrated was higher ( 12 % ; p=0.029 ) , and coughing was less frequent ( 13 % ; p=0.026 ) compared with use of a cup . We conclude that using a spoon to administer food after palatoplasty is better than using a cup OBJECTIVE To compare the effectiveness of squeezable and rigid feeding bottles for infants with clefts . DESIGN Patients were r and omly assigned at birth to feeding with a squeezable bottle ( assisted feeding ) or to feeding with a rigid bottle and were followed for 1 year . The data were analyzed on the basis of intention to treat . SETTING The trial was conducted within the existing arrangements for hospital and home care for children with clefts within the National Health Service in the north of Engl and . PATIENTS The patients were 101 consecutively born children with cleft lip and /or palate who were otherwise healthy . All patients completed the trial . Two were excluded from the analysis when unrelated developmental problems became apparent . MAIN OUTCOME MEASURES Anthropometric measures -nude weight , crown-heel length ( CHL ) , and occipito-frontal circumference (OFC)-were recorded . RESULTS There were statistically significant differences between the two groups in weight at 12 months ( p = .038 , with an adjusted mean difference of 0.43 kg ) and in head circumference ( p = .004 with an adjusted mean difference of 0.77 cm ) , indicating increased growth in the squeezable bottle group . The difference in CHL was not significant at conventional levels ( p = .082 ) . Whereas 25 of 52 ( 48 % ) rigid bottles required modification by the health visitor , this was needed for only 4 of 49 ( 8 % ) squeezable bottles . There was a highly significant difference when numbers of modifications for each method were compared ( p < .0001 ) . Despite modifications , six infants feeding with a rigid bottle ( 11 % ) were transferred to a squeezable bottle due to problems with feeding , but none were transferred from squeezable to rigid bottles . Thus , the squeezable bottle generally appeared to be a more satisfactory method , requiring less support or intervention after initial instruction . CONCLUSIONS Both feeding methods achieved similar anthropometric outcomes , with a beneficial effect on head circumference and weight in the assisted feeding group . We recommend that this last observation be treated with caution . The squeezable bottles were easier to use , and we recommend that they be routinely prescribed Objective To evaluate the nutritional status and behavior of the surgical wound following cheiloplasty . Setting Hospital for Rehabilitation of Craniofacial Anomalies , University of São Paulo ( HRAC/USP ) , Bauru , São Paulo , Brazil . Participants Forty-five nursing children aged 3 to 13 months old , either bottle-fed or spoon-fed , su bmi tted to cheiloplasty during the study period . Results The results did not demonstrate significant differences between the study groups regarding gender , age , nutritional status , and condition of the surgical wound . Upon completion of the study , the infants of both groups were eutrophic , presenting increase in growth and development , with no hematoma , significant edema , sutural dehiscence , bleeding , or infection at the operated area . Conclusions Both kinds of nursing , spoon- and bottle-feeding , had the same influence on nutritional status and wound condition in both study groups . We suggest that bottle-feeding should be tried in patients in the postoperative period of cheiloplasty , because this method was used after surgery without causing any damage to the lip surgical wound Although bottle-feeding after cheiloplasty is widely accepted , postoperative feeding regimen after palatoplasty is still controversial . The aim of this prospect i ve r and omized study was to evaluate the effect of bottle-feeding on early postoperative course after palatoplasty in a relatively homogeneous group of patients . Eighty-two consecutive patients with nonsyndromic cleft palate undergoing 2-flap palatoplasty by a single surgeon were r and omized to feeding from a bottle with the usual nipple ( G1 , N = 42 ) or to feeding with a spoon , cup , or syringe ( G2 , N = 40 ) . Complication rates , postoperative sedative use , oral intake for the first 6 days , and relative weight gain at 1 and 2 months were compared . There were no significant complications such as bleeding or respiratory problem . The overall complication rate including wound dehiscence and oronasal fistula was similar in G1 and G2 ( 11.9 % versus 12.5 % , P = 1.000 ) as was postoperative sedative use and mean daily oral intake for the first 5 days . Mean intake on the sixth day was significantly higher in G1 . There were no significant between-group differences in relative weight gain after 1 and 2 months . In conclusion , bottle-feeding had no adverse effect on the early postoperative course after palatoplasty including complication rate , oral intake , and weight gain . These findings suggest that an unrestricted feeding regimen is appropriate immediately after palatoplasty Objective To compare the efficacy of the three feeding techniques commonly used in authors ’ setup in improving the weight gain pattern of children with orofacial cleft . Methods A cohort prospect i ve study was employed . A total sample of 150 infants at the age of 2 mo with cleft of both lip and palate were recruited and followed bimonthly until their first birthday to assess the pattern of weight gain . The subjects were categorized into three groups based on their habitual feeding techniques such as Group I : Paladai fed ; Group II : Bottle fed and Group III : Spoon fed with 50 subjects in each group . The three groups were counseled on nutritional aspects , correct infant positioning and hygienic practice s. Results The mean weight of the Group I subjects was observed to be higher than the other two groups at every visit and was also found to be statistically significant at p < 0.001 . Over all comparison proved that the weight gain of 1.364 ± 0.191 , 1.348 ± 0.284 and 1.450 ± 0.205 and the velocity of weight gain , kg per week of 0.17 ± 0.023 , 0.168 ± 0.035 and 0.181 ± 0.025 of Group I at 4 , 6 and 8th mo respectively were significantly higher than the other two groups ( p < 0.001 ) . Conclusions Of the three feeding techniques adopted by the mothers of infants with orofacial cleft , it was noted that paladai feeding was better than the bottle or spoon-feeding AIMS To determine the effect of nasogastric ( NG ) feeding compared with oral feeding on morphine requirements after primary cleft palate repair , and secondarily on enteral intake . METHODS This was a pilot study involving 50 infants , aged five to ten months , who were r and omised to receive NG or oral feeding after palate repair . All infants received the same anaesthetic and analgesic management . Post-operatively , paracetamol and ibuprofen were administered regularly and intravenous ( IV ) morphine was given on dem and using a nurse-controlled analgesia device . The primary outcome measure was the total morphine consumption in the first 24 hours . Secondary outcome measures included the numbers of painful episodes and the volumes of IV fluid and enteral feed administered . RESULTS Of the 50 infants enrolled , 18 and 23 received either NG or oral feeding , respectively , and completed the study . Numbers of painful episodes and morphine consumption in the first 24 hours were similar in each group . Volumes of feed administered in the first 24 hours were significantly different : the NG group received approximately three times more than the oral group . Nine of the oral group required IV fluids in the 24 hours compared with none in the NG group . CONCLUSION NG feeding was more effective than oral feeding in the first 24 hours after surgery , but numbers of painful episodes recorded were similar . Further research is required |
11,916 | 24,766,648 | Our systematic review finds encouraging but limited evidence for the effectiveness of acupuncture treatment for acute postoperative pain after back surgery . | OBJECTIVES Acupuncture is commonly used as a complimentary treatment for pain management .
However , there has been no systematic review summarizing the current evidence concerning the effectiveness of acupuncture for acute postoperative pain after back surgery .
This systematic review aim ed at evaluating the effectiveness of acupuncture treatment for acute postoperative pain ( ≤1 week ) after back surgery . | For clinical trials of acupuncture , it would be desirable to have a sham procedure that is indistinguishable from the real treatment , yet inactive . A sham needle has been design ed which telescopes instead of penetrating the skin . The Park Sham Device involves an improved method of supporting the sham needle and requires validation . The objective of these studies was to test whether the sham procedure using the new device was 1 ) indistinguishable from the same procedure using real needles in acupuncture naïve subjects , and 2 ) inactive , where the specific needle sensation ( de qi ) is taken as a surrogate measure of activity . The studies were design ed as subject and assessor blind , r and omised controlled trials . Study 1 ) included 58 patients enrolled in a clinical trial of acupuncture for acute stroke . Study 2 ) included 63 healthy , acupuncture naïve , adult volunteers . The interventions used were real or sham acupuncture using the Park Sham Device . Study 1 ) was set in a district general hospital , and study 2 ) in a university laboratory . The outcome measure in study 1 ) was the form of treatment that patients believed they had received . In study 2 ) the outcome measure was experience of de qi , as judged by three acupuncture experts . No patient in either group ( study 1 ) believed he or she had been treated with the sham needle . In 40 volunteers ( study 2 ) for whom experts achieved consensus , the relative risk of experiencing de qi with real acupuncture to that with sham acupuncture was 15.38 ( 95 % CI 2.26 to 104.86 ) . The inter-rater reliability of all 13 experts ( study 2 ) , calculated from their judgements on 10 subjects selected by r and omisation , was 0.52 ( 95 % CI 0.19 to 0.61 ) . In conclusion , the results suggest that the procedure using the new device is indistinguishable from the same procedure using real needles in acupuncture naïve subjects , and is inactive , where the specific needle sensation ( de qi ) is taken as a surrogate measure of activity . It is therefore a valid control for acupuncture trials . The findings also lend support to the existence of de qi , a major concept underlying traditional Chinese acupuncture OBJECTIVE To compare the differences of therapeutic effect in lower limb sensation disorder after lumbar disc herniation operation treated with plum-blossom needle along meridians and Methylcobalamin with oral administration , and explore the best time for plum-blossom needle intervention . METHODS Eighty cases of lower limb sensation disorder caused by nucleus pulposus discectomy of lumbar disc herniation were r and omly divided into a plum-blossom needle group ( 40 cases ) and a western medication group ( 40 cases ) . In plum-blossom needle group , tapping with plum-blossom needle along meridians was received , the meridians located at sensation areas which were dominated by relevant segmental nerve root in operation were selected : the lower limb section of the Spleen Meridian of Foot-Taiyin was selected for operation at L3/L4 ; the lower limb section of the Gall Bladder Meridian of Foot-Shaoyang was selected for operation at L4 /L5 ; the lower limb section of the Bladder Meridian of Foot-Taiyang was selected for operation at L5/S1 ; once treatment was applied every 3 days , and 20 times treatments were applied totally . In western medication group , Methylcobalamin was orally taken for 500 microg , 3 times a day . The recovery of lower limb sensation disorder was evaluated and compared by the comprehensive evaluation method of sensory function of body nerve after 2 months in both groups . RESULTS The total effective rate was 90.0 % ( 36/40 ) in plum-blossom needle group , superior to that of 60.0 % ( 24/40 ) in western medication group ( P < 0.05 ) . In plum-blossom needle group , the effect for the cases which received treatment within one month after operation was superior to that received treatment during 1 - 3 months after operation ( P < 0.05 ) ; and there was no significant differences between the cases which received the treatment during 1 - 3 months after operation and more than 3 months after operation ( P > 0.05 ) . CONCLUSION The therapeutic effect of lower limb sensation disorder after lumbar disc herniation operation treated with plum-blossom needle along meridians is superior to that of Methylcobalamin with oral administration ; the plum-blossom needle intervention within one month after operation can receive the best effect & NA ; Motion style acupuncture treatment ( MSAT ) was more effective for pain relief and functional recovery than diclofenac injection in acute low back pain patients with disability . & NA ; Review s of the efficacy of acupuncture as a treatment for acute low back pain ( aLBP ) have shown that there is insufficient evidence for its effect and that more research is needed . Motion style acupuncture treatment ( MSAT ) is novel in that it requires a part of the patient ’s body to move passively or actively while acupuncture needles are retained . A multicenter , r and omized , comparative effectiveness trial was conducted to evaluate the effects of MSAT in aLBP with severe disability . A total of 58 aLBP patients with severe functional disability ( defined per Oswestry Disability Index [ ODI ] ≥60 % ) were recruited and assigned r and omly to receive 1 session of either conventional diclofenac injection ( n = 29 ) or MSAT ( n = 29 ) . The primary outcome measured improvement in LBP using the 10‐point numerical rating scale of LBP , and the secondary outcome assessed disability using the Oswestry Disability Index at 30 minutes and at 2 , 4 , and 24 weeks after treatment . Analyses were by intention to treat . The numerical rating scale of the MSAT group decreased 3.12 ( 95 % confidence interval = 2.26 , 3.98 ; P < .0001 ) more than that of the injection group and the Oswestry Disability Index of the MSAT group decreased 32.95 % ( 95 % confidence interval = 26.88 , 39.03 ; P < .0001 ) more than that of the injection group , respectively . The difference between the 2 groups maintained statistical significance at 2 and 4 weeks after treatment . These results suggest that MSAT has positive effects on immediate pain relief and the functional recovery of aLBP patients with severe disability Acupuncture is increasingly used , so it is important to establish whether its benefits outweigh its risks . Numerous case reports of adverse events show that acupuncture is not free of risk , but accurate data from prospect i ve investigations is scarce . A prospect i ve survey was undertaken using intensive event monitoring . Forms were developed for reporting minor events each month and significant events as they occurred . The sample size was calculated to identify any adverse events that occurred more frequently than once in 10,000 consultations . Acupuncturists were recruited from two professional organisations in the UK . Seventy-eight acupuncturists , all doctors or physiotherapists , reported a total of 2178 events occurring in 31,822 consultations , an incidence of 684 per 10,000 consultations . The most common minor adverse events were bleeding , needling pain , and aggravation of symptoms ; aggravation was followed by resolution of symptoms in 70 % of cases . There were 43 significant minor adverse events reported , a rate of 14 per 10,000 , of which 13 ( 30 % ) interfered with daily activities . One patient suffered a seizure ( probably reflex anoxic ) during acupuncture , but no adverse event was classified as serious . Avoidable events included forgotten patients , needles left in patients , cellulitis and moxa burns . In conclusion , the incidence of adverse events following acupuncture performed by doctors and physiotherapists can be classified as minimal ; some avoidable events do occur . Acupuncture seems , in skilled h and s , one of the safer forms of medical intervention Management of acute and chronic low back and leg pain often includes the use of acupuncture . The effectiveness of this form of therapy is dependent upon compliance , which in turn is dependent on availability , response , treatment of proper acupoints , and the placebo effect . We hypothesized that classical acupuncture would be more effective than placebo acupuncture . One hundred and thirty-two patients with acute and chronic low back and leg pain were examined before and after surgery for lumbar disc protrusion . Diagnosis was based on CT and MRT findings . Patients received acupuncture drug-free throughout the study period . The visual analogue scale was used to assess pain intensity before and after ( i.e. 30 min . 60 min . 2 h and 6 h ) acupuncture . Classical acupuncture result ed in a significant reduction in pain that become increasingly stronger during the 6h study period . Placebo acupuncture lead to same early pain relief that did not reach statistic significant and then declined thereafter OBJECTIVE This study aim ed to examine the adjuvant effects of auricular acupres-sure in augmenting intravenous patient-controlled analgesia with morphine and droperidol for postoperative lumbar surgery patients in terms of postoperative pain relief satisfaction , and the incidence of postoperative nausea and vomiting ( PONV ) . METHODS In this single-blind experimental study , 94 subjects were r and omly assigned to the experimental group in which patients received auricular acupressure to six auricular acupoints or a control group without acupressure . Data were collected using the American Pain Society Patient Outcome Question naire . Descriptive analyses , t tests , chi(2 ) tests , Mann-Whitney tests , and the generalized estimating equation model were used . RESULTS The experimental group had lower average pain scores than the control group , but no between-group difference was found . Analgesic dose and satisfaction were similar in both groups . The incidence of PONV was low and similar in both groups . CONCLUSION Although this study did not demonstrate adjuvant effects of auricular acupressure on postoperative pain , analgesic dose , analgesic satisfaction and PONV , most subjects were satisfied with the pain management even though they were subjected to moderate pain because of insufficient analgesia . Further studies should reconfirm the effects of auricular acupressure on analgesia provided by intravenous patient-controlled analgesia in postoperative patients , and its influence on the frequency and duration of analgesia administration OBJECTIVE To investigate the clinical effects of acupuncture after surgical operation in patients with prolapse of the lumbar intervertebral disc ( PLID ) . METHODS Sixty-nine patients in this series , who had undergone the removal of nucleus pulposus and the intervertebral fusion as well , were r and omly divided into a treatment group of 35 cases and a control group of 34 cases . The former was treated by acupuncture and conventional rehabilitation therapy , and the latter only by the rehabilitation therapy . The therapeutic effects were evaluated according to the scoring system stipulated by Japanese Orthopedics Association ( JOA ) . RESULTS In the treatment group , the average functional recovery rates in 3-month , 6-month and one-year periods were respectively 49.93 % , 90.31 % and 95.08 % ; while the rates were repesctively 26.24 % , 63.42 % and 71.36 % in the control group , showing statistically significant difference between the two groups ( P<0.05 ) . CONCLUSIONS Acupuncture can confirmatively promote the functional recovery for ' patients with prolapse of the lumbar intervertebral disc after surgical removal of nucleus pulposus and with intervertebral fusion Seventy two patients , from 15 to 60 years old , in good physical status and su bmi tted to surgery in the upper or lower abdominal , rectal or lumbar areas were studied . In the immediate postoperative period , they were r and omly divided in three groups and each group was su bmi tted to one of the following treatments : intravenous meperidine , transcutaneous nerve stimulation ( TNS ) or electroacupuncture ( EA ) . Each treatment was divided in two phases with one hour interval between them . Each phase was constituted of 30 minutes of stimulation in case of TNS and EA and fractionated administration of meperidine in all groups . The pain level was evaluated through a visual analogue scale before and after each phase of treatment . The results were compared among groups and , on each group , between the phases of treatment . In all surgery types , the postoperative pain relief presented by TNS and EA groups of patients was greater than that of meperidine treated group . But , the analgesia presented by the EA treated group of patients lasted longer and increased with the repetition of treatment . The differences of behaviour of TNS and EA analgesia suggest that their neurochemical mechanisms may not be the same OBJECTIVES The purpose of this study was to evaluate the effect of acupoint electrical stimulation with patient-controlled analgesia ( PCA ) on reducing acute pain , nausea , and vomiting after surgery for nontraumatic spinal cord injury . METHODS A r and omized , controlled , repeated measures research design was used . Ninety-nine patients undergoing lumbar spinal surgery were r and omly assigned to one of three groups . Patients in experimental group 1 ( EG1 ) received true acupoint electrical simulation three times , whereas those in experimental group 2 ( EG2 ) received sham acupoint manually . Patients in the control group ( CG ) received no acupoint intervention . All patients were measured for pain , initial dem and for PCA , dem and for opiates , opiate dose , vital signs , and postoperative nausea and vomiting ( PONV ) . RESULTS Significant differences were found in postoperative pain , respiratory rate , blood pressure , and opiate doses across time in the three groups with better outcomes observed in EG1 than in EG2 . However , no between-group difference was found in initial dem and for PCA or in PONV . CONCLUSIONS The study demonstrates that acupoint electrical stimulation improves acute postoperative pain management without adversely affecting vital signs after surgery for nontraumatic spinal injury . More studies are needed to evaluate the effects ofacupoint electrical stimulation on PONV and postoperative pain following other surgical procedures Recent reports have highlighted the importance of having good evidence on the safety of acupuncture . 1 2 Sound evidence on the risks associated with acupuncture is , however , scarce.3 Our primary aim , therefore , was to describe the type and frequency of adverse events after acupuncture . A secondary aim was to examine mild transient reactions associated with acupuncture , some of which may indicate a positive response to treatment . The study involved a prospect i ve postal audit of treatments undertaken during a four week period in 2000 . All 1848 professional acupuncturists who were members of the British Acupuncture Council and were practising in the United Kingdom were invited to record details of adverse events and mild transient reactions after treatment . St and ardised self report forms were used . Participating practitioners also provided information on themselves , including age , sex , length of training , and years of practice . To have a BACKGROUND A problem acupuncture research has to face is the concept of a control group . If , in control groups , non-acupoint needling is done , physiological acupuncture effects are implied . Therefore the effects shown in this group are often close to those shown in the acupuncture group . In other trials , control groups have received obviously different treatments , such as transcutaneous electrical nervous stimulation or TENS-laser treatment ; it is not clear if the effects of acupuncture are due only to the psychological effects of the treatment . METHODS We developed a placebo acupuncture needle , with which it should be possible to simulate an acupuncture procedure without penetrating the skin . In a cross-over experiment with 60 volunteers we tested whether needling with the placebo needle feels any different from real acupuncture . FINDINGS Of 60 volunteers , 54 felt a penetration with acupuncture ( mean visual analogue scale [ VAS ] 13.4 ; SD 10.58 ) and 47 felt it with placebo ( VAS 8.86 ; SD 10.55 ) , 34 felt a dull pain sensation ( DEQI ) with acupuncture and 13 with placebo . None of the volunteers suspected that the needle may not have penetrated the skin . INTERPRETATION The placebo needle is sufficiently credible to be used in investigations of the effects of acupuncture Study Design . Prospect i ve observational cohorts . Objective . To describe sociodemographic and clinical features , and nonoperative ( medical ) re source utilization before enrollment , in patients who are c and i date s for surgical intervention for intervertebral disc herniation ( IDH ) , spinal stenosis ( SpS ) , and degenerative spondylolisthesis ( DS ) according to SPORT criteria . Summary of Background Data . Intervertebral disc herniation , spinal stenosis , and degenerative spondylolisthesis with stenosis are the three most common diagnoses of low back and leg symptoms for which surgery is performed . There is a paucity of descriptive literature examining large patient cohorts for the relationships among baseline characteristics and medical re source utilization with these three diagnoses . Methods . The Spine Patient Outcomes Research Trial ( SPORT ) conducts three r and omized and three observational cohort studies of surgical and nonsurgical treatments for patients with IDH , SpS , and DS . Baseline data include demographic information , prior treatments received , and functional status measured by SF-36 and the Oswestry Disability Index ( ODI-AAOS/Modems version ) . The data presented represent all 1,411 patients ( 743 IDH , 365 SpS , 303 DS ) enrolled in the SPORT observational cohorts . Multiple logistic regression was used to generate independent predictors of utilization adjusted for sociodemographic variables , diagnosis , and duration of symptoms . Results . The average age was 41 years for the IDH group , 64 years for the SpS group , and 66 years for the DS group . At enrollment , IDH patients presented with the most pain as reported on the SF-36 ( BP 26.3 vs. 33.2 SpS and 33.8 DS ) and were the most impaired ( ODI 51 vs. 42.3 SpS and 41.5 DS ) . IDH patients used more chiropractic treatment ( 42 % vs. 33 % SpS and 26 % DS ) , had more Emergency Department ( ED ) visits ( 21 % vs. 7 % SpS and 4 % DS ) , and used more opiate analgesics ( 49 % vs. 29 % SpS and 27 % DS ) . After adjusting for age , gender , diagnosis , education , race , duration of symptoms , and compensation , Medicaid patients used significantly more opiate analgesics ( 58 % Medicaid vs. 41 % no insurance , 42 % employer , 33 % Medicare , and 32 % private ) and had more ED visits compared with other insurance types ( 31 % Medicaid vs. 22 % no insurance , 16 % employer , 3 % Medicare , and 11 % private ) . Conclusion . IDH patients appear to have differences in sociodemographics , re source utilization , and functional impairment when compared with the SpS/DS patients . In addition , the differences in re source utilization for Medicaid patients may reflect differences in access to care . The data provided from these observational cohorts will serve as an important comparison to the SPORT r and omized cohorts in the future The analgesic effects of acupuncture are well-documented . Aqueous acupuncture , or point injection , is a conveniently modified modern acupuncture method . This matched controlled trial was carried out to evaluate the effects of aqueous acupuncture in postoperative pain control . A total of 12 patients were selected as age- , sex- and operative-style-matched controls . In treating group , 2 to 5 ml of 20 % glucose solution was injected into Ho-Ku ( LI 4 ) and Yang-Ling-Chuan ( GB 34 ) when patients had regained conciousness from operation anesthesia . The pain intensity were recorded as score system included verbal , sleep disturbance and use of narcotics . In comparisons with the control group , the intensity of postoperative pain , and the amounts and frequency of narcotics used were significantly lower in the study group , especially for the first 12 postoperative hours . Aqueous acupuncture is a convenient and effective procedure in postoperative pain control OBJECTIVE To assess the value of compound anesthesia of transcutaneous electrical point stimulation and Remifentanil and the efficacy of this method on postoperative acute pain . METHODS Sixty cases with vertebral lamina internal fixation decompression operation were selected and r and omly divided into 2 groups , an observation group and a control group , 30 cases in each group . The patients in the observation group received compound anesthesia of transcutaneous electrical point stimulation at Hegu ( LI 4 ) , Laogong ( PC 8) , Neiguan ( PC 6 ) and Waiguan ( TE 5 ) 30 min before anesthesia induction with HANS stimulator and then Remifentanil anesthesia . During the operation , the stimulation was lasted for 30 min and ceased for 30 min until the end of operation . The patients in the control group received simple Remifentanil anesthesia . The dosage of the narcotic , changes of both blood pressure and heart rate during operation , before and after extubation and the pain degree , etc . were investigated in the two groups . RESULTS ( 1 ) The dosage of Isoflurane , ( 0.52 + /- 0.33)vol% , in the observation group was significantly lower than ( 1.12 + /- 0.18 ) vol% in the control group ( P < 0.01 ) . ( 2 ) Both blood pressure and heart rate during operation , before and after extubation in the observation group were lower than those before operation ( P < 0.01 ) , and both the blood pressure and heart rate during operation in the control group were lower than those before operation ( P < 0.01 ) . The blood pressure after extubation in the observation group was significantly lower than that of the control group ( P < 0.01 ) , and the heart rate before and after extubation in the observation group was significantly lower than that of the control group ( P < 0.01 ) . ( 3 ) The time of extubation and palinesthesia in the observation group were significantly shorter than those in the control group ( P < 0.01 ) . ( 4 ) In the observation group , the VAS scores after palinesthesia in 26 cases were < 4 , and in 4 cases were > or = 5 , while in the control group , the scores in 4 cases were < 4 and in 20 cases > or = 5 , with a significant difference between the two groups ( P < 0.01 ) . CONCLUSION Compound anesthesia of transcutaneous electrical point stimulation and Remifentanil can reduce the dosage of narcotics , shorten the time of palinesthesia and effectively prevent and treat acute pain after Remifentanil anesthesia BACKGROUND Acupoint electrical stimulation ( AES ) is commonly used for pain management . However , its true or placebo effect to achieve pain relief needs to be verified . OBJECTIVE This study aim ed to examine the true effect of AES to reduce postoperative pain in patients with spinal surgery receiving patient-controlled analgesia ( PCA ) . METHOD A placebo- and sham-controlled study was conducted . Participants were r and omly assigned to intervention with AES at true acupoints ( the AES group , n=30 ) , AES at sham acupoints ( the sham group , n=30 ) , or no intervention with AES ( the control group , n=30 ) . Outcomes were assessed according to the amount of pain experienced and analgesics used . RESULTS There were significant differences among the three groups in pain relief across time , and the occurrence of PCA button pushed and amount of analgesics used . The beneficial effects of AES were discernible when compared to the sham and the control . CONCLUSIONS AES at the true acupoints effectively reduced postoperative pain and analgesic usage . AES has now been implemented into healthcare and it is recommended that nurses be provided with the opportunity to earn their AES skills . More studies evaluating the effects of AES over a longer period and on pain after different surgical procedures are suggested |
11,917 | 12,779,304 | For patients , it leads to increased dependency and complicates other comorbid conditions .
Results The best evidence for or against screening for dementia would be derived from a well- design ed RCT of screening with health outcomes .
New screening in primary care practice could therefore potentially double the number of patients who receive a diagnosis of dementia . | Dementia is an acquired syndrome of decline in memory and at least one other cognitive domain , such as language , visuospatial , or executive function , that is sufficient to interfere with social or occupational function in an alert person ( 1 ) .
Many diseases can cause the dementia syndrome ( hereafter called dementia ) .
Alzheimer disease and cerebrovascular ischemia ( vascular dementia ) are the two most common causes , and some cases of dementia involve both of these disorders .
Although some potentially reversible conditions , such as hypothyroidism or vitamin B12 deficiency , are often thought to cause dementia , no more than 1.5 % of cases of mild to moderate dementia are fully reversible ( 2 ) .
Age is the best-studied and strongest risk factor for dementia .
Other risk factors for Alzheimer disease include having a first-degree relative with a history of Alzheimer disease and having the apolipoprotein E 4 genotype ( 3 - 5 ) .
Cardiovascular risk factors such as hypertension are associated with an increased risk for both Alzheimer disease and vascular dementia ( 5 - 7 ) .
The aging of the U.S. population has been accompanied by a dramatic increase in the prevalence of dementia .
Three percent to 11 % of persons older than 65 years of age and 25 % to 47 % of those older than 85 years of age have dementia ( 8 - 13 ) .
In 1997 , the number of persons with Alzheimer disease in the United States was estimated to be 2.3 million , more than 90 % of whom were 60 years of age and older ( 14 ) .
Dementia causes a high burden of suffering for patients , their families , and society ( 15 - 21 ) .
For families , it leads to anxiety , depression , and increased time spent caring for a loved one .
More than 50 % of persons with dementia , including many with mild but some with moderate dementia , have never received a diagnosis of dementia from a physician ( 23 - 27 ) .
This raises the possibility that screening tests might be able to identify persons with undiagnosed dementia and thereby permit patients and their families to receive care at an earlier stage in the disease process .
Finally , knowledge of dementia at an early stage could improve health outcomes through more effective treatment .
Experts do not agree about the definition of mild cognitive impairment , and other review s have not found evidence of effective treatment for persons with this problem ( 29 , 30 ) .
First , the accuracy of many screening instruments has been research ed , but to a limited degree . | BACKGROUND Vascular dementia is the second commonest form of dementia , and vascular factors contribute to the development of dementia in many patients with Alzheimer 's disease . Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors . It has shown broad , sustained benefits in patients with Alzheimer 's disease . We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer 's disease combined with cerebrovascular disease . METHODS Eligible patients were r and omly assigned galantamine 24 mg/day ( n=396 ) or placebo ( n=196 ) in a multicentre , double-blind , 6-month trial . Primary endpoints were cognition ( Alzheimer 's disease assessment scale , cognitive subscale [ ADAS-cog ] ) and global functioning ( clinician 's interview-based impression of change plus caregiver input [ CIBIC-plus ] ) . Secondary endpoints included assessment s of activities of daily living and behavioural symptoms . Patients were monitored for adverse events . Analyses were on the basis of observed case or last observation carried forward . FINDINGS Galantamine showed greater efficacy than placebo on ADAS-cog ( galantamine change -1.7 [ SE 0.4 ] vs placebo 1.0 [ 0.5 ] ; treatment effect 2.7 points ; p<0.0001 ) and CIBIC-plus ( 213 [ 74 % ] vs 95 [ 59 % ] patients remained stable or improved , p=0.0001 ) . Activities of daily living and behavioural symptoms were also significantly improved compared with placebo ( p=0.002 and p=0.016 , respectively ) . Galantamine was well tolerated . INTERPRETATION Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients OBJECTIVE To determine the long-term effectiveness of comprehensive support and counseling for spouse-caregivers and families in postponing or preventing nursing home placement of patients with Alzheimer disease ( AD ) . DESIGN R and omized controlled intervention study . SETTING Outpatient research clinic in the New York City metropolitan area . PARTICIPANTS Referred , volunteer sample of 206 spouse-caregivers of AD patients who enrolled in the study during a 3 1/2-year period . All patients were living at home at baseline and had at least 1 relative living in the area . INTERVENTION Caregivers in the treatment group were provided with 6 sessions of individual and family counseling within 4 months of enrollment in the study and were required to join support groups . In addition , counselors were available for further counseling at any time . MAIN OUTCOME MEASURE Time from enrollment of caregivers in the study to placement of the AD patients in a nursing home . RESULTS Using Kaplan-Meier survival analysis , we estimated that the median time ( weighted average of estimates for male and female caregivers ) from baseline to nursing home placement of AD patients was 329 days longer in the treatment group than in the control group ( z=2.29 ; P=.02 ) . The relative risk ( RR ) from a Cox proportional hazard model of nursing home placement ( intent-to-treat estimate ) after adjusting for caregiver sex , patient age , and patient income was 0.65 ( 95 % confidence interval [ CI ] , 0.45 to 0.94 ; P=.02 ) , indicating that caregivers were approximately two thirds as likely to place their spouses in nursing homes at any point in time if they were in the treatment group than if they were in the control group . Treatment had the greatest effect on risk of placement for patients who were mildly demented ( RR , 0.18 ; 95 % CI , 0.04 to 0.77 ) or moderately demented ( RR , 0.38 ; 95 % CI , 0.17 to 0.82 ) . CONCLUSIONS A program of counseling and support can substantially increase the time spouse-caregivers are able to care for AD patients at home , particularly during the early to middle stages of dementia when nursing home placement is generally least appropriate Spouse-caregivers of Alzheimer 's disease patients were r and omly assigned to either a treatment group ( individual and family counseling , support group participation , and ad hoc consultation ) or a control group ( only routine support ) . In the first year after intake , the treatment group had less than half as many nursing home placements as the control group . This suggests that a comprehensive counseling program can reduce the socioeconomic impact of Alzheimer 's disease . Nursing home placement also was affected by the patient 's need for assistance with activities of daily living , patient income , and the age of the patients and caregivers BACKGROUND The purpose of this study was to evaluate the utility ( i.e. , positive and negative predictive value ) of the 7 Minute Screen in identifying patients with probable Alzheimer 's disease ( AD ) in a primary care practice . A second objective was to estimate the number of undiagnosed AD patients in a typical primary care practice . METHODS One hundred thirty-seven successive admissions ( 96 % ) of patients over the age of 60 to a primary care practice over a 53-day period who completed informed consent documents were administered the 7 Minute Screen . All patients who screened positive ( n = 13 ) and a r and om sample of those who screened negative ( n = 26 ) returned for full diagnostic evaluation . Positive predictive value ( PPV ) and negative predictive value ( NPV ) of the 7 Minute Screen were determined using the criterion st and ard of clinical diagnosis established by examination , history , and laboratory studies . Test-retest reliability and time for administration were also determined . RESULTS Of the 137 patients evaluated , 13 screened positive and 124 screened negative . Eleven of the 13 patients who screened positive were willing to return to the primary care practice for follow-up evaluation . A r and om sample of 26 patients who screened negative all agreed to return for follow-up evaluation . Of the 11 patients who screened positive and who returned for evaluation , 10 were subsequently diagnosed with probable AD . The remaining patient was diagnosed with mixed dementia . The caregivers of the two patients who refused to return were contacted and both indicated that the patients were having significant cognitive problems as verified by an activities of daily living scale . Of the 26 patients who screened negative , 25 were judged to be cognitively normal and the 26th was judged to have mild cognitive impairment . DISCUSSION In successive admissions of patients over the age of 60 in a primary care practice , the 7 Minute Screen showed a PPV of 91 % and an NPV of 96 % in identifying patients who were subsequently identified with AD or other dementing disorder . These data suggest that this may be a useful instrument in identifying patients who should undergo diagnostic evaluation for AD and other dementing disorders . Additionally , extrapolation from the data in this practice suggests that there may be between 75 and 100 AD patients in the typical primary care practice , many of whom may not be diagnosed We studied 56 subjects , 30 patients with a clinical diagnosis of Alzheimer ’s disease ( AD ) and 26 healthy controls , using two telephone screens for cognitive impairment , a self-report interview referred to as the TELE and the Telephone Interview for Cognitive Status ( TICS ) . The sensitivity and specificity of the TELE to differentiate AD patients from healthy controls was 90.0 and 88.5 % and those of the TICS were 86.7 and 88.5 % , respectively . When receiver operator characteristic curves were constructed , the area under the curve for the TELE was 96.0 % ( SE 2.4 % ) and for the TICS 90.3 % ( SE 4.2 % ) . Pearson ’s correlation between the TELE and the Mini-Mental State Examination ( MMSE ) was 0.87 ( p < 0.0001 ) and between the TICS and the MMSE 0.86 ( p < 0.0001 ) . The correlation between the TELE and the sum of the boxes of the Clinical Dementia Rating scale ( CDR-SB ) was –0.71 ( p < 0.0001 ) and –0.75 between the TICS and the CDR-SB ( p < 0.0001 ) . These results indicate that both screens are sensitive and specific instruments for differentiating AD patients from healthy controls and have a strong correlation with face-to-face measures of cognitive function Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type ( DAT ) has gained increasing importance in recent years . Even though a curative treatment of the disease is currently impossible , various drugs can be used to slow down its progression . In the present study the influence of oral treatment with 240 mg/day of Ginkgo biloba special extract EGb 761 ( Tebonin ® forte , manufactured by Dr. Willmar Schwabe , Karlsruhe ) on the clinical course of DAT was investigated in a double-blind , r and omized , placebo-controlled parallel-group design in 20 out patients . The duration of treatment was 3 months . The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory . Other psychometric tests ( trailmaking test , ADAS , CGI ) and electrophysiological investigations ( EEG topography ) were evaluated descriptively . Although the active-treatment group , with a mean sum score of 19.67 points in the S.K.T. , had a poorer baseline level than the placebo group ( 18.11 points ) , it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points . The differences between the baseline and final values formed the basis for a statistical group comparison , which gave a result favourable to EGb 761 , at a significance level of p < .013 . In addition to this psychometric confirmation of efficacy , certain descriptive trends were found at the psychopathological ( Clinical Global Impression ) and dynamic functional ( EEG findings ) levels , which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system . Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance , probably because of the small sample size OBJECTIVE To determine the efficacy of donepezil hydrochloride for the treatment of Alzheimer disease in patients drawn from clinical practice . DESIGN Two-center , r and omized , placebo-controlled , double-masked crossover study . SETTING Memory disorders units at Massachusetts General and Brigham and Women 's hospitals , Boston . PATIENTS Sixty individuals ( 30 men and 30 women ; mean + /- SD age , 75.0+/-9.5 years ) with probable Alzheimer disease and scores of 20 or less on the information-memory-concentration subscale of the Blessed Dementia Scale . INTERVENTIONS Placebo wash-in , followed in r and omized sequence by ( 1 ) donepezil hydrochloride therapy , 5 mg/d , for 6 weeks , followed by placebo washout for 6 weeks and ( 2 ) placebo treatment for 6 weeks . PRIMARY OUTCOME MEASURE Change in Alzheimer 's Disease Assessment Scale cognitive subscale scores from the beginning to the end of the two 6-week treatment periods . RESULTS Among patients completing treatment and testing for both periods ( n = 48 ) , subscale scores improved ( mean + /- SEM ) 2.17+/-0.98 points ( 95 % confidence interval , 0.20 - 4.10 points ) during donepezil therapy relative to placebo therapy ( P = .04 ) . Scores returned toward baseline within 3 weeks of drug washout . There was no associated change in caregiver-rated global impression ( donepezil vs placebo : proportion improved , 0.24 vs 0.22 ; proportion worsened , 0.27 vs 0.35 ; P = .34 ) or on specific tests of explicit memory or verbal fluency . Contrary to studies with tacrine , the presence of the apolipoprotein E epsilon4 allele did not predict donepezil treatment failure . Most common adverse events related to donepezil therapy were nausea ( 5 patients ) , diarrhea ( 3 patients ) , and agitation ( 3 patients ) . Serious events possibly related to drug use were seizure , pancreatitis , and syncope ( 1 patient each ) . CONCLUSION This independent confirmation of data from phase 3 trials suggests that donepezil therapy modestly improves cognition in patients with Alzheimer disease who are encountered in clinical practice Dementia induces morbidity not only in the patients but also in the families taking care of them . Many studies described the impact of care-giving on physical and psychological health . Support groups were design ed to alleviate the burden of care-givers . The objective of this study was to measure the efficacy of a support group programme for care-givers of demented patients in the community . Forty-one primary care-givers were r and omly assigned to a study ( n=23 ) or a control group ( n=18 ) . Subjects of the study group attended a structured programme of eight 2-h sessions . These weekly sessions consisted of information on the disease , role-playing on management of behavior problems , discussion on emotional impact of care-giving , and learning of stress management techniques . Subjects of the control group were referred to informal monthly meetings of the Alzheimer 's Society . Subjects of both groups were evaluated at the entry ( T1 ) , after 8 weeks ( T2 ) and after 8 months ( T3 ) . The outcome variables were the Burden Interview , the Revised Memory and Behavior Problems Checklist , the Brief Symptoms Inventory , the Alzheimer 's Disease Knowledge Test and a question naire on health care utilization . Compared with the control group , subjects of the study group yielded only a significant increase in knowledge about the disease ( p<0.0001 ) but no significant difference on the other outcome variables . It is concluded that this type of support group programme seems to have only a minimal impact on morbidity and on the burden of care-givers . These results are similar with two other studies examining the same issue BACKGROUND Mild cognitive impairment ( MCI ) is considered to be a transitional stage between aging and Alzheimer disease ( AD ) . OBJECTIVE To determine whether MCI represents early-stage AD by examining its natural history and neuropathologic basis . DESIGN A prospect i ve clinical and psychometric study of community-living elderly volunteers , both nondemented and minimally cognitively impaired , followed up for up to 9.5 years . Neuropathologic examinations were performed on participants who had undergone autopsy . SETTING An AD research center . PARTICIPANTS All participants enrolled between July 1990 and June 1997 with Clinical Dementia Rating ( CDR ) scores of 0 ( cognitively healthy ; n = 177 ; mean age , 78.9 years ) or 0.5 ( equivalent to MCI ; n = 277 ; mean age , 76.9 years ) . Based on the degree of clinical confidence that MCI represented dementia of the Alzheimer type ( DAT ) , 3 subgroups of individuals with CDR scores of 0.5 were identified : CDR 0.5/DAT , CDR 0.5/incipient DAT , and CDR 0.5/uncertain dementia . MAIN OUTCOME MEASURE Progression to the stage of CDR 1 , which characterizes mild definite DAT . RESULTS Survival analysis showed that 100 % of CDR 0.5/DAT participants progressed to greater dementia severity over a 9.5-year period . At 5 years , rates of progression to a score of CDR 1 ( or greater ) for DAT were 60.5 % ( 95 % confidence interval [ CI ] , 50.2%-70.8 % ) for the CDR 0.5/DAT group , 35.7 % ( 95 % CI , 21.0%-50.3 % ) for the CDR 0.5/incipient DAT group , 19.9 % ( 95 % CI , 8.0%-31.8 % ) for the CDR 0.5/uncertain dementia group , and 6.8 % ( 95 % CI , 2.2%-11.3 % ) for CDR 0/controls . Progression to greater dementia severity correlated with degree of cognitive impairment at baseline . Twenty-four of the 25 participants with scores of CDR 0.5 had a neuropathologic dementing disorder , which was AD in 21 ( 84 % ) . CONCLUSIONS Individuals currently characterized as having MCI progress steadily to greater stages of dementia severity at rates dependent on the level of cognitive impairment at entry and they almost always have the neuropathologic features of AD . We conclude that MCI generally represents early-stage AD Donepezil has been shown to be well tolerated and to improve cognition and global function in patients with mild to moderately severe Alzheimer ’s disease ( AD ) . The current trial was undertaken to investigate further the efficacy and safety of donepezil , in a multinational setting , in patients with mild to moderately severe AD . This 30-week , placebo-controlled , parallel-group study consisted of a 24-week , double-blind treatment phase followed by a 6-week , single-blind , placebo washout . Eight hundred and eighteen patients with mild to moderately severe AD were r and omly allocated to treatment with single , daily doses of 5 or 10 mg donepezil , or placebo . The two primary efficacy measures were : a cognitive performance test , the Alzheimer ’s Disease Assessment Scale-cognitive subscale ( ADAS-cog ) and a global evaluation , the Clinician ’s Interview-Based Impression of Change with caregiver input ( CIBIC plus ) . Secondary outcome measures included the Sum of the Boxes of the Clinical Dementia Rating Scale ( CDR-SB ) , a modified Interview for Deterioration in Daily living activities in Dementia ( IDDD ) and a patientrated quality of life assessment . Statistically significant improvements in cognitive and global function were observed , as evaluated by ADAS-cog and CIBIC plus , respectively , in both the 5 and 10 mg/day donepezil groups , compared with placebo . Treatment-associated changes were also observed in functional skills , as shown by improved scores on the CDR-SB and the complex-tasks component of the IDDD . A dose – response effect was evident , with the 10 mg/day donepezil group demonstrating greater benefits in all outcome measures than the 5 mg/day group . Donepezil was well tolerated by this patient population and did not produce any clinical ly significant laboratory test abnormalities . The results of this study confirm that donepezil is effective and well tolerated in treating the symptoms of mild to moderately severe AD A r and om sample of 467 persons over age 65 years from the population of an urban US community , stratified by age , sex , and performance on a brief memory test , underwent clinical evaluation for dementing illness in 1982 - 1984 . Of these persons , 134 had probable Alzheimer 's disease , 166 had possible Alzheimer 's disease , and 167 had no evidence of Alzheimer 's disease . Over a median follow-up period of 4.9 years following evaluation , 165 ( 35 % ) died . Overall , persons with probable Alzheimer 's disease had a relative risk of death 1.44 ( 95 % confidence interval ( Cl ) 1.05 - 1.96 ) times that of the unaffected . Level of cognitive impairment and the presence of cachexia upon physical examination both strongly and independently modified risk of death . Among those with probable Alzheimer 's disease , mortality for those with mild or moderate cognitive impairment and no evidence of cachexia was comparable to that of the unaffected . However , among those with probable Alzheimer 's disease and either severe cognitive impairment or cachexia , the risk of death was substantially higher . Persons with probable Alzheimer 's disease who had both severe cognitive impairment and clear cachexia had a risk of death 4.60 ( 95 % Cl 1.63 - 13.1 ) times that of unaffected persons In Western countries , vascular dementia ( VaD ) is the most common form of cognitive deterioration after Alzheimer 's disease . Therapeutic trials in VaD have so far failed to yield satisfactory results . One explanation of this failure may be the etiological and clinical heterogeneity of the included patients . Patients with subcortical VaD , defined on a clinical and radiological basis , may constitute a more homogeneous group . Thus , we conducted a post-hoc subgroup analysis of the Sc and inavian Multi-Infa rct Dementia Trial that evaluated the efficacy and safety of oral nimodipine administered for 6 months in 259 patients . The original patients sample was divided on the basis of head CT in those with subcortical VaD ( n=92 , 45 nimodipine , 47 placebo ) and those with multi-infa rct dementia ( n=167 , 83 nimodipine , 84 placebo ) . While in the total trial population a treatment effect could not be proved , in this subgroup analysis , the subcortical VaD patients treated with nimodipine performed better on the majority of neuropsychological tests and functional scales in comparison with patients on placebo . No trend could be evidence d in the multi-infa rct dementia patients . Treatment efficacy was in particular suggested for the Zahlen-Verbindungs-Test , Fuld-Object-Memory Evaluation , Word Fluency , and for the Instrumental Activities of Daily Living scale . The results did not reach statistical significance in this small sample . Our study preliminarily indicates that nimodipine could be effective in patients with small vessel subcortical VaD and supports the rationale for a further controlled and adequately powered trial to test nimodipine in patients with subcortical Background : Previous studies suggest a potential benefit from nonsteroidal anti-inflammatory drugs ( NSAIDs ) in Alzheimer ’s disease ( AD ) . Prescribing NSAIDs , however , carries the risk of significant gastrointestinal adverse events . Objectives : To study whether treatment with an NSAID prevents expected decline in AD patients and evaluate whether co-administration of the gastro-protective agent , misoprostol , with an NSAID is safe in AD . Methods : The efficacy and safety of diclofenac in combination with misoprostol ( D/M ) was evaluated in 41 patients with mild-moderate AD in a prospect i ve 25-week , r and omized , double-blind placebo-controlled trial . Efficacy measures comprised the Alzheimer ’s Disease Assessment Scale cognitive and noncognitive subsections , Global Deterioration Scale , Clinical Global Impression of Change , Mini-Mental State Examination , Instrumental Activities of Daily Living , Physical Self-Maintenance Scale , and a caregiver-rated Global Impression of Change . Results : There were no group differences with any of the outcome measures in an intent-to-treat analysis . There were some nonsignificant trends for the placebo group to have deteriorated more than the D/M-treated patients . Withdrawal rates were 12 of 24 in the D/M group and 2 of 17 in the placebo group . There were no serious drug-related adverse events . Conclusions : This pilot study , with small treatment numbers , did not demonstrate a significant effect of NSAID treatment in AD , but the trends observed justify further investigations with a larger number of participants . D/M is safe in AD patients , but its tolerability is not optimal BACKGROUND There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer 's disease . METHODS We conducted a double-blind , placebo-controlled , r and omized , multicenter trial in patients with Alzheimer 's disease of moderate severity . A total of 341 patients received the selective monoamine oxidase inhibitor selegiline ( 10 mg a day ) , alpha-tocopherol ( vitamin E , 2000 IU a day ) , both selegiline and alpha-tocopherol , or placebo for two years . The primary outcome was the time to the occurrence of any of the following : death , institutionalization , loss of the ability to perform basic activities of daily living , or severe dementia ( defined as a Clinical Dementia Rating of 3 ) . RESULTS Despite r and om assignment , the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups , and this variable was highly predictive of the primary outcome ( P<0.001 ) . In the unadjusted analyses , there was no statistically significant difference in the outcomes among the four groups . In analyses that included the base-line score on the Mini-Mental State Examination as a covariate , there were significant delays in the time to the primary outcome for the patients treated with selegiline ( median time , 655 days ; P=0.012 ) , alpha-tocopherol ( 670 days , P=0.001 ) or combination therapy ( 585 days , P=0.049 ) , as compared with the placebo group ( 440 days ) . CONCLUSIONS In patients with moderately severe impairment from Alzheimer 's disease , treatment with selegiline or alpha-tocopherol slows the progression of disease Objective : To examine the effects of donepezil compared with placebo on the preservation of function in patients with AD over a 1-year period . Methods : This was a prospect i ve , 54-week , double-blind , placebo-controlled , survival to endpoint study . Patients were required to have at entry : a diagnosis of probable AD ( National Institute of Neurological and Communicative Disorders and Stroke criteria ) ; Mini-Mental State Examination score of 12 to 20 ; Clinical Dementia Rating of 1 or 2 ; modified Hachinski ischemia score ≤4 ; and capability of performing 8 of 10 instrumental activities of daily living and 5 of 6 basic activities of daily living . Patients ( n = 431 ) were r and omized to placebo or donepezil ( 5 mg/day for 28 days , 10 mg/day thereafter ) . Outcome measures were the AD Functional Assessment and Change Scale , the Mini-Mental State Examination , and Clinical Dementia Rating scale . At each visit , investigators determined whether predefined criteria for clinical ly evident decline in functional status had been met . Patients who met the endpoint criteria were discontinued per protocol . Results : Donepezil extended the median time to clinical ly evident functional decline by 5 months versus placebo . The probability of patients treated with donepezil remaining in the study with no clinical ly evident functional loss was 51 % at 48 weeks , compared with 35 % for placebo . The Kaplan – Meier survival curves for the two treatment groups were different ( p = 0.002 , log-rank test ) . Conclusions : Patients with AD continue to show detectable disease progression over time , but treatment with donepezil for 1 year was associated with a 38 % reduction in the risk of functional decline compared with placebo OBJECTIVES To study whether a low , " normal " sumscore ( i.e. , 24 or higher ) on the Mini-Mental Status Examination ( MMSE ) near the cutpoint usually employed for identifying persons with cognitive impairment predicts later development of dementia . DESIGN A prospect i ve study of a r and om sample of nondemented persons aged 75 years and older , according to DSM-III criteria , with follow-ups after 3 and 6 years . PARTICIPANTS The subjects were 215 persons living at home , mean age 81 years , 81 % women . Their mean MMSE sumscore at the start of the study ( T0 ) was 27.9 ( range 24 - 30 ) . MAIN RESULTS A low MMSE sumscore at T0 was identified as a statistically strongly significant predictor of dementia after 3 years ( P < .001 ) , when more than 40 % of those with a sumscore of 24 or 25 at T0 had become demented . A similar , although weaker and statistically nonsignificant , trend was observed for the risk after 6 years in relation to MMSE scoring at baseline . CONCLUSION Persons with a sumscore of 24 or 25 and classified as not suffering from dementia according to the DSM-III criteria are at high risk of developing dementia within 3 years OBJECTIVE To estimate the predictive value of four IADLs on 3- and 5-year incident dementia . DESIGN Prospect i ve cohort study . SETTING A community survey in 37 r and omly selected parishes . SUBJECTS A r and om sample of French community dwellers aged 65 and older included in the PAQUID study followed-up at 3 ( 1582 subjects ) and 5 years ( 1283 subjects ) . MAIN OUTCOME MEASURES Incidence of dementia at 3 and 5 years , diagnosed by two-step screening : ( 1 ) MMS and DSM-III-R ; ( 2 ) diagnosis of dementia confirmed by a neurologist . RESULTS A score summing up the number of dependencies at baseline on four IADLs is a predictor of 3-year but not of 5-year incident dementia . Increase in the level of dependence between baseline and 3-year follow-up is associated with an increased risk of incident dementia at 5-year follow-up . CONCLUSION These four IADLs can help to identify older subjects at high risk of dementia who should then undergo neuropsychological testing BACKGROUND Dementia with Lewy bodies is a common form of dementia in the elderly , characterised clinical ly by fluctuating cognitive impairment , attention deficits , visual hallucinations , parkinsonism , and other neuropsychiatric features . Neuroleptic medication can provoke severe sensitivity reactions in patients with dementia of this type . Many deficits in cholinergic neurotransmission are seen in the brain of patients with Lewy-body dementia ; therefore , drugs enhancing central cholinergic function represent a rationally-based therapeutic approach to this disorder . Rivastigmine , a cholinesterase inhibitor , was tested in a group of clinical ly characterised patients with Lewy-body dementia . METHODS A placebo-controlled , double-blind , multicentre study was done in 120 patients with Lewy-body dementia from the UK , Spain , and Italy . Individuals were given up to 12 mg rivastigmine daily or placebo for 20 weeks , followed by 3 weeks rest . Assessment by means of the neuropsychiatric inventory was made at baseline , and again at weeks 12 , 20 , and 23 . A computerised cognitive assessment system and neuropsychological tests were also used , and patients underwent close medical and laboratory safety analysis . FINDINGS Patients taking rivastigmine were significantly less apathetic and anxious , and had fewer delusions and hallucinations while on treatment than controls . Almost twice as many patients on rivastigmine ( 37 , 63 % ) , than on placebo ( 18 , 30 % ) , showed at least a 30 % improvement from baseline . In the computerised cognitive assessment system and the neuropsychological tests , patients were significantly faster and better than those on placebo , particularly on tasks with a substantial attentional component . Both predefined primary efficacy measures differed significantly between rivastigmine and placebo . After drug discontinuation differences between rivastigmine and placebo tended to disappear . Known adverse events of cholinesterase inhibitors ( nausea , vomiting , anorexia ) were seen more frequently with rivastigmine than with placebo , but safety and tolerability of the drug in these mostly multimorbid patients were judged acceptable . INTERPRETATION Rivastigmine 6 - 12 mg daily produces statistically and clinical ly significant behavioural effects in patients with Lewy-body dementia , and seems safe and well tolerated if titrated individually Causes of cognitive impairment in the elderly include dementia , delirium , toxic effects of medications , trauma , and psychiatric illness . Dementia is the most common cause , and it implies a decline in cognitive function severe enough to interfere with social functioning . The estimated prevalence of dementia is 3 % to 6 % for community-dwelling elderly persons aged 65 years and older [ 1 - 4 ] , but the prevalence of dementia increases with advancing age [ 1 , 2 , 5 , 6 ] and is more common among elderly patients in primary care setting s , hospitals , or nursing homes [ 7 , 8 ] . The annual cost of caring for a patient with Alzheimer disease is estimated to be $ 47 000 [ 9 ] , and total national costs for senile dementia in 1991 were estimated to be more than $ 67 billion [ 10 ] . In addition , patients with dementia have been shown to have greater mortality than elderly patients without dementia [ 5 ] . Given the prevalence , costs , and morbidity of cognitive impairment , and the availability of several brief screening instruments [ 11 - 13 ] , screening for cognitive impairment among elderly patients seen in primary care has been recommended [ 14 - 20 ] . Early recognition and diagnosis of cognitive impairment are believed to be beneficial for at least three reasons . First , a diagnosis provides some comfort to the patient and family by explaining the changes in the patient 's behavior and also allows the practitioner to counsel the patient and family about prognosis . Second , an accurate diagnosis of cognitive impairment and assessment of its functional and social effects may facilitate access to rehabilitative , social , and financial services , as well as help inform decisions about competency and guardianship [ 21 - 23 ] . Third , early recognition may allow an opportunity to alter the course of the cognitive impairment . Physicians may be able to do so if diagnostic evaluations show a reversible or partially reversible cause [ 24 - 26 ] or if the rate of progression of a dementing illness or a comorbid illness can be slowed [ 27 - 29 ] . Indeed , routine diagnostic investigations for reversible causes of dementia have been recommended [ 19 , 20 , 24 ] . However , the prevalence of reversible causes of dementia and the clinical utility of routine diagnostic investigations are still being debated [ 13 , 30 - 35 ] . Thus , although early documentation of cognitive impairment offers many other benefits , clinicians might appropriately choose either an extensive or a limited diagnostic evaluation for any given patient . Our study had four objectives . First , we determined the prevalence of cognitive impairment by screening a group of urban , elderly , primary care patients using the Short Portable Mental Status Question naire ( SPMQ ) . Second , we describe their primary care physicians ' rates of documentation and evaluation of cognitive impairment . Third , we compare use of health services in the year after the patient 's screening examination . Fourth , we compare practice patterns and use of health services among patients with documented and those with undocumented cognitive impairment . Methods Patients Our study was done in the General Medicine Practice of the Regenstrief Health Center , a multispecialty ambulatory care clinic associated with an urban county hospital [ 36 ] . The General Medicine Practice is a university-affiliated primary care practice staffed by 35 general internists on the faculty and 118 internal medicine residents . Beginning in January 1991 , all patients aged 60 years and older were screened for cognitive impairment , depression , and alcoholism during their regularly scheduled visits . We excluded prisoners , patients residing in a nursing home , patients unable to speak English , and patients who had hearing impairment . The screening instruments included the Short Portable Mental Status Question naire [ 37 ] , the Center for Epidemiologic Studies Depression scale ( CES-D ) [ 38 ] , and the CAGE alcoholism question naire [ 39 ] . Professional research assistants administered the screening interview to patients at the time of scheduled office visits . Screening scores on the SPMQ completed for the purpose s of our study were not revealed to the primary care physicians . Patients with 3 to 4 errors on the SPMQ were considered to have mild cognitive impairment , and patients with 5 or more errors were considered to have moderate to severe cognitive impairment . We corrected the SPMQ score for years of education by allowing an additional error for patients with 8 or fewer years of education [ 37 ] , but we did not correct scores for race . When administered to community-dwelling elderly persons , the SPMQ has a specificity of greater than 90 % and a sensitivity of 50 % to 82 % ( cutoff , 3 or more errors ) [ 12 , 40 ] . The positive predictive value of the test in a community-dwelling patient sample was 87 % , and the validity was tested against structured psychiatric assessment s [ 37 ] . We used the st and ard cutoff score of 16 or greater on the CES-D to indicate significant symptoms of depression [ 38 ] . Patients with two or more positive responses on the CAGE question naire were considered to have evidence of alcoholism [ 39 ] . Interview data were merged with information routinely collected and stored in the patients ' electronic medical records [ 41 ] . These data included all outpatient diagnoses as recorded by the patients ' physicians . The ICD-9-CM codes for the individual diagnoses for each patient were collapsed into 1 of 40 unique categories . We report only the 20 most common diagnoses . We also determined whether each patient had ever had any of the following : tests for hemoglobin concentrations , serum chemistries , thyroid function , erythrocyte sedimentation rate , syphilis ( VDRL or fluorescent treponemal antibody absorption or Treponema pallidum microhemagglutination assay ) , serum cobalamin levels , and serum folate levels ; radiograph of the chest ; neuroimaging ( computed tomography or magnetic resonance imaging ) ; lumbar puncture ; or electroencephalography . We determined whether patients had had neurologic evaluation in the year before or in the year after the screening date and whether they had been prescribed any of the major classes of central nervous system-active medications ( anticholinergics , narcotics , antidepressants , benzodiazepines , or major tranquilizers ) in the year after the screening date . We determined whether patients had ever received pneumococcal vaccination and whether they had received influenza vaccination or colon cancer screening ( hemoccult test , barium enema , sigmoidoscopy , or colonoscopy ) in the year after the screening date . We determined whether female patients had had mammography and Papanicolaou smears in the year after the screening date . We also determined whether patients had been prescribed aspirin , a nonsteroidal anti-inflammatory drug , or estrogen replacement in each of the 2 years before the screening date . For use of health services in the year after the screening date , we determined the following : whether patients had been hospitalized or had visited the emergency department and the mean number of these episodes among patients with at least one of these visits ; the mean number of outpatient visits , including those to medical and surgical subspecialty clinics ; and total outpatient charges , including charges for office visits , outpatient diagnostic testing , and pharmacy services . Mortality was determined as of December 1992 using hospital discharge condition , death summaries , autopsy reports , and the Indiana State Board of Health 's death certificate files . Statistical Analysis For dichotomous variables , we used chi-square tests to compare frequencies among patients with no cognitive impairment , mild cognitive impairment , or moderate to severe cognitive impairment . We used analysis of variance to compare the mean log-transformed values for continuous and count variables among these three groups . We also looked for significant differences between those with documented cognitive impairment and those with undocumented impairment . A patient with documented cognitive impairment had an SPMQ score of 5 or greater and had dementia ( or a synonymous term such as the organic brain syndrome or Alzheimer disease ) listed in their outpatient medical record . With moderate to severe cognitive impairment as the dependent variable , we next used logistic regression to determine which variables were independently associated with cognitive impairment . Because the data used in these models are cross-sectional , these analyses can not ascribe causality . The multivariable regression was done to determine whether age , education , and race were independently correlated with cognitive impairment even when we controlled for comorbid conditions . In the first model , we included all comorbid medical illnesses as independent variables . In the second model , we included the significant variables from the first model in addition to the demographic variables , with significant bivariate relations including age , sex , years of education , and low serum albumin level . The calculation of patients ' SPMQ scores for these models did not include corrections for race or education . For these analyses , we r and omly divided the data set in half for derivation and validation sets . We also did logistic regression analyses to determine if cognitive impairment was independently correlated with hospitalization , emergency department visits , outpatient visits , use of preventive health care services , or mortality after we controlled for age , race , and education . Results From January 1991 to May 1993 , we contacted 4413 patients aged 60 years and older during routine visits to the primary care practice ; 3954 ( 90 % ) of these patients completed the SPMQ . One hundred fifteen patients refused the screening examination , 284 were ineligible , and 60 could not complete the SPMQ . Among all patients screened , the mean age was 68 years ( range , 60 to 102 years ) , 68.8 % were women , 63.4 % were black , 43.6 % had 8 or fewer years of education , 10.5 % had evidence of CONTEXT Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease ( AD ) in women . OBJECTIVE To determine whether estrogen replacement therapy affects global , cognitive , or functional decline in women with mild to moderate AD . DESIGN The Alzheimer 's Disease Cooperative Study , a r and omized , double-blind , placebo-controlled clinical trial conducted between October 1995 and January 1999 . SETTING Thirty-two study sites in the United States . PARTICIPANTS A total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy . INTERVENTIONS Participants were r and omized to estrogen , 0.625 mg/d ( n = 42 ) , or 1.25 mg/d ( n = 39 ) , or to identically appearing placebo ( n = 39 ) . One subject withdrew after r and omization but before receiving medication ; 97 subjects completed the trial . MAIN OUTCOME MEASURES The primary outcome measure was change on the Clinical Global Impression of Change ( CGIC ) 7-point scale , analyzed by intent to treat ; secondary outcome measures included other global measures as well as measures of mood , specific cognitive domains ( memory , attention , and language ) , motor function , and activities of daily living ; compared by the combined estrogen groups vs the placebo group at 2 , 6 , 12 , and 15 months of follow-up . RESULTS The CGIC score for estrogen vs placebo was 5.1 vs 5.0 ( P = .43 ) ; 80 % of participants taking estrogen vs 74 % of participants taking placebo worsened ( P = .48 ) . Secondary outcome measures also showed no significant differences , with the exception of the Clinical Dementia Rating Scale , which suggested worsening among patients taking estrogen ( mean posttreatment change in score for estrogen , 0.5 vs 0.2 for placebo ; P = .01 ) . CONCLUSIONS Estrogen replacement therapy for 1 year did not slow disease progression nor did it improve global , cognitive , or functional outcomes in women with mild to moderate AD . The study does not support the role of estrogen for the treatment of this disease . The potential role of estrogen in the prevention of AD , however , requires further research Although sleep problems are common among dementia caregivers , there has been no research thus far describing treatment of such problems using behavioral techniques . In this study , 36 elderly dementia caregivers with disturbed sleep were r and omly assigned to either a brief behavioral intervention or a wait list control . The active treatment consisted of st and ard sleep hygiene , stimulus control , and sleep compression strategies as well as education about community re sources , stress management , and techniques to reduce patient disruptive behaviors . Caregivers in active treatment showed significant improvements in sleep at post-treatment and 3-month follow up . No significant differences between groups were observed for caregiver mood , burden , or patient behavior problems , suggesting that sleep improvements were not an artifact of depression treatment . Treatment responders tended to be younger and more compliant with treatment recommendations than non-responders . Results suggest that behavioral techniques may well be a viable alternative to medication for sleep problems in aging caregivers Objective : To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD . Methods : Patients ( n = 286 ; mean age , 72.5 years ) with possible or probable AD from five Northern European countries were r and omized to receive either donepezil ( n = 142 ; 5 mg/day for 28 days , followed by 10 mg/day ) or placebo ( n = 144 ) for 1 year . Results : The study was completed by 66.9 % of the donepezil- and 67.4 % of the placebo-treated patients . The benefit of donepezil over placebo was demonstrated by the Gottfries-Bråne-Steen ( a global assessment for rating dementia symptoms ) total score at weeks 24 , 36 , and 52 ( p < 0.05 ) and at the study end point ( week 52 , last observation carried forward ; p = 0.054 ) . Advantages of donepezil over placebo were also observed in cognition and activities of daily living ( ADL ) assessed by the Mini-Mental State Examination at weeks 24 , 36 , and 52 , and the end point ( p < 0.02 ) and by the Progressive Deterioration Scale at week 52 and the end point ( p < 0.05 ) . Adverse events ( AE ) were recorded for 81.7 % of donepezil- and 75.7 % of placebo-treated patients , with 7 % of donepezil- and 6.3 % of placebo-treated patients discontinuing because of AE . Treatment response to donepezil was not predicted by APOE genotype or sex in this population . Conclusion : As the first 1-year , multinational , double-blinded , placebo-controlled study of a cholinesterase inhibitor in AD , these data support donepezil as a well tolerated and effective long-term treatment for patients with AD , with benefits over placebo on global assessment , cognition , and ADL OBJECTIVE To estimate the frequency and correlates of undetected dementia in community-dwelling older people . DESIGN Secondary analysis of data from the Canadian Study of Health and Aging ( CSHA ) prevalence survey of dementia . SETTING All 10 provinces of Canada excluding Indian reserves and military units . PARTICIPANTS A total of 252 community-dwelling older adults diagnosed with dementia in the CSHA survey . MAIN OUTCOME MEASURE Undetected dementia , defined as occurring in persons who meet st and ard diagnostic criteria for dementia but who report never having seen a doctor for memory problems . RESULTS Of the 252 subjects , 64 % had undetected dementia . Subjects with mild functional impairment were significantly more likely to have undetected dementia ( odds ratio = 2.4 , 95 % confidence interval 1.2 , 5.0 ) . Older subjects and those with mild cognitive impairment showed a trend toward undetected dementia , although the results did not achieve statistical significance . Educational level , number of comorbid conditions , and degree of social support were not significantly associated with undetected dementia . CONCLUSIONS A large number of older persons are living in the community with undetected dementia . These older people may be at significant risk for delirium , motor vehicle accidents , medication errors , and financial difficulties . As preventive strategies are developed and new cognitive enhancing therapies emerge , we need to reexamine our current guidelines about screening for cognitive impairment in older adults Twenty-one depressed patients with probable Alzheimer 's disease ( AD ) were r and omized to receive a 6-week treatment with clomipramine or placebo in a study with a double-blind crossover design . Main outcome measures were Hamilton Depression , Mini-Mental State ( MMSE ) , and Functional Independence Measure ( FIM ) scores . Mood improved significantly on both clomipramine and placebo , but clomipramine was significantly more effective than placebo during the first 6-week treatment period . Patients started on clomipramine maintained improvement during the washout and placebo periods , whereas patients started on placebo worsened during the washout period . However , patients on clomipramine showed significantly lower MMSE scores overall than patients on placebo . No significant drug effects were found on FIM scores . Clomipramine proved to be a useful treatment of depression in patients with probable AD OBJECTIVES To study caregivers ' decisions to end home care for relatives with dementia ; to study the changes in caregiver functioning over time . DESIGN A prospect i ve longitudinal follow-up study . SETTING Individual homes and chronic care facilities in Montreal . PARTICIPANTS 157 caregiver-dependent dyads , followed up 2 years later ; dependents had been diagnosed as having progressive dementia . MEASUREMENTS A st and ard interview and a series of st and ardized psychological question naires were given to caregivers , assessing their functioning and their appraisal s of the dependent person in their care . Dependents received the Mini-Mental State Examination . MAIN RESULTS Caregivers cited patient deterioration as the most common reason for ending home care . Most caregivers did not prepare their relative before institutionalization . Most caregivers were satisfied with having ended home care and believed the decision was positive for themselves and their dependent , but a sizable minority of caregivers and dependents had difficulty adjusting to the end of home care . Repeated measures multivariate analyses indicated that caregivers who had discontinued home care because of placement or death of the dependent had improved functioning and quality of life and better health than caregivers still providing home care . CONCLUSIONS Caregivers most frequently cite deteriorating patient conditions as the main causes of ending home care . Caregiver exhaustion is the single most frequently given reason . Caregivers who were still providing home care at the end of the study were functioning less well than caregivers who had ended home care , despite having initially functioned at better levels Support group programmes have been proposed to alleviate the care-givers ' burden and postpone institutionalisation of demented patients . Experimental studies on these programmes failed to detect any impact on care-givers ' burden , but none have examined the effect on institutionalisation . The objective of this paper is to assess the impact of a support group programme for care-givers on the institutionalisation of demented patients . Forty-five care-givers of community-dwelling demented patients were allocated r and omly to the study group ( n = 24 ) and the control group ( n = 21 ) . Subjects in the study group attended a structured programme of 8 weekly sessions of 3 h each . Subjects assigned to the control group were referred to the informal monthly meetings of the Alzheimer 's Society . Using survival analysis , the median length of time until institutionalisation was 30 months from the time of the entry into the study . At 24 months , the probability of being institutionalised was 0.33 in the study group and 0.45 in the control group . This difference was not statistically significant ( log-rank test : chi2 = 1.02 ; P = 0.31 ) . These results emphasize the lack of scientific evidence about efficacy of such programmes and the need for a large multi-centre study on this topic In a study carried out in 21 general practice s in Mannheim , Germany , a stratified r and om sample ( N = 507 ) of patients over the age of 65 years was drawn from the total of nearly 4000 who were medically documented . Eighty per cent of the sample were examined , using the Hierarchic Dementia Scale to test cognitive functioning and the CAMDEX criteria to assess global clinical severity . Repeat assessment after a mean interval of 27 months showed that all new cases of clinical dementia had arisen in persons with mild deficits initially and represented one-fifth of this group . The first- assessment ratings of cognitive function proved to be strongly predictive of risks for age-corrected mortality , admission to long-term care and dependency at follow-up , as well as of further progressive cognitive decline The purpose of this experimental study was to compare the effects of skill training , a traditional stimulation approach , and regular care ( control group ) on the ability to perform the basic activities of daily living of nursing home residents with dementia . Sixty-three subjects were r and omly selected and r and omly assigned to the three groups . Ability to perform the basic activities of daily living ( ADLs ) and progress toward meeting individually set ADL-related goals were measured . Significant differences were found in two of the three measures used . In general , the greatest improvement was found in the skill training group , modest improvement in the simulation group , and decline in the control group BACKGROUND Laboratory and epidemiologic studies suggest that anti-inflammatory/immunosuppressive therapy may be useful in the treatment of AD . In preliminary studies , a regimen of low to moderate dose prednisone was found to suppress peripheral inflammatory markers without adverse effects in subjects with AD . METHODS We conducted a r and omized , placebo-controlled multicenter trial to determine whether prednisone treatment slowed the rate of cognitive decline in AD . The active treatment regimen consisted of an initial dose of 20 mg of prednisone daily for 4 weeks tapered to a maintenance dose of 10 mg daily for 1 year , followed by gradual withdrawal during an additional 16 weeks . The primary outcome measure was the 1-year change in the cognitive subscale of the AD Assessment Scale . RESULTS A total of 138 subjects were r and omized to the drug and placebo groups . There was no difference in cognitive decline between the prednisone and placebo treatment groups in the primary intent-to-treat analysis , or in a secondary analysis considering completers only . Subjects treated with prednisone showed behavioral decline compared with those in the placebo group . CONCLUSION A low-dose regimen of prednisone is not useful in the treatment of AD BACKGROUND The majority of patients with Alzheimer 's disease live outside institutions and there is considerable serious psychological morbidity among their carers . AIMS To evaluate whether family intervention reduces the subjective burden of care in carers of patients with Alzheimer 's disease and produces clinical benefits in the patients . METHOD A prospect i ve single-blind r and omised controlled trial with three-month follow-up in which the experimental group received family intervention and was compared with two control groups . RESULTS There were significant reductions in distress and depression in the intervention group compared with control groups at post-treatment and follow-up . There were significant reductions in behavioural disturbance at post-treatment and an increase in activities at three months in patients in the intervention group . Based on an improvement on the General Health Question naire result ing in a carer converting from a case to a non-case , the number to treat was three immediately post-treatment and two at follow-up . CONCLUSIONS Family intervention can have significant benefits in carers of patients with Alzheimer 's disease and has a positive impact on patient behaviour OBJECTIVE To describe the theory , elements and practice of a successful caregiver training programme ; and report the 8-year outcome . DESIGN Prospect i ve , r and omized control trial and longitudinal follow-up over approximately 8 years . SETTING Psychiatry unit , general teaching hospital , Sydney , Australia . PARTICIPANTS 96 persons less than 80 years old with mild to moderate dementia and their cohabiting caregivers . INTERVENTIONS All patients received a 10-day structured memory retraining and activity programme . Caregivers in the immediate and wait-list caregiver training groups received a structured , residential , intensive 10-day training programme , boosted by follow-ups and telephone conferences over 12 months . Those in the wait-list group entered the programme after waiting 6 months . The third group of caregivers received 10 days ' respite ( while patients underwent their memory retraining programme ) and 12 months booster sessions as for the other groups . MAIN OUTCOME MEASURES Nursing home admission ; time until patient death . MAIN RESULTS 64 % of patients whose caregivers were in the immediate training group , 53 % of wait-list group patients and 70 % of memory retraining patients had died . Nursing home admission had occurred in 79 % of the immediate training , 83 % of the delayed and 90 % of the memory retraining group . Eight-year survival analysis indicated that patients whose caregivers received training stayed at home significantly longer ( p = 0.037 ) and tended to live longer ( p = 0.08 ) . CONCLUSIONS Caregiver training programmes demonstrably can delay institutionalization of people with dementia Background : Treatment of agitation is a crucial problem in the care of patients with AD . Although antipsychotic and antidepressant medications and behavior management techniques ( BMT ) have each been used to treat agitation , clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment design s. Objective : To compare haloperidol , trazodone , and BMT with placebo in the treatment of agitation in AD out patients . Methods : A total of 149 patients with AD and their caregivers participated in a r and omized , placebo-controlled , multicenter trial . Blind assessment was conducted at baseline and after 16 weeks of treatment . The three active treatments were haloperidol , trazodone , and BMT . The Alzheimer ’s Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure . Secondary outcomes included patient agitation , cognition , and function , and caregiver burden . Results : Thirty-four percent of subjects improved relative to baseline . No significant differences on outcome were obtained between haloperidol ( mean dose , 1.8 mg/d ) , trazodone ( mean dose , 200 mg/d ) , BMT , or placebo . Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm . No other significant difference in adverse events was seen . Symptoms did not respond differentially to the different treatments . Conclusions : Comparable modest reductions in agitation occurred in patients receiving haloperidol , trazodone , BMT , and placebo . More effective pharmacologic , nonpharmacologic , and combination treatments are needed OBJECTIVE This study evaluated the efficacy and safety of sertraline in the treatment of major depression in 22 out patients with Alzheimer 's disease . METHOD Twelve of the 22 patients were given sertraline and 10 were given placebo by r and om group assignment for 12 weeks . Response to treatment was measured by using the Cornell Scale for Depression in Dementia . The patients were also assessed with the Hamilton Depression Rating Scale , the activities of daily living subscale of the Psychogeriatric Dependency Rating Scales , and the Mini-Mental State . RESULTS After 12 weeks of double-blind , placebo-controlled treatment , nine of the patients given sertraline and two of those given placebo were at least partial responders . Patients given sertraline had significantly greater mean declines from baseline in Cornell Scale for Depression in Dementia scores ; the bulk of antidepressant response occurred by the third week of treatment . CONCLUSIONS Sertraline is superior to placebo in reducing depression in patients with Alzheimer 's disease who also suffer from major depression This pilot study compared haloperidol , fluoxetine , and placebo for reduction of agitation in 15 out patients with AD . The two drugs were no more effective than placebo at reducing agitation in these subjects ; however , both drugs produced more toxicity than did placebo OBJECTIVE The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer 's disease . METHOD In a 6-week r and om-assignment , double-blind , placebo-controlled trial ( phase A ) , haloperidol , 2 - 3 mg/day ( st and ard dose ) , and haloperidol , 0.50 - 0.75 mg/day ( low dose ) , were compared in 71 out patients with Alzheimer 's disease . For the subsequent 6-week double-blind crossover phase ( phase B ) , patients taking st and ard- or low-dose haloperidol were switched to placebo , and patients taking placebo were r and omly assigned to st and ard- or low-dose haloperidol . RESULTS For the 60 patients who completed phase A , st and ard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation . Response rates according to three sets of criteria were greater with the st and ard dose ( 55%-60 % ) than the low dose ( 25%-35 % ) and placebo ( 25%-30 % ) . The advantage of st and ard dose over low dose was replicated in phase B. In phase A , extrapyramidal signs tended to be greater with the st and ard dose than in the other two conditions , primarily because of a subgroup ( 20 % ) who developed moderate to severe signs . Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects . CONCLUSIONS The results indicated a favorable therapeutic profile for haloperidol in doses of 2 - 3 mg/day , although a subgroup developed moderate to severe extrapyramidal signs . A starting dose of 1 mg/day with gradual , upward dose titration is recommended . The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer 's disease patients with psychosis and disruptive behaviors The Monongahela Valley Independent Elders Survey ( MoVIES ) used a multiphase process to identify demented persons among 1,366 r and omly selected noninstitutionalized individuals 65 years and older . Raw test scores from a cognitive screening battery were used to identify cognitively impaired individuals who were referred for a clinical evaluation . Subsequently , test scores were adjusted for education and gender within age strata . Adjusting test scores affected sensitivity for dementia only among the most educated , increasing sensitivity among younger subjects and decreasing among the older subjects . Specificity increased among the least educated and the oldest subjects . Overall , the adjusted criteria did not perform as well as the unadjusted criteria in this sample . Adjustment for education will not necessarily improve the ability of a screening battery for cognitive function to identify demented persons , particularly if unadjusted scores perform well |
11,918 | 23,416,440 | In cases of reduction mammaplasty , when antibiotics are administered as a single preoperative dose , the risk of developing surgical-site infection is halved .
With augmentation mammaplasty , there was no effect on infection rates with any antibiotic regimen .
For augmentation mammaplasty , there is no evidence to refute current guidelines , based on recommendations obtained from other forms of implant surgery . | BACKGROUND The use of systemic prophylactic antibiotics to reduce surgical-site infection in aesthetic breast surgery remains controversial .
The aim of this review is to weigh the available evidence with respect to reducing surgical-site infection . | Epidemiologic data on local complications after breast augmentation are scarce . In particular , few prospect ively collected data are available on modern breast implants on this issue . Using data from the Danish Registry for Plastic Surgery of the Breast , the authors examined determinants of surgery-requiring complications and capsular contracture grade s III to IV among 2277 women who underwent cosmetic breast implantation from June 1999 through April 2003 . During an average follow-up period of 1.6 years after implantation , 4.3 % of these women ( 3 % of implants ) required secondary surgery as a result of short-term complications . The most frequent clinical indications for surgery were displacement of the implant ( 38 % ) , capsular contracture grade s III to IV ( 16 % ) , ptosis ( 13 % ) , and hematoma ( 11 % ) . Overall , the authors found that inframammary incision and subgl and ular placement were associated with decreased risks of developing complications requiring surgical intervention , whereas implants larger than 350 mL increased the risk of such complications ( relative risk [ RR ] , 2.3 ; 95 % confidence interval [ CI ] , 1.3–4.0 ) . Thirty-nine Baker III to IV capsular contractures were identified , of which 22 were treated surgically within the study period . Submuscular placement of the implant decreased the risk of capsular contracture grade s III to IV ( RR , 0.3 ; 95 % CI , 0.2–0.8 ) , whereas surgical routes other than inframammary and drainage of implant cavity were associated with increased risk of capsular contracture . Current surgical practice s and modern implants used for breast augmentation produce fewer short-term complications than procedures and devices of the past . This prospect i ve study indicates that surgical procedures are more important predictors for local ( short-term ) complications than implant or patient characteristics Background : The role of prophylactic antibiotics in reduction mammaplasty remains controversial . However , most surgeons choose to use antibiotics . In addition to cost and potential allergic reactions , unnecessary administration of antibiotics can suppress host natural flora and produce resistant organisms . Methods : Fifty patients were sequentially assigned to one of three study limbs : ( 1 ) no antibiotics , ( 2 ) preoperative antibiotics only , or ( 3 ) preoperative and postoperative antibiotics . The study was design ed to include approximately 17 patients in each group . Cephalosporin antibiotics were used unless there was any question of allergy , in which case an alternative antibiotic regimen was used . Preoperative data collected on patients included age , body mass index , history of diabetes mellitus , peripheral vascular disease , previous breast surgery , steroid therapy , and tobacco use . Operative data included specimen weight , operative time , estimated blood loss , prolonged intraoperative hypotension , adjunctive axillary and breast tail liposuction , and intraoperative breast tissue culture . Results : The patient population in the three limbs of the study was similar . Thus , there was no significant difference among the groups insofar as the preoperative data were concerned ( p > 0.20 ) : age , body mass index , diabetes mellitus , peripheral vascular disease , previous breast surgery , and steroid or tobacco use . Furthermore , no significant difference ( p > 0.12 ) was noted among intraoperative data in the three groups : specimen weight , operative time , estimated blood loss , prolonged hypotension , adjunctive breast liposuction , and positive bacterial culture from intraoperative breast tissue sample s. Ninety percent of positive intraoperative breast tissue cultures revealed Staphylococcus epidermidis . Using strict criteria , the infection rate ranged from 19 to 20 percent . There was no significant difference ( p > 0.91 ) in rate of infection among the three study limbs . There was , however , a significant reduction ( p = 0.002 ) in delayed wound healing in the group that received preoperative antibiotics only . Among the studied risk factors for infection , only positive intraoperative culture of breast tissue was significant ( p = 0.008 ) for development of infection . There was a significant association between delayed wound healing and infection ( p = 0.003 ) . Conclusions : This prospect i ve study did not find that prophylactic antibiotics in reduction mammaplasty have an effect on infection ; however , a single preoperative dose significantly improved wound healing Over a 9-month period from September of 1991 to May of 1992 , 339 patients were included in a r and omized , double-blind , placebo-controlled study using azithromycin as the prophylactic agent to determine whether it effects a clinical ly meaningful reduction in postoperative surgical infections in plastic surgery . Azithromycin was given as prophylaxis in 171 patients and placebo in 168 patients . The study medication was a single oral dose taken at 8 P.M. the day before surgery . The patients were followed up for a minimum of 4 weeks after surgery . The patients who received wound infection prophylaxis had 5.1 percent infections compared with 20.5 percent in the placebo group ( p = 0.00009 ) . Eighty percent of all wound infections were first seen after discharge , explaining why plastic surgeons might overlook their infectious complications . There was a significant reduction in postoperative complications ( p = 0.04 ) and in the additional use of antibiotics postoperatively ( p = 0.007 ) in the prophylaxis group . Subgroup analysis showed a significant reduction in surgical infections in breast surgery ( p < 0.05 ) and reconstructive surgery with flaps ( p < 0.05 ) . No effect of the prophylactic regime was demonstrated in patients undergoing secondary surgery for cleft lip and palate disease This prospect i ve study was conducted to assess the influence of antibiotics use on surgical site infections ( SSI ) rates after reduction mammaplasty . Patients undergoing reduction mammaplasty were assigned to group 1 ( n = 50 ) , which received intravenous cephalotin pre- and postoperatively , besides oral cephalexin for 6 days after discharge , or to group 2 ( n = 50 ) , which received no antibiotics . Patients were followed up weekly for 30 days , regarding to SSI , by a blinded surgeon . The Centers for Disease Control and Prevention definitions and classification of SSI were adopted . There was no statistical difference between the groups in regard to age , body mass index , duration of operation , and total resection weight . SSI rates were 2 % and 14 % in groups 1 and 2 , respectively ( P = 0.03 ) . In group 2 , older patients and those with higher resection weight had significant higher SSI rates ( P = 0.02 and P = 0.04 , respectively ) . We observed that antibiotics use decreased SSI rates after reduction mammaplasty The use of prophylactic antibiotics in reduction mammoplasty has been r and om and its efficacy unproven . This study review ed 106 consecutive inferior pedicle technique reduction mammoplasties . Two groups were identified ; 47 patients received prophylactic antibiotics and 59 patients did not . The decision of who received prophylactic antibiotics was r and om based on resident rotation and resident preoperative orders . The demographics were equal between the antibiotic group and the control group . The wound infection rate and the rate of delayed healing were examined in both groups . There were no statistically significant differences in the infection rate or the rate of delayed wound healing in either the antibiotic group or the control group . Individual risk factors were also studied in each group . These risk factors included obesity , older age , smoking history , and large reductions . The use of prophylactic antibiotics did not reduce the infection rate in any of these high-risk groups . Comparing the individual risk factors for the remainder of the patient population showed that the infection rate was higher in obese patients but was unaffected by prophylactic antibiotics . Delayed healing was also higher in larger reductions but also was unaffected by the use of prophylactic antibiotics . We conclude that the use of prophylactic antibiotics in reduction mammoplasty is not efficacious in reducing the rate of wound infection or delayed healing The main drawback with augmentation mammaplasty using implants is capsular contracture . The cause of this complication is still unknown . Silicone particles , hematoma , and bacterial contamination are some of the etiologic factors discussed . In this r and omized , double-blind study on 76 breast-augmented women , 50 percent of the patients had preoperative prophylaxis with benzylpeni-cillin and dicloxacillin . Bacteria sample s were taken intra-operatively . The number of negative cultures increased significantly with antibiotic prophylaxis . In four follow-ups during the first postoperative year , the rate of contractures was evaluated by subjective and objective methods . The results showed no statistically significant difference between the placebo and the antibiotic group with respect to the incidence of capsular contracture In a prospect i ve , r and om , double-blind , and concurrently controlled clinical study of 124 patients having augmentation mammaplasty , using multiple independent subjective judges as well as objective compressibility measurements , the use of a variety of local antibacterials in or around inflatable retromammary prosthetic implants reduced the early postoperative onset of class III to IV capsular contracture by sevenfold ( 85 percent ) and the final incidence by more than half ( 50 percent ) ( p < 0.01 ) . We believe this study provides the most unequivocal evidence to date that the cause of capsular contracture in retromammary augmentation is periprosthetic bacterial contamination . Irrigation with a 5 percent povidone-iodine ( 50 percent Betadine ) solution was as effective as other techniques and is currently our procedure of choice We assessed the efficacy of perioperative antibiotic prophylaxis for surgery in a r and omized , double-blind trial of 1218 patients undergoing herniorrhaphy or surgery involving the breast , including excision of a breast mass , mastectomy , reduction mammoplasty , and axillary-node dissection . The prophylactic regimen was a single dose of cefonicid ( 1 g intravenously ) administered approximately half an hour before surgery . The patients were followed up for four to six weeks after surgery . Blinding was maintained until the last patient completed the follow-up and all diagnoses of infection had been made . The patients who received prophylaxis had 48 percent fewer probable or definite infections than those who did not ( Mantel-Haenszel risk ratio , 0.52 ; 95 percent confidence interval , 0.32 to 0.84 ; P = 0.01 ) . For patients undergoing a procedure involving the breast , infection occurred in 6.6 percent of the cefonicid recipients ( 20 of 303 ) and 12.2 percent of the placebo recipients ( 37 of 303 ) ; for those undergoing herniorrhaphy , infection occurred in 2.3 percent of the cefonicid recipients ( 7 of 301 ) and 4.2 percent of the placebo recipients ( 13 of 311 ) . There were comparable reductions in the numbers of definite wound infections ( Mantel-Haenszel risk ratio , 0.49 ) , wounds that drained pus ( risk ratio , 0.43 ) , Staphylococcus aureus wound isolates ( risk ratio , 0.49 ) , and urinary tract infections ( risk ratio , 0.40 ) . There were also comparable reductions in the need for postoperative antibiotic therapy , non-routine visits to a physician for problems involving wound healing , incision and drainage procedures , and readmission because of problems with wound healing . We conclude that perioperative antibiotic prophylaxis with cefonicid is useful for herniorrhaphy and certain types of breast surgery The aim of this r and omized clinical trial was to determine whether a single intravenous dose of 2 g flucloxacillin could prevent wound infection after primary non‐reconstructive breast surgery |
11,919 | 22,633,318 | Percutaneous biopsy for diagnostic assessment of SRMs can avoid unnecessary surgeries and support treatment decisions , especially in patients at high surgical risk .
Biopsies can confirm histologic success after thermal ablation of SRMs and support the selection of the appropriate systemic therapy for metastatic RCC .
There is increasing evidence that further diagnostic and prognostic information can be obtained from renal tumour biopsies with the use of immunohistochemistry , cytogenetic and molecular analysis , and high-throughput gene expression profiling . | CONTEXT The use of percutaneous biopsy of renal tumours has been traditionally reserved for selected cases because of uncertainties regarding its safety , accuracy , and clinical utility .
With the adoption of modern biopsy techniques and increasing expertise in interpreting biopsy specimens , renal tumour biopsy today has limited morbidity and allows histologic diagnosis in the majority of cases in centres with expertise .
OBJECTIVE To review the current rationale , indications , and outcomes of percutaneous biopsies and histologic characterisation of renal tumours .
EVIDENCE SYNTHESIS In recent years , the increasing incidence of incidental small renal masses ( SRMs ) , the development of conservative and minimally invasive treatments for low-risk renal cell carcinoma ( RCC ) , and the discovery of novel targeted treatments for metastatic disease have provided the rationale for exp and ing the indications for renal tumour biopsy .
CONCLUSIONS Percutaneous biopsies have increasing indications and can significantly contribute to clinical management of renal tumours but are still underutilised in clinical practice . | INTRODUCTION Ablative therapy is increasing for the management of small renal masses . Laparoscopic as well as percutaneous cryotherapy and radiofrequency ablation ( RFA ) have been utilized . Herein we review our experience with renal biopsy immediately prior to laparoscopic RFA . METHODS AND MATERIAL S A prospect ively collected data base containing all patients who underwent laparoscopic RFA by three different surgeons at two different institutions was review ed . Renal biopsies were performed in each patient during transperitoneal laparoscopy after mobilization of the kidney and prior to RFA . The biopsy needle was passed percutaneously via a sheath through the abdominal wall . Multiple core biopsies ( 3 - 5 ) were taken under visual and ultrasonic guidance . All were su bmi tted for permanent pathologic sectioning . RESULTS 138 patients underwent renal biopsy prior to RFA . Mean tumor size was 3.0 cm ( range 1.0 - 6.9 ) . The mean age was 72 years ( range 39 - 90 ) . There were 42 females and 96 males . Mean blood loss was 28 ml ( 0 - 400 ml ) . Only 5 patients lost more than 50 ml , and in each case the bleeding was associated with complicated renal mobilization and dissection prior to biopsy . Final pathology revealed renal cell carcinoma in 95 , oncocytic neoplasm in 26 , and angiomyolipoma in 9.8 patients were considered to have nondiagnostic biopsies . In this group , final pathology revealed benign cysts in 3 , inconclusive specimens in 3 , fibrosis in 1 , and normal tissue in 1 . Hence , a clear diagnosis was possible in 130 of 138 patients , which is 94.2 % . RCC was diagnosed in 68.8 % of the patients , and in 73.1 % of the conclusive biopsies . Eight patients had perioperative complications , including low- grade fevers ( 2 ) perirenal/retroperitonal hematoma ( 2 ) , pleural tear/pneumothorax ( 2 ) , CHF exacerbation , and wound infection . CONCLUSIONS In our multicenter experience , renal biopsy of 138 renal lesions at the time of laparoscopic RFA had a diagnostic yield of 94.2 % . RCC was diagnosed in 68.8 % of the patients , and in 73.1 % of the conclusive biopsies BACKGROUND Besides clinical tumour size , other anatomical aspects of the renal tumour are routinely considered when evaluating the feasibility of elective nephron-sparing surgery ( NSS ) . OBJECTIVE To propose an original , st and ardised classification of renal tumours suitable for NSS based on their anatomical features and size and to evaluate the ability of this classification to predict the risk of overall complications result ing from the surgery . DESIGN , SETTING , AND PARTICIPANTS We enrolled prospect ively 164 consecutive patients who underwent NSS for renal tumours at a tertiary academic referral centre from January 2007 to December 2008 . INTERVENTION Open partial nephrectomy without vessel clamping . MEASUREMENTS All tumours were classified by integrating size with the following anatomical features : anterior or posterior face , longitudinal , and rim tumour location ; tumour relationships with renal sinus or urinary collecting system ; and percentage of tumour deepening into the kidney . We generated an algorithm evaluating each anatomical parameter and tumour size ( the preoperative aspects and dimensions used for an anatomical [ PADUA ] score ) to predict the risk of complications . RESULTS AND LIMITATIONS Overall rates of complication were significantly correlated to all the evaluated anatomical aspects , excluding clinical size and anterior or posterior location of the tumour . By multivariate analysis , PADUA scores were independent predictors of the occurrence of any grade complications ( hazard ratio [ HR ] for score 8 - 9 vs 6 - 7 : 14.535 ; HR for score ≥10 vs 6 - 7 : 30.641 ) . Potential limitations were the limited number of patients with T1b tumours included in the study and the lack of laparoscopically treated patients . Further external validation of the PADUA score is needed . CONCLUSIONS The PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS . The use of an appropriate score can help clinicians stratify patients suitable for NSS into subgroups with different complication risks and can help research ers evaluate the real comparability among patients undergoing NSS with different surgical approaches PURPOSE The majority of cytogenetic studies in renal cell carcinoma ( RCC ) have been impaired by small sample size , retrospective character , and lack of a survival end point . We prospect ively studied the prognostic impact of cytogenetic abnormalities on a larger cohort of patients having up to 108 months of follow-up . PATIENTS AND METHODS Tumors of 282 patients who underwent nephrectomy for clear cell RCC were cytogenetically analyzed . Results were correlated with pathological factors and disease-specific survival . RESULTS The most frequently observed cytogenetic abnormalities were loss of 3p ( 60 % ) , gain of 5q ( 33 % ) , loss of 14q ( 28 % ) , trisomy 7 ( 26 % ) , loss of 8p ( 20 % ) , loss of 6q ( 17 % ) , loss of 9p ( 16 % ) , loss of 4p ( 13 % ) , and loss of chromosome Y in men ( 55 % ) . Tumors with loss of 3p presented at lower TNM stages . Loss of 4p , 9p , and 14q were all associated with higher TNM stages , higher grade , and greater tumor size . A deletion of 3p was associated with better prognosis ( P = .03 ) , while loss of 4p ( P < .001 ) , loss of 9p ( P < .01 ) , and loss of 14q ( P < .01 ) were each associated with worse prognosis . Loss of the Y chromosome led to improved progression-free survival in metastatic patients ( P = .02 ) . In multivariate analysis , loss of 9p was retained as an independent prognostic factor . CONCLUSION This cytogenetic study serves as a proof of principal that genetic information , such as loss of chromosome 9 , can be obtained from widely available technology , and can provide additional prognostic information to st and ard clinicopathologic variables PURPOSE We review our single center experience in the management of renal angiomyolipoma ( AML ) in patients who were treated with active surveillance ( AS ) or invasive treatment protocol s. PATIENTS AND METHODS A prospect ively evaluated data base was review ed , and we identified 91 patients with the diagnosis of renal AML who presented between June 1985 and February 2009 . Patient characteristics , clinical presentation , treatment modalities , and patient outcomes were evaluated . Patients on AS were analyzed for successful completion of the surveillance protocol considering age , symptomatic presentation , and tumor size as potential predictors of invasive treatment . RESULTS A total of 91 patients with AMLs were identified . The mean patient age was 57 years . Seventy-three ( 83.9 % ) patients presented incidentally , and 14 ( 16 % ) patients were symptomatic at presentation . Forty-five patients were treated with AS , 4 underwent embolization , and 38 patients had extirpative surgery . After a median follow-up of 54.8 months ( range 0.2 - 211.7 mos ) , there was a mean growth rate of 0.088 cm/year in the group who were treated with AS . AS failed in three patients . Two patients had retroperitoneal bleeding during the observation period , and one patient manifested an expeditious growth rate of 0.7 cm/year and underwent a radical nephrectomy . CONCLUSIONS AML is a renal tumor that usually exhibits a benign course . Surgical removal and embolization are the st and ard invasive treatment modalities . AS for AMLs is associated with a slow and consistent growth rate ( 0.088 cm/year ) , typically has minimal morbidity , and is a reasonable option in selected patients . Symptomatic presentation and size ( > 3 cm ) are not predictive for necessitating an invasive procedure BACKGROUND Most early stage kidney cancers are renal cell carcinomas ( RCCs ) , and most are diagnosed incidentally by imaging as small renal masses ( SRMs ) . Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize . OBJECTIVE To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and /or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression . INTERVENTION Patients underwent serial imaging and needle core biopsies . MEASUREMENTS We measured rates of change in tumor diameter ( growth measured by imaging ) and progression to ≥ 4 cm , doubling of tumor volume , or metastasis with histology on biopsy . RESULTS AND LIMITATIONS Local progression occurred in 25 patients ( 12 % ) , plus 2 progressed with metastases ( 1.1 % ) . Of the 178 subjects with 209 SRMs , 127 with 151 SRMs had>12 mo of follow-up with two or more images , with a mean follow-up of 28 mo . Their tumor diameters increased by an average of 0.13 cm/yr . Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate . Limitations included no central review of imaging and pathology and a short follow-up . CONCLUSIONS This is the first SRM active surveillance study to correlate growth with histology prospect ively . In the first 2 yr , the rate of local progression to higher stage is low , and metastases are rare . SRMs appear to grow very slowly , even if biopsy proven to be RCC . Many patients with SRMs can therefore be initially managed conservatively with serial imaging , avoiding the morbidity of surgical or ablative treatment Purpose Exploratory subgroup analyses from the phase 3 global advanced renal cell carcinoma ( ARCC ) trial were conducted to assess the influence of tumor histology on outcome of patients treated with temsirolimus ( Torisel ™ ) or interferon-α ( IFN ) . Patients and methods Patients with ARCC including clear cell and other types such as papillary and chromophobe histologies received either IFN ( 3 million units [ MU ] subcutaneously three times weekly , escalating to 18 MU ) or temsirolimus ( 25 mg intravenously weekly ) . Results Approximately 80 % of patients had clear cell and 20 % of patients had other histologies , the majority of which were papillary . Patients with clear cell and other RCC histologies , treated with temsirolimus , demonstrated comparable median overall and progression-free survival . In contrast , patients with other RCC histologies , treated with IFN , demonstrated shorter median overall and progression-free survival than patients with clear cell RCC . Hazard ratios for death for treatment with temsirolimus versus IFN were less than 1 for patients regardless of tumor histology . For patients treated with temsirolimus , 59 % with clear cell and 68 % with other RCC histologies experienced tumor reductions . For patients treated with IFN , 35 % with clear cell and 14 % with other RCC histologies had tumor reductions . However , temsirolimus did not appear to improve the objective response rate compared to IFN . Temsirolimus result ed in a superior clinical benefit rate compared with IFN , regardless of tumor histology . Conclusion Temsirolimus appears to be efficacious in patients with clear cell and non-clear cell histologies and can , therefore , be used for the treatment of all types of RCC PURPOSE We present 5 to 11-year ( median 8) oncological outcomes after laparoscopic renal cryoablation . MATERIAL S AND METHODS Between September 1997 and October 2008 we performed renal cryoablation in 340 patients , of whom 80 treated laparoscopically by a single surgeon before October 2003 had a minimum 5-year followup . Followup involved magnetic resonance imaging on postoperative day 1 , at 3 , 6 and 12 months , and annually thereafter . Cryolesion biopsy was performed at 6 months . All data were prospect ively accrued . RESULTS In the 80 patients with minimum 5-year followup mean age was 66 years , mean tumor size was 2.3 cm ( range 0.9 to 5.0 ) , median American Society of Anesthesiologists score was 3 and mean body mass index was 28 kg/m(2 ) . Five patients had local recurrence , 2 had locoregional recurrence with metastasis and 4 had distant metastasis without locoregional recurrence . Six patients died of cancer . In the 55 patients with biopsy proven renal cell cancer at a median followup of 93 months ( range 60 to 132 ) 5-year overall , disease specific and disease-free survival rates were 84 % , 92 % and 81 % , and 10-year rates were 51 % , 83 % and 78 % , respectively . On multivariate analysis previous radical nephrectomy for RCC was the only significant predictor of disease-free and disease specific survival ( p = 0.023 and 0.030 , respectively ) . CONCLUSIONS Laparoscopic renal cryoablation is effective oncological treatment for a renal mass in select patients . A disease specific survival rate of 92 % at 5 years and 83 % at 10 years is possible . Preceding radical nephrectomy for renal cell carcinoma was the only independent factor predicting disease-free and disease specific survival OBJECTIVES To determine the accuracy and clinical utility of fine needle aspiration ( FNA ) of small , solid renal masses . METHODS A total of 25 patients with small ( less than 5.0 cm ) , solid , clinical ly localized renal masses were prospect ively identified and evaluated with computed tomography guided FNA with analysis for presence of malignant cells and determination of nuclear grade . The final pathologic findings were used for comparison in each case . All patients had renal cell carcinoma and were managed with radical or partial nephrectomy ; 3 had low- grade lesions ( Fuhrman 's grade 1/4 ) , 2 had high- grade lesions ( Fuhrman 's grade 4/4 ) , and all other patients had intermediate- grade lesions ( Fuhrman 's grade 2/4 or 3/4 ) on final histopathologic assessment . RESULTS Overall , 10 aspirations yielded diagnostic malignant cells , and 9 were read as rare as rare atypical cells suspicious for malignancy . The remainder were negative ( n = 6 ) . Correlation with final nuclear grade was observed in eight instances and discordance in two instances . Subcapsular hematomas were observed at the time of surgery in 10 patients , but in no instance was the operation adversely affected . CONCLUSIONS The diagnostic yield of FNA of small , solid renal masses appears to be too low to justify the potential morbidity of the procedure Purpose : The goal of this study was to evaluate immunohistochemical and cytogenetic features and their prognostic value in papillary renal cell carcinoma ( PRCC ) subtypes . Experimental Design : One hundred fifty-eight cases of PRCC were identified and reclassified by subtype . Tumoral expression of 29 molecular markers was determined by immunohistochemistry . Cytogenetic analyses were done on a prospect i ve series of 65 patients . Associations with clinicopathologic information and disease-specific survival were assessed . Results : Fifty-one patients ( 32 % ) had type 1 and 107 ( 68 % ) type 2 PRCC . Type 2 patients had worse Eastern Cooperative Oncology Group performance status , higher T stages , nodal and distant metastases , higher grade s , and a higher frequency of necrosis , collecting system invasion and sarcomatoid features . Type 2 showed greater expression of vascular endothelial growth factor (VEGF)-R2 in the tumor epithelium , and of VEGF-R3 in both tumor epithelium and endothelium . Loss of chromosome 1p , loss of 3p , and gain of 5q were exclusively observed in type 2 , whereas type 1 more frequently had trisomy 17 . Type 2 PRCC was associated with worse survival than type 1 , but type was not retained as an independent prognostic factor . Lower PTEN , lower EpCAM , lower gelsolin , higher CAIX , and higher VEGF-R2 and VEGF-R3 expression , loss of 1p , 3p , or 9p , and absence trisomy 17 were all associated with poorer prognosis . Conclusions : Type 2 PRCC is associated with more aggressive clinicopathologic features and worse outcome . Molecular and chromosomal alterations can distinguish between PRCC subtypes and influence their prognosis . The effect of 3p loss on survival in PRCC is opposite to the relationship seen in clear cell RCC Purpose In some cases with uncertain renal tumour lesions , it would be helpful to perform biopsies for the preoperative differential diagnosis . In our study , we evaluated the benefit of multi-colour interphase fluorescence in situ hybridization ( M-FISH ) on fine-needle core biopsies in uncertain renal masses . Methods We prospect ively performed three ultrasound-guided percutaneous biopsies in 25 patients with indeterminate renal masses preoperatively . Histopathology was performed on two remaining cores sample s. M-FISH was performed on one core for chromosomes 1 , 2 , 6 , 9 , 7 , 17 , the loci 3p24pter , and 3p13p14 . After interphase FISH evaluation , we classified tumours and compared the results with histopathological findings . Results 16 were classified as renal malignancies : 14 ( 56 % ) clear cell renal cell carcinomas ( RCCs ) , 1 papillary RCCs ( 4 % ) , and 1 “ adenocarcinoma ” ( 4 % ) . Seven patients ( 28 % ) had a benign tumour , i.e. 6 ( 24 % ) were oncocytomas and 1 was classified as leiomyoma ( 4 % ) . In two cases ( 8 % ) , no renal neoplasms were found . In 19 out of 21 cases ( 90.5 % ) , the preoperative diagnostic fine-needle biopsy matched the final histological findings . The combination of histopathological examination and M-FISH leads to a higher ( 95.5 vs. 90.5 % ) diagnostic fidelity as histology alone . Conclusions Ultrasound-guided percutaneous renal tumour biopsy is an accurate and safety method for the histopathologic evaluation of uncertain renal masses . The M-FISH represents a new highly sensitive and specific method to confirm histopathological classification in less than 24 h which can be used in routine laboratory diagnosis PURPOSE We examined the growth of tissue proven renal oncocytoma on serial imaging to improve our underst and ing of its natural history . MATERIAL S AND METHODS We review ed the charts of 69 patients with oncocytoma diagnosed by biopsy or surgery between 2004 and 2010 . A total of 29 cases were managed by active surveillance for at least 12 months and had 3 or more imaging events . Tumor size was documented and the average tumor growth rate was calculated using a r and om coefficient model . Interaction terms were used to investigate correlations between variables of interest , including age at diagnosis , gender , symptom status , laterality , initial tumor size , surveillance duration and number of imaging events . RESULTS At a mean surveillance duration of 40 months 80 % of oncocytomas increased in size . Based on the r and om coefficient model the estimated average growth rate was 0.16 mm monthly ( 95 % CI 0.097 - 0.228 , p < 0.0001 ) . We identified no variables that significantly correlated with growth . CONCLUSIONS Despite its low metastatic potential renal oncocytoma appears to progress locally with a growth rate similar to that of RCC . Thus , absent tumor growth on serial imaging is not a robust prognostic factor for benign histology . Biopsy remains the mainstay of diagnosis . At centers where it can be performed safely and accurately , active surveillance of tissue proven oncocytoma appears to be safe in the short term . Alternative management includes partial nephrectomy and minimally invasive approaches . To our knowledge this is the largest study of oncocytoma natural history OBJECTIVE Modern imaging modalities increase the detection of small ( < or=4 cm ) renal tumors , of which about 20 % are benign . As a result , minimal invasive treatments , such as radiofrequency ablation and cryotherapy , and surveillance strategies are gaining popularity . Information that would be helpful when choosing the most appropriate management strategy for this patient group could be obtained from pretherapeutic image-guided biopsy . METHODS Under computed tomography (CT)-fluoroscopic guidance 78 patients with solid renal tumors prospect ively underwent 18-gauge core biopsy . In addition , using the same sheath , fine-needle aspiration was taken in 44 patients and analyzed cytologically . The renal masses were subsequently removed surgically and evaluated histologically . RESULTS Mean patient age was 63+/-13.5 yr ; mean tumor size was 4+/-1.8 cm . The sensitivity of core biopsy and fine-needle aspiration for the detection of renal cell carcinoma ( RCC ) was 93.5 % and 90.6 % , respectively ; Fuhrman grade was correctly predicted in 76 % and 28 % and the correct histologic subtype was identified 91 % and 86 % , respectively . Cytology from fine-needle aspiration revealed a sensitivity in detecting malignant and benign lesions of 100 % and 75 % , respectively . Two of the renal tumors diagnosed as oncocytomas on core biopsy were hybrid tumors with scattered areas of oncocytomas and chromophobe RCC . Complications of CT-guided biopsy included one marginal pneumothorax , which resolved under conservative management , and four small perirenal hematomas detected at follow-up ultrasonography not requiring further therapy . CONCLUSION CT-guided percutaneous preoperative renal tumor biopsy had a high diagnostic accuracy , particularly in predicting malignancy PURPOSE We prospect ively determined the accuracy of computerized tomography ( CT ) and needle biopsy of solid renal masses . MATERIAL S AND METHODS A total of 100 patients with a solid renal mass who were scheduled for operation were prospect ively evaluated . CT was performed before radical or partial nephrectomy . Biopsy of the surgical specimens was done twice through the tumor using an 18 gauge biopsy gun . Specimens were sent for permanent section and review by 2 pathologists blinded to each other and to the whole tissue specimens . Images were review ed by 2 radiologists blinded to each other and to the results of pathological analysis . Results of CT and permanent biopsy were compared with the results of whole tissue specimen analysis . RESULTS Specimens were obtained from 59 radical and 41 partial nephrectomies . Malignant neoplasms were present in 85 patients ( 85 % ) . Overall accuracy was 77 % and 72 % , the nondiagnostic rate was 20 % and 21 % , sensitivity was 81 % and 83 % , and specificity was 60 % and 33 % . For the 2 radiologists overall accuracy was 60 % and 66 % , the nondiagnostic rate was 31 % and 23 % , sensitivity was 70 % and 77 % , and specificity was 20 % and 20 % , respectively . CONCLUSIONS Overall permanent biopsy results were accurate in more than 72 % of cases and CT was accurate in more than 60 % . However , because the nondiagnostic rate for CT and needle biopsy was 20 % and 31 % , respectively , and specificity was low , we do not recommend routine preoperative CT and subsequent needle biopsy to guide treatment decision making . Rather , cases must be decided individually BACKGROUND Percutaneous needle core biopsy has become established in the management of small renal masses ≤ 4 cm ( SRMs ) . Recent series have reported success rates of ≥ 80 % . Nondiagnostic results continue to be problematic . OBJECTIVE To determine the results of SRM biopsy and the outcomes of nondiagnostic biopsy and repeat biopsy . DESIGN , SETTING , AND PARTICIPANTS Patients undergoing renal tumor biopsy ( RTB ) for suspected renal cell carcinoma ( RCC ) were included in a prospect ively maintained data base . MEASUREMENTS The data base was analyzed retrospectively to determine the pathology and outcomes of SRM biopsy . Outcomes of patients with nondiagnostic biopsy were determined . Patients undergoing repeat biopsy were identified and their outcomes analyzed . RESULTS AND LIMITATIONS Three hundred forty-five biopsies were performed ( mean diameter : 2.5 cm ) . Biopsy was diagnostic in 278 cases ( 80.6 % ) and nondiagnostic in 67 cases ( 19.4 % ) . Among diagnostic biopsies , 221 ( 79.4 % ) were malignant , 94.1 % of which were RCC . Histologic subtyping and grading of RCC was possible in 88.0 % and 63.5 % of cases , respectively . Repeat biopsy was performed in 12 of the 67 nondiagnostic cases , and a diagnosis was possible in 10 ( 83.3 % ) . Eight lesions were malignant and two were oncocytic neoplasms . Pathology was available for 15 masses after initial nondiagnostic biopsy ; 11 ( 73 % ) were malignant . Larger tumor size and a solid nature on imaging predicted a successful biopsy on multivariate analysis . Grade 1 complications were experienced in 10.1 % of cases , with no major bleeding and no seeding of the biopsy tract . There was one grade 3a complication ( 0.3 % ) . This is a retrospective study and some data are unavailable on factors that may affect biopsy success rates . Repeat biopsy was not st and ard practice prior to this analysis . CONCLUSIONS RTB can be performed safely and accurately in the investigation of renal masses ≤ 4 cm . A nondiagnostic biopsy should not be considered a surrogate for the absence of malignancy . Repeat biopsy can be performed with similar accuracy , providing a diagnosis for most patients BACKGROUND The association between tumor complexity and postoperative complications after partial nephrectomy ( PN ) has not been well characterized . OBJECTIVE We evaluated whether increasing renal tumor complexity , quantitated by nephrometry score ( NS ) , is associated with increased complication rates following PN using the Clavien-Dindo classification system ( CCS ) . DESIGN , SETTING , AND PARTICIPANTS We queried our prospect ively maintained kidney cancer data base for patients undergoing PN from 2007 to 2010 for whom NS was available . INTERVENTIONS All patients underwent PN . MEASUREMENTS Tumors were categorized into low- ( NS : 4 - 6 ) , moderate- ( NS : 7 - 9 ) , and high-complexity ( NS : 10 - 12 ) lesions . Complication rates within 30 d were grade d ( CCS : I-5 ) , stratified as minor ( CCS : I or 2 ) or major ( CCS : 3 - 5 ) , and compared between groups . RESULTS AND LIMITATIONS A total of 390 patients ( mean age : 58.0 ± 11.9 yr ; 66.9 % male ) undergoing PN ( 44.6 % open , 55.4 % robotic ) for low- ( 28 % ) , moderate- ( 55.6 % ) , and high-complexity ( 16.4 % ) tumors ( mean tumor size : 3.74 ± 2.4 cm ; median : 3.2 cm ) from 2007 to 2010 were identified . Tumor size , estimated blood loss , and ischemia time all significantly differed ( p<0.0001 ) between groups ; patient age , body mass index ( BMI ) , and operative time were comparable . When stratified by CCS , minor and major complication rates for all patients were 26.7 % and 11.5 % , respectively . Minor complication rates were comparable ( 26.6 vs. 24.9 vs 32.8 % ; p=0.45 ) , whereas major complication rates differed ( 6.4 vs. 11.1 vs. 21.9 % ; p=0.009 ) among tumor complexity groups . Controlling for age , gender , BMI , type of surgical approach , operative duration , and tumor complexity , prolonged operative time ( odds ratio [ OR ] : 1.01 ; confidence interval [ CI ] , 1.0 - 1.02 ) and high tumor complexity ( OR : 5.4 ; CI , 1.2 - 24.2 ) were associated with the postoperative development of a major complication . Lack of external validation is a limitation of this study . CONCLUSIONS Increasing tumor complexity is associated with the development of major complications after PN . This association should be vali date d externally and integrated into the decision-making process when counseling patients with complex renal tumors PURPOSE Followup after radio frequency ablation and cryotherapy for small renal lesions lacks pathological analysis . The definition of successful tumor ablation has been the absence of contrast enhancement on posttreatment magnetic resonance imaging or computerized tomography . We hypothesized that adding post-ablation kidney biopsy would help confirm treatment success . MATERIAL S AND METHODS From April 2002 to March 2006 a total of 109 renal lesions in 88 patients were ablated with percutaneous radio frequency ablation and from September 1997 to January 2006 a total of 192 lesions in 176 patients were treated with laparoscopic cryoablation . Patients were followed with radiographic imaging and post-ablation biopsy at 6 months . RESULTS Radiographic success at 6 months was 85 % ( 62 cases ) and 90 % ( 125 ) for radio frequency ablation and cryoablation , respectively . At 6 months 134 lesions ( 45 % ) were biopsied and success in the radio frequency ablation cohort decreased to 64.8 % ( 24 cases ) , while cryoablation success remained high at 93.8 % ( 91 ) . Six of 13 patients ( 46.2 % ) with a 6-month positive biopsy after radio frequency ablation demonstrated no enhancement on posttreatment magnetic resonance imaging or computerized tomography . In patients treated with cryoablation all positive biopsies revealed posttreatment enhancement on imaging just before biopsy . CONCLUSIONS We observed a poor correlation between radiographic imaging and pathological analysis . We recommend post-radio frequency ablation followup biopsy due to the significant risk of residual renal cell cancer without radiographic evidence , although to our knowledge the clinical significance of these viable cells remains to be determined . In contrast , radiographic images of renal lesions treated with cryotherapy appeared to correlate adequately with corresponding histopathological findings in our series CONTEXT AND OBJECTIVES The European Association of Urology Guideline Group for renal cell carcinoma ( RCC ) has prepared these guidelines to help clinicians assess the current evidence -based management of RCC and to incorporate the present recommendations into daily clinical practice . EVIDENCE ACQUISITION The recommendations provided in the current up date d guidelines are based on a thorough review of available RCC guidelines and review articles combined with a systematic literature search using Medline and the Cochrane Central Register of Controlled Trials . EVIDENCE SYNTHESIS A number of recent prospect i ve r and omised studies concerning RCC are now available with a high level of evidence , whereas earlier publications were based on retrospective analyses , including some larger multicentre validation studies , meta-analyses , and well- design ed controlled studies . CONCLUSIONS These guidelines contain information for the treatment of an individual patient according to a current st and ardised general approach . Up date d recommendations concerning diagnosis , treatment , and follow-up can improve the clinical h and ling of patients with RCC |
11,920 | 24,633,164 | An instrument that globally assesses the cervix , such as computer-assisted colposcopy , optical spectroscopy , and dynamic spectral imaging , would provided the most comprehensive estimate of disease and is therefore best suited when treatment is preferred .
Electrical impedance spectroscopy , confocal microscopy , and optical coherence tomography provide information at the cellular level to estimate histology and are therefore best suited when deferment of treatment is preferred .
If a device is to eventually replace the colposcope , it will likely combine technologies to best meet the needs of the target population , and as such , no single instrument may prove to be universally appropriate . | OBJECTIVE To describe novel innovations and techniques for the detection of high- grade dysplasia . | BACKGROUND AND OBJECTIVES Optical coherence tomography ( OCT ) permits high-resolution imaging of tissue subsurfaces up to 2 mm in depth . The purpose of this study was to evaluate the accuracy and reproducibility of OCT in the characterization of cervical intraepithelial neoplasia ( CIN ) and to distinguish between different CIN grade s. STUDY DESIGN / MATERIAL S AND METHODS Colposcopy-guided OCT images were taken from unsuspicious and suspicious areas in women with suspected CIN . Each woman then underwent directed biopsies . All OCT images were separately evaluated by two blinded investigators and later compared to the corresponding histology based on a 6- grade classification ( normal , inflammation , CIN 1 , CIN 2 , CIN 3 , squamous carcinoma ) . Sensitivity and specificity of OCT in detecting CIN were determined . To assess the interobserver agreement , kappa coefficients were calculated from the ratings of each investigator for each OCT image seen . RESULTS A total of 210 OCT images were compared with the corresponding histology in 120 women undergoing colposcopy for suspected CIN . Sensitivity calculated for both investigators was 98 % and 96 % respectively with the threshold at CIN1 and 86 % and 84 % respectively with the threshold at CIN2 . Thirty nine ( 38 ) false positive results reduced the specificity to 39 % and 41 % respectively with the threshold at CIN1 . Defining the threshold at CIN2 the specificity increased to 64 % and 60 % respectively . Unweighted kappa from a dichotomous classification with the threshold at CIN1 was 0.69 ( 95 % CI , 0.54 - 0.84 ) and 0.62 ( 95 % CI , 0.51 - 0.73 ) with the threshold at CIN2 . CONCLUSION OCT is highly sensitive in identifying pre-invasive and invasive cancer of the uterine cervix . Improvements in resolution and the development of new light sources and optics may improve the specificity as well as the differentiation of cervical dysplasia . The interobserver agreement was substantial OBJECTIVE To assess whether the use of a novel optical detection system ( ODS ) as an adjunct to colposcopy increases the detection of biopsy-confirmed CIN 2,3 . METHODS This is a multicenter two-arm r and omized trial comparing colposcopy alone with colposcopy plus a pre-commercial ODS system that utilizes fluorescence , white light tissue reflectance , and cervical video imaging . Patients were recruited from 13 colposcopy clinics in a variety of practice setting s. 2299 women referred for the evaluation of an abnormal cervical cytology were r and omized with stratification by cytology ; subsequently 113 women were excluded for a variety of reasons . The main study outcomes were differences in true-positive rates ( CIN 2,3 and cancer identified ) and false-positive rates between the study arms . RESULTS The true-positive ( TP ) rates were 14.4 % vs. 11.4 % ( p=0.035 , one-sided ) for the combined colposcopy and ODS arm compared to colposcopy-only arm , respectively , in women with either an atypical squamous cell ( ASC ) or low- grade squamous intraepithelial lesion ( LSIL ) cytology result . TP rates were similar between the two arms among women referred for the evaluation of HSIL . The 26.5 % gain in true-positives observed with the use of ODS and colposcopy among women referred for an ASC or LSIL cytology was achieved with only a fractional increase in number of biopsies obtained per patient ( 0.30 ) and a modest increase in false-positive rate ( 4 % ) . In the combined colposcopy and ODS arm among women with ASC or LSIL , the PPV of biopsies indicated by ODS was 15.0 % and the PPV of biopsies indicated by colposcopy was 15.2 % . Joint hypothesis testing indicates that ODS and colposcopy provides benefit compared to colposcopy alone among women with ASC or LSIL . CONCLUSIONS Combining ODS with colposcopy provides a clinical ly meaningful increase in the detection of CIN 2,3 in women referred for the evaluation of mildly abnormal cytology results Objective : Our aim was to present our initial clinical experience using a novel exoscopically based colposcopy system ( VITOM ) for the evaluation of cervical , vulvar , and vaginal diseases . Material s and Methods : Women referred to the Charite Cervix Center , Charite University , Berlin , Germany , were included . Patients with abnormal Pap smear results , vulvar lesions , or a biopsy report of neoplasia of the lower genital tract were included into the study . The VITOM was used for colposcopic evaluation and directed biopsies . Colposcopic findings were reported according to the criteria of the Committee on Nomenclature of the International Federation of Cervical Pathology and Colposcopy . Histologic diagnosis was described as normal , low- grade lesion , high- grade lesion ( including cervical intraepithelial neoplasia 2,3 , vulvar intraepithelial neoplasia 2,3 , vaginal intraepithelial neoplasia 2,3 ) , or cancer . Results : We recruited 76 patients ( 54 with cervical , 4 with vaginal , and 18 with vulvar disease ) to the prospect i ve study . Four patients were pregnant . Of patients with cervical disease , 29 % had a history of previous conization and 3.7 % had a history of trachelectomy . The sensitivity , specificity , negative predictive value , and positive predictive value of the VITOM for cervical intraepithelial neoplasia 2 , 3 were 90 % , 77 % , 90 % and 77 % , respectively . Concordance of exocolposcopic impressions and histologic results was higher in high- grade lesions ( K = 0.68 , 95 % CI = 0.32 - 0.87 , p < .001 ) than in low- grade lesions ( K = 0.41 , 95 % CI = 0.1 - 0.41 , p < .05 ) . Conclusions : Exocolposcopy with the VITOM is accurate and shows good correlation to histologic findings in high- grade disease of the lower genital tract . The potential advantages include patient and trainee involvement in examination , decision making , and documentation Cervical intraepithelial neoplasia 3 ( CIN3 ) is the precursor of mostsquamous carcinomas and serves as a surrogate end point . However , small CIN3 lesions are rarely associated with concurrent invasion . We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance ( ASCUS ) or low- grade squamous intraepithelial lesion ( LSIL ) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer . We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study , focusing on ASCUS referrals . ASCUS referrals underwent r and omized management [ colposcopy for repeat cytology of high- grade squamous intraepithelial lesion ( HSIL ) , colposcopy for oncogenic human papillomavirus ( HPV ) detection or repeat HSIL , or immediate colposcopy ] ; then all were followed with repeat cytology for 2 years , followed by colposcopy and aggressive treatment . We assessed all CIN3 lesions qualitatively and measured 39 of them . CIN3 lesions were overwhelmingly small . Compared with enrollment , lesions found at follow-up or exit involved fewer tissue fragments ( P < 0.01 ) and showed less diffuse gl and involvement ( P = 0.03 ) . CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [ versus immediate colposcopy ( P = 0.04 ) or repeat cytology of HSIL ( P = 0.02 ) ] , and none showed diffuse gl and involvement . The median distal-proximal length was 6.5 mm ( median replacement of total epithelium = 5 % ) in the 39 measured cases . We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion , particularly if managed using HPV testing , suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened population The objective of this study was to assess the performance of cervical impedance spectroscopy in the detection of cervical intraepithelial neoplasia ( CIN ) using the new MKIII impedance probe . A prospect i ve observational study recruited women referred to colposcopy with an abnormal Papanicolaou smear . A pencil probe incorporating four gold electrodes was used to measure electrical impedance spectra from cervical epithelium . Colposcopy examinations , including probe positioning , were video recorded to allow for correlation between results obtained from colposcopic impression , histopathologic examination of colposcopic punch biopsies , and impedance measurements . Cervical impedance – derived parameters R , S , R/S , C , and Fc were assessed to see if significant difference in values obtained in CIN and normal epithelium existed . The performance of the probe in identifying women with CIN was also assessed . One hundred seventy-six women were recruited and 1168 points analyzed . Parameters R , S , and Fc showed significant separation of CIN or squamous intraepithelial lesion ( SIL ) from squamous , mature metaplastic , and columnar epithelium . Sensitivities of 74 % and specificity of 53 % can be achieved in identifying CIN 2/3 ( High- grade SIL ) in screened women . We conclude that cervical impedance spectrometry provides a potentially promising real-time screening tool for CIN with similar sensitivity and specificity to currently used screening tests . Further research is ongoing to develop the probe for potential clinical use OBJECTIVE To evaluate the efficacy of an electrical impedance probe ( Epitheliometer ) in the diagnosis of high grade cervical intraepithelial neoplasia ( CIN ) in women referred with cervical smear abnormalities and to assess the effect of acetic acid ( AA ) and tissue boundaries on the measurements . METHODS A prospect i ve observational study was undertaken in the colposcopy clinic . One hundred and sixty-five women , either with a clinical indication or abnormal cervical cytology , were recruited into the study . A pencil type probe was used to record impedance spectra from 12 points on the cervix before and after the application of 5 % AA . Spectra were also recorded from tissue boundaries . Colposcopic examinations , including probe positioning , were video recorded to allow for correlations between histopathological diagnosis of colposcopically directed biopsies , colposcopic impression and the diagnosis based on impedance measurements . RESULTS Receiver operating characteristic ( ROC ) curves were derived . The areas under the curves ( AUCs ) to discriminate original squamous from high grade CIN were 0.80 ( pre AA ) and 0.79 ( post AA ) . Comparison of these curves showed no significant difference , indicating that application of AA does not produce a large change in spectra . The probe could distinguish tissue boundaries from homogeneous tissue points . CONCLUSION The Epitheliometer has the potential to be used as an adjunct to colposcopy in the diagnosis of high grade CIN . It has the advantage of real time results , decreasing the need for diagnostic cervical biopsies , and facilitates a wider use of the ' see and treat ' policy without the risk of overtreatment Fluorescence spectroscopy has shown promise for the in vivo , real-time detection of cervical neoplasia . However , selection of excitation wavelength has in the past been based on in vitro studies and the availability of light sources . The goal of this study was to determine optimal excitation wavelengths for in vivo detection of cervical neoplasia . Fluorescence excitation-emission matrices ( EEMs ) were measured in vivo from 351 sites in 146 patients . Data were analyzed in pairs of diagnostic classes to determine which combination of excitation wavelengths yields classification algorithms with the greatest sensitivity and specificity . We find that 330 - 340- , 350 - 380- , and 400 - 450-nm excitation yield the best performance . The sensitivity and specificity for discrimination of squamous normal tissue and high- grade squamous intraepithelial lesion ( HGSIL ) were 71 % and 77 % on cross validation using three excitation wavelengths . These results are comparable with those found in earlier in vivo studies ; however , in this study we find that the proportion of sample s which are HGSIL influences performance . Furthermore stratification of sample s within low- grade squamous intraepithelial lesion and HGSIL also appears to influence diagnostic performance . Future diagnostic studies should be carried out at these excitation wavelengths in larger groups so that data can be stratified by diagnostic subcategory , age and menopausal status . Similarly , large studies should be done in screening population Large phase II trials of fluorescence and reflectance spectroscopy using a fiber optic probe in the screening and diagnostic setting s for detecting cervical neoplasia have been conducted . We present accrual and histopathology data , instrumentation , data processing , and the preliminary results of interdevice consistencies throughout the progression of a trial . Patients were recruited for either a screening trial ( no history of abnormal Papanicolaou smears ) or a diagnostic trial ( a history of abnormal Papanicolaou smears ) . Colposcopy identified normal and abnormal squamous , columnar , and transformation zone areas that were subsequently measured with the fiber probe and biopsied . In the course of the clinical trial , two generations of spectrometers ( FastEEM2 and FastEEM3 ) were design ed and utilized as optical instrumentation for in vivo spectroscopic fluorescence and reflectance measurements . Data processing of fluorescence and reflectance data is explained in detail and a preliminary analysis of the variability across each device and probe combination is explored . One thous and patients were recruited in the screening trial and 850 patients were recruited in the diagnostic trial . Three clinical sites attracted a diverse range of patients of different ages , ethnicities , and menopausal status . The fully processed results clearly show that consistencies exist across all device and probe combinations throughout the diagnostic trial . Based on the stratification of the data , the results also show identifiable differences in mean intensity between normal and high- grade tissue diagnosis , pre- and postmenopausal status , and squamous and columnar tissue type . The mean intensity values of stratified data show consistent separation across each of the device and probe combinations . By analyzing trial spectra , we provide more evidence that biographical variables such as menopausal status as well as tissue type and diagnosis significantly affect the data . Underst and ing these effects will lead to better modeling parameters when analyzing the performance of fluorescence and reflectance spectroscopy Objective . The objective of the study was to evaluate the potential safety and effectiveness of tissue spectroscopy for the diagnosis of cervical cancer in a prospect i ve multicenter study of women scheduled for colposcopy on the basis of an abnormal Pap test or other risk factor . Material s and Methods . Five hundred seventy-two women underwent spectroscopy of the cervix during their colposcopy visit . Spectroscopy measurements taken over a scan period of 4 minutes and 30 seconds were integrated by a cross-vali date d pattern recognition model and compared with biopsy results to yield sensitivity and specificity of cervical spectroscopy . Results . The median age of subjects enrolled in the study was 27.7 years . The sensitivity of cervical spectroscopy was 95.1 % with a corresponding 55.2 % specificity for benign lesions . Several potential confounding factors ( eg , mucous , blood , patient motion , ambient light ) were examined to determine their potential impact on the accuracy of the test . Ambient light seemed to have the greatest effect , but no single factor contributed significantly to the results . The subjects did not experience any adverse events from undergoing the test . Conclusions . Spectroscopy of the cervix has the potential to accurately detect cervical moderate and high- grade dysplasia while also reducing the false-positive rate for benign cervices . The test is relatively simple to implement and was well accepted by subjects enrolled in the study A new colposcopic sign ( sharpness of peripheral margins ) was grade d into three objective categories representing sub clinical papillomaviral infection , lower grade dysplasia , and grade 3 cervical intraepithelial neoplasia . Colposcopic features were prospect ively recorded in 72 women and then correlated with histologic findings . Histologic diagnoses were evenly spread within the disease spectrum : 18 patients had sub clinical papillomaviral infection without associated dysplasia ; 15 had grade 1 , 16 had grade 2 , and 23 had grade 3 cervical intraepithelial neoplasia with or without koilocytotic atypia . Differences in the pattern of the peripheral margin were discriminatory throughout the entire diagnostic range . Predictive accuracy of this new colposcopic sign ( 79 % ) compared favorably with that of color ( 72 % ) , vascular atypia ( 81 % ) , and iodine staining ( 72 % ) . Each criterion was independent of the other three . Hence , combining these four individual signs into a colposcopic index was 97 % correct in forecasting approximate histologic findings . Because formulation of the colposcopic index is based on critical analysis rather than pattern recall , the use of this method will greatly simplify the otherwise arduous task of learning colposcopy Objectives : To determine the sensitivity and specificity of optical coherence tomography ( OCT ) as an adjunct to unaided visual inspection using acetic acid ( VIA ) in the detection of cervical intraepithelial neoplasia 2 ( CIN 2 ) in a real-time clinical evaluation . Background : This clinical study was a prospect i ve cross-sectional comparative trial that screened 1000 patients ( aged 30 - 50 years ) in a low-re source setting . Women with abnormal cervical cytology or positive human papillomavirus ( HPV ) tests were referred for further evaluation including VIA , OCT imaging , colposcopy , and cervical biopsies . Methods : The VIA diagnoses were coded by quadrant . The OCT was then performed in all VIA-positive areas and at the squamocolumnar junction in all 4 quadrants . All patients were colposcoped ; assessed by quadrant with biopsies at 2 , 4 , 8 , and 10 o'clock ; all abnormal areas were biopsied ; and endocervical curettage was performed . Data were analyzed using generalized estimating equations and logistic regression . Results : Of the 1000 patients , 175 ( 17.5 % ) were HPV positive , 93 ( 9.3 % ) had abnormal cervical cytology greater than or equal to atypical squamous cells of undetermined significance , and 211 ( 21.1 % ) were either HPV positive or had abnormal cytology . The VIA , OCT , colposcopy , and biopsies were completed on 183 ( 86.7 % ) of 211 women . For VIA alone , the sensitivity and specificity in detecting lesions greater than or equal to CIN 2 was 43 % and 96 % . With the addition of OCT , the sensitivity increases to 62 % with a specificity of 80 % . Conclusions : With the addition of OCT , the sensitivity of VIA increased in all analyses for the detection of greater than or equal to CIN II , with a loss in specificity . We hope that the potential of this technology will be realized when a computer algorithm is generated to aid in image interpretation A portable fluorimeter was developed and utilized to acquire fluorescence spectra from 381 cervical sites in 95 patients at 337 , 380 and 460 nm excitation immediately prior to colposcopy . A multivariate statistical algorithm was used to extract clinical ly useful information from tissue spectra acquired in vivo . Two full-parameter algorithms were developed using tissue fluorescence emission spectra at all three excitation wavelengths ( 161 excitation-emission wavelength pairs ) for cervical precancer ( squamous intraepithelial lesion [ SIL ] ) detection : a screening algorithm that discriminates between SIL and non-SIL with a sensitivity of 82 + /- 1.4 % and specificity of 68 + /- 0.0 % , and a diagnostic algorithm that differentiates high- grade SIL from non-high- grade SIL with a sensitivity and specificity of 79 + /- 2 % and 78 + /- 6 % , respectively . Multivariate statistical analysis was also employed to reduce the number of fluorescence excitation-emission wavelength pairs needed to redevelop algorithms that demonstrate a minimum decrease in classification accuracy . Two reduced-parameter algorithms that employ fluorescence intensities at only 15 excitation-emission wavelength pairs were developed : the screening algorithm differentiates SIL from non-SIL with a sensitivity of 84 + /- 1.5 % and specificity of 65 + /- 2 % and the diagnostic algorithm discriminates high- grade SIL from non-high- grade SIL with a sensitivity and specificity of 78 + /- 0.7 % and 74 + /- 2 % , respectively . Both the full-parameter and reduced-parameter screening algorithms discriminate between SIL and non-SIL with a similar specificity ( + /-5 % ) and a substantially improved sensitivity relative to Pap smear screening . A comparison of the full-parameter and reduced-parameter diagnostic algorithms to colposcopy in expert h and s indicates that all three have a very similar sensitivity and specificity for differentiating high- grade SIL from non-high- grade SIL Objective : Determine the sensitivity and specificity of optical coherence tomography ( OCT ) as an adjunct to colposcopy in the detection of cervical intraepithelial neoplasia ( CIN ) grade 2 or higher in a real-time clinical evaluation . Background : Optical coherence tomography ( OCT ) uses infrared light similar to ultrasound pulse-echo imaging . Image resolution is optimal in the 1-to-3-mm range . This study is the third in our series of OCT investigations and our first real-time clinical trial . The study was conducted at the Peking University Shenzhen Hospital , Shenzhen , China . Methods : Nonpregnant women 18 years or older with abnormal cervical cytologic findings or a positive high-risk human papillomavirus test result were recruited . Women were assessed ; and diagnoses , recorded by cervical quadrant first with colposcopy , followed by colposcopic directed OCT . A biopsy of the abnormal areas was performed . In normal quadrants , biopsy specimens were obtained at the 2- , 4- , 8- , and 10-o'clock positions at the squamocolumnar junction depending on the quadrant . An endocervical curettage was also done . Individual OCT diagnoses were paired with colposcopic impressions and biopsy specimens to assess its role as a paired secondary screen . Data were analyzed using generalized estimating equations to control for correlation within a woman . Results : One thous and two hundred thirty-seven paired diagnoses from 299 women were analyzed . Median age was 36 years . Ninety-six women ( 8 % ) had a diagnosis of CIN 2 or higher . Evaluation by quadrant showed that the sensitivity for CIN 2 or higher decreased by adding OCT to colposcopy , but the specificity increased from 83 % to 93 % . Conclusions : We continue to try to improve sensitivity by improving the near-infrared light source , decreasing the scan time to 8 frames per second , and using a larger diameter ( 5 mm ) fiberoptic probe with a newly design ed application specific probe sheath OBJECTIVES The purpose of this study was to determine the relative importance of colposcopically directed biopsy , r and om biopsy , and endocervical curettage ( ECC ) in diagnosing > or = cervical intraepithelial neoplasia ( CIN ) II . Study design During a screening study , 364 women with satisfactory colposcopy and > or = CIN II were diagnosed . All colposcopically detected lesions were biopsied . If colposcopy showed no lesion in a cervical quadrant , a r and om biopsy was obtained at the squamocolumnar junction in that quadrant . ECC was then performed . RESULTS The diagnosis of > or = CIN II was made on a colposcopically directed biopsy in 57.1 % , r and om biopsy in 37.4 % , and ECC in 5.5 % of women . The yield of > or = CIN II for r and om biopsy when cytology was high grade ( 17.6 % ) exceeded that when cytology was low grade ( 2.8 % ) . One of 20 women diagnosed solely by ECC had invasive cancer . CONCLUSION Even when colposcopy is satisfactory , ECC should be performed . If cytology is high grade , r and om biopsies should be considered OBJECTIVE Optical coherence tomography ( OCT ) is a non-invasive high-resolution imaging technique that permits characterization of microarchitectural features of tissue up to 2 mm in depth in real time . The purpose of this study was to evaluate the feasibility of OCT for the identification of precancerous ( cervical intraepithelial neoplasia ( CIN ) ) and cancerous lesions of the uterine cervix . METHODS We conducted a prospect i ve study on the use of OCT in women with suspected CIN . OCT images were obtained on colposcopy from non-suspicious and suspicious areas , and were evaluated independently by two investigators and later compared with the corresponding histology . The sensitivity , specificity , negative and positive predictive values and accuracy of the new technique in identifying CIN or carcinoma were calculated . RESULTS Of a total of 610 OCT images , 97 from suspicious areas in 60 women were compared with the corresponding histology . Sixty-three of 67 CIN lesions and four invasive carcinomas were diagnosed correctly on evaluation of the OCT images by the first observer . There were 69 true-positive , 11 true-negative , 13 false-positive and four false-negative results , giving a sensitivity of 95 % and a specificity of 46 % . CONCLUSION OCT is a rapid , easy-to-use modality that provides real-time , microarchitectural information of the cervical epithelium . Further refinement of this technology will lead to OCT systems with a significantly higher resolution and may result in better differentiation of cancerous and precancerous lesions OBJECTIVE The purpose of this study was to assess the in vivo optical detection of high- grade cervical intraepithelial neoplasia ( 2/3 + ) on the whole cervix with a noncontact , spectroscopic device . STUDY DESIGN Cervical scanning devices collected intrinsic fluorescence and broadb and white light spectra and video images from 604 women during routine colposcopy examinations at 6 clinical centers . A statistically significant data set was developed of intrinsic fluorescence and white light-induced cervical tissue spectra that was correlated to expert histopathologic determination . On the basis of a retrospective analysis of the acquired data , a classification algorithm was developed , vali date d , and optimized . RESULTS Intrinsic fluorescence , backscattered white light , and video imaging each contribute complementary information to diagnostic algorithms for high- grade cervical neoplasia . More than 10000 measurements that were made on colposcopically identified tissue from > 500 subjects were the basis for algorithm training and testing . Algorithm performance demonstrated a sensitivity of approximately 90 % . This performance was confirmed by various training methods . With the use of a multivariate classification algorithm , optical detection is predicted to detect 33 % more high- grade cervical intraepithelial neoplasia ( 2/3 + ) than colposcopy alone . CONCLUSION Full cervix optical interrogation for the detection of high- grade cervical intraepithelial neoplasia is feasible and appears capable of detecting more high- grade cervical intraepithelial neoplasia than colposcopy alone . With the use of this classification algorithm , a multisite , r and omized controlled trial is underway that compares the combination of optical detection and colposcopy versus colposcopy alone OBJECTIVE The aim of this study was to design a cervical cancer screening algorithm for the developing world that is highly sensitive for cervical intraepithelial neoplasia ( CIN ) II , III , and cancer and highly specific for CIN II and III , making it possible to ablate the transformation zone without histologic confirmation . METHODS In rural Shanxi Province , China , we examined 1997 women ages 35 - 45 . Each subject underwent a self-test for intermediate and high-risk HPV ( by HC-II assay ) , fluorescence spectroscopy , a liquid-based Pap ( read manually and by computer and used as a direct test for HPV ) , a visual inspection ( VIA ) diagnosis , and colposcopy with multiple cervical biopsies . RESULTS Mean age was 39.1 + /- 3.16 years , mean number of births was 2.6 + /- 0.93 . Based on tests administered , 4.3 % subjects had > or = CIN II . All subjects with > or = CIN II had either a ThinPrep Pap ( > or = ASCUS ) or a positive HPV direct test . The sensitivity and specificity for the detection of > or = CIN II were , respectively , 83 and 86 % for the HPV self-test , 95 and 85 % for the HPV direct test , 94 and 78 % for the ThinPrep Pap ( > or = ASCUS ) , 77 and 98 % for the ThinPrep Pap ( > or = HGSIL ) , 94 and 9 % for fluorescence spectroscopy , 71 and 74 % for VIA , and 81 and 77 % for colposcopy . CONCLUSION Based on these data and the existing healthcare infrastructure in China , we believe that further refinement of primary HPV screening using central ized labs is indicated . Self-testing in the local villages may be effective with improvements in the devices and techniques Objective To evaluate the clinical usefulness of a computerbased system that stores and analyzes high-resolution digital colposcopic images . Methods Three hundred patients referred to our institutions for evaluation of abnormal cervical cytology underwent colposcopy with development of digital images . The first 70 patients were used to st and ardize the system . The images obtained from 188 evaluable patients were analyzed and scored by software according to internationally recognized colposcopic criteria . The results were compared with traditional colposcopic diagnoses and with corresponding histology results using K statistics for inter-observer agreement and McNemar test for significance . Results The exact concordance rate between computeraided impressions and histology ( 85.1 % , K = 0.77 ) was significantly higher ( P < .001 ) than that observed between traditional colposcopic findings and histology ( 66 % , K = 0.40 ) . The computer-assisted colposcopy was much more accurate than traditional colposcopy in diagnosing high grade lesions ( 91.2 versus 61.8 % of exact concordance , P < .001 ) as well as normal histology ( 74.1 versus 34.5 % , P < .001 ) , but not significantly different when evaluating low grade lesions ( 89.6 versus 86.5 % ) . Conclusion The integration of computer imaging and colposcopy can improve the colposcopic diagnostic accuracy . An inexperienced colposcopist may benefit from computerized support to obtain the most appropriate histologic specimen , and eventually access to distant consultation via modem or through on-line services . An additional advantage is the ability to develop a space-saving permanent record of digitized images readily available to review a patient 's cervical history or perform effective programs of quality control in colposcopy Describes a novel optical imaging method for the in vivo early detection , quantitative staging , and mapping of cervical cancer and precancer . A multispectral imaging system was developed , which is capable of performing time-resolved imaging spectroscopy . The system was used in order to assess quantitatively the alterations in the light scattering properties of the cervix , induced selectively and reversibly in cervical neoplasias , after the application of acetic acid solution . Spectral imaging and analysis of cervix show that the maximum contrast between acetic acid responsive and nonresponsive areas is obtained at 525/spl plusmn/15 nm , which is further enhanced by cutting off the regular component of tissue reflection , with the aid of two linear cross polarizers . Successive snapshot imaging at this spectral b and enables the quantitative assessment of the temporal alterations in the intensity of the backscattered light , in any spatial location of the examined area . Initial clinical trials show that optical contrast enhancement results in a notable improvement of the sensitivity in detecting incipient lesions . It was also shown that the measured temporal characteristics of the phenomenon contain specific information , which enables the differentiation between neoplastic and nonneoplastic lesions , as well as between neoplasias of different grade . The demonstrated improved sensitivity and specificity highlight the potential of the method in both clinical research and noninvasive diagnosis |
11,921 | 23,043,518 | There was high- quality evidence of a small reduction in respiratory infection in childcare setting s. There was high- quality evidence for a large reduction in respiratory infection with a h and hygiene intervention in squatter settlements in a low-income setting .
There was moderate- to high- quality evidence of no effect on secondary transmission of influenza in households that had already experienced an index case .
While h and hygiene interventions have potential to reduce transmission of influenza and acute respiratory tract infections , their effectiveness varies depending on setting , context and compliance | H and hygiene may be associated with modest protection against some acute respiratory tract infections , but its specific role in influenza transmission in different setting s is unclear . | The objective of this study was to assess the effectiveness of a hygiene program in reducing the incidence of respiratory and diarrheal diseases in toddlers attending day care centers . A r and omized field trial was conducted in 52 day care centers in Quebec , Canada , between September 1 , 1996 and November 30 , 1997 . Absences for any reasons and the daily occurrence of colds and /or diarrhea in toddlers were recorded on calendars by the educators . The number of fecal coliforms on children 's h and s and on educators ' h and s was measured during three unannounced visits . Overall , 1,729 children were followed in 47 day care centers for a total of 153,643 child-days . The incidence rate of diarrhea was considerably reduced by the effect of monitoring ( IRR = 0.73 , 95 % CI = 0.54,0.97 ) , and the intervention reduced the incidence rate of upper respiratory tract infections ( IRR = 0.80 , 95 % CI = 0.68,0.93 ) . Monitoring alone also had an important effect in reducing the level of bacterial contamination on children 's and educators ' h and s. The results indicate that both an intervention program and monitoring alone play a role in reducing infections in children attending day care centers Please cite this paper as : Simmerman et al. ( 2011 ) Findings from a household r and omized controlled trial of h and washing and face masks to reduce influenza transmission in Bangkok , Thail and . Influenza and Other Respiratory Viruses 5(4 ) , 256–267 Background Evidence is needed on the effectiveness of non‐pharmaceutical interventions ( NPIs ) to reduce influenza transmission . Methodology We studied NPIs in households with a febrile , influenza‐positive child . Households were r and omized to control , h and washing ( HW ) , or h and washing plus paper surgical face masks ( HW + FM ) arms . Study nurses conducted home visits within 24 hours of enrollment and on days 3 , 7 , and 21 . Respiratory swabs and serum were collected from all household members and tested for influenza by RT‐PCR or serology . Principal Findings Between April 2008 and August 2009 , 991 ( 16·5 % ) of 5995 pediatric influenza‐like illness patients tested influenza positive . Four hundred and forty‐two index children with 1147 household members were enrolled , and 221 ( 50·0 % ) were aged < 6 years . Three hundred and ninety‐seven ( 89·8 % ) households reported that the index patient slept in the parents ’ bedroom . The secondary attack rate was 21·5 % , and 56/345 ( 16·3 % ; 95 % CI 12·4–20·2 % ) secondary cases were asymptomatic . H and ‐washing subjects reported 4·7 washing episodes/day , compared to 4·9 times/day in the HW + FM arm and 3·9 times/day in controls ( P = 0·001 ) . The odds ratios ( ORs ) for secondary influenza infection were not significantly different in the HW arm ( OR = 1·20 ; 95 % CI 0·76–1·88 ; P‐0.442 ) , or the HW + FM arm ( OR = 1·16 ; 95 % CI .0·74–1·82 ; P = 0.525 ) . Conclusions Influenza transmission was not reduced by interventions to promote h and washing and face mask use . This may be attributable to transmission that occurred before the intervention , poor facemask compliance , little difference in h and ‐washing frequency between study groups , and shared sleeping arrangements . A prospect i ve study design and a careful analysis of sociocultural factors could improve future NPI studies Background : Laboratory-based evidence is lacking regarding the efficacy of nonpharmaceutical interventions ( NPIs ) such as alcohol-based h and sanitizer and respiratory hygiene to reduce the spread of influenza . Methods : The Pittsburgh Influenza Prevention Project was a cluster-r and omized trial conducted in 10 elementary schools in Pittsburgh , PA , during the 2007 to 2008 influenza season . Children in 5 intervention schools received training in h and and respiratory hygiene , and were provided and encouraged to use h and sanitizer regularly . Children in 5 schools acted as controls . Children with influenza-like illness were tested for influenza A and B by reverse-transcriptase polymerase chain reaction . Results : A total of 3360 children participated in this study . Using reverse-transcriptase polymerase chain reaction , 54 cases of influenza A and 50 cases of influenza B were detected . We found no significant effect of the intervention on the primary study outcome of all laboratory-confirmed influenza cases ( incidence rate ratio [ IRR ] : 0.81 ; 95 % confidence interval [ CI ] : 0.54 , 1.23 ) . However , we did find statistically significant differences in protocol -specified ancillary outcomes . Children in intervention schools had significantly fewer laboratory-confirmed influenza A infections than children in control schools , with an adjusted IRR of 0.48 ( 95 % CI : 0.26 , 0.87 ) . Total absent episodes were also significantly lower among the intervention group than among the control group ; adjusted IRR 0.74 ( 95 % CI : 0.56 , 0.97 ) . Conclusions : NPIs ( respiratory hygiene education and the regular use of h and sanitizer ) did not reduce total laboratory-confirmed influenza . However , the interventions did reduce school total absence episodes by 26 % and laboratory-confirmed influenza A infections by 52 % . Our results suggest that NPIs can be an important adjunct to influenza vaccination programs to reduce the number of influenza A infections among children Transmission of enteric pathogens is facilitated in child day care centers , including family day care homes , by frequent and intimate exposure among susceptible hosts , with diaper changing as the highest-risk procedure for such transmission . The objective of this study was to evaluate the effectiveness of an intervention program in decreasing the incidence of infectious disease symptoms in children attending family day care homes during a 12-month period . Each of 24 family day care homes was r and omly assigned to an intervention or control group . The intervention included four components : ( 1 ) a h and washing educational program and ( 2 ) use of vinyl gloves , ( 3 ) use of disposable diaper changing pads , and ( 4 ) use of an alcohol-based h and rinse by the day care provider . Symptoms of enteric disease ( diarrhea and vomiting ) were significantly reduced in intervention family day care homes ( p less than or equal to 0.05 ) , whereas respiratory symptoms were not significantly different between intervention and control family day care homes ( p = 0.35 ) . Diarrhea was reported in 1 of every 100 child care days , representing one diarrhea episode per month in a typical family day care home INTRODUCTION The purpose was to determine the effectiveness of an instructional program on h and washing . The hypothesis stated that an instructional program on germs and h and washing in child care could significantly reduce the spread of infectious diseases in the test center . METHOD A longitudinal study was conducted in a field setting with a test group and a control group of 3- to 5-year-old children and their teachers in two similar child care setting s. For 21 weeks illnesses and symptoms of infectious diseases were assessed with a health assessment checklist . The test group received a developmentally appropriate instructional program on germs and h and washing . The teachers in the test group attended workshops on infectious diseases and h and washing . The control group maintained their usual h and washing procedures . RESULT At weeks 1 through 11 benchmark data were collected . At weeks 12 through 21 , peak cold and flu season , the test group had significantly fewer colds than the control group ( chi-squared analysis , 4.338 , 1 df , p < .05 ) ; thus the hypothesis was confirmed . DISCUSSION H and washing has been recognized as one way to manage the spread of infectious diseases in child care centers . H and washing helped to reduce colds at the test center where frequent and proper h and washing practice s were incorporated into the curriculum through an intervention program Background Previous controlled studies on the effect of non-pharmaceutical interventions ( NPI ) - namely the use of facemasks and intensified h and hygiene - in preventing household transmission of influenza have not produced definitive results . We aim ed to investigate efficacy , acceptability , and tolerability of NPI in households with influenza index patients . Methods We conducted a cluster r and omized controlled trial during the p and emic season 2009/10 and the ensuing influenza season 2010/11 . We included households with an influenza positive index case in the absence of further respiratory illness within the preceding 14 days . Study arms were wearing a facemask and practicing intensified h and hygiene ( MH group ) , wearing facemasks only ( M group ) and none of the two ( control group ) . Main outcome measure was laboratory confirmed influenza infection in a household contact . We used daily question naires to examine adherence and tolerability of the interventions . Results We recruited 84 households ( 30 control , 26 M and 28 MH households ) with 82 , 69 and 67 household contacts , respectively . In 2009/10 all 41 index cases had a influenza A ( H1N1 ) pdm09 infection , in 2010/11 24 had an A ( H1N1 ) pdm09 and 20 had a B infection . The total secondary attack rate was 16 % ( 35/218 ) . In intention-to-treat analysis there was no statistically significant effect of the M and MH interventions on secondary infections . When analysing only households where intervention was implemented within 36 h after symptom onset of the index case , secondary infection in the pooled M and MH groups was significantly lower compared to the control group ( adjusted odds ratio 0.16 , 95 % CI , 0.03 - 0.92 ) . In a per- protocol analysis odds ratios were significantly reduced among participants of the M group ( adjusted odds ratio , 0.30 , 95 % CI , 0.10 - 0.94 ) . With the exception of MH index cases in 2010/11 adherence was good for adults and children , contacts and index cases . Conclusions Results suggest that household transmission of influenza can be reduced by the use of NPI , such as facemasks and intensified h and hygiene , when implemented early and used diligently . Concerns about acceptability and tolerability of the interventions should not be a reason against their recommendation .Trial registration The study was registered with Clinical Trials.gov ( Identifier NCT00833885 ) Background The economical impact of absenteeism and reduced productivity due to acute infectious respiratory and gastrointestinal disease is normally not in the focus of surveillance systems and may therefore be underestimated . However , large community studies in Europe and USA have shown that communicable diseases have a great impact on morbidity and lead to millions of lost days at work , school and university each year . H and disinfection is acknowledged as key element for infection control , but its effect in open , work place setting s is unclear . Methods Our study involved a prospect i ve , controlled , intervention-control group design to assess the epidemiological and economical impact of alcohol-based h and disinfectants use at work place . Volunteers in public administrations in the municipality of the city of Greifswald were r and omized in two groups . Participants in the intervention group were provided with alcoholic h and disinfection , the control group was unchanged . Respiratory and gastrointestinal symptoms and days of work were recorded based on a monthly question naire over one year . On the whole , 1230 person months were evaluated . Results H and disinfection reduced the number of episodes of illness for the majority of the registered symptoms . This effect became statistically significant for common cold ( OR = 0.35 [ 0.17 - 0.71 ] , p = 0.003 ) , fever ( OR = 0.38 [ 0.14 - 0.99 ] , p = 0.035 ) and coughing ( OR = 0.45 [ 0.22 - 0.91 ] , p = 0.02 ) . Participants in the intervention group reported less days ill for most symptoms assessed , e.g. colds ( 2.07 vs. 2.78 % , p = 0.008 ) , fever ( 0.25 vs. 0.31 % , p = 0.037 ) and cough ( 1.85 vs. 2.00 % , p = 0.024 ) . For diarrhoea , the odds ratio for being absent became statistically significant too ( 0.11 ( CI 0.01 - 0.93 ) . Conclusion H and disinfection can easily be introduced and maintained outside clinical setting s as part of the daily h and hygiene . Therefore it appears as an interesting , cost-efficient method within the scope of company health support programmes . Trial registration numberIS RCT N : IS RCT BACKGROUND During the influenza A(H1N1 ) p and emic , antiviral prescribing was limited , vaccines were not available early , and the effectiveness of nonpharmaceutical interventions ( NPIs ) was uncertain . Our study examined whether use of face masks and h and hygiene reduced the incidence of influenza-like illness ( ILI ) . METHODS A r and omized intervention trial involving 1437 young adults living in university residence halls during the 2006 - 2007 influenza season was design ed . Residence halls were r and omly assigned to 1 of 3 groups-face mask use , face masks with h and hygiene , or control- for 6 weeks . Generalized models estimated rate ratios for clinical ly diagnosed or survey-reported ILI weekly and cumulatively . RESULTS We observed significant reductions in ILI during weeks 4 - 6 in the mask and h and hygiene group , compared with the control group , ranging from 35 % ( confidence interval [ CI ] , 9%-53 % ) to 51 % ( CI , 13%-73 % ) , after adjusting for vaccination and other covariates . Face mask use alone showed a similar reduction in ILI compared with the control group , but adjusted estimates were not statistically significant . Neither face mask use and h and hygiene nor face mask use alone was associated with a significant reduction in the rate of ILI cumulatively . CONCLUSIONS These findings suggest that face masks and h and hygiene may reduce respiratory illnesses in shared living setting s and mitigate the impact of the influenza A(H1N1 ) p and emic . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00490633 BACKGROUND More than 3.5 million children aged less than 5 years die from diarrhoea and acute lower respiratory-tract infection every year . We undertook a r and omised controlled trial to assess the effect of h and washing promotion with soap on the incidence of acute respiratory infection , impetigo , and diarrhoea . METHODS In adjoining squatter settlements in Karachi , Pakistan , we r and omly assigned 25 neighbourhoods to h and washing promotion ; 11 neighbourhoods ( 306 households ) were r and omised as controls . In neighbourhoods with h and washing promotion , 300 households each were assigned to antibacterial soap containing 1.2 % triclocarban and to plain soap . Fieldworkers visited households weekly for 1 year to encourage h and washing by residents in soap households and to record symptoms in all households . Primary study outcomes were diarrhoea , impetigo , and acute respiratory-tract infections ( ie , the number of new episodes of illness per person-weeks at risk ) . Pneumonia was defined according to the WHO clinical case definition . Analysis was by intention to treat . FINDINGS Children younger than 5 years in households that received plain soap and h and washing promotion had a 50 % lower incidence of pneumonia than controls ( 95 % CI ( -65 % to -34 % ) . Also compared with controls , children younger than 15 years in households with plain soap had a 53 % lower incidence of diarrhoea ( -65 % to -41 % ) and a 34 % lower incidence of impetigo ( -52 % to -16 % ) . Incidence of disease did not differ significantly between households given plain soap compared with those given antibacterial soap . INTERPRETATION H and washing with soap prevents the two clinical syndromes that cause the largest number of childhood deaths globally-namely , diarrhoea and acute lower respiratory infections . H and washing with daily bathing also prevents impetigo Limited vaccine availability and the potential for resistance to antiviral medications have led to calls for establishing the efficacy of non-pharmaceutical measures for mitigating p and emic influenza . Our objective was to examine if the use of face masks and h and hygiene reduced rates of influenza-like illness ( ILI ) and laboratory-confirmed influenza in the natural setting . A cluster-r and omized intervention trial was design ed involving 1,178 young adults living in 37 residence houses in 5 university residence halls during the 2007–2008 influenza season . Participants were assigned to face mask and h and hygiene , face mask only , or control group during the study . Discrete-time survival models using generalized estimating equations to estimate intervention effects on ILI and confirmed influenza A/B infection over a 6-week study period were examined . A significant reduction in the rate of ILI was observed in weeks 3 through 6 of the study , with a maximum reduction of 75 % during the final study week ( rate ratio [ RR ] = 0.25 , [ 95 % CI , 0.07 to 0.87 ] ) . Both intervention groups compared to the control showed cumulative reductions in rates of influenza over the study period , although results did not reach statistical significance . Generalizability limited to similar setting s and age groups . Face masks and h and hygiene combined may reduce the rate of ILI and confirmed influenza in community setting s. These non-pharmaceutical measures should be recommended in crowded setting s at the start of an influenza p and emic . Trail Registration Clinical trials.gov BACKGROUND High attack rates of Influenzavirus among school-aged children tend to be expected to cause significant disruption of usual activities at school and at home . OBJECTIVE To quantify the effect of influenza season on illness episodes , school absenteeism , medication use , parental absenteeism from work , and the occurrence of secondary illness in families among a cohort of children enrolled in an elementary school during the 2000 - 2001 influenza season . DESIGN Prospect i ve survey study . SETTING Kindergarten through eighth grade elementary school in Seattle , Wash. PATIENTS OR OTHER PARTICIPANTS All children enrolled in the school were eligible for the study . Study participants were 313 children in 216 families . MAIN OUTCOME MEASURES The primary outcome measure was missed school days . Secondary outcomes measures included total illness episodes , febrile illness episodes , medication usage , physician visits , parental workdays missed , and secondary illnesses among family members of children in the study cohort . Differences between the rates of study events among participants when influenza was circulating and the event rates during the winter season when influenza was not circulating were used to calculate influenza-attributable excess events . RESULTS Total illness episodes , febrile illness episodes , analgesic use , school absenteeism , parental industrial absenteeism , and secondary illness among family members were significantly higher during influenza season compared with the noninfluenza winter season . For every 100 children followed up for this influenza season , which included 37 school days , an excess 28 illness episodes and 63 missed school days occurred . Similarly , for every 100 children followed up , influenza accounted for an estimated 20 days of work missed by the parents and 22 secondary illness episodes among family members . CONCLUSION Influenza season has significant adverse effects on the quality of life of school-aged children and their families OBJECTIVE Child care outside the home increases children 's infections substantially . We have to evaluate the possibilities for reducing the transmission of infections by an infection prevention program . DESIGN AND METHODS A 15-month r and omized controlled trial involving 20 day-care centers was conducted to evaluate the efficacy of an infection prevention program . The program was introduced in 10 centers and the other matched 10 centers served as controls . Records were made of the occurrence of infections and absences from care or work because of infections among the children , their parents and the personnel of the day-care centers . RESULTS Both the children and the personnel in the program centers had significantly fewer infections than those in the control centers , the reduction being 9 % [ 95 % confidence interval ( 95 % CI ) , 4 to 16 % , P < 0.002 ] among 3-year-old children and 8 % ( 95 % CI 0 to 14 % , P = 0.049 ) among the older children . The children at the program centers received 24 % fewer prescriptions of antimicrobials ( 95 % CI 22 to 27 % , P < 0.001 ) . Likewise there were 2.5 man-year fewer absences from work on the part of parents because of a child 's illness during 1 year in the program centers , a 24 % difference ( 95 % CI 18 to 29 % , P < 0.001 ) . CONCLUSIONS Effective prevention of infections is possible in child day-care centers , and this can benefit both the families and the personnel . Such a program is cost-effective even if a specialist nurse implements it The purpose of the study was to evaluate the effect of intensified hygiene with frequent h and washing and several educational procedures in day-care centres . The study was conducted as a controlled trial , with an intervention group and an observation group . There was a 34 % reduction in expected sickness in children in the intervention group . In the categories diarrhoea and eye-infection there was a significant drop in sickness . We conclude that broad intervention concerning h and -hygiene has a positive effect on sickness in children attending day-care centres Background . Acute upper respiratory infections are common in children who attend child care , and preventing transmission of disease in this setting depends on actions by child care staff . We set out to discover whether transmission of respiratory infections in child care could be reduced by improved infection control procedures . Methods . We performed a cluster , r and omized , controlled trial of an infection control intervention conducted in child care centers in 1 city in Australia . The intervention was training of child care staff about transmission of infection , h and washing , and aseptic nosewiping technique . Implementation of the intervention was recorded by an observer . Illness was measured by parent report in telephone interviews every 2 weeks . Results . There were 311 child-years of surveillance for respiratory symptoms . By multivariable analysis , there was no significant reduction in colds in intervention center children across the full age range . However , a significant reduction in respiratory illness was present in children 24 months of age and younger . When compliance with infection control practice s was high , colds in these children were reduced by 17 % . Conclusions . This trial supports the role of direct transmission of colds in young children in child care . The ability of infection control techniques to reduce episodes of colds in children in child care was limited to children 24 months of age and under 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 BACKGROUND AND OBJECTIVES H and washing prevents communicable illness . We evaluated the effect of a m and atory , scheduled h and -washing program in elementary school children on absenteeism due to acute communicable illness . METHODS The study was conducted at Trombley Elementary School in Grosse Pointe Park , Mich. The intervention group , approximately half of the school children ( n = 143 , including all grade s 1 - 5 ) , washed their h and s a minimum of four scheduled times a day . The control group ( n = 162 ) continued h and -washing practice s as usual . RESULTS Of the 37 school days examined , children in the h and -washing group were absent fewer days than the control group due to all acute communicable illness ( relative risk = .75 ) . There were less days of absence due to gastrointestinal symptoms ( relative risk = .43 ) . The difference in absence due to respiratory symptoms was not statistically significant . CONCLUSIONS A scheduled h and -washing program will reduce acute communicable ( gastrointestinal ) illnesses in elementary school-age children Background We studied the efficacy of different time-interval applications of alcohol h and gel as a strategy for the prevention of influenza-like illness ( ILI ) in preschool-age children . Methods We performed a classroom-based cluster r and omization at a kindergarten school in Bangkok , Thail and . A total of 1437 children were placed into 3 test groups , based on the frequency of alcohol h and gel use for h and hygiene : only before lunch ( q lunch ) , every 120 minutes ( q 120 ) , and every 60 minutes ( q 60 ) . The primary outcome was a change in the school absenteeism rate caused by ILI . Results The rates of absenteeism from confirmed ILI ( sick days/present days ) were 0.026 in the q lunch group , 0.025 in the q 120 group , and 0.017 in the q 60 group . Significant reductions in absenteeism rates were seen when comparing the q 60 group with the q 120 group ( rate difference , 0.009 ; 95 % confidence interval [ CI ] , −0.002 to 0.015 ; P = .008 ) and comparing the q 60 group with the q lunch group ( rate difference , 0.0096 ; 95 % CI , 0.004 - 0.016 ; P = .002 ) . No such differences were detected between the q 120 and q lunch groups ( rate difference , 0.001 ; 95 % CI , 0.005 - 0.007 ; P = .743 ) . Conclusions The compulsory hourly use of alcohol gel as classroom h and disinfection could significantly reduce the rate of absenteeism from ILI in preschool-age children To evaluate the effectiveness of an intensive h and hygiene campaign on reducing absenteeism caused by influenza-like illness ( ILI ) , diarrhea , conjunctivitis , and laboratory-confirmed influenza , we conducted a r and omized control trial in 60 elementary schools in Cairo , Egypt . Children in the intervention schools were required to wash h and s twice each day , and health messages were provided through entertainment activities . Data were collected on student absenteeism and reasons for illness . School nurses collected nasal swabs from students with ILI , which were tested by using a qualitative diagnostic test for influenza A and B. Compared with results for the control group , in the intervention group , overall absences caused by ILI , diarrhea , conjunctivitis , and laboratory-confirmed influenza were reduced by 40 % , 30 % , 67 % , and 50 % , respectively ( p<0.0001 for each illness ) . An intensive h and hygiene campaign was effective in reducing absenteeism caused by these illnesses H and washing is the most effective way to prevent the spread of communicable disease . The purpose of this double-blind , placebo-controlled study was to assess whether an alcohol-free , instant h and sanitizer containing surfactants , allantoin , and benzalkonium chloride could reduce illness absenteeism in a population of 769 elementary school children and serve as an effective alternative when regular soap and water h and washing was not readily available . Prior to the study , students were educated about proper h and washing technique , the importance of h and washing to prevent transmission of germs , and the relationship between germs and illnesses . Children in kindergarten through the 6th grade ( ages 5–12 ) were assigned to the active or placebo h and -sanitizer product and instructed to use the product at scheduled times during the day and as needed after coughing or sneezing . Data on illness absenteeism were tracked . After 5 weeks , students using the active product were 33 % less likely to have been absent because of illness when compared with the placebo group Objective .Good h and hygiene may reduce the spread of infections in families with children who are in out-of-home child care . Alcohol-based h and sanitizers rapidly kill viruses that are commonly associated with respiratory and gastrointestinal ( GI ) infections . The objective of this study was to determine whether a multifactorial campaign centered on increasing alcohol-based h and sanitizer use and h and -hygiene education reduces illness transmission in the home . Methods .A cluster r and omized , controlled trial was conducted of homes of 292 families with children who were enrolled in out-of-home child care in 26 child care centers . Eligible families had ≥1 child who was 6 months to 5 years of age and in child care for ≥10 hours/week . Intervention families received a supply of h and sanitizer and biweekly h and -hygiene educational material s for 5 months ; control families received only material s promoting good nutrition . Primary caregivers were phoned biweekly and reported respiratory and GI illnesses in family members . Respiratory and GI-illness – transmission rates ( measured as secondary illnesses per susceptible person-month ) were compared between groups , adjusting for demographic variables , h and -hygiene practice s , and previous experience using h and sanitizers . Results .Baseline demographics were similar in the 2 groups . A total of 1802 respiratory illnesses occurred during the study ; 443 ( 25 % ) were secondary illnesses . A total of 252 GI illnesses occurred during the study ; 28 ( 11 % ) were secondary illnesses . The secondary GI-illness rate was significantly lower in intervention families compared with control families ( incidence rate ratio [ IRR ] : 0.41 ; 95 % confidence interval [ CI ] : 0.19–0.90 ) . The overall rate of secondary respiratory illness was not significantly different between groups ( IRR : 0.97 ; 95 % CI : 0.72 - 1.30 ) . However , families with higher sanitizer usage had a marginally lower secondary respiratory illness rate than those with less usage ( IRR : 0.81 ; 95 % CI : 0.65 - 1.09 ) . Conclusions .A multifactorial intervention emphasizing alcohol-based h and sanitizer use in the home reduced transmission of GI illnesses within families with children in child care . H and sanitizers and multifaceted educational messages may have a role in improving h and -hygiene practice s within the home setting |
11,922 | 29,908,037 | We did not find evidence for possible subgroup effects based on stone location or α-blocker type .
CONCLUSIONS In patients with ureteric stones , α-blockers likely increase stone clearance but probably also slightly increase the risk of major adverse events .
Subgroup analyses suggest that α-blockers may be less effective in smaller ( ≤5 mm ) than larger stones ( > 5 mm ) | OBJECTIVE To assess the effects of α-blockers compared to st and ard therapy or placebo for ureteric stones of ≤10 mm confirmed by imaging in adult patients presenting with symptoms of ureteric stone disease . | OBJECTIVES To study the efficacy of alfuzosin compared with tamsulosin in the management of lower ureteral stones . METHODS A total of 102 patients with stones < 1 cm size and located in the lower ureter were enrolled in the present study and r and omized into 3 equal groups . Group 1 patients ( n = 34 ) received 0.4 mg tamsulosin daily , group 2 patients ( n = 34 ) received 10 mg alfuzosin daily , and group 3 patients ( n = 34 ) received placebo ( control group ) . The patients were given 75 mg diclofenac injection intramuscularly on dem and and were followed up for 4 weeks . RESULTS The average stone size for groups 1 , 2 , and 3 was comparable ( 6.17 , 6.70 , and 6.35 mm , respectively ) . Stone expulsion was observed in 28 of 34 patients ( 82.3 % ) in group 1 , 24 of 34 patients ( 70.5 % ) in group 2 , and 12 of 34 patients ( 35.2 % ) in group 3 . The average expulsion time for groups 1 , 2 , and 3 was 12.3 , 14.5 , and 24.5 days , respectively . The results of both study groups ( groups 1 and 2 ) were superior to those in the placebo group ( P = .003 and P = .001 , respectively ) , but the study failed to show any statistically significant differences between tamsulosin and alfuzosin ( P = .25 ) . Alfuzosin was associated with fewer side effects than tamsulosin , especially in terms of retro grade ejaculation . CONCLUSIONS Medical treatment of lower ureteral calculi with tamsulosin and alfuzosin result ed in a significantly increased stone expulsion rate , decreased expulsion time , and a reduced need for analgesic therapy Abstract Objective : To evaluate and compare the efficacy of tamsulosin and alfuzosin as medical expulsive therapy for ureteric stones . Patients and methods : In all , 112 patients with ureteric stones of ⩽10 mm , located along the ureter , were r and omly divided into three groups . In group I , 32 patients received no α-blockers ( controls ) , in group II 40 patients received tamsulosin 0.4 mg daily , and in group III 40 patients received alfuzosin 10 mg daily . All patients were given analgesia and antibiotics when indicated . The follow-up was weekly for 4 weeks . Results : The mean stone size and age were comparable in the three groups . The stone expulsion rate was 44 % , 85 % and 75 % in groups I , II and III , respectively . Half of the stones in group II passed within 2 weeks , half in group III passed within 3 weeks , while more than half of the stones in group I did not pass even after 4 weeks . The mean number of painful episodes was 2.45 , 1.38 and 1.64 in groups I , II and III , respectively . The drug-related side-effects reported by patients were mild and transient . Conclusion : The use of tamsulosin or alfuzosin as medical expulsive therapy for ureteric stones in the three sections of the ureter ( upper , middle and lower ) was safe and effective , as shown by the increased overall stone expulsion rate , reduced stone expulsion time and fewer pain episodes . Tamsulosin was associated with a greater rate of stone expulsion than was alfuzosin BACKGROUND Using a selective α-blocker for medical expulsive therapy ( MET ) is a cost-effective treatment approach widely used for ureteral stones . OBJECTIVE To evaluate the efficacy of silodosin , a selective α-1a receptor antagonist , in this setting . DESIGN , SETTING , AND PARTICIPANTS This was a multicenter , phase 2 study conducted in adult patients with a unilateral ureteral calculus of 4 - 10 mm . Of 239 patients in the safety population , six discontinued due to adverse events . INTERVENTION Patients were r and omized 1:1 to receive silodosin 8 mg or placebo for up to 4 wk . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was spontaneous stone passage , analyzed using logistic regression . Secondary outcomes included time to stone passage , emergency room ( ER ) visits , hospital admissions , analgesic use , and incidence and severity of pain . RESULTS AND LIMITATIONS No significant differences between the silodosin and placebo groups were observed for passage rate of all stones ( 52 % vs 44 % , respectively ; p=0.2 ) . However , silodosin achieved a significantly greater rate of distal ureter stone passage than placebo ( p=0.01 ) . Significant differences were not observed for ER visits , hospital admission , or use of analgesics . The number of patients in the intent-to-treat population was slightly below the calculated sample size ( 232 vs 240 ) and sample sizes were not calculated for subgroup analyses . CONCLUSIONS This is among the first prospect i ve , r and omized , multi-institutional trials to examine the efficacy of a selective α-1a antagonist as MET in patients with ureteral calculi and did not demonstrate a benefit to the entire ureter . However , silodosin was found to be well tolerated and beneficial in facilitating the passage of distal ureteral stones , warranting additional future studies on distal stone elimination . PATIENT SUMMARY In this report , we looked at the efficacy of silodosin for the treatment of ureteral stones . We found that silodosin increased passage of distal ureteral stones BACKGROUND Recent large high- quality trials have question ed the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones . OBJECTIVE To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo . DESIGN , SETTING , AND PARTICIPANTS We conducted a double-blind , placebo-controlled study of 3296 patients with distal ureteral stones , across 30 centers , to evaluate the efficacy and safety of tamsulosin . INTERVENTION Participants were r and omly assigned ( 1:1 ) into tamsulosin ( 0.4 mg ) or placebo groups for 4 wk . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point of analysis was the overall stone expulsion rate , defined as stone expulsion , confirmed by negative findings on computed tomography , over a 28-d surveillance period . Secondary end points included time to stone expulsion , use of analgesics , and incidence of adverse events . RESULTS AND LIMITATIONS Among 3450 patients r and omized between September 1 , 2011 , and August 31 , 2013 , 3296 ( 96 % ) were included in the primary analysis . Tamsulosin benefits from a higher stone expulsion rate than the placebo ( 86 % vs 79 % ; p<0.001 ) for distal ureteral stones . Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones ( > 5 mm ) . Considering the secondary end points , tamsulosin-treated patients reported a shorter time to expulsion ( p<0.001 ) , required lower use of analgesics compared with placebo ( p<0.001 ) , and significantly relieved renal colic ( p<0.001 ) . No differences in the incidence of adverse events were identified between the two groups . CONCLUSIONS Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic . Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones > 5 mm , but no effect for stones ≤5 mm . PATIENT SUMMARY In this report , we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones . We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic BACKGROUND α-Blockers induce selective relaxation of ureteral smooth muscle with subsequent inhibition of ureteral spasms and dilatation of the ureteral lumen . The aim of the study was to evaluate the efficacy and safety of the α-blocker tamsulosin hydrochloride in patients with ureteral colic owing to a distal ureteral stone . METHODS This was a multicenter , placebo-controlled , r and omized , double-blind study . Patients with emergency admission for ureteral colic with a 2- to 7-mm-diameter radio-opaque distal ureteral stone were included in the study . They received tamsulosin ( 0.4 mg/d ) or matching placebo until stone expulsion or day 42 , whichever came first . The main end point was time to stone expulsion between inclusion and day 42 . Sequential statistical analysis was performed using the triangular test . RESULTS A total of 129 patients with acute renal colic were recruited from emergency wards between February 1 , 2002 , and December 8 , 2006 , in 6 French hospitals . Of these 129 r and omized patients ( placebo , 63 ; tamsulosin , 66 ) , 7 were excluded from analyses : 5 for major deviations from inclusion criteria , 1 for stone expulsion before the first treatment administration , and 1 for consent withdrawal . At inclusion , mean ( SD ) stone diameters were 3.2 ( 1.2 ) and 2.9 ( 1.0 ) mm in the placebo and tamsulosin groups , respectively ( P = .23 ) . Expulsion delay distributions during 42 days did not show any difference ( P = .30 ) . The numbers of patients who spontaneously expelled their stone within 42 days were 43 of 61 ( 70.5 % ) and 47 of 61 ( 77.0 % ) in the placebo and tamsulosin groups , respectively ( P = .41 ) . Corresponding delays were 10.1 ( 10.0 ) and 9.6 ( 9.8 ) days ( P = .82 ) . Other secondary end points and tolerance were not different between groups . CONCLUSION Although well tolerated , a daily administration of 0.4 mg of tamsulosin did not accelerate the expulsion of distal ureteral stones in patients with ureteral colic . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00151567 Objectives A prospect i ve , multicenter , r and omized , double-blind , placebo-controlled trial evaluated the effects of naftopidil 75 mg for medical expulsive therapy for a single ureter stone . Material s and methods Patients diagnosed with a ureter stone were prescribed aceclofenac 100 mg or a combined medication of tramadol 37.5 mg and acetaminophen 325 mg . Patients then r and omly received either naftopidil 75 mg or placebo . Primary endpoint was the stone passage rate at 14 days after medication . Results The 150 patients enrolled in 6 institutions r and omly received either naftopidil ( n = 75 ) or placebo ( n = 75 ) . The percentages of ureter stone passed spontaneously 14 days after medication was 60.9 % in the naftopidil group and 53.3 % in the placebo group . Stone-free rates and the total use of analgesics showed no significant differences between the two groups . Stone-free rates at 14 days after medication were decreased when maximal stone size was increased : 39.4 % ( ≥ 5 mm ) , 15.5 % ( ≥ 6 mm ) , and 7.0 % ( ≥ 7 mm ) . Conclusions The use of naftopidil 75 mg once daily was not effective in increasing spontaneous stone passage rates or reducing analgesic use . The maximal stone size < 6 mm and the follow-up for two weeks would be appropriate for applying medical expulsive therapy to patients with a single ureter stone Purpose We evaluated and compared the efficacy of tamsulosin and alfuzosin in the medical treatment of symptomatic , uncomplicated distal ureteral stones . Material s and Methods A total of 87 patients with distal ureteral stones of ≤10 mm were r and omly divided into 3 groups . Group I patients ( n=29 ) received 0.4 mg tamsulosin daily , group II patients ( n=30 ) received 10 mg alfuzosin daily , and group III patients ( n=28 ) were not given tamsulosin or alfuzosin . Patients in all groups received Diclofenac sodium regularly for 1 week and then on dem and . Follow-up was done on a weekly basis for 30 days . Results The mean stone size was comparable in the 3 groups ( 4.97±2.24 , 5.47±2.13 , and 5.39±1.81 mm , respectively ) . The stone expulsion rate was 86.2 % , 76.6 % , and 50 % in groups I , II , and III , respectively . The difference in groups I and II with respect to group III was significant ( p=0.0028 and 0.035 ) . The mean expulsion time for groups I to III was 7.52±7.06 , 8.26±7.34 , and 13.90±6.99 days , respectively . The expulsion time was significantly shorter in groups I and II than in group III ( p=0.0097 and 0.026 ) . Patients taking tamsulosin and alfuzosin had fewer pain attacks than did group III patients ( 1.24±0.57 vs. 1.43±0.67 vs. 1.75±1.17 ) . Only 3 cases of drug side effects , 2 in group I and 1 in group II , were recorded . Conclusions The use of tamsulosin or alfuzosin for the medical treatment of lower ureteric stones proved to be safe and effective . Moreover , tamsulosin did not have any significant benefits over alfuzosin Background : Alpha – 1 blockers decrease the tension and release the spasm of smooth muscles and thus lessen the obstruction and irritation symptoms in the lower urinary tract ( LUTS ) . They make a faster passing of calculi from the terminal part of the ureters possible . Objectives : The goal of this study was to objective ly assess the improvement of difficulties caused by obstructions in ureterolithiasis localized in the lower part of the ureters of 104 r and omly chosen patients ( pts . ) in a double-blind study . Methods : During a period of 2 and half years ( June 1999–January 2002 ) 104 pts . suffering from ureterolithiasis of the lower urinary tract were treated and observed . Patients were divided into two groups : A ( n:53 ; later only 51 were evaluated ) which was subjected to st and ard treatment and group B ( n:51 ) where the st and ard treatment was supplemented by the alpha – 1 blocker . As alpha – 1 blocker one capsule of Tamsulosin /OMNIC 0.4 / was administered daily . Results : With alpha – 1 blocker , we have registered a more speedy passing of calculi from the terminal parts of ureters in 17.6 % of pts . Recurrence of renal colics was less frequent and occurred in one of eight pts . as compared with group A ( without the alpha – 1 blocker ) where a recurrence of the renal colic was observed in about every fifth pts . In group A ( n:51 ) , 62.8 % of the pts . passed the calculi , whereas in group B ( n:51 ) , where st and ard treatment was supplemented by the administration of the alpha – 1 blocker Tamsulosin , this percentage increased to 80.4 % . Conclusion : The treatment by alpha – 1 blockers considerably decreased not only LUTS but also helped to accelerate the passing of minor calculi from the terminal parts of the ureters of 80.4 % of pts . It seems that alpha – 1 blockers potentiate the spasmoanalgetic action of drugs used in st and ard methods of treatment BACKGROUND Numerous r and omised trials have confirmed the efficacy of medical expulsive therapy with tamsulosin in patients with distal ureteral stones ; however , to date , no r and omised , double-blind , placebo-controlled trials have been performed . OBJECTIVE The objective of this trial was to evaluate the efficacy of medical expulsive therapy with tamsulosin in a r and omised , double-blind , placebo-controlled setting . DESIGN , SETTING , AND PARTICIPANTS Patients presenting with single distal ureteral stones < or = 7 mm were included in this trial . INTERVENTION Patients were r and omised in a double-blind fashion to receive either tamsulosin or placebo for 21 d. The medication was discontinued after either stone expulsion or intervention . Abdominal computed tomography was performed to assess the initial and final stone status . MEASUREMENTS AND LIMITATIONS : The primary end point was the stone expulsion rate . Secondary end points were time to stone passage , the amount of analgesic required , the maximum daily pain score , safety of the therapy , and the intervention rate . RESULTS Ten of 100 r and omised patients were excluded from the analysis . No statistically significant differences in patient characteristics and stone size ( median : 4.1 mm [ tamsulosin arm ] vs 3.8 mm [ placebo arm ] , p=0.3 ) were found between the two treatment arms . The stone expulsion rate was not significantly different between the tamsulosin arm ( 86.7 % ) and the placebo arm ( 88.9 % ; p=1.0 ) . Median time to stone passage was 7 d in the tamsulosin arm and 10 d in the placebo arm ( log-rank test , p=0.36 ) . Patients in the tamsulosin arm required significantly fewer analgesics than patients in the placebo arm ( median : 3 vs 7 , p=0.011 ) . A caveat is that the exact time of stone passage was missing for 29 patients . CONCLUSIONS Tamsulosin treatment does not improve the stone expulsion rate in patients with distal ureteral stones < or = 7 mm . Nevertheless , patients may benefit from a supportive analgesic effect . CLINICAL TRIALS.GOV : NCT00831701 PURPOSE To evaluate the efficacy of the addition of tamsulosin to our st and ard expulsive pharmacologic therapy for the treatment of distal-ureteral stones . PATIENTS AND METHODS A series of 96 patients referred to our department for the management of symptomatic distal-ureteral calculi were r and omly divided into group 1 ( N = 46 ) who received diclofenac ( 100 mg/daily ) plus aescin ( 80 mg/daily ) and group 2 ( N = 50 ) who received the same therapy plus tamsulosin ( 0.4 mg/daily ) for a maximum of 2 weeks . There were no differences between the groups with respect to age , sex , or stone size . The primary endpoint was the expulsion rate . Expulsion time , need for analgesics , need for hospitalization , and drug side effects were the secondary endpoints . RESULTS The expulsion rate was significantly higher in group 2 ( 90 % ) than in group 1 ( 58.7 % ; P = 0.01 ) , and group 2 achieved stone passage in a shorter time ( mean 4.4 v 7.5 days , respectively ; P = 0.005 ) . Lower analgesic use was found in group 2 ( P = 0.003 ) , as well as significantly fewer hospitalizations for recurrent colic ( P = 0.01 ) . Both groups experienced few side effects associated with expulsive therapy . CONCLUSIONS A conservative approach should be considered as an option in the management of uncomplicated distal-ureteral stones . Even if the best pharmacologic expulsive regimen remains to be established , the use of the selective alpha-blocker tamsulosin is recommended in this setting PURPOSE We evaluated the efficacy of alfuzosin as medical expulsive therapy for distal ureteral stone passage . MATERIAL S AND METHODS A total of 76 patients with a distal ureteral calculus provided consent for the study . Patients were r and omized between placebo and study medication , and investigators and patients were blinded to the r and omization scheme . Followup was done on a weekly basis and continued until the patient was rendered stone-free . The patient blood pressure , discomfort level , stone position on imaging , number of remaining pills and any adverse events were assessed . Statistical analysis was performed with the Student t test with p < 0.05 considered significant . RESULTS The overall spontaneous stone passage rate was 75 % , including 77.1 % for placebo and 73.5 % for alfuzosin ( p = 0.83 ) . Mean + /- SD time needed to pass the stone was 8.54 + /- 6.99 days for placebo vs 5.19 + /- 4.82 days for alfuzosin . ( p = 0.003 ) . There was no difference in the size or volume of stones that passed spontaneously between the placebo and alfuzosin arms , as measured on baseline computerized tomography ( 4.08 + /- 1.17 and 3.83 + /- 0.95 mm , p = 0.46 ) and by a digital caliper after stone expulsion ( 3.86 + /- 1.76 and 3.91 + /- 1.06 mm , respectively , p = 0.57 ) . When comparing the improvement from the baseline pain score , the alfuzosin arm experienced a greater decrease in pain score in the days after the initial emergency department visit to the date of stone passage ( p = 0.0005 ) . CONCLUSIONS Alfuzosin improves the patient discomfort associated with stone passage and decreases the time to distal ureteral stone passage but it does not increase the rate of spontaneous stone passage OBJECTIVES To evaluate whether alpha1-blockers have any impact on stone clearance in patients with lower ureteral stones who underwent either shock wave lithotripsy ( SWL ) or were followed up with st and ard hydration , analgesics , and anti-inflammatory treatment . METHODS A total of 78 patients ( 56 men and 22 women ) who had lower ureteral stones located at the distal 5 cm of the ureter were divided into four groups . The first group consisted of 30 patients ( 38.5 % ) with stones less than 5 mm ( range 3 to 5 ) who were r and omly divided into two subgroups . Group 1 consisted of 15 patients ( 19.2 % ) who were followed up with oral hydration and diclofenac sodium . Group 2 consisted of 15 patients ( 19.2 % ) who received tamsulosin 0.4 mg daily in addition to the st and ard regimens . The second two groups consisted of 48 patients ( 61.5 % ) with stones greater than 5 mm ( range 6 to 15 ) who underwent SWL . These patients were also r and omly divided between those who did not ( group 3 , n = 24 ) and those who did ( group 4 , n = 24 ) receive tamsulosin 0.4 mg daily . All patients were re-evaluated with plain abdominal x-rays and helical computed tomography 15 days after the beginning of treatment . RESULTS Of the 78 patients , 36 ( 46.2 % ) became stone free . The stone-free rate was 20 % , 53.3 % , 33.3 % , and 70.8 % for group 1 , 2 , 3 , and 4 , respectively . The best results were achieved in those who underwent SWL plus tamsulosin treatment ( group 4 ) . The differences between the stone-free rates for groups 3 versus 4 ( P = 0.019 ) and the tamsulosin versus control groups ( P = 0.0015 ) were statistically significant . CONCLUSIONS The addition of tamsulosin to conventional treatment seemed beneficial in terms of stone clearance of lower ureteral stones , and this effect was more evident for larger stones , especially when combined with SWL Introduction : Renal stones are common disorders that affect approximately 5 % to 10 % of the population and the incidence of renal stones is rising . Treatment of ureteral stones is an important part of urologists and minimally invasive procedures such as ESWL and ureteroscopy effectiveness has been proven in various studies . However , these methods are not completely safe and are expensive and can be complicated . Purpose of this study is to evaluate the effectiveness of tamsulosin in the medical treatment of distal ureteral stones . Patients and methods : A total of 96 patients with distal ureteral stones or UVj are r and omly divided into two study group ( 50 patients ) and control group ( 46 patients ) . Patients in the control group allowed to freely consuming fluids ( hydration ) and indomethacin 100 mg PRN . Study group in addition to indomethacin and daily analgesic 0.4 mg tamsulosin was administered . All subjects in terms of analgesic dose , duration of expulsion and expulsion were studied . Results : Spontaneous expulsion of stone was occurred in 62.5 % ( 30 patients out of 46 ) of control group patients and 82 % ( 41 patients out of 50 ) that there was no significant difference ( P>0.05 ) . Average time to fix the stone in control group 4.7±8.03 days ( range 2 to 28 days ) and in the study group , 3.7±5.70 days ( range 1 to 23 days ) is significantly different ( P>0.05 ) . The average amount of analgesic consumption in the control group was 2.3±4.31 and in the study group was 1.48±2.15 that showed significant differences ( P<0.05 ) . Conclusions : In this study , although the addition of tamsulosin to conservative treatment of distal ureteral stones in the distal ureteral stone expulsion showed no significant difference between the two groups , but the reduction in the duration of expulsion , reduce pain and reduce the need for analgesic has been beneficial Purpose Typically in Korea , for a st and ard dose ( 0.4 mg ) of tamsulosin , two low doses ( 0.2 mg ) are administered . The aim of this study was to evaluate and compare the efficacy of tamsulosin ( 0.2 mg and 0.4 mg ) and alfuzosin ( 10 mg ) in the treatment of lower ureteral stones . Material s and Methods A total of 141 patients presenting with a single 4- to 10-mm sized lower ureteral stone were r and omly assigned to 4 groups . Patients in group 1 ( n=41 ) and group 2 ( n=30 ) received an oral dose of 0.2 mg tamsulosin once and twice daily , respectively , and patients in group 3 ( n=36 ) received a daily oral dose of 10 mg alfuzosin . Patients in group 4 ( n=34 ) received trospium chloride only . The spontaneous passage of stones , the stone expulsion time , and adverse effects were evaluated . Results There were no significant differences in patient background , including age , sex , BMI , stone size , stone side , and symptom duration . The spontaneous stone passage rate through the ureter was higher and the stone expulsion time was faster in groups 1 , 2 , and 3 than in group 4 . There were no statistically different changes in groups 1 , 2 , and 3 . The adverse effects observed in all groups were comparable and were mild . Conclusions Tamsulosin at 0.2 mg and 0.4 mg and alfuzosin ( 10 mg ) proved to be safe and effective . A first cycle of medical expulsive therapy with tamsulosin 0.2 mg could be considered as an option in the management of single lower ureteral stone BACKGROUND Meta-analyses of previous r and omised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic , but emphasised the need for high- quality trials with wide inclusion criteria . We aim ed to fulfil this need by testing effectiveness of these drugs in a st and ard clinical care setting . METHODS For this multicentre , r and omised , placebo-controlled trial , we recruited adults ( aged 18 - 65 years ) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals . Participants were r and omly assigned by a remote r and omisation system to tamsulosin 400 μg , nifedipine 30 mg , or placebo taken daily for up to 4 weeks , using an algorithm with centre , stone size ( ≤5 mm or > 5 mm ) , and stone location ( upper , mid , or lower ureter ) as minimisation covariates . Participants , clinicians , and trial personnel were masked to treatment assignment . The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of r and omisation , analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data . This trial is registered with the European Clinical Trials Data base , EudraCT number 2010 - 019469 - 26 , and as an International St and ard R and omised Controlled Trial , number 69423238 . FINDINGS Between Jan 11 , 2011 , and Dec 20 , 2013 , we r and omly assigned 1167 participants , 1136 ( 97 % ) of whom were included in the primary analysis ( 17 were excluded because of in eligibility and 14 participants were lost to follow-up ) . 303 ( 80 % ) of 379 participants in the placebo group did not need further intervention by 4 weeks , compared with 307 ( 81 % ) of 378 in the tamsulosin group ( adjusted risk difference 1·3 % [ 95 % CI -5·7 to 8·3 ] ; p=0·73 ) and 304 ( 80 % ) of 379 in the nifedipine group ( 0·5 % [ -5·6 to 6·5 ] ; p=0·88 ) . No difference was noted between active treatment and placebo ( p=0·78 ) , or between tamsulosin and nifedipine ( p=0·77 ) . Serious adverse events were reported in three participants in the nifedipine group ( one had right loin pain , diarrhoea , and vomiting ; one had malaise , headache , and chest pain ; and one had severe chest pain , difficulty breathing , and left arm pain ) and in one participant in the placebo group ( headache , dizziness , lightheadedness , and chronic abdominal pain ) . INTERPRETATION Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic . FUNDING UK National Institute for Health Research Health Technology Assessment Programme Purpose To compare the efficacy of α1D-receptor antagonist Naftopidil and α1A/D-receptor antagonist Tamsulosin in management of distal ureteral stones . Material s and methods A total of 131 patients with distal ureteral stones were included in the study from December 2008 to September 2010 . The patients were r and omized to 3 groups : group 1 ( 43 patients ) , those receiving 10 mg naftopidil once daily ; group 2 ( 45 patients ) , those receiving 0.4 mg tamsulosin once daily ; and group 3 ( 43 patients ) were given a watchful waiting and served as control group . All patients were followed up for 2 weeks . Ultrasonography and kidney-ureters-bladder ( KUB ) were performed on day 7 and 14 . At the end of the follow-up period , patients who failed to expel the stone were scheduled to undergo ESWL or ureteroscopy . Results Stone expulsion was observed in 31 patients in group 1 ( 72.1 % ) , 37 patients in group 2 ( 82.2 % ) , and 13 patients in group 3 ( 30.2 % ) . A statistically significant difference was noted with Chi-square testing between groups 1 and 3 , and groups 2 and 3 ( P = 0.000 and P = 0.000 , respectively ) . Average time to expulsion was 7.6 ± 2.26 days ( range 1–12 days ) in group 1 , 7.7 ± 1.94 days ( range 2–11 days ) in group 2 , and 9.4 ± 2.48 days ( range 6–14 days ) in group 3 . A statistically significant difference was observed in time to expulsion between groups 1 and 3 , and groups 2 and 3 ( P = 0.000 , P = 0.001 , respectively ) by ANOVA testing . The side effects encountered in the study groups were generally mild and did not require cessation of therapy in any patient . Conclusions Naftopidil could significantly increase spontaneous passage of distal ureteral stones with low side effects . The stone expulsion rate is similar for the tamsulosin Low-dose ( 0.2 mg/day ) and st and ard-dose ( 0.4 mg/day ) tamsulosin were studied in a r and omized controlled trial of 75 out patients with distal ureteroliths in Thail and . Group 1 ( n = 25 ; control ) received oral sodium diclofenac 50 mg twice a day for 10 days ; group 2 ( n = 25 ) received oral sodium diclofenac 50 mg twice a day for 10 days , with oral tamsulosin 0.2 mg once a day up to 28 days ; and group 3 ( n = 25 ) received oral sodium diclofenac 50 mg twice a day for 10 days , with oral tamsulosin 0.4 mg once a day up to 28 days . For groups 1 , 2 and 3 , respectively , the expulsion rates were 4 % , 40 % and 68 % ( significantly different for group 1 vs group 2 , and for group 1 vs group 3 ) and mean expulsion times were 23.00 , 9.30 and 10.76 days . Both doses of tamsulosin increased stone expulsion rate and decreased expulsion time in comparison with the control , and have been shown to be safe and effective in Asian patients PURPOSE To evaluate the clinical role of an alpha(1a-1d)-specific blocker in the medical expulsive therapy of symptomatic lower ureteral stones . MATERIAL S AND METHODS This prospect i ve study was carried out from May 2005 to December 2006 and involved 95 patients . All patients , who had symptomatic lower ureteral stones < 10 mm diameter , were enrolled in this prospect i ve study , and were r and omly divided into three groups using the statistical software programs Plus 1.0 and Plus 2.10 . Group 1 ( 32 patients ) received tamsulosin ( 0.4 mg daily ) , group 2 ( 32 patients ) received terazosin ( 2 mg daily ) , group 3 ( 31 patients ) acted as controls . All patients were diagnosed with x-rays of the kidneys , ureters , and bladder , urinary ultrasonography , and intravenous urography . All patients received the same analgesic regimen and sublingual buprenorphine on dem and . The number of colic episodes , lower urinary tract symptoms , analgesic dosages , and the number of days required for spontaneous passage of the stones were all recorded in a diary . RESULTS Expulsion was observed in 26 of 32 patients in group 1 ( 81 % ) , 25 of 32 in group 2 ( 78 % ) , and 17 of 31 in group 3 ( 55 % ) . The average expulsion time for groups 1 , 2 , and 3 were 6.3 , 6.3 , and 10.1 days , respectively . Mean analgesic dosage per patient in groups 1 , 2 , and 3 were 231 , 256 , and 347 mg , respectively . A statistically significant difference was observed between groups 1 and 2 with respect to group 3 for all three of these parameters . Adverse effects were also seen in 5 of 32 patients in group 2 ( 16 % ) , a statistically significant difference with regard to groups 1 and 3 . CONCLUSIONS Medical treatment with alpha(1a-1d)-blocker proved to be safe and effective as demonstrated by the increased stone expulsion rate and reduced expulsion time , as well as the need for analgesics PURPOSE Few studies have investigated the efficacy of silodosin , a recently introduced selective alpha 1-A adrenoceptor antagonist , in medical expulsive therapy ( MET ) for ureteral calculi . The results of these studies , which all evaluated the efficacy of 8 mg/day , indicate that silodosin is a potential treatment for ureteral calculi . This study investigated the efficacy of 4 mg/day of silodosin for MET of distal ureteral stones 4 to 10 mm in diameter . MATERIAL AND METHOD After 70 patients had been r and omized into 2 groups of 35 patients each , both the control and experimental groups ( groups 1 and 2 , respectively ) were advised to take 75 mg/day of diclofenacsodiumas needed for pain relief but only the experimental group to take 4 mg/day of silodosin . After 21 days , the groups were compared regarding the stone expulsion rate and duration , number of renalcolicepisodes , and analgesicdosage . RESULTS The median expulsion rates were 71.4 % and 91.4 % in groups 1 and 2 , respectively , and the difference between them was significant ( P=0.031 ) . The median expulsion duration s were 12.91±6.14 and 8.03±4.99 days , respectively , and the difference between them was significant ( P<0.001 ) . No significant differences were found regarding the median number of renal colic episodes or median analgesic dosage . While no patients in group 1 experienced side effects , 5 patients ( 14 % ) in group 2 experienced retro grade ejaculation . CONCLUSION These results indicate that 4 mg/day of silodos in facilitates the expulsion of distal ureteral stones 4 to 10 mm in diameter but does not significantly reduce the number of renal colic episodes or analgesic dosage The objective of this study is to assess the efficacy of an alpha-1 adrenergic receptor blocking agent on the spontaneous passage of proximal ureteral calculi ≤10 mm . 92 patients having single radio-opaque proximal ureteral stone ≤10 mm were r and omized into two groups . Group 1 patients ( n = 50 ) were followed with classical conservative approach and patients in Group 2 ( n = 42 ) additionally received tamsulosin , 0.4 mg/day during 4 weeks follow-up . The stone passage rates , stone expulsion time , VAS score , change in colic episodes , and hospital re-admission rates for colicky pain were compared . The patients were furthermore stratified according to stone diameters < 5 and 5–10 mm . The data of these subgroups were also compared . Stone expulsion rates showed statistically significant difference between tamsulosin receivers and non-receivers ( 35.7 vs 30 % , p = 0.04 ) . Time to stone expulsion period was also shortened in those receiving tamsulosin ( 8.4 ± 3.3 vs 11.6 ± 4.1 days , p = 0.015 ) . Likewise , the mean VAS score and renal colic episodes during follow-up period were significantly diminished in Group 2 patients ( 4.5 ± 2.3 vs 8.8 ± 2.9 , p < 0.01 and 66.6 vs 36 % , p = 0.001 , respectively ) . Among the stones < 5 mm , tamsulosin receiving patients had higher spontaneous passage rate ( 71.4 vs 50 % , p < 0.001 ) . The prominent effect of tamsulosin on the 5–10 mm stones was the relocation of the stones to a more distal part of ureter ( 39.3 vs 18.7 % , p = 0.001 ) . Administration of tamsulosin in the medical management of proximal ureteral calculi can facilitate the spontaneous passage rate in the stone < 5 mm and the relocation of the stones between 5 and 10 mm to more distal part of the ureter In this article , we investigated the effect of the combined use of tamsulosin and potassium citrate ( Uralyt-U ® ) for the treatment of uric acid stones in the distal ureter . The study was design ed as a prospect i ve , double blind r and omized controlled trial . A total of 191 adult patients with radiolucent distal ureteral calculi were recruited . We included patients with solitary stones ≥5 mm with mild or moderate hydronephrosis and a normal contralateral tract . The patients were r and omized into four equal groups ( the placebo , tamsulosin , Uralyt-U ® , and the combined treatment groups ) . The patients were treated for a maximum duration of 4 weeks or until stone expulsion . The stone size in all groups ranged from 5 to 11 mm ( 7.69 ± 1.7 mm ) . The total expulsion rate of the stones was significantly lower in the control group ( 26.1 % ) compared with that of any of the other three groups ( 68.8 , 58.7 , and 84.8 % respectively ) ( P < 0.05 ) . Meanwhile , the difference between the Uralyt-U ® group and the combined treatment group was also statistically significant ( P < 0.05 ) . When we studied the patients with stones > 8 mm as a separate subgroup to find the effect of the used drugs on the relatively large stones , we detected that the expulsion rate of these stones was significantly higher in the patients who received the combined treatment in comparison with any of the other three groups ( P < 0.05 ) . In conclusion , the use of urinary alkalization with tamsulosin can increase the frequency of spontaneous passage of distal ureteral uric acid stones especially those of 8–11 mm STUDY OBJECTIVE The alpha-adrenergic antagonist tamsulosin hydrochloride has become an increasingly common adjunct in the treatment of ureteral calculi ; however , its efficacy in a general emergency department ( ED ) population has not been investigated . METHODS We conducted a r and omized , controlled trial of adult ED patients with distal ureteral calculi diagnosed by computed tomography scan . Patients were r and omized to receive either a 10-day course of ibuprofen and oxycodone plus tamsulosin or ibuprofen and oxycodone alone . The primary outcome measure was successful spontaneous ureteral stone expulsion at 14 days . Secondary outcomes included time to stone passage , self-reported pain scores , number of colicky pain episodes , unscheduled return ED/ primary care visits , number of days of missed work/usual function , amount of analgesic used , and adverse events . RESULTS Eighty subjects were enrolled in the study , with 77 completing the trial . Mean stone size was 3.6 mm ( 95 % confidence interval [ CI ] 3.4 to 3.9 ) . Successful spontaneous stone expulsion at 14 days was similar between the groups , with 27 ( 77.1 % ) subjects in the tamsulosin group and 24 ( 64.9 % ) subjects in the st and ard therapy group reporting spontaneous stone passage , a difference of 12 % ( 95 % CI -8.4 % to 32.8 % ) . At 2- , 5- , and 14-day follow-up , there were no clinical ly important ( or statistically significant ) differences between the groups for any secondary outcome measure . No adverse events were reported in either group . CONCLUSION In this cohort of adult ED patients with distal ureteral calculi , treatment with tamsulosin did not substantially improve any of the studied outcome measures compared with treatment with ibuprofen and oxycodone alone PURPOSE Naftopidil is a specific alpha1D-adrenergic receptor antagonist . We performed the current r and omized , controlled study to determine the expulsive role of naftopidil for distal ureteral stones . MATERIAL S AND METHODS From March 2006 to January 2007 , 60 patients with distal ureteral stones were r and omly divided into groups 1 and 2 . Group 1 served as the control and underwent watchful waiting , while group 2 received 50 mg naftopidil daily in the morning . All patients were instructed to drink a minimum of 2 l water daily . The stone expulsion rate and time , potential side effects of naftopidil , number of pain episodes and requirements for pain medication were documented during the 14-day followup . RESULTS All patients in groups 1 and 2 completed the study . There was no difference between the groups in patient age , sex and stone size . The stone expulsion rate was significantly higher in group 2 than in group 1 ( 90.0 % vs 26.7 % , p < 0.01 ) . No significant difference in expulsion time was noted between the groups . No patients experienced obvious naftopidil side effects or ureteral colic . Multivariate analysis using a Cox proportional hazards model indicated that the probability of expulsion was increased 5.263 times ( 95 % CI 2.304 - 12.024 ) in group 2 compared with that in group 1 ( p < 0.001 ) . CONCLUSIONS The selective alpha1D-blocker naftopidil can significantly facilitate spontaneous passage of distal ureteral stones with few side effects , providing a new choice for medical expulsive therapy BACKGROUND Many minimally invasive interventional techniques as well as expectant treatment exist for the management of lower ureteric calculi . This study was conducted to evaluate th efficacy of tamsulosin as an expulsive pharmacologic therapy for the treatment of distal uretern stone . METHODS This r and omized control trial included 100 patients over 18 years of age wit stone Size > or = mm in distal 1/3 of ureter . Patients were r and omly assigned into two groups ( A & B Group A Patients were given Capsule Tamsulosin 0.4 mg , 1 daily up to 4 weeks while group B patients were given placebo , 1 Capsule daily up to 4 weeks . The primary endpoint was expulsio rate . A written informed consent was taken from all the patients . Expulsion time , need for analgesics , need for hospitalization and drug side effects were secondary endpoints . RESULTS A total of 49 patients in group A and 48 patients in group B reported back , therefore 97 out of 10 patients were evaluated . Mean age of the patients was 36.34 years ( range 18 - 57 years ) . Mea stone size was 5.78 mm ( range 4 - 8 mm ) in greatest dimension . A stone expulsion rate of 85.71C ( 42 patients ) was noted in group A and 54.20 % ( 26 patients ) in group B. Group A revealed statistically significant advantage in term of stone expulsion rate ( p=0.032 ) . Considering expulsio time in days group A showed statistically significant advantage ( p=0.015 ) . Regarding age , se ) stone size and stone lateralization ( right/left ) , there was no significant difference between th group A and B. No drug side effects were noted in both the groups . CONCLUSION By usin tamsulosin a higher stone expulsion rates can be achieved in a shorter time . More r and omize control trials are required to establish tamsulosin as a st and ard medical expulsive treatment PURPOSE We analyze the natural history of stone passage in patients with ureterolithiasis , and define factors predictive of spontaneous passage . MATERIAL S AND METHODS A total of 75 patients with ureteral calculi were prospect ively followed for stone passage . Clinical data included patient gender and age , stone size and location , pain medication requirements and interval to stone passage . Of the 75 patients 13 ( 17 % ) required intervention and 62 ( 83 % ) were followed until spontaneous stone passage . Stones requiring intervention were not included in the time to passage analysis . RESULTS Of the 75 patients 41 ( 55 % ) had ureteral stones 2 mm . or smaller with an average time to stone passage of 8.2 days and only 2 ( 4.8 % ) required intervention , 18 ( 24 % ) had stones between 2 and 4 mm . with an average time to stone passage of 12.2 days and 3 ( 17 % ) required intervention , and 16 had stones 4 mm . or greater with an average time to stone passage of 22.1 days and 8 required intervention . For 95 % of stones to pass it took 31 days for those 2 mm , or less , 40 days for those 2 to 4 mm . and 39 days for those 4 to 6 mm . Multivariate analysis revealed that size , location and side were statistically related to stone passage interval ( p = 0.012 ) . Stones that were smaller , more distal and on the right side were more likely to pass spontaneously and required fewer interventions . CONCLUSIONS Interval to stone passage is highly variable and dependent on stone size , location and side . Degree of pain , and patient gender and age had no bearing on the time to stone passage . Of ureteral stones 95 % 2 to 4 mm . pass spontaneously but passage may take as long as 40 days . Intervention may be required in 50 % of ureteral calculi greater than 5 mm OBJECTIVES To assess the clinical role of corticosteroids in the medical expulsive therapy of symptomatic distal ureteral stones . METHODS Between January 2004 and September 2005 , 114 patients with symptomatic distal ureteral stones with a > /=5 mm diameter were enrolled in this prospect i ve study and divided into four groups based on the urologist ( of four ) who treated them in the emergency unit . Group A ( 33 patients ) received tamsulosin ( 0.4 mg daily ) , group B ( 24 patients ) received deflazacort ( 30 mg daily ) , group C ( 33 patients ) received both ( 0.4 mg tamsulosin+30 mg deflazacort daily ) , and control group D ( 24 patients ) received only analgesics . The treatment duration was 10 d to prevent the side-effects of prolonged corticosteroid therapy . The end points were the expulsion rate , analgesic consumption , number of ureteroscopies , and safety . RESULTS The groups were comparable in terms of age , sex , and stone location . The stone diameter was 5.96+/-0.33 mm for group A , 5.83+/-0.4 mm for group B , 5.88+/-0.23 mm for group C , and 5.71+/-0.5 mm ( p>0.05 ) for group D. The rates of expulsion for the four groups were 60 % , 37.5 % , 84.8 % , and 33.3 % , respectively . There was a significant difference between group C and the other groups ( p<0.001 ) . The mean analgesic consumption was 42.5+/-0.4 mg for group A , 50+/-0.3 mg for group B , 27.3+/-0.5 mg for group C , and 81+/-0.33 mg for group D , with a significant difference between group C and the other groups ( p<0.001 ) . During the treatment period , only two cases of drug side-effects related to tamsulosin ( without any drop-outs ) were recorded . CONCLUSION When the medical expulsive therapy for symptomatic distal ureteral stones is considered , the use of steroids ( deflazacort ) proves efficient only when administered together with alpha(1)-blockers ( tamsulosin ) . In addition , tamsulosin used on its own as a medical expulsive therapy can be considered as an alternative treatment for those patients who are not suitable for steroid therapy , as it is generally efficient Abstract Purpose To investigate the effect of sexual intercourse on the spontaneous passage of distal ureteral stones 5–10 mm in size . Methods A total of 190 male patients with distal ureteral stones were r and omly divided into three groups . Patients in group 1 were administered tamsulosin 0.4 mg/day ( n = 60 ) . Patients in group 2 were asked to have sexual intercourse at least three times a week ( n = 66 ) . Patients in group 3 received st and ard medical therapy alone and acted as the controls ( n = 64 ) . The expulsion rate was controlled after 2 and 4 weeks . Differences between the groups were analyzed statistically by the Chi-square and Student ’s t test . p < 0.05 was considered as statistically significant . Results The mean ages of the patients in groups 1 , 2 , and 3 were 34.4 ± 13.5 ( 18–60 ) , 38.6 ± 14.1 ( 18–63 ) , and 36.92 ± 12.4 ( 18–59 ) years , respectively ( p > 0.05 ) . The mean stone size was 7.09 ± 1.4 mm in group 1 , 7.01 ± 1.4 mm in group 2 , and 7.1 ± 1.3 mm in group 3 ( p > 0.05 ) . Spontaneous passage rates in groups 1 , 2 , and 3 were 81.6 , 81.8 , and 51.5 % , respectively , and it was significantly higher in group 1 ( p = 0.0394 ) and group 2 ( p = 0.0350 ) . There was no significant difference between groups 1 and 2 ( p = 0.9925 ) . The analgesic needs in groups 1 , 2 , and 3 were found to be 1.3 ± 0.4 , 1.2 ± 0.6 , and 1.4 ± 0.4 times , respectively , and were significantly lower in the sexual intercourse group than in the control group ( p = 0.0276 ) . Conclusions Tamsulosin and sexual intercourse increase the spontaneous passage of distal ureteral stones 5–10 mm in size . At least three sexual intercourses per week seem to be at least as effective as tamsulosin . Sexual intercourse also reduces the need for analgesics in ureteric colic due to ureteral stones We aim ed to investigate the efficacy of two different doses of doxazosin , 4 and 8 mg , in medical expulsive therapy ( MET ) . This prospect i ve r and omized study included a total of 66 patients with distal ureteral stones which were radio-opaque and ≤10 mm . All patients were r and omly divided into three groups : Group 1 included 25 patients receiving 4 mg doxazosin . Group 2 included 22 patients receiving 8 mg doxazosin . Diclofenac 100 mg p.o . and daily 1500–2000 cc hydration were advised to the patients in Groups 1 and 2 to relieve pain . Group 3 consisted of 19 patients who were defined as control group and received only hydration and analgesics . The mean age of the patients was 30 ± 7.6 , 37.9 ± 11.5 and 33 ± 11.3 in Group 1 , Group 2 and Group 3 , respectively . The mean stone size was 6.6 ± 1.4 , 7.1 ± 1.5 and 6.6 ± 1.5 in Group 1 , Group 2 and Group 3 , respectively . The stone expulsion rate of the patient groups was 18/25 ( 72 % ) , 15/22 ( 68.1 % ) and 5/19 ( 25.3 % ) . There were significantly fewer pain episodes and lower analgesic requirement in Groups 1 and 2 ( p = 0.021 ) . However , the difference between Group 1 and Group 2 was non-significant ( p = 0.207 ) . Given the data of the present study , doxazosin , an alpha receptor blocker , exhibited equal efficacy with 4 or 8 mg doses in MET and was used safely and efficiently in ureteral stones < 10 mm . The findings of the present study showed that 4 mg dose is effective , when doxazosin is preferred for MET Recently , we reported that α1A adrenoceptor ( AR ) is the main participant in phenylephrine-induced human ureteral contraction . We therefore decided to carry out a prospect i ve r and omized study to evaluate the effects of silodosin , a selective α1A AR antagonist , as a medical expulsive therapy for ureteral stones . A total of 187 male patients , who were referred to our department for the management of symptomatic unilateral ureteral calculi of less than 10 mm , were r and omly divided into two groups : group A ( 92 patients ) , who were instructed to drink 2 L of water daily , and group B ( 95 patients ) , who received the same instruction and were also given silodosin ( 8 mg/daily ) for a maximum of 8 weeks . Expulsion rate , mean expulsion time and need for analgesics were examined . Overall , the mean expulsion time was 15.19 ± 7.14 days for group A and 10.27 ± 8.35 days for group B ( P = 0.0058 ) . In cases involving distal ureteral stones , the mean expulsion time was 13.40 ± 5.90 and 9.29 ± 5.91 days , respectively ( P = 0.012 ) . For stones of 1 - 5 mm in diameter , the mean expulsion time was 14.28 ± 6.35 and 9.56 ± 8.45 days , respectively ( P = 0.017 ) . For stones of 6 - 9 mm in diameter , the stone expulsion rate was 30.4 % and 52.2 % ( P = 0.036 ) , and the mean expulsion time was 21.00 ± 9.9 and 11.33 ± 8.31 days , respectively ( P = 0.038 ) . Herein , we report the first on silodosin in the management of ureteral lithiasis . Our findings suggest that silodosin might have potential as a medical expulsive therapy for ureteral stones OBJECTIVES To evaluate the activity of the therapeutic agents ( tamsulosin and /or tolterodine ) used to accelerate the expulsion of stones and to reduce the probable complications during observation of the medical treatment of distal ureteral stones to allow spontaneous passage . METHODS A total of 120 patients with distal ureteral stones were included in the study . Patients with stones less than 10 mm and allowing urinary flow were included in the study . The patients were studied in four r and omly divided groups . Group 1 patients received tamsulosin 0.4 mg/day , group 2 patients received tamsulosin 0.4 mg/day plus tolterodine 2 mg ( twice a day ) , group 3 patients received tolterodine 2 mg ( twice a day ) , and group 4 patients did not receive any medical treatment ( control group ) . RESULTS Differences among the four groups in patient age and stone dimension were not statistically significant ( P > 0.05 ) . The stone expulsion rates were greater ( P < 0.05 ) in groups 1 and 2 than in groups 3 and 4 . A significant variation ( P < 0.05 ) regarding the time to stone expulsion was observed in groups 1 and 2 . CONCLUSIONS In our study , the use of tamsulosin for the expulsion of distal ureteral stones was effective ; however , the use of tolterodine provided no additional advantages Abstract We evaluated the efficacy of tamsulosin and nifedipine in medical expulsive therapy ( MET ) in patients with distal ureteral stone . In addition , we tried to determine the predictive value of Hounsfield Unit ( HU ) of the stone in the success of MET . A total of 75 patients with a distal ureteral stone of 5–10 mm diameter were r and omly divided into three groups . Group 1 ( n = 25 ) received tamsulosin 0.4 mg/d ; group 2 ( n = 25 ) received nifedipine 10 mg/day p.o and group 3 ( n = 25 ) received diclofenac sodium 50 mg p.o . when required . At the beginning of each treatment , the HU of the stone was also measured using a non-contrast computerized tomography in all the patients . The results were evaluated at week four . The mean age of the patients was 36.8 ( range , 16–68 ) years . Stone expulsion was observed in 19 ( 76 % ) patients in group 1 , 16 ( 64 % ) patients in group 2 and 9 ( 36 % ) patients in group 3 ( pgroup1 - 3 = 0.004 , pgroup2 - 3 = 0.048 and pgroup1 - 2 = 0.355 ) . The mean expulsion time was 9 , 9.1 and 10.3 d , respectively ( pgroup1 - 3 < 0.001 , pgroup2 - 3 < 0.001 and pgroup1 - 2 = 0.619 ) . The mean diclofenac sodium dose per patient was 544 , 602 and 1408 mg in groups 1 , 2 and 3 , respectively ( pgroup1 - 3 < 0.001 , pgroup2 - 3 < 0.001 and pgroup1 - 2 = 0.977 ) . The mean HU of the stone in patients with and without a successful MET was 363 and 389 , respectively ( p = 0.462 ) . Our results showed that MET with both nifedipine and tamsulosin provided a similar increase in the expulsion rate for distal ureteral stones . HU does not seem to be a predictive parameter for stone expulsion OBJECTIVES To assess the clinical efficacy of doxazosin as the medical-expulsive therapy for distal ureterolithiasis . METHODS A total of 65 patients with a symptomatic 4 - 7 mm distal ureteral stone were included in the study . Patients were r and omized to 1 of the 2 treatment groups . Group 1 ( n=32 patients ) was the control group and received diclofenac sodium 50 mg for their pain and group 2 ( n=33 patients ) received doxazosin ( 2 mg daily at the night ) along with diclofenac sodium 50 mg . The treatment duration was until stone expulsion or 28 days , whichever come first . The primary endpoint of the study was the stone expulsion rate . The secondary endpoints included time to stone expulsion , use of analgesics , and number of emergency room visits , hospitalizations , and drug side effects . Statistical analyses were performed using chi-square test and Fisher exact test . RESULTS Both groups were comparable in terms of demographic , clinical , and stone-related parameters . Stone expulsion rate was significantly higher in the treatment group ( 38 % for group 1 and 70 % for group 2 , P=.009 ) while the expulsion time was significantly lesser in group 2 patients ( P=.005 ) . During the treatment period , we observed significant differences between the 2 groups in the number of pain episodes and analgesic used ( P=.0001 ) . None of the patients in either groups reported adverse drug-related events . CONCLUSIONS Doxazosin significantly improves stone expulsion and is associated with decreased colic frequency and use of analgesia . It is also well tolerated with no adverse drug-related events Objective Recently , we reported that alpha 1A-adrenoceptor ( AR ) is the main participant in phenylephrine-induced human ureteral contraction . We therefore decided to carry out a prospect i ve r and omized study to evaluate the effects of silodosin , a selective alpha 1A AR antagonist , as a medical expulsive therapy ( MET ) for distal ureteral stones . Methods A total of 112 male patients , who were referred to our department for the management of symptomatic unilateral distal ureteral calculi of less than 10 mm , were r and omly divided into two groups : group A ( 56 patients ) who were instructed to drink 2 L of water daily and group B ( 56 patients ) who received the same instruction and were also given silodosin ( 8 mg/daily ) for a maximum of 4 weeks . Expulsion rate , expulsion time and need for analgesics were examined . Results The expulsion rate was 55.3 % ( 56 patients ) for group A and 72.7 % ( 55 patients ) for group B ( P = 0.106 ) . The expulsion rate for < 5 mm was 92.9 % ( 28 patients ) for group A and 69.2 % ( 26 patients ) for group B ( P = 0.053 ) . The expulsion rate for ≥5 mm was 17.9 % ( 28 patients ) for group A and 75.9 % ( 29 patients ) for group B ( P = 0.001 ) . The expulsion time was 13.40 ± 5.90 and 9.29 ± 5.91 days , respectively ( P = 0.012 ) . Analgesics were required 1.5 ± 3.1 and 0.3 ± 0.9 times , respectively ( P = 0.382 ) . Stone size in expulsion cases was 3.64 ± 1.25 and 5.23 ± 2.32 mm , respectively ( P = 0.003 ) . Conclusions Stone size has been identified as an important predictive factor for stone expulsion . Therefore , it is important that administration of silodosin can facilitate expulsion of 1.5 mm or larger distal ureteral stones , as compared to control . We believe that silodosin might have potential as a MET for distal ureteral stones OBJECTIVE To evaluate the efficacy of low dose tamsulosin for facilitating spontaneous passage of ureteral stones in Japanese male patients . METHODS A total of 71 patients with symptomatic ureteral stones , 10 mm or smaller in size , were r and omly allocated into groups 1 and 2 . Group 1 received tamsulosin ( 0.2 mg/day ) for a maximum of 4 weeks and group 2 received no medication . The primary endpoint was the stone expulsion rate and the secondary endpoints were stone expulsion time and analgesic use . RESULTS There were no significant differences between the groups in terms of age , stone size and location . The stone expulsion rate was significantly higher in group 1 than in group 2 ( 77 % vs 50 % , P = 0.002 ) . No significant differences were noted in the stone expulsion time and analgesic use between the groups . CONCLUSION Low dose tamsulosin can significantly facilitate spontaneous passage of ureteral stones without significant side-effects in Japanese male patients OBJECTIVE To investigate the effect of sexual intercourse on spontaneous passage of distal ureteral stones . MATERIAL AND METHODS The patients were r and omly divided into 3 groups with r and om number table envelope method . Patients in group 1 were asked to have sexual intercourse at least 3 - 4 times a week . Patients in group 2 were administered tamsulosin 0.4 mg/d . Patients in group 3 received st and ard medical therapy alone and acted as the controls . The expulsion rate was controlled after 2 and 4 weeks . Differences in the expulsion rate between groups were compared with the chi-square test for 3 × 2 tables . P < .05 was considered as statistically significant . RESULTS The mean stone size was 4.7 ± 0.8 mm in group 1 , 5 ± 1 mm group 2 , and 4.9 ± 0.8 mm group 3 ( P = .4 ) . Two weeks later , 26 of 31 patients ( 83.9 % ) in the sexual intercourse group , and 10 of 21 patients ( 47.6 % ) in tamsulosin group passed their stones , whereas 8 of 23 patients ( 34.8 % ) in the control group passed their stones ( P = .001 ) . The mean stone expulsion time was 10 ± 5.8 days in group 1 , 16.6 ± 8.5 days in group 2 , and 18 ± 5.5 days in group 3 ( P = .0001 ) . CONCLUSION Our results have indicated that patients who have distal ureteral stones ≤6 mm and a sexual partner may be advised to have sexual intercourse 3 - 4 times a week to increase the probability of spontaneous passage of the stones OBJECTIVE To study the impact of tamsulosin on the rate of spontaneous passage of distal ureteral stones . METHODS A total of 100 patients with stones sized 10 mm or smaller , located in the distal part of the ureter were included . Patients were r and omly assigned to 2 equal groups . Group 1 received 0.4 mg tamsulosin once daily and group 2 received placebo . The investigators and the patients were masked to the type of treatment . Patients were followed-up until passage of the stone , or for a maximum of 4 weeks . The number of pain episodes , need for analgesia , stone expulsion rate and time , and possible side effects of medications were observed in both groups . RESULTS Apart from 4 patients in the placebo group who were lost to follow-up , all patients complied with the prescribed medications and continued the study . Stone expulsion occurred in 41 of 50 patients ( 82 % ) in group 1 and in 28 of 46 patients ( 61 % ) in group 2 ( P = .02 ) . The chance of stone expulsion was 3 times higher in the tamsulosin group ( relative risk [ RR ] = 2.93 ; 95 % CI , 1.152 - 7.45 ) . In group 1 , patients with stones sized < or = 5 mm showed a significantly higher expulsion rate compared to those with larger stones ( > 5 mm ) . Age , gender , and stone laterality had no significant impact on the expulsion rate . The expulsion time was significantly shorter in the tamsulosin group ( 6.4 + /- 2.77 days vs 9.87 + /- 5.4 days for groups 1 and 2 , respectively ) . Moreover , the frequency of pain episodes , the need for diclofenac , and its total dosage were significantly lower in the tamsulosin group . Side effects observed in both groups were comparable and mild , and no patient withdrew because of them . CONCLUSIONS Tamsulosin is a safe and effective drug that enhances spontaneous passage of distal ureteral stones sized 10 mm or smaller STUDY OBJECTIVE We assess the efficacy and safety of tamsulosin compared with placebo as medical expulsive therapy in patients with distal ureteric stones less than or equal to 10 mm in diameter . METHODS This was a r and omized , double-blind , placebo-controlled , multicenter trial of adult participants with calculus on computed tomography ( CT ) . Patients were allocated to 0.4 mg of tamsulosin or placebo daily for 28 days . The primary outcomes were stone expulsion on CT at 28 days and time to stone expulsion . RESULTS There were 403 patients r and omized , 81.4 % were men , and the median age was 46 years . The median stone size was 4.0 mm in the tamsulosin group and 3.7 mm in the placebo group . Of 316 patients who received CT at 28 days , stone passage occurred in 140 of 161 ( 87.0 % ) in the tamsulosin group and 127 of 155 ( 81.9 % ) with placebo , a difference of 5.0 % ( 95 % confidence interval -3.0 % to 13.0 % ) . In a prespecified subgroup analysis of large stones ( 5 to 10 mm ) , 30 of 36 ( 83.3 % ) tamsulosin participants had stone passage compared with 25 of 41 ( 61.0 % ) with placebo , a difference of 22.4 % ( 95 % confidence interval 3.1 % to 41.6 % ) and number needed to treat of 4.5 . There was no difference in urologic interventions , time to self-reported stone passage , pain , or analgesia requirements . Adverse events were generally mild and did not differ between groups . CONCLUSION We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage , time to stone passage , pain , or analgesia requirements . In the subgroup with large stones ( 5 to 10 mm ) , tamsulosin did increase passage and should be considered It has recently been demonstrated that specific adrenoceptors subtypes ( α1A/α1D ) are prevalent in the distal part of the ureter , a finding supporting the interesting results obtained by different groups with the use of tamsulosin in the treatment of distal ureteral calculi . We performed a prospect i ve r and omized study to evaluate the effects of the addition of tamsulosin on our st and ard pharmacological therapy for the treatment of selected ureteral stones . A total of 64 patients referred to our department for the management of symptomatic ureteral calculi were considered . Patients were r and omly divided into two treatment groups : group A ( n=32 ) who received diclofenac ( 100 mg/daily ) plus aescin ( 80 mg/daily ) and group B ( n=32 ) who received the same therapy plus tamsulosin ( 0.4 mg/daily ) for a maximum of 2 weeks . No significant differences were found between the groups for age , gender distribution and mean stone size measured in the single largest dimension at presentation . The stone expulsion rate was 60 % ( 19/32 patients ) for group A and 88 % for ( 28/32 ) for group B with a mean expulsion time of 7.4±2.2 ( range 3.5–12 ) and 4.8±2.7 days ( range 1.8–10.5 ) , respectively . Group B showed a significant advantage in terms of both expulsion rate ( P=0.01 ) and expulsion time ( P=0.005 ) . Different analgesics from those used in the st and ard treatment regimen were required in ten patients in group A ( 31 % ) but only three patients in group B ( 9 % ) . This difference was significant ( P=0.003 ) . Hospitalization for recurrent colic was needed in 21 % of patients in group A ( 7/32 ) and in 9 % in group B ( 3/32 ) ( P=0.01 ) . Only two patients in each group ( 6 % ) experienced minor side effects associated with the expulsive therapy . Our data confirm the efficacy of tamsulosin in the treatment of distal ureteral stones up to 1 cm . This selective α-blocker should therefore be included in the pharmacological regimen of patients when a conservative approach is considered in the treatment of ureteral lithiasis OBJECTIVE The objective of the study is to determine if tamsulosin initiated in the emergency department ( ED ) decreases the time to ureteral stone passage at 1 week or time to pain resolution , compared to placebo . METHODS We performed a prospect i ve , r and omized , double-blinded , placebo-controlled trial of tamsulosin vs placebo in ED patients with ureterolithiasis on computed tomography . Patients were identified and enrolled between April 2007 and February 2009 and were r and omized to either 0.4 mg of tamsulosin or placebo for 1 week . We contacted participants using a telephone survey on post-ED visit days 1 , 2 , 3 , and 7 . The primary outcome was time to stone passage , with secondary outcomes being maximum pain score and amount of pain medication required . RESULTS Of the 127 patients enrolled during this study , 15 were lost to follow-up , and 12 required surgical interventions before the 7-day mark , leaving 100 patients for analysis . Of the 100 patients , 53 received tamsulosin and 47 received placebo . There was no difference between groups in percentage of male , mean age , initial serum creatinine , average stone size , stone location , and history of prior stone . The probability that the patient did not pass a stone at 7 days was not different between tamsulosin and placebo , 62.1 % ( 95 % confidence interval , 49.1%-75.1 % ) vs 54.4 % ( 95 % confidence interval , 40.3%-68.6 % ; P = .58 ) . There was no significant difference in the high pain score ( P = .12 ) or hydrocodone/acetaminophen intake ( P = .76 ) between treatment groups at any of the time points . CONCLUSION This study reveals no difference in the proportion of stone passage or high pain score and pain medication utilization at 7 days between tamsulosin and placebo PURPOSE alpha1-Adrenergic blockers have recently been shown to increase the rate of spontaneous passage of distal ureteral stones . We compared efficacy of 3 different alpha1-adrenergic blockers for this purpose . MATERIAL S AND METHODS A total of 114 patients between 18 and 65 years old who had lower ureteral stones were included in the study . Patients were r and omly divided into 4 groups . Group 1 consisted of 28 patients and acted as the control group . Group 2 comprised 29 patients who received tamsulosin , group 3 was 28 patients receiving terazosin and group 4 was 29 patients receiving doxazosin . These agents were given for up to a month and hydration was also recommended simultaneously . Every week patients were controlled with x-rays of the kidneys , ureters , bladder and urinary ultrasonography . Meanwhile the number of pain episodes , analgesic dosage and the number of days for spontaneous passage of the calculi through the ureter were also recorded . RESULTS There were no differences between the groups with respect to age , weight , height , sex and stone size . The calculi passed through the ureter spontaneously in 15 patients in group 1 ( 53.57 % ) , in 23 patients in group 2 ( 79.31 % ) , in 22 patients in group 3 ( 78.57 % ) , and in 22 patients in group 4 ( 75.86 % ) . In groups 2 to 4 the number of pain episodes , expulsion time and analgesic dosage were found to be lower compared with those in group 1 . CONCLUSIONS alpha1-Adrenergic blockers increase the frequency of spontaneous passage of the distal ureteral calculi . All 3 agents tested were equally efficacious AIM Medical expulsive therapy ( MET ) using alpha-blockers is effective for distal ureteral calculi ( UC ) . We aim ed to evaluate the efficacy of tamsulosin for proximal UC expulsion . MATERIAL S AND METHODS An open-label r and omized controlled trial was conducted with 108 patients who agreed to conservative management for single , radiopaque , proximal UC ≤ 6 mm and were r and omized into group A ( n = 54 , conservative managements only ) or B ( n = 54 , 0.2 mg tamsulosin once a day ) . The primary end-point was stone passage rates ( SPR ) in the intention-to-treat population in 4 treatment weeks . The secondary end-points were estimated in per- protocol population and were time to stone passage , post-trial Euro- quality -of-life ( EuroQOL ) score , oral analgesic requirements , and willingness to undergo conservative treatment again . RESULTS The two groups were well balanced in terms of baseline patient and stone characteristics . Seventy nine patients ( 73.2 % ; 35 of group A and 44 of group B ) completed the study protocol . The overall SPR was 60.2 % ( 65/108 ) . Group B had a higher SPR ( 74.1 % ; 40/54 ) than group A ( 46.3 % ; 25/54 ; p = 0.003 ) and a significantly shorter time to stone passage ( mean days , A : 19.6 vs. B : 14.3 , p = 0.005 ) . The groups did not differ in post-trial EuroQOL score or oral analgesic requirements , whereas 74.3 % ( 26/35 ) of group A and 90.9 % ( 40/44 ) of group B were willing to undergo conservative treatment again ( p = 0.048 ) . Univariate logistic regression analysis showed that stone size ( OR = 1.447 , p = 0.045 ) and tamsulosin treatment ( OR = 3.314 , p = 0.004 ) significantly predicted stone expulsion . On multivariate analysis , only tamsulosin was statistically significant ( OR=3.198 , p = 0.021 ) . CONCLUSIONS Tamsulosin was associated with significantly higher stone expulsion rate and shorter expulsion time in proximal UC ≤ 6 mm compared with conservative managements only . Our results indicate that similar to patients with distal UC , MET using tamsulosin is a reasonable treatment option for patients with proximal UC Purpose To compare the efficiency and spontaneous expulsion rates of tamsulosin and Rowatinex in patients with distal ureteral stones . Methods Between March and July 2009 , 90 patients with distal ureteral stones < 10 mm in size were included in the study . Patients were r and omized in 3 groups : Group 1 ( n = 31 , those received 0.4 mg tamsulosin once daily ) , Group 2 ( n = 30 , those received 100 mg Rowatinex capsules 3 times a day ) , and Group 3 ( n = 29 , those received diclofenac 100 mg once daily ) . All patients were followed up for 10 days . Results and conclusions Mean age of the patients was 42.4 ± 16.1 ( range , 22–75 ) , 46.5 ± 16.5 ( range , 22–76 ) , and 43.5 ± 16.6 ( range , 18–71 ) years in Groups 1–3 , respectively . On admission , 37.8 % had hematuria and 78.9 % had lower urinary tract symptoms ( LUTS ) . No statistically significant differences were detected between the three groups regarding patient age , gender , mean stone size , stone location , stone site , additional analgesic requirement , number of ureteral colics during the treatment , and upper urinary tract dilation . The mean stone expulsion time was 3.5 days in Group 1 , 6 days in Group 2 , and 7 days in Group 3 ( P = 0.02 ) . Stone expulsion rate was significantly high in Group 1 compared to Group 2 ( P = 0.002 ) . Similarly , stone expulsion rate was significantly high in Group 1 compared to Group 3 ( P = 0.001 ) . Medical treatment with tamsulosin seems to be effective in patients with distal ureteral stones < 10 mm in size . However , use of Rowatinex does not seem to have any significant effect on clearance rate of distal ureteral calculi Objective . To evaluate the potential role of tamsulosin in the medical treatment of distal ureteral stones . Material and methods . Ninety patients with symptomatic distal ureteral calculi were enrolled . They were r and omly divided into two groups : Group A ( n=45 ) received diclofenac 100 mg on dem and for 4 weeks plus levofloxacin 250 mg daily for the first week and were well hydrated ; and Group B ( n=45 ) received the same therapy plus tamsulosin 0.4 mg/daily for 4 weeks . Abdominal ultrasound scans and KUB X-rays were performed weekly . Stone expulsion rates , time to expulsion , pain episodes and analgesic usage were determined . Intervention by means of shock-wave lithotripsy ( SWL ) or ureteroscopy was evaluated . Results . The stone expulsion rate was 51.1 % for Group A , compared to 88.9 % for Group B ( p=0.001 ) . The average time to expulsion was 12.53±2.12 days for Group A and 7.32±0.78 days for Group B ( p=0.04 ) . The number of pain episodes was significantly lower in Group B and mean use of analgesics was lower for Group B ( 0.14±0.5 vials ) than Group A ( 2.78±2.7 vials ) . Twenty-two patients in Group A failed to pass their stones after 4 weeks but only five in Group B. Of the patients who were not stone-free , 19 were treated with SWL and eight underwent ureteroscopy . Conclusion . Our study reveals the efficacy of tamsulosin for the treatment of distal ureteral stones . Tamsulosin should be added to the st and ard medical approach for treating these stones PURPOSE To evaluate efficacy and outcome of tamsulosin therapy for 4 mm-10 mm uncomplicated distal ureteral stones . MATERIAL S AND METHODS A total of 150 patients ( adults with newly diagnosed single unilateral distal ureteral 4 mm-10 mm stones ) were double blindly r and omized into GA or GB . All patients received traditional treatment of hydration and analgesia as needed . Additionally , patients received either placebo ( GA ) or 0.4 mg tamsulosin ( GB ) oral tablets once daily . Treatment and follow up were continued for up to 4 weeks . Endpoints were spontaneous stone passage rates ( SPR ) and passage time for different stone sizes within 4 weeks study period . RESULTS Analysis included 75 patients , in each group , with comparable characteristics . Overall SPR was 56 % in GA and 81.3 % in GB ; achieving significant absolute risk reduction ( ARR = 25.3 % ; p < 0.01 ) and number needed to treat ( NNT ) of 3.95 . SPR for stones < or= 6 mm was 69.2 % in GA versus 90.7 % in GB ( ARR = 21.5 % , p < 0.01 ) . For stones 7 mm-10 mm , SPR was 26.1 % in GA and 57.1 % in GB ( ARR = 31.0 % , p < 0.01 ) . NNT for < or= 6 mm and 7 mm-10 mm stones was 4.65 and 3.23 , respectively ( p < 0.05 ) . Median time for passage of < or= 6 mm stones was 17 versus 9 days in GA and GB ; while for 7 mm-10 mm stones it was 20 versus 15 days , respectively . During the first two weeks , 77.8 % of < or= 6 mm stones in GB have passed versus 23.8 % of 7 mm-10 mm stones . Analgesia consumption was significantly less in GB ( p < 0.01 ) . No significant adverse effects were observed . CONCLUSIONS Tamsulosin therapy for uncomplicated distal ureteral calculi augments SPR , shortens passage time and decrease need for analgesia . Particularly , tamsulosin shortens the passage time for smaller stones , and augments the passage rate for larger stones To evaluate , in a prospect i ve r and omized pilot study , the effectiveness and safety of tamsulosin , administered in patients with distal ureteric stones and who have already undergone an unsuccessful first cycle of medical expulsive therapy ( MET ) OBJECTIVE To evaluate the safety and efficacy of alfuzosin treatment on rate and time of stone expulsion in patients with uncomplicated distal ureteral stones . PATIENTS AND METHODS Prospect i ve , r and omized , open-label , controlled study . Patients > 18 years of age presenting to the outpatient urology clinic with uncomplicated radio-opaque stones located in the distal third of the ureter and of size ≤ 10 mm were included . Patients were r and omly assigned to either a control group ( n=26 ) and received st and ard of care management ( daily oral hydration and diclofenac 75 mg IM on dem and ) or to the alfuzosin group ( n=28 ) and received alfuzosin SR 5 mg twice daily in addition to st and ard of care management . Patients were followed weekly at office visits and twice weekly by telephone for 4 weeks or until stone expulsion . Assessment s included stone passage rate and time , and patients were monitored for occurrence of adverse drug events , complications , number of pain episodes , analgesic consumption , and number of hospital revisits . Mann-Whitney , χ(2 ) , and Fisher exact test were used for data analysis . RESULTS All 54 patients completed the study . Stone expulsion rate was higher in the alfuzosin arm ( 53.6 % , 15/28 ) compared to the control arm ( 26.9 % , 7/26 , p=0.04 ) . Median stone passage time was lower in the alfuzosin group than in the control group ( 9 vs 19 days , respectively , p=0.006 ) . Ureteral sepsis , uncontrollable pain , and hospitalization readmissions were reported in the control group only . There were no differences between groups in number of pain episodes , pain scores , or analgesic consumption . Alfuzosin therapy was tolerable with only minor adverse effects ( headache , dizziness , mild postural hypotension , and rhinitis ) . CONCLUSION Alfuzosin is safe and effective in increasing stone expulsion rates and shortening stone passage times for uncomplicated distal ureteral stones |
11,923 | 30,260,991 | Conclusions The technical content of brief behaviour interventions was identified in a reliable and st and ardized way providing preliminary indications on potentially effective techniques to achieve behaviour change | Background Behaviour-change interventions have been consistently considered an essential part of comprehensive HIV , STI and unintended pregnancy prevention .
In 2015 , the World Health Organization review ed and assessed existing evidence on brief behavioural interventions , leading to the publication of Brief sexuality-related communication : recommendations for a public health approach .
This guideline recommends the use of brief behaviour intervention and communication programmes to promote sexual health and to prevent HIV , STIs , and unintended pregnancies in primary health services , particularly sexual and reproductive health services . | We report results from a r and omized controlled trial design ed to evaluate the efficacy of a video-based sexual risk reduction intervention and to measure assessment reactivity . Patients ( N = 1010 ; 56 % male ; 69 % African American ) receiving care at a sexually transmitted infection ( STI ) clinic were assigned to one of four conditions formed by crossing assessment condition ( i.e. , sexual health vs. general health ) with intervention condition ( i.e. , sexual risk reduction intervention vs. general health promotion ) . After completing their assigned baseline assessment , participants received their assigned intervention , and subsequently returned for follow-up assessment s at 3 , 6 , 9 , and 12 months . Participants in all conditions reduced their self-reported sexual risk behavior , and the incidence of new STIs declined from baseline through the follow-ups ; however , there was no effect of intervention or assessment condition . We conclude that further risk reduction will require more intensive interventions , especially in STI clinics that already provide excellent clinical care . ResumenPresentamos los result ados de un estudio experimental aleatorizado con grupo de control diseñado para evaluar la eficacia de una intervención basada en un video para reducir el comportamiento sexual de riesgo y para medir reactividad . Se crearon cuatro condiciones experimentales al cruzar las condiciones de evaluación ( es decir , salud sexual versus salud general ) con las de intervención ( es decir , reducción de comportamiento sexual de riesgo versus promoción de la salud general ) . Los pacientes , ( N = 1010 ; 56 % hombres ; 69 % afroamericanos ) que recibían atención en una clínica de infecciones de transmisión sexual ( ITS ) , fueron asignados a unas de las cuatro condiciones experimentales . Después de completar la evaluación inicial a la que fueron asignados , los participantes recibieron la intervención correspondiente y posteriormente regresaron para el seguimiento a los 3 , 6 , 9 y 12 meses . Los participantes en todas las condiciones redujeron su comportamiento de riesgo sexual , medido mediante un cuestionario que completaron ellos mismos , y la incidencia de nuevas infecciones de transmisión sexual se redujo compar and o cada seguimiento con la línea base . Sin embargo , no se observó efecto de la intervención o condición de comparación . Llegamos a la conclusión de que para reducir en mayor medida el comportamiento de riesgo sexual se requieren intervenciones más intensivas , sobre todo en las clínicas de ITS en las que ya se proporciona una excelente atención clínica OBJECTIVES We tested the efficacy of a brief intervention to promote correct and consistent use of condoms among Black male youths attending sexually transmitted infection ( STI ) clinics in 3 southern US cities . METHODS In 2010 to 2012 , we screened ( n = 1102 ) and enrolled ( n = 702 ) youths aged 15 to 23 years who identified as Black and reported recent ( past 2 months ) sexual activity and r and omized them to a private , brief , interactive intervention ( n = 349 ) or an attention-equivalent control condition ( n = 353 ) . Assessment s occurred at baseline and 2 and 6 months after the intervention . RESULTS At 6 months , with adjustment for age and pretest nonequivalence of the outcome variable , an estimated odds ratio ( EOR ) of 1.63 ( 95 % confidence interval [ CI ] = 1.07 , 2.49 ; P = .02 ) indicated efficacy for correct condom use . An adjusted generalized estimating equations model with both 2- and 6-month condom use variables produced an EOR of 1.49 ( 95 % CI = 1.06 , 2.08 ; P = .02 ) . We did not observe significant effects on chlamydia and gonorrhea incidence . CONCLUSIONS This brief intervention , delivered as part of STI clinical care , could help alleviate the disproportionate STI-HIV burden among young Black men Background We evaluated brief combination interventions to simultaneously reduce sexual and injection risks among female sex workers who inject drugs ( FSW-IDUs ) in Tijuana and Ciudad Juarez , Mexico during 2008–2010 , when harm reduction coverage was exp and ing rapidly in Tijuana , but less so in Juarez . Methods FSW-IDUs ≥18 years reporting sharing injection equipment and unprotected sex with clients within the last month participated in a r and omized factorial trial comparing four brief , single-session conditions combining either an interactive or didactic version of a sexual risk intervention to promote safer sex in the context of drug use , and an injection risk intervention to reduce sharing of needles/injection paraphernalia . Women underwent quarterly interviews and testing for HIV , syphilis , gonorrhea , Chlamydia and Trichomonas , blinding interviewers and assessors to assignment . Poisson regression with robust variance estimation and repeated measures ordinal logistic regression examined effects on combined HIV/STI incidence and receptive needle sharing frequency . Findings Of 584 initially HIV-negative FSW-IDUs , retention was ≥90 % . After 12 months , HIV/STI incidence decreased > 50 % in the interactive vs. didactic sex intervention ( Tijuana : AdjRR:0.38,95 % CI:0.16–0.89 ; Juarez : AdjRR:0.44,95 % CI:0.19–0.99 ) . In Juarez , women receiving interactive vs. didactic injection risk interventions decreased receptive needle-sharing by 85 % vs. 71 % , respectively ( p = 0.04 ) ; in Tijuana , receptive needle sharing declined by 95 % , but was similar in active versus didactic groups . Tijuana women reported significant increases in access to syringes and condoms , but Juarez women did not . Interpretation After 12 months in both cities , the interactive sexual risk intervention significantly reduced HIV/STI incidence . Exp and ing free access to sterile syringes coupled with brief , didactic education on safer injection was necessary and sufficient for achieving robust , sustained injection risk reductions in Tijuana . In the absence of exp and ing syringe access in Juarez , the injection risk intervention achieved significant , albeit more modest reductions , suggesting that community-level interventions incorporating harm reduction are more powerful than individual-level interventions . Trial Registration clinical trials.gov Objective : To test the efficacy of brief , safer-sex counseling by medical providers of HIV-positive patients during medical visits . Setting : Six HIV clinics in California . Design : Clinics were r and omized to intervention arms evaluated with cohorts of r and omly selected patients measured before and after the intervention . Participants : Five-hundred and eighty-five HIV-positive persons , sexually active prior to enrollment . Interventions : Prevention counseling from medical providers supplemented with written information . Two clinics used a gain-framed approach ( positive consequences of safer-sex ) , two used a loss-frame approach ( negative consequences of unsafe sex ) , and two were attention-control clinics ( medication adherence ) . Interventions were given to all patients who attended the clinics . Outcome measure : Self-reported unprotected anal or vaginal intercourse ( UAV ) . Results : Among participants who had two or more sex partners at baseline , UAV was reduced 38 % ( P < 0.001 ) among those who received the loss-frame intervention . UAV at follow-up was significantly lower in the loss-frame arm [ odds ratio ( OR ) , 0.42 ; 95 % confidence interval ( CI ) , 0.19–0.91 ; P = 0.03 ] compared with the control arm . Using generalized estimating equations ( GEE ) to adjust for clustering did not change the conclusions ( OR , 0.34 ; 95 % CI , 0.24–0.49 ; P = 0.0001 ) . Similar results were obtained in participants with casual partners at baseline . No effects were seen in participants with only one partner or only a main partner at baseline . No significant changes were seen in the gain-frame arm . Conclusions : Brief provider counseling emphasizing the negative consequences of unsafe sex can reduce HIV transmission behaviors in HIV-positive patients presenting with risky behavioral profiles Objective : To evaluate the effectiveness of a clinician-delivered intervention , implemented during routine clinical care , in reducing unprotected sexual behavior of HIV-infected patients . Design : A prospect i ve clinical trial comparing the impact of a clinician-delivered intervention arm vs. a st and ard-of-care control arm on unprotected sexual behavior of HIV-infected patients . Setting : The 2 largest HIV clinics in Connecticut . Participants : A total of 497 HIV-infected patients , aged ≥18 years , receiving HIV clinical care . Intervention : HIV clinical care providers conducted brief client-centered interventions at each clinical encounter that were design ed to help HIV-infected patients reduce unprotected sexual behavior . Main Outcome Measures : Unprotected insertive and receptive vaginal and anal intercourse and unprotected insertive oral sex ; unprotected insertive and receptive vaginal and anal intercourse only . Results : HIV-infected patients who received the clinician-delivered intervention showed significantly reduced unprotected insertive and receptive vaginal and anal intercourse and insertive oral sex over a follow-up interval of 18 months ( P < 0.05 ) . These behaviors increased across the study interval for patients in the st and ard-of-care control arm ( P < 0.01 ) . For the measure of unprotected insertive and receptive vaginal and anal sex only , there was a trend toward a reduction in unprotected sex among intervention arm participants over time ( P < 0.09 ) , and a significant increase in unprotected sex in the st and ard-of-care control arm ( P < 0.01 ) . Conclusions : A clinician-delivered HIV prevention intervention targeting HIV-infected patients result ed in reductions in unprotected sex . Interventions of this kind should be integrated into routine HIV clinical care OBJECTIVE To determine whether condom use among high-risk female adolescents could be increased by a behavioral intervention , with the use of infection with Chlamydia trachomatis as a biomarker of condom practice s. DESIGN Prospect i ve , r and omized , controlled intervention . SETTING Urban family planning and sexually transmitted disease clinics . PARTICIPANTS Two hundred nine female adolescents , aged 15 through 19 years , who were treated for C. trachomatis genitourinary infection , were r and omly assigned to st and ard ( control ) or experimental ( behavioral intervention ) groups . One hundred twelve subjects returned for follow-up 5 to 7 months after enrollment and comprise the study subjects . MEASUREMENTS Subjects completed a multiinstrument question naire measuring sexual behavior , condom practice s , attitudes and beliefs , cognitive complexity , sociodemographics , and motivation at enrollment and follow-up . Endourethral and endocervical sites were sample d for C. trachomatis . RESULTS Among the 112 subjects who returned for repeated examination , those who had received the experimental intervention reported increased use of condoms by their sexual partners for protection against sexually transmitted diseases ( odds ratio = 2.4 ; p = 0.02 ) and for vaginal intercourse ( odds ratio = 3.1 ; p = 0.005 ) at the 6-month follow-up . Multivariable logistic regression analysis controlling for condom use at enrollment demonstrated that the experimental intervention ( odds ratio = 2.8 ; p = 0.03 ) and the higher cognitive complexity ( odds ratio = 4.6 ; p = 0.02 ) independently contributed to greater condom use at follow-up . Despite greater use of condoms among the group who had received the intervention , use remained inconsistent and rates of reinfection with C. trachomatis were not significantly different ( 26 % vs 17 % ; p = 0.3 ) . CONCLUSION Although a brief behavioral intervention among high-risk female adolescents can increase condom use by their sexual partners , incident infection does not appear to be reduced , because condom use remained inconsistent Background Sexually transmitted disease ( STD ) prevention remains a public health priority . Simple , practical interventions to reduce STD incidence that can be easily and inexpensively administered in high-volume clinical setting s are needed . We evaluated whether a brief video , which contained STD prevention messages targeted to all patients in the waiting room , reduced acquisition of new infections after that clinic visit . Methods and Findings In a controlled trial among patients attending three publicly funded STD clinics ( one in each of three US cities ) from December 2003 to August 2005 , all patients ( n = 38,635 ) were systematic ally assigned to either a theory-based 23-min video depicting couples overcoming barriers to safer sexual behaviors , or the st and ard waiting room environment . Condition assignment alternated every 4 wk and was determined by which condition ( intervention or control ) was in place in the clinic waiting room during the patient 's first visit within the study period . An intent-to-treat analysis was used to compare STD incidence between intervention and control patients . The primary endpoint was time to diagnosis of incident laboratory-confirmed infections ( gonorrhea , chlamydia , trichomoniasis , syphilis , and HIV ) , as identified through review of medical records and county STD surveillance registries . During 14.8 mo ( average ) of follow-up , 2,042 patients ( 5.3 % ) were diagnosed with incident STD ( 4.9 % , intervention condition ; 5.7 % , control condition ) . In survival analysis , patients assigned to the intervention condition had significantly fewer STDs compared with the control condition ( hazard ratio [ HR ] , 0.91 ; 95 % confidence interval [ CI ] , 0.84 to 0.99 ) . Conclusions Showing a brief video in STD clinic waiting rooms reduced new infections nearly 10 % overall in three clinics . This simple , low-intensity intervention may be appropriate for adoption by clinics that serve similar patient population s. Trial registration : http://www . Clinical Trials.gov ( # NCT00137670 ) Background Reducing substance use and unprotected sex by HIV-positive persons improves individual health status while decreasing the risk of HIV transmission . Despite recommendations that health care providers screen and counsel their HIV-positive patients for ongoing behavioral risks , it is unknown how to best provide “ prevention with positives ” in clinical setting s. Positive Choice , an interactive , patient-tailored computer program , was developed in the United States to improve clinic-based assessment and counseling for risky behaviors . Methodology and Findings We conducted a parallel groups r and omized controlled trial ( December 2003–September 2006 ) at 5 San Francisco area outpatient HIV clinics . Eligible patients ( HIV-positive English-speaking adults ) completed an in-depth computerized risk assessment . Participants reporting substance use or sexual risks ( n = 476 ) were r and omized in stratified blocks . The intervention group received tailored risk-reduction counseling from a “ Video Doctor ” via laptop computer and a printed Educational Worksheet ; providers received a Cueing Sheet on reported risks . Compared with control , fewer intervention participants reported continuing illicit drug use ( RR 0.81 , 95 % CI : 0.689 , 0.957 , p = 0.014 at 3 months ; and RR 0.65 , 95 % CI : 0.540 , 0.785 , p<0.001 at 6 months ) and unprotected sex ( RR 0.88 , 95 % CI : 0.773 , 0.993 , p = 0.039 at 3 months ; and RR 0.80 , 95 % CI : 0.686 , 0.941 , p = 0.007 at 6 months ) . Intervention participants reported fewer mean days of ongoing illicit drug use ( -4.0 days vs. -1.3 days , p = 0.346 , at 3 months ; and -4.7 days vs. -0.7 days , p = 0.130 , at 6 months ) than did controls , and had fewer casual sex partners at ( −2.3 vs. −1.4 , p = 0.461 , at 3 months ; and −2.7 vs. −0.6 , p = 0.042 , at 6 months ) . Conclusions The Positive Choice intervention achieved significant cessation of illicit drug use and unprotected sex at the group-level , and modest individual-level reductions in days of ongoing drug use and number of casual sex partners compared with the control group . Positive Choice , including Video Doctor counseling , is an efficacious and appropriate adjunct to risk-reduction efforts in outpatient setting s , and holds promise as a public health HIV intervention . Trial Registration Clinical trials.gov Background : HIV is ravaging southern Africa , and HIV transmission risk behaviors are facilitated by alcohol use in sexual context s. There are no known interventions that directly target HIV risk behavior among people who drink and are at risk for HIV in Africa . Purpose : To test a behavioral risk reduction counseling intervention for use in sexually transmitted infection ( STI ) clinics in southern Africa . Methods : A r and omized intervention trial was conducted with 143 STI clinic patients in Cape Town , South Africa . Participants received an experimental 60-minute HIV and alcohol risk reduction behavioral skills intervention or a control 20-minute HIV education condition . Participants were followed for 3 and 6 months after the intervention , with 73 % retention . Results : Overall , the experimental intervention demonstrated more than a 25 % increase in condom use and a 65 % reduction in unprotected intercourse over the 6-month follow-up period , with risk reduction significantly greater for the experimental condition than for the control condition at both follow-ups . Alcohol use in sexual context s [ F(1,94 ) = 6.2 ; P < 0.05 ] and expectancies that alcohol enhances sexual experiences [ F(1,94 ) = 8.3 ; P < 0.01 ] were also significantly lower for the experimental condition at the 3-month follow-up . Conclusions : An HIV prevention counseling intervention reduced HIV transmission risks for up to 6 months in this STI clinic population . Effects may be sustained with structural interventions to reduce alcohol use in sexual context s and support risk reduction behavior changes over the long-term Objective . To determine if sexually transmitted diseases ( STDs ) , including human immunodeficiency virus ( HIV ) infection , risk assessment , and education tools provided as part of office-based primary care reduce adolescent risky sexual behaviors . Design . A r and omized intervention trial with 3- and 9-month follow-up . Setting . Five staff-model managed care sites in Washington , DC ( n = 19 pediatricians ) . Patients . Consecutive 12- to 15-year-olds receiving a general health examination ; 81 % minority . Participation rate = 215/432 ( 50 % ) . Nine-month follow-up rate = 197/215 ( 92 % ) . Intervention . Audiotaped STD risk assessment and education about staying safe ( safer = condoms , safest = abstinence ) . Main Outcome Measures . Adolescent-reported sexual intercourse and condom use . Results . More intervention adolescents reported pediatrician discussion on 11/13 sexual topics . Although more vaginal intercourse ( odds ratio [ OR ] = 2.46 , 95 % confidence interval [ CI ] = 1.04–5.84 ) was reported in the intervention group at 3 months , this was not true of overall sexual intercourse ( OR = 1.55 , 95 % CI = .73–3.32 ) . More sexually active adolescents reported condom use in the intervention group at 3 months ( OR = 18.05 , 95 % CI = 1.27–256.03 ) . At 9 months , there were no group differences in sexual behaviors ; however , more signs of STD were reported by the control ( 7/103 ) than the intervention group ( 0/94 ) . Conclusions . STD risk assessment and education tools administered in a single office visit facilitated STD/HIV prevention education . Any impact on sexual activity and condom use was short-lived . Further research is needed to develop brief , office-based sexual risk reduction for young adolescents Theory-based sexual risk reduction interventions are often demonstrated effective , but few studies have examined the mechanisms that mediate their behavior changes . In addition , critical context ual factors , such as alcohol use , are often not accounted for by social cognitive theories and may add to the explanatory value of intervention effects . The purpose of this study is to examine the underlying mechanisms driving condom use following a brief sexual risk reduction intervention grounded in the information , motivation , behavioral skills ( IMB ) model of behavior change . We examined IMB theoretical constructs and alcohol-related context ual factors as potential mediators in separate models . Patients ( n = 617 ) from an STI clinic in Cape Town , South Africa were r and omly assigned to either a brief risk reduction intervention or an education-only control condition . We assessed IMB , and alcohol-related variables at baseline , 3 , 6 , 9 , and 12 months and modeled IMB constructs and alcohol-related factors as mediators of behavior change . Results of growth-curve mediational modeling showed that 1 year after counseling , the intervention indirectly affected sexual risk behavior through alcohol-related constructs , but not IMB constructs . Alcohol use and related factors play critical roles in explaining HIV and STI risk reduction intervention effects . Interventions that directly address alcohol use as a factor in sexual risk behavior and behavior change should be the focus of future research Objectives Novel interventions to address sexual risk taking and slow rates of STIs are urgently needed , in particular among black men who have sex with men ( MSM ) in the USA . Serosorting , or limiting condomless sex acts to partners of the same HIV status , is commonly practised among MSM , yet can lead to STI and remains largely unaddressed by public health agencies . Methods A two-arm , r and omised controlled trial was conducted from 2012 to 2015 . This trial assessed the effects of a single-session , sexual partner selection and risk decision intervention ( experimental arm ) versus a single-session , Centers for Disease Control and Prevention-based , sexual risk reduction intervention ( control arm ) on psychosocial measures , sexual risk taking and STI . Results At study follow-ups , multiple beneficial changes were observed on sexual risk beliefs measures ( ie , changes in serosorting and condom use beliefs , and HIV risk perceptions ) and sexual risk taking among the experimental arm relative to the control arm . Overall main effects , however , of the intervention on STI outcomes on year-long follow-ups were non-significant . There was evidence for short-term effects on STI outcomes , and self-report of multiple STIs and STI symptoms demonstrated positive effects over the follow-up period . Conclusions Brief interventions to address sexual risk taking can result in short-term beneficial outcomes and can be incorporated into currently existing infrastructure at healthcare agencies . Additional intervention will be necessary for demonstrating long-term results . Trial registration number NCT02128594 CONTEXT High-risk sexual behavior is increasingly prevalent among men who have sex with men ( MSM ) and among men with a history of repeat testing for HIV . OBJECTIVES The study assessed whether one counseling intervention session focusing on self-justifications ( thoughts , attitudes , or beliefs that allow the participant to engage in high-risk sexual behaviors ) at most recent unprotected anal intercourse ( UAI ) is effective in reducing future high-risk behaviors among HIV-negative men . DESIGN , SETTING , AND PARTICIPANTS A r and omized , controlled , counseling intervention trial was conducted at an anonymous testing site in San Francisco , California , between May 1997 and January 2000 . Participants were 248 MSM with a history of at least one previous negative HIV test result and self-reported UAI ( receptive or insertive ) in the previous 12 months with partners of unknown or discordant HIV status . Two intervention groups received st and ard HIV test counseling plus a cognitive-behavioral intervention , and two control groups received only st and ard HIV test counseling . Follow-up evaluation was at 6 and 12 months . MAIN OUTCOME MEASURE Number of episodes of UAI with non primary partners ( of unknown or discordant HIV status ) in the 90 days preceding the interview was measured via self-report during face-to-face interview . RESULTS A novel counseling intervention focusing on self-justifications significantly decreased the proportion of participants reporting UAI with non primary partners of unknown or discordant HIV status at 6 and 12 months ( from 66 % to 21 % at 6 months and to 26 % at 12 months , p = .002 ; p < .001 ) as compared with a control group when added to st and ard client-centered HIV counseling and testing . CONCLUSIONS A specific , single-session counseling intervention focusing on a reevaluation of a person 's self-justifications operant during a recent occasion of high-risk behavior may prove useful in decreasing individual risk behavior and thus limiting community-level HIV transmission Background : South Africa has the world ’s fastest growing AIDS epidemic . There is an urgent need for effective HIV risk reduction interventions in South Africa . Objective : The objective of this study was to develop and test the potential efficacy of a brief theory-based HIV prevention counseling intervention for sexually transmitted infection ( STI ) clinic patients in South Africa . Method : STI clinic patients in Cape Town ( N = 228 ) were assessed at baseline and r and omized to receive either : 1 ) a single 60-minute session motivational/skills-building HIV risk reduction counseling intervention or 2 ) a 20-minute HIV information/education session . Participants completed 1- and 3-month follow ups with 80 % retention . Results : The 60-minute motivational/skills risk reduction counseling demonstrated significantly greater risk reduction practice s , lower rates of unprotected intercourse , and greater likelihood of receiving HIV testing after the intervention . Conclusions : Brief theory-based HIV prevention counseling may significantly reduce HIV risk behaviors for STI clinic patients in South Africa OBJECTIVES We examined the efficacy of a brief behavioral intervention to promote condom use among female sex workers in Tijuana and Ciudad Juarez , Mexico . METHODS We r and omized 924 female sex workers 18 years or older without known HIV infection living in Tijuana and Ciudad Juarez who had recently had unprotected sex with clients to a 30-minute behavioral intervention or a didactic control condition . At baseline and 6 months , women underwent interviews and testing for HIV , syphilis , gonorrhea , and chlamydia . RESULTS We observed a 40 % decline in cumulative sexually transmitted illness incidence ( P = .049 ) in the intervention group . Incidence density for the intervention versus control groups was 13.8 versus 24.92 per 100 person-years for sexually transmitted illnesses combined ( P = .034 ) and 0 versus 2.01 per 100 person-years for HIV ( P < .001 ) . There were concomitant increases in the number and percentage of protected sex acts and decreases in the number of unprotected sex acts with clients ( P < .05 ) . CONCLUSIONS This brief behavioral intervention shows promise in reducing HIV and sexually transmitted illness risk behaviors among female sex workers and may be transferable to other re source -constrained setting Background : Brief face-to-face-behavioral interventions have been shown to be efficacious , but are costly to sustain and to widely disseminate . This study evaluated the efficacy of a 15-minute theory-based behavioral intervention design ed to increase condom use and reduce new cases of Neisseria gonorrhoeae and Chlamydia trachomatis . Methods : Participants were r and omly assigned via the computer to the intervention or the comparison group stratified by gender and their baseline stage of change ( motivational readiness ) for using condoms consistently ( 100 % ) with their main partners . Behavioral data and biologic specimens for testing of Neisseria gonorrhoeae and Chlamydia trachomatis were obtained at baseline and at 6 months post intervention . The intervention was delivered via an audio , multimedia , computerized application that provided individualized interventions to patients based on their responses to assessment items ; comparison patients interacted with a 15-minute , computerized , multiple health risk assessment with no intervention . Results : The majority of the sample ( N = 430 ) was black ( 88 % ) ; 54.5 % women ; with a mean age = 24.5 . Assuming all participants who did not return to the clinic at 6 months were not using condoms consistently , 32 % of the treatment group versus 23 % in the comparison group reported consistent condom use ( P = 0.03 ) . The combined Neisseria gonorrhoeae and Chlamydia trachomatis incidence declined to 6 % in the intervention group versus 13 % in the comparison group ( P = 0.04 ) . Results from a regression analysis revealed that the only statically significant predictor of sexually transmitted diseases infection at the follow-up was group assignment ( OR = 1.91 , 95 % confidence index = 1.09–3.34 ; P = 0.043 ) . Conclusions : These findings suggest that brief , interactive , computer-delivered interventions provided at the evaluation visit increase condom use and reduce sexually transmitted diseases without putting additional burden on clinicians or staff Women experiencing homelessness are at heightened risk for HIV , yet risk reduction interventions specifically design ed for this population are lacking . This study reports on a pilot efficacy trial of a brief evidence -based intervention , Sister To Sister ( STS ) , that we specifically adapted for homeless women in the temporary/emergency setting s where they typically seek services . Seventy-nine women , recruited from three service sites in Los Angeles County , were assigned to the 40-min adapted STS intervention or an information-only control group . At 30-day follow-up , intervention participants reported significantly greater condom use , intentions to use condoms , and sexual impulse control ( as well as marginally higher positive condom beliefs and condom self-efficacy ) compared to control participants . Results provide preliminary evidence that HIV risk reduction can be achieved for homeless women through a brief skill-based intervention . A r and omized controlled trial employing a longer follow-up period to monitor outcomes will be necessary to determine efficacy of the adapted intervention Latino men who have sex with men ( MSM ) are disproportionately impacted by HIV/AIDS , but few behavioral interventions address their prevention needs . Adaptation of evidence -based interventions is a pragmatic strategy that builds upon lessons learned and has the potential to fill gaps in prevention programming . Yet there are few reports of how transfers are executed and whether effectiveness is achieved . This research reports on the adaptation of VOICES/VOICES , a single-session intervention design ed for heterosexual adults , into No Excuses/Sin buscar excuses for Latino MSM . To test the adapted intervention , 370 at-risk Latino MSM were enrolled in a r and omized trial . At a three-month follow-up , there was a sharper decrease in unprotected intercourse in the intervention group compared to controls ( 59 % vs. 39 % , ANOVA p < 0.05 , F = 4.10 ) . Intervention participants also reported more condom use at last intercourse ( AOR = 1.69 ; 95 % CI 1.02–2.81 , p < 02 ) . Findings support use of adapted models for meeting prevention needs of high-priority population s . ResumenLos hombres latinos que tienen relaciones sexuales con hombres ( HSH ) son afectados desproporcionadamente por el VIH/SIDA , pero pocas intervenciones de comportamiento se dirigen a las necesidades de prevención de este grupo . La adaptación de intervenciones basadas en evidencias es una estrategia pragmática fundada en lecciones aprendidas y tiene el potencial de cubrir lo que carecen los programas de prevención . Aun así , existen pocos reportes de cómo adaptar las intervenciones y si estas son eficaces . Esta investigación informe sobre cómo VOCES/VOICES , una intervención de una sesión diseñada para adultos heterosexuales , fue adaptada a la intervención Sin buscar excusas para HSH latinos . Para probar la eficacia de la intervención adaptada , 370 HSH latinos de alto riesgo fueron enlistados en un estudio r and omizado . A los tres meses de seguimiento , se encontró que hubo una gran disminución de sexo anal sin protección en el grupo de intervención comparado con el grupo de control ( 59 % versus 39 % , ANOVA p < 0.05 , F = 4.10 ) . Los participantes del grupo de intervención reportaron también más uso del condón en la última vez que tuvieron sexo anal ( AOR = 1.69 , 95 % CI 1.02–2.81 , p < 0.02 ) . Estos result ados apoyan el uso de los modelos adaptados para resolver necesidades de prevención en poblaciones de prioridad de alto riesgo Objectives : To test the efficacy and acceptability of a single-session personalized cognitive counseling ( PCC ) intervention delivered by paraprofessionals during HIV voluntary counseling and testing . Methods : HIV-negative men who have sex with men ( MSM ; n = 336 ) were r and omly allocated to PCC or usual counseling ( UC ) between October 2002 and September 2004 . The primary outcome was the number of episodes of unprotected anal intercourse ( UAI ) with any non primary partner of nonconcordant HIV serostatus in the preceding 90 days , measured at baseline , 6 months , and 12 months . Impact was assessed as “ intent to treat ” by r and om-intercept Poisson regression analysis . Acceptability was assessed by a st and ardized client satisfaction survey . Results : Men receiving PCC and UC reported comparable levels of HIV nonconcordant UAI at baseline ( mean episodes : 4.2 vs. 4.8 , respectively ; P = 0.151 ) . UAI decreased by more than 60 % to 1.9 episodes at 6 months in the PCC arm ( P < 0.001 vs. baseline ) but was unchanged at 4.3 episodes for the UC arm ( P = 0.069 vs. baseline ) . At 6 months , men receiving PCC reported significantly less risk than those receiving UC ( P = 0.029 for difference to PCC ) . Risk reduction in the PCC arm was sustained from 6 to 12 months at 1.9 ( P = 0.181 ) , whereas risk significantly decreased in the UC arm to 2.2 during this interval ( P < 0.001 vs. 6 months ; P = 0.756 vs. PCC at 12 months ) . Significantly more PCC participants were “ very satisfied ” with the counseling experience ( 78.2 % ) versus UC participants ( 59.2 % ) ( P = 0.002 ) . Conclusions : Both interventions were effective in reducing high-risk sexual behavior among MSM repeat testers . PCC participants demonstrated significant behavioral change more swiftly and reported a more satisfying counseling experience than UC participants Objective : To evaluate the feasibility , fidelity , and effectiveness of a human immunodeficiency virus ( HIV ) prevention intervention delivered to HIV-infected patients by counselors during routine clinical care in KwaZulu-Natal , South Africa . Methods : A total of 152 HIV-infected patients , aged 18 years and older , receiving clinical care at an urban hospital in South Africa , were r and omly assigned to intervention or st and ard-of-care control counselors . Intervention counselors implemented a brief risk reduction intervention at each clinical encounter to help patients reduce their unprotected sexual behavior . Self-report question naires were administered at baseline and 6 months to assess number of unprotected sex events in previous 3 months . Results : Intervention was delivered in 99 % of routine patient visits and included a modal 8 of 8 intervention steps . Although HIV-infected patients in both conditions reported more vaginal and anal sex events at 6-month follow-up than at baseline , patients who received the counselor-delivered intervention reported a significant decrease over time in number of unprotected sexual events . There was a marginally significant increase in these events among patients in the st and ard-of-care control condition . Conclusions : A counselor-delivered HIV prevention intervention targeting HIV-infected patients seems to be feasible to implement with fidelity in the South African clinical care setting and effective at reducing unprotected sexual behavior Background and Objective : Video‐based patient education has been effective in a variety of clinical setting s. The authors studied the efficacy of a video‐based educational intervention in an inner‐city public sexually transmitted diseases ( STD ) clinic . Goal : To evaluate the efficacy of video‐based patient education in reducing STD infections subsequent to a clinic visit . Design : African‐American and Hispanic men attending a large public STD clinic were assigned at r and om to either an experimental video‐based educational intervention or a control condition in which they received regular clinic services . Patients in the experimental group were exposed to video‐based interventions that provided information about STDs and their prevention , portrayed positive attitudes about condom use , and modeled appropriate strategies for encouraging condom use in different sexual relationships . During 1992 , 2,004 subjects were tracked for an average of 17 months through the New York City STD surveillance data base for the occurrence of new STD infections . Results : The overall rate of new infection among male STD clinic patients was 24.2 % . Rate of new infection was significantly lower among those exposed to video‐based prevention education than among controls ( 22.5 % compared with 26.8 % , p < .05 ) . Subjects reporting multiple sex partners had a significantly higher new infection rate but also experienced the greatest impact of educational intervention . There was a 32.2 % new infection rate among high‐risk controls compared with a 24.8 % rate among high‐risk intervention groups ( p < 0.025 ) . Conclusion : Results of this r and omized clinical trial indicate that using video‐based patient education to supplement regular STD clinic services and provider interactions can be effective in reducing rates of new STD infection , particularly among those at greatest risk OBJECTIVE We evaluated the efficacy of a brief , clinic-based , safer sex program administered by a lay health adviser for young heterosexual African American men newly diagnosed with a sexually transmitted disease ( STD ) . METHODS Subsequent to STD diagnosis , eligible men ( N = 266 ; aged 18 - 29 years ) were r and omized to either a personalized , single-session intervention ( delivered by a lay health adviser ) or st and ard of care . We conducted behavioral assessment s at baseline and 3 months postintervention ( retention was 74.1 % ) . We also conducted a 6-month clinic record review . RESULTS Compared to men r and omized to the control condition , those receiving the intervention were significantly less likely to acquire subsequent STDs ( 50.4 % vs 31.9 % ; P = .002 ) and more likely to report using condoms during last sexual intercourse ( 72.4 % vs 53.9 % ; P = .008 ) . They also reported fewer sexual partners ( mean 2.06 vs 4.15 ; P < .001 ) and fewer acts of unprotected sex ( mean 12.3 vs 29.4 ; P = .045 ) . Based on a 9-point rating scale , men in the intervention group had higher proficiency scores for condom application skills ( mean difference = 3.17 ; P < .001 ) . CONCLUSION A brief clinic-based intervention delivered by a lay health adviser may be an efficacious strategy to reduce incident STDs among young heterosexual African American men The study examined the efficacy of a brief theory-based counseling intervention to reduce sexual HIV risk behaviors among STI clinic patients in St. Petersburg , Russia . Men and women ( n = 307 ) were recruited to receive either : ( 1 ) a 60-minute motivational/skills-building counseling session dealing with sexual HIV risk reduction , or ( 2 ) written HIV prevention information material . Participants completed baseline , three- and six-month assessment s in the period between July 2009 and May 2011 . Compared to the control group , the face-to-face counseling intervention showed significant increases in the percentage of condom use and consistent condom use , and significant decreases in the number of unprotected sexual acts and frequency of drug use before sex . Intervention effects dissipated by 6 months . The brief counseling intervention may effectively reduce HIV sexual risk behaviors and enhance protective behaviors among STI clinic patients in Russia . Short-term positive effects were achieved with a single one hour counseling session . ResumenEl estudio examinó la eficacia de una intervención breve para reducir el riesgo de transmisión sexual del VIH entre los pacientes de una clinica de infecciones de transmisión sexual en San Petersburgo , Rusia . Hombres y mujeres ( n = 307 ) fueron reclutados para recibir : ( 1 ) una sesión de 60 minutos de una intervención para desarrollar la motivación y de las habilidades de reducción de los comportamientos sexuales de riesgo del VIH , o ( 2 ) información por escrito de la prevención del VIH . Los participantes completaron las evaluaciones al inicio del estudio , 3 y 6 meses en el período comprendido entre julio de 2009 y mayo de 2011 . En comparación con los controles , el breve intervención mostraron incrementos significativos en el porcentaje del uso del condón , el uso consistente del condón , y disminuciones significativas en el número de relaciones sexuales sin protección y en el uso de drogas antes de tener sexo . Los efectos fueron significativos en las evaluaciones tres meses después de la intervención . La intervención breve puede reducir efectivamente los comportamientos sexuales de riesgo del VIH y mejorar las conductas de protección entre los pacientes de la clínica de ITS en Rusia . Efectos se podría lograr con una hora sesión de consejeria PURPOSE One objective of translational science is to identify elements of human immunodeficiency virus ( HIV ) risk-reduction interventions that have been shown to be effective and find new ways of delivering these interventions to the community to ensure that they reach the widest possible audience of at-risk individuals . The current study reports the development and evaluation of a computer-delivered , theory-based , individually tailored HIV risk-reduction intervention . METHODS This study evaluated the effectiveness of a custom computerized HIV/AIDS risk reduction intervention at increasing HIV/AIDS preventive behaviors in a r and omized trial with 157 college students . The intervention content and delivery were based on the Information-Motivation-Behavioral Skills Model of Health Behavior Change and used Motivational Interviewing techniques . Participants completed a baseline assessment of HIV prevention information , motivation , behavioral skills and behavior , attended two brief computer-delivered intervention sessions , and completed a follow-up assessment . RESULTS As compared to the control group ( a nutrition education tutorial ) , participants who interacted with the computer-delivered HIV/AIDS risk reduction intervention exhibited a significant increase in risk reduction behavior . Specifically , participants reported a greater frequency of keeping condoms available and displayed greater condom-related knowledge at a four-week follow-up session ; among sexually active participants , there was a significant increase in self-reported condom use . CONCLUSIONS Delivery of brief individually tailored HIV/AIDS risk reduction interventions via computer may be an effective HIV/AIDS prevention approach for adolescents . More research is needed to further support the effectiveness of this type of intervention and determine the generalizability of these findings to economically and educationally disadvantaged adolescents Objective : The objective of this study was to compare 2 interventions promoting condoms and vaginal microbicides to prevent sexually transmitted disease ( STD ) . Study : Women ( N = 427 ) attending an STD clinic were r and omly assigned to 2 clinician-delivered interventions and followed up monthly to assess condom/microbicide use and incidence of gonorrhea , chlamydia , and syphilis . Results : During follow up , condom use rates were 69 % ( enhanced ) and 49 % ( basic ) and microbicide use rates were 44 % and 29 % , respectively . STD rates did not significantly differ between intervention groups . Perfect condom use ( regardless of intervention arm ) was associated with a 3-fold decrease in STD rates ( relative risk [ RR ] , 0.3 ; 95 % confidence interval [ CI ] , 0.1–0.8 ) . Using a vaginal microbicide during ≥50 % of the acts of intercourse was associated with reduced STD rates ( RR , 0.5 ; 95 % CI , 0.3–1.0 ) across intervention groups and condom use categories . Conclusions : The enhanced intervention increased use of condoms and vaginal microbicide ; however , STD rates did not decrease because a protective effect was seen only among perfect barrier users , and the enhanced intervention only modestly increased perfect use OBJECTIVES We examined the effects of a brief counseling intervention design ed to reduce HIV risk behaviors and sexually transmitted infections ( STIs ) among patients receiving STI services in Cape Town , South Africa . METHODS After r and omization to either a 60-minute risk reduction counseling session or a 20-minute HIV-STI educational session , patients completed computerized sexual behavior assessment s. More than 85 % of the participants were retained at the 12-month follow-up . RESULTS There were 24 % fewer incident STIs and significant reductions in unprotected vaginal and anal intercourse among participants who received risk reduction counseling relative to members of the control condition . Moderator analyses showed shorter lived outcomes for heavy alcohol drinkers than for lighter drinkers . The results were not moderated by gender . CONCLUSIONS Brief single-session HIV prevention counseling delivered to STI clinic patients has the potential to reduce HIV infections . Counseling should be enhanced for heavier drinkers , and sustained outcomes will require relapse prevention techniques . Disseminating effective , brief , and feasible behavioral interventions to those at highest risk for HIV infection should remain a public health priority |
11,924 | 28,921,500 | A small single trial contributed evidence of moderate quality that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group . | BACKGROUND Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity .
In those affected by the more severe forms , regular blood transfusions are required which may lead to iron overload .
Accumulated iron from blood transfusions may be deposited in vital organs including the heart , liver and endocrine organs such as the pituitary gl and s which can affect growth hormone production .
Growth hormone deficiency is one of the factors that can lead to short stature , a common complication in people with thalassaemia .
Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency .
OBJECTIVES To assess the benefits and safety of growth hormone therapy in people with thalassaemia . | Abstract Objective : The objective of this study was to psychometrically evaluate a tool to measure adult caregivers ’ level of satisfaction with the delivery device used to administer injections of recombinant human growth hormone ( rhGH ) to a child – the Satisfaction Measure of the Injection of Growth Hormone Therapy ( SMIGHTy * SMIGHTy is a trademark of Genentech , Inc. , South San Francisco , CA , USA . ) question naire . Research design and methods : One hundred caregivers who administer rhGH to a child using an injection device completed the SMIGHTy question naire at baseline and 7–14 days later , and also completed other measures of treatment adherence and treatment satisfaction at baseline . Main outcome measures : SMIGHTy reliability ( inter-item and test – retest ) and external validity ( association with other study measures ) were assessed . Results : Analyses revealed good inter-item agreement and test – retest reliability for the SMIGHTy question naire . External validity , measured by associations with adherence and other measures of treatment satisfaction , was high . Study limitations : This study assessed only adult caregivers ; the instrument was not vali date d for use by young or adult patients . Conclusions : The SMIGHTy instrument is more comprehensive than existing instruments for assessing the growth hormone treatment experience . It is multidimensional , assesses both positive and negative aspects of the treatment experience ( Device Satisfaction , Negative Events , Benefits ) , and has separate measures of overall satisfaction and preference The causes of growth retardation of children with thalassaemia major are multifactorial . We studied the GH response to provocation by clonidine and glucagon , measured the circulating concentrations of insulin , IGF-I , IGF-binding protein-3 ( IGFBP-3 ) and ferritin , and evaluated IGF-I generation after a single dose of GH ( 0.1 mg/kg per dose ) in 15 prepubertal patients with thalassaemia , 15 age-matched children with constitutional short stature ( CSS ) ( height st and ard deviation score less than -2 , with normal GH response to provocation ) and 11 children with isolated GH deficiency ( GHD ) . Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon ( 6.2 + /- 2.3 and 6.8 + /- 2.1 microg/l respectively ) than the CSS group ( 18.6 + /- 2.7 and 16.7 + /- 3.7 microg/l respectively ) . They had significantly decreased circulating concentrations of IGF-I and IGFBP-3 ( 47.5 + /- 19 ng/ml and 1.2 + /- 0.27 mg/l respectively ) compared with those with CSS ( 153 + /- 42 ng/ml and 2.06 + /- 0.37 mg/l respectively ) , but the IGF-I and IGFBP-3 concentrations were not different from those with GHD ( 56 + /- 25 ng/ml and 1.1 + /- 0.32 mg/l respectively ) . These data demonstrate that the GH-IGF-I-IGFBP-3 axis in thalassaemic children is defective . Serum ferritin concentration correlated significantly with GH peak response to provocation ( r = -0.36 , P < 0.05 ) and circulating IGF-I ( r = -0.47 , P < 0.01 ) and IGFBP-3 ( r = -0.42 , P < 0.01 ) concentrations . In the IGF-I generation test , after GH injection , the thalassaemic children had significantly lower IGF-I and IGFBP-3 levels 86.7 + /- 11.2 ng/ml and 2.05 + /- 0.51 mg/l respectively ) than those in the CSS group ( 226 + /- 45.4 ng/ml and 2.8 + /- 0.43 mg/l respectively ) . The IGF-I response was significantly higher in children with GHD ( 158 + /- 50 ng/ml ) than in thalassaemic children . Six short ( height st and ard deviation score less than -2 ) thalassaemic children who had defective GH response to provocation ( < 10 microg/l ) , all the children with GHD and eight short normal children ( CSS ) were treated for 1 year with human GH ( 18 units/m2 per week divided into daily s.c . doses ) . After 1 year of GH therapy there was a marked acceleration of growth velocity in both thalassaemic children ( from 3.8 + /- 0.6 cm/year to 7.2 + /- 0.8 cm/year ) and controls . However , the linear acceleration of growth velocity on GH therapy was significantly slower in thalassaemic children ( 3.3 + /- 0.3 cm/year increment ) compared with those with CSS ( 5.3 + /- 0.4 cm/year increment ) and GHD ( 6.9 + /- 1.2 cm/year increment ) ( P < 0.05 ) . Their circulating IGF-I concentration ( 105 + /- 36 ng/ml ) was significantly lower than those for CSS ( 246 + /- 58 ng/ml ) and GHD ( 189 + /- 52 ng/ml ) after 1 year of GH therapy . These data prove that some children with beta-thalassaemia major have a defective GH-IGF-I-IGFBP-3 axis and suggest the presence of partial resistance to GH Background : Quality of life ( QoL ) as it is related with growth hormone deficiency ( GHD ) is a matter of controversy . Methods : We analyzed QoL in 95 children aged 8–18 years with isolated GHD ( 72 % male ) treated with growth hormone ( GH ) . These children were compared to 190 age- and gender-matched healthy children with similar height [ height < 10th percentile ; control group 1 ( CG1 ) ] and age- and gender-matched 285 healthy children of normal stature ( control group 2 : CG2 ) . QoL was measured by the KINDL ® question naire referring to six domains ( physical well-being , emotional well-being , self-esteem , family , friends , and school ) . Results : QoL was significantly reduced in CG1 ( effect-size 0.21 ) compared to CG2 , while QoL was not significantly altered in children with GHD . In multiple linear regression analyses adjusted to age , gender , BMI , migration background , and socioeconomic status , decreasing height-SDS was associated with poorer QoL ( especially emotional well-being ) , and treatment with GH was related significantly to better self-esteem . Increase of height-SDS in children treated with GH was associated positively with QoL and all its subscales except family and school . Conclusions : These findings suggest psychological consequences of short stature in children and an improvement of QoL in children treated with GH with the focus on self-esteem and emotional well-being To assess whether delaying puberty may improve final height in GH-deficient children with a poor height prediction at early puberty , we studied 24 girls with isolated GH deficiency until they reached their final height , in a controlled trial . Patients were taking recombinant human GH ( r-hGH ) substitutive therapy from 2.1 + /- 0.5 yr ( 0.1 IU/kg.day sc ) before entering the study , without showing any improvement in height prediction ( 149.6 + /- 2.9 vs.150.3 + /- 2.2 cm ) on entering puberty . Fourteen girls agreed to add a GnRH agonist ( GnRHa ) to r-hGH , whereas the remaining 10 decided against it and served as controls . At the start of the study , girls treated with or without GnRHa had similar auxological characteristics ( bone age , 10.9 + /- 0.6 vs. 10.7 + /- 1.3 yr ; height SD score for chronological age , -1.87 + /- 0.3 vs. -1.82 + /- 0.2 ) , including pubertal development . The GnRHa ( long-acting D-Trp-6-GnRH ) was given at 60 microg/kg i m every 28 days for 1.9 + /- 0.9 yr , then patients continued the r-hGH at the same dosage ( 3.1 + /- 0.7 yr ) . At the end of the study , bone age was 16.2 + /- 0.3 yr in GnRHa-treated girls and 16.6 + /- 0.9 yr in controls . Bone maturation was significantly slower during GnRHa ( 1.4 + /- 0.2 yr ) , and height SD score for bone age improved ( -0.31 + /- 0.3 ) in comparison with controls ( 2.6 + /- 0.4 yr and -1.35 + /- 0.3 SD score ; P < 0.001 and P < 0.0001 , respectively ) . As a result , girls given the combined therapy reached a final height higher than that of controls ( height SD score , -0.39 + /- 0.5 vs. -1.45 + /- 0.2 ; P < 0.0001 ) and also higher than their midparental height ( -1.1 + /- 0.5 ; P < 0.0005 ) . Controls reached their midparental height . In conclusion , our results demonstrate that slowing pubertal development with the administration of GnRHa for a limited time may improve final height in GH-deficient girls selected because of a poor height prediction at early puberty We measured the final height ( FH ) of 25 short polytransfused thalassemia major ( Th ) patients ( 18 males ) with a reduced GH reserve treated for 3.3±1.2 yr with recombinant GH ( rhGH ) , 0.2 mg/kg/week sc . At baseline , all patients were clinical ly prepubertal ; their chronological ( CA ) and bone ages ( BA ) were 13.6±2.0 and 11.4±1.6 yr , respectively . In 9 out of 18 males and 5 out of 7 females , the onset of puberty occurred spontaneously during the treatment . At the end of the rhGH administration , the height of the enrolled children was not significantly increased when calculated for CA ( HxCA ) , while it was significantly decreased ( p=0.004 ) when calculated for BA ( HxBA ) ; the BA increase ( 3.29±1.65 yr ) was significantly higher ( p<0.001 ) than the height age increase ( 2.16±0.98 yr ) . The FHxCA showed a significant increase ( p=0.001 ) compared to both baseline and the end of therapy , while the FHxBA was significantly decreased ( p<0.001 ) compared with the corresponding value at baseline . At the end of therapy , both HxCA and HxBA result ed positively related to the BA at baseline ( r=0.50 and 0.42 , p=0.012 and 0.034 , respectively ) . FH was positively correlated with CA ( r=0.63 , p=0.001 ) , BA ( r=0.68 , p<0.001 ) and HxBA ( r=0.59 , p=0.002 ) evaluated at baseline , and with both HxCA and HxBA ( r=0.82 and 0.74 , respectively , p<0.001 ) , evaluated at the end of treatment . A negative correlation was found between FH and the length of treatment ( r=−0.56 , p=0.004 ) . Our data seem to exclude that prolonged rhGH therapy could improve FH in Th patients ; on the contrary , a negative effect may be hypothesized Patients with beta-thalassemia major ( beta-thalassemia ) frequently have bone disorders of multifactorial etiology . We attempted to analyze the relationship between the bone mineral density ( [ BMD ] measured by dual-photon absorptiometry ) and auxanologic parameters , degree of siderosis , function of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein-3 ( IGFBP3 ) axis , calcium-phosphate balance , parathyroid hormone ( PTH ) , and cytokines ( interleukin-1beta [ IL-1 ] and tumor necrosis factor-alpha [ TNF-alpha ] ) in 30 prepubertal children with beta-thalassemia major and 15 age-matched children with constitutional short stature ( CSS ) , who have normal glucose tolerance and thyroid function . Children with beta-thalassemia had a significantly decreased BMD and mean BMD% for age and sex ( 0.75+/-0.24 g/cm2 and 71%+/-10 % , respectively ) versus children with CSS ( 1.06+/-0.3 g/cm2 and 92%+/-7 % , respectively ) . Thalassemic patients had significantly lower circulating concentrations of IGF-I and IGFBP3 ( 49+/-21 ng/mL and 1.2+/-0.25 mg/L , respectively ) compared with control children ( 153+/-42 ng/mL and 2.1+/-0.37 mg/L , respectively ) . The GH response to provocation by clonidine and glucagon was defective ( peak GH < 7 microg/L ) in 12 of the 30 thalassemic children . Serum concentrations of IL-1beta and TNF-alpha did not differ among the two study groups . Hypocalcemia was detected in five of the 30 thalassemic patients : hypoparathyroidism was diagnosed in two of the five and rickets in the other three . BMD was highly correlated with the circulating concentrations of IGF-I and IGFBP3 , as well as with the auxanologic parameters ( age , weight , height , height st and ard deviation score [ HSDS ] , and body mass index [ BMI ] ) . It is suggested that increasing the circulating IGF-I concentration through aggressive nutritional therapy and /or GH/IGF-I therapy with supplementation with vitamin D and /or calcium might improve bone growth and mineralization and prevent the development of osteoporosis and consequent fractures in these patients . Such therapy requires blinded controlled trials BACKGROUND To evaluate the growth hormone reserve and the growth hormone response to recombinant human growth hormone ( GH ) in prepubertal thalassemic children with growth retardation . METHODS Twenty thalassemic patients with short stature and delayed bone age were studied . Patients were r and omized into GH-treated ( n = 10 ) and non-GH treated ( control ; n = 10 ) groups . The GH-treated group received recombinant human (rh)-GH ( Genotropin ) at the dose of 0.7 IU/kg per week for 12 months . RESULTS There was a significant discordance between GH response to pharmacologic stimuli and physiological secretion of GH/GHRH testing . Following the administration of rhGH , growth velocity increased from 2.47 + /- 0.48 cm/year to 6.27 + /- 0.76 cm/year ( P = 0.005 ) , whereas there was not a similar change in the non-GH-treated group . The height velocities of the two groups during the 1 year follow-up period were significantly different ( 6.27 + /- 0.76 vs 3.99 + /- 0.34 cm/year ; P = 0.025 ) . There were significant differences between the height velocity improvements and height velocity st and ard deviation scores of the two groups as well . CONCLUSION The present study has demonstrated that rhGH is a safe and efficacious mode of treatment in thalassemic children OBJECTIVE Despite regular transfusion and desferoxamine treatment , growth failure Is commonly seen In adolescent children with β‐thalassaemla major . The growth failure has been thought to be due to GH resistance rather than GH deficiency . We Investigated the effect of GH on short non‐GH deficient children with β‐thalassaemia OBJECTIVE To investigate puberty in a group of thalassemic patients with delayed or arrested pubertal development and to compare the effects of hormonal and L-carnitine therapy on puberty in those patients . PATIENTS Thirty-two -thalassemic patients with arrested or failure of puberty were enrolled for 1 year in this study . METHOD Clinical pubertal assessment and laboratory investigations were done for all patients at the beginning , 6 months later clinical pubertal assessment was done . Patients were divided into two groups ( 16 each ) : first group received L-carnitine therapy , while the second group received hormonal therapy . Pubertal and laboratory assessment were done 6 months after hormonal and L-carnitine therapy . RESULTS Failure of puberty was confirmed in 71.4 % of boys and 33.3 % of girls , while arrested puberty was observed in 28.6 % of boys and 66.7 % of girls . All girls had amenorrhea , primary amenorrhea in 88.9 % and secondary amenorrhea in 11.1 % . Menses occurred in 20 % of female patients after L-carnitine therapy and in 37.5 % of them after hormonal therapy . Improvement of pubertal staging was observed in 50 % of males after L-carnitine therapy compared to 75 % of them after hormonal therapy . While improvement of pubertal staging was seen in 90 % of females after L-carnitine therapy compared to 100 % of females after hormonal treatment . However , these results showed no significant difference between both groups . CONCLUSION Delayed puberty in beta-thalassemia major is either due to failure of gonads or failure of the whole hypothalamic pituitary gonadal axis . L-carnitine as well as hormonal replacement therapy had a positive effect on puberty in the thalassemic patients . Further studies are needed to clarify the role of L-carnitine on puberty in these patients The cluster r and omized trial with a concurrent economic evaluation is considered the gold st and ard evaluative design for the conduct of implementation research evaluating different strategies to promote the transfer of research findings into clinical practice . This has implication s for the planning of such studies , as information is needed on the effects of clustering on both effectiveness and efficiency outcomes . This paper describes the design considerations specific to implementation research studies , focusing particularly on the estimation of sample size requirements and on the need for reliable information on intracluster correlation coefficients for both effectiveness and efficiency outcomes The aim of the study was to assess the efficacy of GH therapy in GH-deficient children treated before the age of 3 yr . A noncomparative multicenter prospect i ve study included 49 children ( 22 girls and 27 boys ) with isolated GH deficiency ( n = 19 ) or multiple pituitary hormone deficiency ( n = 30 ) treated with daily s.c . injections ( 0.6 U/kg.week ) for 3 - 5 yr . They were divided into two groups according to their height SD score for chronological age ( CA ) at the initiation of therapy : group A consisted of 8 patients presenting an initial height within the normal range ( < 2 SD below the mean ) followed for 2 - 5 yr , and group B consisted of 25 children followed for 5 yr among 41 patients with initial growth retardation . In group A , the mean height SD score increased from -1.1 + /- 0.6 to 0.35 + /- 1.0 SD ( P < 0.001 ) in the first year and remained in the normal range throughout the following 4 yr . In group B after 4 yr of treatment , the mean height SD score for age had increased from -3.6 + /- 1.0 SD ( time zero ) to -0.9 + /- 1.2 SD . During the fourth year of therapy , the mean height gain of 0.2 + /- 0.2 SD was significant ( P < 0.001 ) . After 5 yr of treatment , a plateau was reached with a corresponding height SD score ( CA ) of -0.8 + /- 1.2 SD ( 95 % confidence interval between -1.3 and -0.2 SD ) . This value remained significantly below normal for age ( P < 0.001 ) , indicating that catch-up growth was incomplete . Only four patients ( 16 % ) remained below -2SD for CA . The 5-yr height gain was negatively correlated with the height SD score at the start of treatment ( r = -0.6 ; P < 0.005 ) and the first year height gain was the most predictive parameter . There was no significant influence of intrauterine growth retardation , body mass index and age at the start of treatment , or parental target height . Bone maturation was significantly retarded over CA by a mean value of 1.1 + /- 0.9 yr ( P < 0.0001 ) , with a mean bone age/CA ratio of 0.8 + /- 0.2 after a mean treatment duration of 5.1 + /- 1.1 yr . In conclusion , the rapid and almost complete return to normal height obtained in this study supports the need for GH treatment in early diagnosed GH-deficient children . The present dosage may be considered the minimum to obtain satisfactory catch-up growth ensuring a favorable outcome for these children . In addition , it allowed growth at a rate normal for age in patients diagnosed before growth retardation |
11,925 | 23,377,698 | Fixed effects meta- analysis revealed higher peak plasma GLP-1 concentrations in patients with type 2 diabetes .
Meta-regression analyses showed that HbA1c and fasting plasma glucose predicted the outcomes iAUC and iAUC min−1 , respectively .
Conclusions /interpretationThe present analysis suggests that patients with type 2 diabetes , in general , do not exhibit reduced GLP-1 secretion in response to an OGTT or meal test , and that deteriorating glycaemic control may be associated with reduced GLP-1 secretion | Aims /hypothesisWe carried out a systematic review of clinical studies investigating glucagon-like peptide-1 ( GLP-1 ) secretion in patients with type 2 diabetes and non-diabetic controls and performed meta-analyses of plasma total GLP-1 concentrations during an OGTT and /or meal test . | BACKGROUND Incretin hormones , such as glucagon-like peptide 1 ( GLP-1 ) and glucose-dependent insulinotropic polypeptide ( GIP ) , play an important role in meal-related insulin secretion . We previously demonstrated that glutamine is a potent stimulus of GLP-1 secretion in vitro . OBJECTIVE Our objective was to determine whether glutamine increases circulating GLP-1 and GIP concentrations in vivo and , if so , whether this is associated with an increase in plasma insulin . DESIGN We recruited 8 healthy normal-weight volunteers ( LEAN ) , 8 obese individuals with type 2 diabetes or impaired glucose tolerance ( OB-DIAB ) and 8 obese nondiabetic control subjects ( OB-CON ) . Oral glucose ( 75 g ) , glutamine ( 30 g ) , and water were administered on 3 separate days in r and om order , and plasma concentrations of GLP-1 , GIP , insulin , glucagon , and glucose were measured over 120 min . RESULTS Oral glucose led to increases in circulating GLP-1 concentrations , which peaked at 30 min in LEAN ( 31.9 + /- 5.7 pmol/L ) and OB-CON ( 24.3 + /- 2.1 pmol/L ) subjects and at 45 min in OB-DIAB subjects ( 19.5 + /- 1.8 pmol/L ) . Circulating GLP-1 concentrations increased in all study groups after glutamine ingestion , with peak concentrations at 30 min of 22.5 + /- 3.4 , 17.9 + /- 1.1 , and 17.3 + /- 3.4 pmol/L in LEAN , OB-CON , and OB-DIAB subjects , respectively . Glutamine also increased plasma GIP concentrations but less effectively than glucose . Consistent with the increases in GLP-1 and GIP , glutamine significantly increased circulating plasma insulin concentrations . Glutamine stimulated glucagon secretion in all 3 study groups . CONCLUSION Glutamine effectively increases circulating GLP-1 , GIP , and insulin concentrations in vivo and may represent a novel therapeutic approach to stimulating insulin secretion in obesity and type 2 diabetes Gastric emptying of a liquid glucose meal was measured with scintigraphic techniques in nine recently diagnosed Type 2 diabetic patients and nine sex- and age-matched nondiabetic control subjects . Seven of the nine Type 2 diabetic patients were receiving oral hypoglycemic therapy which was discontinued the evening prior to the study . The other two diabetic patients were taking no medication . The average gastric half-emptying time was 33.6 min ( s.e.m . = 3.2 ) for the diabetic patients and 64.6 min ( s.e.m . = 4.2 ) for the nondiabetic controls ( p = 0.0005 ) . These measurements indicate rapid gastric emptying in Type 2 diabetic patients which may contribute to worsening of glucose control in these patients OBJECTIVE In patients with type 2 diabetes , but not type 1 diabetes , abnormal secretion of incretins in response to oral nutrients has been described . In healthy youths , we recently reported accentuated glucagon-like peptide 1 ( GLP-1 ) secretion in response to a diet soda sweetened with sucralose and acesulfame-K. In this study , we examined the effect of diet soda on gut hormones in youths with diabetes . RESEARCH DESIGN AND METHODS Subjects aged 12–25 years with type 1 diabetes ( n = 9 ) or type 2 diabetes ( n = 10 ) , or healthy control participants ( n = 25 ) drank 240 mL cola-flavored caffeine-free diet soda or carbonated water , followed by a 75-g glucose load , in a r and omized , cross-over design . Glucose , C-peptide , GLP-1 , glucose-dependent insulinotropic peptide ( GIP ) , and peptide Tyr-Tyr ( PYY ) were measured for 180 min . Glucose and GLP-1 have previously been reported for the healthy control subjects . RESULTS GLP-1 area under the curve ( AUC ) was 43 % higher after ingestion of diet soda versus carbonated water in individuals with type 1 diabetes ( P = 0.020 ) , similar to control subjects ( 34 % higher , P = 0.029 ) , but was unaffected by diet soda in patients with type 2 diabetes ( P = 0.92 ) . Glucose , C-peptide , GIP , and PYY AUC were not statistically different between the two conditions in any group . CONCLUSIONS Ingestion of diet soda before a glucose load augmented GLP-1 secretion in type 1 diabetic and control subjects but not type 2 diabetic subjects . GIP and PYY secretion were not affected by diet soda . The clinical significance of this increased GLP-1 secretion , and its absence in youths with type 2 diabetes , needs to be determined In type-2 diabetes , the overall incretin effect is reduced . The present investigation was design ed to compare insulinotropic actions of exogenous incretin hormones ( gastric inhibitory peptide [ GIP ] and glucagon-like peptide 1 [ GLP-1 ] [ 7 - 36 amide ] ) in nine type-2 diabetic patients ( fasting plasma glucose 7.8 mmol/liter ; hemoglobin A1c 6.3 + /- 0.6 % ) and in nine age- and weight-matched normal subjects . Synthetic human GIP ( 0.8 and 2.4 pmol/kg.min over 1 h each ) , GLP-1 [ 7 - 36 amide ] ( 0.4 and 1.2 pmol/kg.min over 1 h each ) , and placebo were administered under hyperglycemic clamp conditions ( 8.75 mmol/liter ) in separate experiments . Plasma GIP and GLP-1 [ 7 - 36 amide ] concentrations ( radioimmunoassay ) were comparable to those after oral glucose with the low , and clearly supraphysiological with the high infusion rates . Both GIP and GLP-1 [ 7 - 36 amide ] dose-dependently augmented insulin secretion ( insulin , C-peptide ) in both groups ( P < 0.05 ) . With GIP , the maximum effect in type-2 diabetic patients was significantly lower ( by 54 % ; P < 0.05 ) than in normal subjects . With GLP-1 [ 7 - 36 amide ] type-2 diabetic patients reached 71 % of the increments in C-peptide of normal subjects ( difference not significant ) . Glucagon was lowered during hyperglycemic clamps in normal subjects , but not in type-2 diabetic patients , and further by GLP-1 [ 7 - 36 amide ] in both groups ( P < 0.05 ) , but not by GIP . In conclusion , in mild type-2 diabetes , GLP-1 [ 7 - 36 amide ] , in contrast to GIP , retains much of its insulinotropic activity . It also lowers glucagon concentrations Exogenous glucagon-like peptide 1(GLP-1 ) bioactivity is preserved in type 2 diabetic patients , result ing the peptide administration in a near-normalization of plasma glucose mainly through its insulinotropic effect . GLP-1 also reduces meal-related insulin requirement in type 1 diabetic patients , suggesting an impairment of the entero-insular axis in both diabetic conditions . To investigate this metabolic dysfunction , we evaluated endogenous GLP-1 concentrations , both at fasting and in response to nutrient ingestion , in 16 type 1 diabetic patients ( age = 40.5 + /- 14yr , HbA1C = 7.8 + /- 1.5 % ) , 14 type 2 diabetics ( age = 56.5 + /- 13yr , HbA1C = 8.1 + /- 1.8 % ) , and 10 matched controls . In postabsorptive state , a mixed breakfast ( 230 KCal ) was administered to all subjects and blood sample s were collected for plasma glucose , insulin , C-peptide and GLP-1 determination during the following 3 hours . In normal subjects , the test meal induced a significant increase of GLP-1 ( 30 ' , 60 ' : p < 0.01 ) , returning the peptide values towards basal concentrations . In type 2 diabetic patients , fasting plasma GLP-1 was similar to controls ( 102.1 + /- 1.9 vs. 97.3 + /- 4.01 pg/ml ) , but nutrient ingestion failed to increase plasma peptide levels , which even decreased during the test ( p < 0.01 ) . Similarly , no increase in postpr and ial GLP-1 occurred in type 1 diabetics , in spite of maintained basal peptide secretion ( 106.5 + /- 1.5 pg/ml ) . With respect to controls , the test meal induced in both diabetic groups a significant increase in plasma glucagon levels at 60 ' ( p < 0.01 ) . In conclusion , either in condition of insulin resistance or insulin deficiency chronic hyperglycemia , which is a common feature of both metabolic disorders , could induce a progressive desensitization of intestinal L-cells with consequent peptide failure response to specific stimulation BACKGROUND Glucagon-like peptide 1 ( GLP-1 ) has been proposed as a treatment for type 2 diabetes . We have investigated the long-term effects of continuous administration of this peptide hormone in a 6-week pilot study . METHODS 20 patients with type 2 diabetes were alternately assigned continuous subcutaneous infusion of GLP-1 ( n=10 ) or saline ( n=10 ) for 6 weeks . Before ( week 0 ) and at weeks 1 and 6 , they underwent beta-cell function tests ( hyperglycaemic clamps ) , 8 h profiles of plasma glucose , insulin , C-peptide , glucagon , and free fatty acids , and appetite and side-effect ratings on 100 mm visual analogue scales ; at weeks 0 and 6 they also underwent dexascanning , measurement of insulin sensitivity ( hyperinsulinaemic euglycaemic clamps ) , haemoglobin A(1c ) , and fructosamine . The primary endpoints were haemoglobin A(1c ) concentration , 8-h profile of glucose concentration in plasma , and beta-cell function ( defined as the first-phase response to glucose and the maximum insulin secretory capacity of the cell ) . Analyses were per protocol . FINDINGS One patient assigned saline was excluded because no veins were accessible . In the remaining nine patients in that group , no significant changes were observed except an increase in fructosamine concentration ( p=0.0004 ) . In the GLP-1 group , fasting and 8 h mean plasma glucose decreased by 4.3 mmol/L and 5.5 mmol/L ( p<0.0001 ) . Haemoglobin A(1c ) decreased by 1.3 % ( p=0.003 ) and fructosamine fell to normal values ( p=0.0002 ) . Fasting and 8 h mean concentrations of free fatty acids decreased by 30 % and 23 % ( p=0.0005 and 0.01 , respectively ) . Gastric emptying was inhibited , bodyweight decreased by 1.9 kg , and appetite was reduced . Both insulin sensitivity and beta-cell function improved ( p=0.003 and p=0.003 , respectively ) . No important side-effects were seen . INTERPRETATION GLP-1 could be a new treatment for type 2 diabetes , though further investigation of the long-term effects of GLP-1 is needed Background Sleeve gastrectomy ( SG ) and Roux-en-Y gastric bypass ( RYGBP ) are associated with similar type 2 diabetes mellitus ( T2DM ) resolution rates for morbidly obese subjects . However , the mechanisms underlying the resolution of T2DM after SG have not been clarified to date . This study aim ed to compare the early changes in gastrointestinal hormones involved in insulin and glucagon secretion in morbidly obese T2DM subjects undergoing SG or RYGBP . Methods This prospect i ve study investigated 12 subjects with T2DM who had undergone SG ( n = 6 ) or RYGBP ( n = 6 ) . Five body mass index ( BMI ) -matched obese non-diabetic subjects and five BMI -matched obese diabetic subjects served as control subjects . Glucose , insulin , glucagon , glucagon-like peptide 1 ( GLP-1 ) , glucose-dependent insulinotropic polypeptide ( GIP ) , and GLP-2 were determined after a st and ardized mixed liquid meal before surgery and 6 weeks afterward . Results After 6 weeks , five of the six subjects in each surgical group presented with T2DM remission , although the area under the curve (AUC)0–120 of glucose was greater than that of the non-diabetic control subjects ( P < 0.01 ) . Postsurgically , the indices of insulin and glucagon secretion were comparable between the two surgical groups . The AUC0–120 of GLP-1 ( P < 0.05 ) and GLP-2 ( P < 0.05 ) was significantly and comparably enlarged after SG and RYGB . The postsurgical GIP response was significantly associated with the glucagon response throughout the meal test ( ρ = 0.747 ; P < 0.01 ) . Conclusions The data show that in a cohort of morbidly obese T2DM subjects , SG and RYGBP are associated with an early improvement in glucose tolerance , similar changes in insulin and glucagon secretion , and a similar GLP-1 , GIP , and GLP-2 response to a st and ardized mixed liquid meal The incretins glucagon-like peptide-1 ( GLP-1 ) and glucose-dependent insulinotropic polypeptide ( GIP ) regulate postpr and ial insulin release from the beta-cells . We investigated the effects of 3 st and ardized meals with different caloric and nutritional content in terms of postpr and ial glucose , insulin , glucagon , and incretin responses . In a r and omized crossover study , 18 subjects with type 2 diabetes mellitus and 6 healthy volunteers underwent three 4-hour meal tolerance tests ( small carbohydrate [CH]-rich meal , large CH-rich meal , and fat-rich meal ) . Non-model-based and model-based estimates of beta-cell function and incremental areas under the curve of glucose , insulin , C-peptide , glucagon , GLP-1 , and GIP were calculated . Mixed models and Friedman tests were used to test for differences in meal responses . The large CH-rich meal and fat-rich meal result ed in a slightly larger insulin response as compared with the small CH-rich meal and led to a slightly shorter period of hyperglycemia , but only in healthy subjects . Model-based insulin secretion estimates did not show pronounced differences between meals . Both in healthy individuals and in those with diabetes , more CH result ed in higher GLP-1 release . In contrast with the other meals , GIP release was still rising 2 hours after the fat-rich meal . The initial glucagon response was stimulated by the large CH-rich meal , whereas the fat-rich meal induced a late glucagon response . Fat preferentially stimulates GIP secretion , whereas CH stimulates GLP-1 secretion . Differences in meal size and composition led to differences in insulin and incretin responses but not to differences in postpr and ial glucose levels of the well-controlled patients with diabetes Cohort studies are equivocal regarding a relationship between regular nut consumption and reduced risk of type 2 diabetes mellitus . Although acute trials show reductions in postpr and ial glycemia in healthy individuals ingesting 60 to 90 g almonds , trials have not been conducted using a single serving of almonds ( 28 g ) in individuals with type 2 diabetes mellitus . This r and omized crossover trial examined the impact of one serving of almonds at mealtime on postpr and ial glycemia , insulinemia , and plasma glucagon-like peptide-1 in healthy individuals and individuals with type 2 diabetes mellitus . On 2 occasions separated by at least 1 week , 19 adults ( including 7 adults with type 2 diabetes mellitus ) consumed a st and ardized evening meal and fasted overnight before ingesting the test meal ( bagel , juice , and butter ) with or without almonds . A small pilot study ( 6 - 7 subjects per group ) was also conducted to observe whether chronic almond ingestion ( 1 serving 5 d/wk for 12 weeks ) lowered hemoglobin A(1c ) in individuals with type 2 diabetes mellitus . A st and ard serving of almonds reduced postpr and ial glycemia significantly in participants with diabetes ( -30 % , P = .043 ) but did not influence glycemia in participants without diabetes ( -7 % , P = .638 ) . Insulinemia and glucagon-like peptide-1 at 30 minutes postmeal were not impacted by almond ingestion for either group . In the pilot study , regular almond ingestion for 12 weeks reduced hemoglobin A(1c ) by 4 % ( P = .045 for interaction ) but did not influence fasting glucose concentrations . These data show that modest almond consumption favorably improves both short-term and long-term markers of glucose control in individuals with uncomplicated type 2 diabetes mellitus |
11,926 | 29,662,749 | Conclusions : There is a lack of consistency in reporting of AEs among RCTs of cervical arthroplasty .
FDA IDE trials scored better in AE event reporting compared to other studies . | Objectives : Cervical arthroplasty is an increasingly popular treatment of cervical radiculopathy and myelopathy .
An underst and ing of the potential adverse events ( AEs ) is important to help both clinicians and patients .
We sought to provide a comprehensive systematic review of the AEs reported in all r and omized controlled trials ( RCTs ) of cervical disc arthroplasty in an attempt to characterize the quality of reporting . | OBJECTIVE To evaluate the effectiveness and safety of cervical arthroplasty and anterior cervical discectomy fusion methods . METHODS The r and omised clinical trial was conducted at the neurosurgical clinic of University of Harran , Turkey , between February 2009 and January 2010 . The patients had single level disc disorder between C4-C7 levels . Before surgery , all of the patients had taken medical treatment with no improvement . Surgery was conducted with anterior approach , and disc prosthesis or polyetheretherketone cage for fusion were applied after patients were r and omly divided into two groups . For preoperative and postoperative clinical evaluations Neck Disability Index and Visual Analogue Scale were used . Surgical results were evaluated according to Odom 's criterion , and ' excellent ' and ' good ' results were accepted as successful . P<0.05 was taken as statistically significant . RESULTS Of the 42 patients in the study , 23(54.76 % ) were treated with Anterior Cervical Discectomy and Fusion , and 19(45.23 % ) with Cervical Disc Arthroplasty . There were no statistical differences between postoperative mean Visual Analogue Scale score ( p<0.86 ) and Neck Disability Index scores ( p<0.11 ) in the two groups . Average decrease in lordosis angle was 1.2 degree in Arthroplasty group , while it was 1 degree in the Fusion group . Postoperative adjacent segment degeneration was not detected in either group . CONCLUSION Anterior Cervical Discectomy and Fusion , and Cervical Disc Arthroplasty are safe and successful methods for the treatment of single level cervical disc disease . Although the latter is a relatively new technique performed with increased frequency , but its superiority is still uncertain BACKGROUND CONTEXT Cervical total disc replacement ( TDR ) is intended to address radicular pain and preserve functional motion between two vertebral bodies in patients with symptomatic cervical disc disease ( SCDD ) . PURPOSE The purpose of this trial is to compare the safety and efficacy of cervical TDR , ProDisc-C ( Synthes Spine Company , L.P. , West Chester , PA ) , to anterior cervical discectomy and fusion ( ACDF ) surgery for the treatment of one-level SCDD between C3 and C7 . STUDY DESIGN / SETTING The study was conducted at 13 sites . A noninferiority design with a 1:1 r and omization was used . PATIENT SAMPLE Two hundred nine patients were r and omized and treated ( 106 ACDF ; 103 ProDisc-C ) . OUTCOME MEASURES Visual analog scale ( VAS ) pain and intensity ( neck and arm ) , VAS satisfaction , neck disability index ( NDI ) , neurological exam , device success , adverse event occurrence , and short form-36 ( SF-36 ) st and ardized question naires . METHODS A prospect i ve , r and omized , controlled clinical trial was performed . Patients were enrolled and treated in accordance with the US Food and Drug Administration ( FDA ) -approved protocol . Patients were assessed pre- and postoperatively at six weeks , 3 , 6 , 12 , 18 , and 24 months . RESULTS Demographics were similar between the two patient groups ( ProDisc-C : 42.1+/-8.4 years , 44.7 % males ; Fusion : 43.5 + /- 7.1 years , 46.2 % males ) . The most commonly treated level was C5-C6 ( ProDisc-C : 56.3 % ; Fusion=57.5 % ) . NDI and SF-36 scores were significantly less compared with presurgery scores at all follow-up visits for both the treatment groups ( p<.0001 ) . VAS neck pain intensity and frequency as well as VAS arm pain intensity and frequency were statistically lower at all follow-up timepoints compared with preoperative levels ( p<.0001 ) but were not different between treatments . Neurologic success ( improvement or maintenance ) was achieved at 24 months in 90.9 % of ProDisc-C and 88.0 % of Fusion patients ( p=.638 ) . Results show that at 24 months postoperatively , 84.4 % of ProDisc-C patients achieved a more than or equal to 4 degrees of motion or maintained motion relative to preoperative baseline at the operated level . There was a statistically significant difference in the number of secondary surgeries with 8.5 % of Fusion patients needing a re-operation , revision , or supplemental fixation within the 24 month postoperative period compared with 1.8 % of ProDisc-C patients ( p=.033 ) . At 24 months , there was a statistically significant difference in medication usage with 89.9 % of ProDisc-C patients not on strong narcotics or muscle relaxants , compared with 81.5 % of Fusion patients . CONCLUSIONS The results of this clinical trial demonstrate that ProDisc-C is a safe and effective surgical treatment for patients with disabling cervical radiculopathy because of single-level disease . By all primary and secondary measures evaluated , clinical outcomes after ProDisc-C implantation were either equivalent or superior to those same clinical outcomes after Fusion OBJECT The authors report the results of a prospect i ve r and omized multicenter study in which the results of cervical disc arthroplasty were compared with anterior cervical discectomy and fusion ( ACDF ) in patients treated for symptomatic single-level cervical degenerative disc disease ( DDD ) . METHODS Five hundred forty-one patients with single-level cervical DDD and radiculopathy were enrolled at 32 sites and r and omly assigned to one of two treatment groups : 276 patients in the investigational group underwent anterior cervical discectomy and decompression and arthroplasty with the PRESTIGE ST Cervical Disc System ( Medtronic Sofamor Danek ) ; 265 patients in the control group underwent decompressive ACDF . Eighty percent of the arthroplasty-treated patients ( 223 of 276 ) and 75 % of the control patients ( 198 of 265 ) completed clinical and radiographic follow-up examinations at routine intervals for 2 years after surgery . Analysis of all currently available postoperative 12- and 24-month data indicated a two-point greater improvement in the neck disability index score in the investigational group than the control group . The arthroplasty group also had a statistically significant higher rate of neurological success ( p = 0.005 ) as well as a lower rate of secondary revision surgeries ( p = 0.0277 ) and supplemental fixation ( p = 0.0031 ) . The mean improvement in the 36-Item Short Form Health Survey Physical Component Summary scores was greater in the investigational group at 12 and 24 months , as was relief of neck pain . The patients in the investigational group returned to work 16 days sooner than those in the control group , and the rate of adjacent-segment reoperation was significantly lower in the investigational group as well ( p = 0.0492 , log-rank test ) . The cervical disc implant maintained segmental sagittal angular motion averaging more than 7 degrees . In the investigational group , there were no cases of implant failure or migration . CONCLUSIONS The PRESTIGE ST Cervical Disc System maintained physiological segmental motion at 24 months after implantation and was associated with improved neurological success , improved clinical outcomes , and a reduced rate of secondary surgeries compared with ACDF OBJECT There are now 3 r and omized , multicenter , US FDA investigational device exemption , industry-sponsored studies comparing arthroplasty with anterior cervical discectomy and fusion ( ACDF ) for single-level cervical disease with 2 years of follow-up . These 3 studies evaluated the Prestige ST , Bryan , and ProDisc-C artificial discs . The authors analyzed the combined results of these trials . METHODS A total of 1213 patients with symptomatic , single-level cervical disc disease were r and omized into 2 treatment arms in the 3 r and omized trials . Six hundred twenty-one patients received an artificial cervical disc , and 592 patients were treated with ACDF . In the three trials , 94 % of the arthroplasty group and 87 % of the ACDF group have completed 2 years of follow-up . The authors analyzed the 2-year data from these 3 trials including previously unpublished source data . Statistical analysis was performed with fixed and r and om effects models . RESULTS The authors ' analysis revealed that segmental sagittal motion was preserved with arthroplasty ( preoperatively 7.26 ° and postoperatively 8.14 ° ) at the 2-year time point . The fusion rate for ACDF at 2 years was 95 % . The Neck Disability Index , 36-Item Short Form Health Survey Mental , and Physical Component Summaries , neck pain , and arm pain scores were not statistically different between the groups at the 24-month follow-up . The arthroplasty group demonstrated superior results at 24 months in neurological success ( RR 0.595 , I(2 ) = 0 % , p = 0.006 ) . The arthroplasty group had a lower rate of secondary surgeries at the 2-year time point ( RR 0.44 , I(2 ) = 0 % , p = 0.004 ) . At the 2-year time point , the reoperation rate for adjacent-level disease was lower for the arthroplasty group when the authors analyzed the combined data set using a fixed effects model ( RR 0.460 , I(2 ) = 2.9 % , p = 0.030 ) , but this finding was not significant using a r and om effects model . Adverse event reporting was too heterogeneous between the 3 trials to combine for analysis . CONCLUSIONS Both anterior cervical discectomy and fusion as well as arthroplasty demonstrate excellent 2-year surgical results for the treatment of 1-level cervical disc disease with radiculopathy . Arthroplasty is associated with a lower rate of secondary surgery and a higher rate of neurological success at 2 years . Arthroplasty may be associated with a lower rate of adjacent-level disease at 2 years , but further follow-up and analysis are needed to confirm this finding Purpose Heterotopic ossification is a phenomenon in cervical arthroplasty . Previous reports have mainly focused on various semiconstrained devices and only a few publications have focused on ossification around devices that are nonconstrained . The purpose of this study was to assess the occurrence of heterotopic ossification around a nonconstrained cervical device and how it affects clinical outcome 2 years after surgery . Methods Thirty-seven patients were included from a larger cohort of a r and omized controlled trial ( NORCAT ) which compared single-level cervical arthroplasty with fusion . The occurrence of heterotopic ossification was assessed with a CT scan and two neuroradiologists determined its degree . For grading , we used the Mehren/Suchomel classification system ( grade 0–4 ) . The patients were divided by level of ossification , low grade ( 0–2 ) or high grade ( 3–4 ) , and clinical outcomes were compared . Self-rated disability for neck and arm pain ( Neck Disability Index ) , health-related quality of life ( the Short Form-36 and EuroQol-5D ) , and pain ( the Numeric Rating Scale 11 ) were used as clinical outcome measures . Results Heterotopic ossification was encountered in all patients 2 years after surgery . Complete fusion ( grade 4 ) was found in 16 % of participants , and high- grade ossification ( grade 3–4 ) occurred in 62 % . The remaining patients were classified as having low- grade ossification ( grade 2 ) . There were no differences in the clinical outcomes of patients with low- and high- grade ossification . Conclusion High- grade heterotopic ossification and spontaneous fusion 2 years after surgery were seen in a significant number of patients . However , the degree of ossification did not influence the clinical outcome Purpose St and ard surgical treatment for symptomatic cervical disc disease has been discectomy and fusion , but the use of arthroplasty , design ed to preserve motion , has increased , and most studies report clinical outcome in its favor . Few of these trials , however , blinded the patients . We , therefore , conducted the Norwegian Cervical Arthroplasty Trial , and present 2-year clinical outcome after arthroplasty or fusion . Methods This multicenter trial included 136 patients with single-level cervical disc disease . The patients were r and omized to arthroplasty or fusion , and blinded to the treatment modality . The surgical team was blinded to r and omization until nerve root decompression was completed . Primary outcome was the self-rated Neck Disability Index . Secondary outcomes were the numeric rating scale for pain and quality of life question naires Short Form-36 and EuroQol-5Dimension-3 Level . Results There was a significant improvement in the primary and all secondary outcomes from baseline to 2-year follow-up for both arthroplasty and fusion ( P < 0.001 ) , and no observed significant between-group differences at any follow-up times . However , linear mixed model analyses , correcting for baseline values , dropouts and missing data , revealed a difference in Neck Disability Index ( P = 0.049 ) , and arm pain ( P = 0.027 ) in favor of fusion at 2 years . The duration of surgery was longer ( P < 0.001 ) , and the frequency of reoperations higher ( P = 0.029 ) with arthroplasty . Conclusion The present study showed excellent clinical results and no significant difference between treatments at any scheduled follow-up . However , the rate of index level reoperations was higher and the duration of surgery longer with arthroplasty . Trial registration http://www . clinical trials.gov NCT 00735176.19 Study Design . R and omized controlled study . Objective . To compare the rates of adverse events associated with disc arthroplasty versus those of anterior cervical discectomy and arthrodesis with allograft and plate . Summary of Background Data . Cervical disc arthroplasty as a substitute for fusion has been developed to maintain motion and , theoretically , prevent adjacent segment degeneration . Currently , cervical arthroplasty devices are undergoing clinical testing for safety and efficacy . The evaluation of safety is performed by critical analysis of all adverse occurrences following surgery to determine if the new device has a beneficial risk profile for the patient . Methods . Adverse events associated with Bryan Disc arthroplasty and arthrodesis were compared in a prospect i ve r and omized study . Four hundred sixty-three ( 463 ) patients having cervical radiculopathy and or myelopathy at a single level were treated at 31 sites . A total of 242 patients received the disc and 221 patients had anterior cervical discectomy and fusion . All patients were evaluated before surgery and at 1.5 , 3 , 6 , 12 , and 24 months after surgery . Adverse events were recorded concurrently and categorized by severity and as medically or surgically related . Results . No differences in overall medical events occurred between groups . Surgically related events occurred more frequently in the investigational group secondary to more complaints of postoperative dysphagia and late medical events occurred more frequently in the investigational patients . However , the more severe World Health Organization Grade 3 and 4 events occurred more frequently in the arthrodesis patients related to treatment of pseudarthrosis and persistent symptoms . Significantly , more cervical spine reoperations occurred in the fusion group . Only one spinal cord injury occurred and it was in the arthrodesis group and no patients had deep infection or death related to either procedure . Conclusion . Bryan cervical disc replacement and anterior cervical fusion are both safe procedures with a low incidence of significant adverse events related to the procedure . Statistically , more serious adverse events and reoperations occurred in the fusion group while a greater number of less serious surgically related events were seen in the investigational group BACKGROUND In patients with single-level cervical degenerative disc disease , total disc arthroplasty can relieve radicular pain and preserve functional motion between two vertebrae . We compared the efficacy and safety of cervical total disc arthroplasty with that of anterior cervical discectomy and fusion ( ACDF ) for the treatment of single-level cervical degenerative disc disease between C3-C4 and C6-C7 . METHODS Two hundred and nine patients at thirteen sites were r and omly treated with either total disc arthroplasty with ProDisc-C ( n = 103 ) or with ACDF ( n = 106 ) . Patients were assessed preoperatively ; at six weeks and three , six , twelve , eighteen , and twenty-four months postoperatively ; and then annually until seven years postoperatively . Outcome measures included the Neck Disability Index ( NDI ) , the Short Form-36 ( SF-36 ) , postoperative neurologic parameters , secondary surgical procedures , adverse events , neck and arm pain , and satisfaction scores . RESULTS At seven years , the overall follow-up rate was 92 % ( 152 of 165 ) . There were no significant differences in demographic factors , follow-up rate , or patient-reported outcomes between groups . Both procedures were effective in reducing neck and arm pain and improving and maintaining function and health-related quality of life . Neurologic status was improved or maintained in 88 % and 89 % of the patients in the ProDisc-C and ACDF groups , respectively . After seven years of follow-up , thirty secondary surgical procedures had been performed in nineteen ( 18 % ) of 106 patients in the ACDF group compared with seven secondary surgical procedures in seven ( 7 % ) of 103 patients in the ProDisc-C group ( p = 0.0099 ) . There were no significant differences in the rates of any device-related adverse events between the groups . CONCLUSIONS Total disc arthroplasty with ProDisc-C is a safe and effective surgical treatment of single-level symptomatic cervical degenerative disc disease . Clinical outcomes after total disc arthroplasty with ProDisc-C were similar to those after ACDF . Patients treated with ProDisc-C had a lower probability of subsequent surgery , suggesting that total disc arthroplasty provides durable results and has the potential to slow the rate of adjacent-level disease . LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence OBJECT Cervical total disc replacement ( TDR ) is intended to treat neurological symptoms and neck pain associated with degeneration of intervertebral discs in the cervical spine . Anterior cervical discectomy and fusion ( ACDF ) has been the st and ard treatment for these indications since the procedure was first developed in the 1950s . While TDR has been shown to be a safe and effective alternative to ACDF for treatment of patients with degenerative disc disease ( DDD ) at a single level of the cervical spine , few studies have focused on the safety and efficacy of TDR for treatment of 2 levels of the cervical spine . The primary objective of this study was to rigorously compare the Mobi-C cervical artificial disc to ACDF for treatment of cervical DDD at 2 contiguous levels of the cervical spine . METHODS This study was a prospect i ve , r and omized , US FDA investigational device exemption pivotal trial of the Mobi-C cervical artificial disc conducted at 24 centers in the US . The primary clinical outcome was a composite measure of study success at 24 months . The comparative control treatment was ACDF using allograft bone and an anterior plate . A total of 330 patients were enrolled , r and omized , and received study surgery . All patients were diagnosed with intractable symptomatic cervical DDD at 2 contiguous levels of the cervical spine between C-3 and C-7 . Patients were r and omized in a 2:1 ratio ( TDR patients to ACDF patients ) . RESULTS A total of 225 patients received the Mobi-C TDR device and 105 patients received ACDF . At 24 months only 3.0 % of patients were lost to follow-up . On average , patients in both groups showed significant improvements in Neck Disability Index ( NDI ) score , visual analog scale ( VAS ) neck pain score , and VAS arm pain score from preoperative baseline to each time point . However , the TDR patients experienced significantly greater improvement than ACDF patients in NDI score at all time points and significantly greater improvement in VAS neck pain score at 6 weeks , and at 3 , 6 , and 12 months postoperatively . On average , patients in the TDR group also maintained preoperative segmental range of motion at both treated segments immediately postoperatively and throughout the study period of 24 months . The reoperation rate was significantly higher in the ACDF group at 11.4 % compared with 3.1 % for the TDR group . Furthermore , at 24 months TDR demonstrated statistical superiority over ACDF based on overall study success rates . CONCLUSIONS The results of this study represent the first available Level I clinical evidence in support of cervical arthroplasty at 2 contiguous levels of the cervical spine using the Mobi-C cervical artificial disc . These results continue to support the use of cervical arthroplasty in general , but specifically demonstrate the advantages of 2-level arthroplasty over 2-level ACDF . Clinical trial registration no. : NCT00389597 ( Clinical Trials.gov ) Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms Background Anterior cervical discectomy and fusion ( ACDF ) is the gold st and ard for treating symptomatic cervical disc degeneration . Cervical total disc replacements ( TDRs ) have emerged as an alternative for some patients . The purpose of this study was to evaluate the safety and effectiveness of a new TDR device compared with ACDF for treating single-level cervical disc degeneration . Methods This was a prospect i ve , r and omized , controlled , multicenter Food and Drug Administration ( FDA ) regulated Investigational Device Exemption ( IDE ) study . A total of 245 patients were treated ( 164 TDR : 81 ACDF ) . The primary outcome measure was overall success based on improvement in Neck Disability Index ( NDI ) , no subsequent surgical interventions , and no adverse events ( AEs ) classified as major complications . Secondary outcome measures included SF-12 , visual analog scale ( VAS ) assessing neck and arm pain , patient satisfaction , radiographic range of motion , and adjacent level degeneration . Patients were evaluated preoperatively and postoperatively at 6 weeks , 3 , 6 , 12 , 18 , and 24 months . The hypothesis was that the TDR success rate was non-inferior to ACDF at 24 months . Results Overall success rates were 73.6 % for TDR and 65.3 % for ACDF , confirming non-inferiority ( p < 0.0025 ) . TDR demonstrated earlier improvements with significant differences in NDI scores at 6 weeks and 3 months , and VAS neck pain and SF-12 PCS scores at 6 weeks ( p<0.05 ) . Operative level range of motion in the TDR group was maintained throughout follow-up . Radiographic evidence of inferior adjacent segment degeneration was significantly greater with ACDF at 12 and 24 months ( p < 0.05 ) . AE rates were similar . Conclusions Mobi-C TDR is a safe and effective treatment for single-level disc degeneration , producing outcomes similar to ACDF with less adjacent segment degeneration . Level of Evidence : Level I. Clinical relevance : This study adds to the literature supporting cervical TDR as a viable option to ACDF in appropriately selected patients with disc degeneration Study Design . R and omized controlled trial . Objective . Analyze the clinical outcomes at 5 years comparing cervical total disc replacement ( TDR ) with ProDisc-C ( Synthes Spine USA Products ; LLC , West Chester , PA ) with anterior cervical discectomy and fusion ( ACDF ) . Summary of Background Data . Previous reports of 2- and 4-year results have shown that ProDisc-C , a TDR for surgical treatment of patients experiencing single-level symptomatic cervical disc disease between C3 and C7 , is safe and effective . Methods . Two hundred nine patients ( 103 ProDisc-C and 106 ACDF ) from 13 sites were r and omized and treated . Results including neck disability index , visual analog scale ( VAS ) neck and arm pain , Short Form-36 ( SF-36 ) , neurological examination , device success , adverse event occurrence , and VAS patient satisfaction were analyzed . Results . Demographics were similar between the 2 patient groups ( ProDisc-C : 42.1 ± 8.4 yr , 44.7 % males ; ACDF : 43.5 ± 7.1 yr , 46.2 % males ) . Rates of follow-up at 2 years were 98.1 % ProDisc-C and 94.8 % ACDF , and at 5 years 72.7 % ProDisc-C and 63.5 % ACDF . For all clinical outcomes for both groups , there was a statistically and clinical ly significant improvement at 2 and 5 years compared with baseline . At 5 years , ProDisc-C patients had statistically significantly less neck pain intensity and frequency . Both groups scored high VAS satisfaction scores at 5 years , with ProDisc-C 86.56 and ACDF 82.74 . There were no reports of device failures or implant migration with ProDisc-C. The ProDisc-C patients maintained motion at their index level . At 5 years , the ProDisc-C patients had a statistically significantly lower rate of reoperation compared with ACDF patients ( 2.9 % vs. 11.3 % ) . Conclusion . Five-year results show that TDR with ProDisc-C is a safe and effective treatment of single-level symptomatic cervical disc disease . Clinical outcomes were comparable with ACDF . ProDisc-C patients maintained motion at the index level and had significantly less neck pain intensity and frequency as well as a lower probability of secondary surgery OBJECT A prospect i ve , r and omized clinical trial was conducted to compare the Prestige II Cervical Disc with anterior decompression and fusion for the treatment of single-level degenerative disease . St and ardized clinical outcome measures and radiographic examinations were used at prescribed postoperative intervals to compare the treatment groups . METHODS Patients with symptomatic single-level cervical disc disease who met the inclusion /exclusion criteria defined in the protocol were r and omized to receive the Prestige II disc or iliac crest autograft fusion . All patients underwent a st and ardized neurological and radiographic examination and completed outcomes question naires ( Neck Disability Index and Short Form-36 ) preoperatively and at each postoperative interval ( 6 weeks and 3 , 6 , 12 , and 24 months ) . Two independent radiologists review ed all x-ray films and assessed motion at the treated level and adjacent segments . St and ard statistical methods were used to compare all outcome measures . Preliminary results in 55 patients enrolled in the study are presented . Several patients have reached the final ( 24-month ) follow-up interval . Clinical and radiographic results are encouraging , with significant improvement seen in both treatment groups . Radiographic results show that the Prestige II disc maintains motion at the treated level without adjacent-segment compromise . CONCLUSIONS Cervical spine arthroplasty is an exciting and rapidly developing surgical treatment option . An objective comparison with fusion is important to advance this option . This is the first prospect i ve r and omized trial in which cervical arthroplasty is compared with fusion . The preliminary results from this limited number of patients indicate that the Prestige II disc is potentially a viable alternative to fusion for primary cervical disc disease ; however , further clinical studies with larger sample sizes will be required to show statistical equivalence BACKGROUND Reports of clinical trials usually emphasize efficacy results , especially when results are statistically significant . Poor safety reporting can lead to misinterpretation and inadequate conclusions about the interventions assessed . Our aim was to describe the reporting of harm-related results from r and omized controlled trials ( RCTs ) . METHODS We search ed the MEDLINE data base for reports of RCTs published from January 1 , 2006 , through January 1 , 2007 , in 6 general medical journals with a high impact factor . Data were extracted by use of a st and ardized form to appraise the presentation of safety results in text and tables . RESULTS Adverse events were mentioned in 88.7 % of the 133 reports . No information on severe adverse events and withdrawal of patients owing to an adverse event was given in 27.1 % and 47.4 % of articles , respectively . Restrictions in the reporting of harm-related data were noted in 43 articles ( 32.3 % ) with a description of the most common adverse events only ( n = 17 ) , severe adverse events only ( n = 16 ) , statistically significant events only ( n = 5 ) , and a combination of restrictions ( n = 5 ) . The population considered for safety analysis was clearly reported in 65.6 % of articles . CONCLUSION Our review reveals important heterogeneity and variability in the reporting of harm-related results in publications of RCTs Study Design : This was a prospect i ve , r and omized , controlled multicenter trial . Objective : The purpose of this study was to compare clinical outcomes at 4-year follow-up of patients receiving cervical total disk replacement ( TDR ) with those receiving anterior cervical discectomy and fusion ( ACDF ) . Summary of Background Data : ACDF has been the traditional treatment for symptomatic disk degeneration . Several studies found single-level TDR to be as safe and effective as ACDF at ≥2 years follow-up . Methods : Patients from 23 centers were r and omized in a 2:1 ratio with 164 receiving the investigational device ( Mobi-C Cervical Disc Prosthesis ) and 81 receiving ACDF using an anterior plate and allograft . Patients were evaluated preoperatively and 6 weeks , 3 , 6 , 12 , 18 , 24 , 36 , and 48 months postoperatively . Outcome assessment s included a composite success score , Neck Disability Index , visual analog scales assessing neck and arm pain , patient satisfaction , major complications , subsequent surgery , segmental range of motion , and adjacent-segment degeneration . Results : The composite success rate was similar in the 2 groups at 48-month follow-up . Mean Neck Disability Index , visual analog scale , and SF-12 scores were significantly improved in early follow-up in both groups with improvements maintained throughout 48 months . On some measures , TDR had significantly greater improvement during early follow-up . At no follow-up were TDR scores significantly worse than ACDF scores . Subsequent surgery rate was significantly higher for ACDF compared with TDR ( 9.9 % vs. 3.0 % , P<0.05 ) . Range of motion was maintained with TDR having a mean baseline value of 8 degrees compared with 10 degrees at 48 months . The incidence of adjacent-segment degeneration was significantly higher with ACDF at inferior and superior segments compared with TDR ( inferior : 50 % vs. 30 % , P<0.025 ; superior : 53 % vs. 34 % , P<0.025 ) . Conclusions : Significant improvements were observed in pain and function . TDR patients maintained motion and had significantly lower rates of reoperation and adjacent-segment degeneration compared with ACDF . This study supports the safety and efficacy of TDR in appropriately selected patients OBJECTIVE The aim of this study was to assess long-term clinical safety and effectiveness in patients undergoing anterior cervical surgery using the Prestige LP artificial disc replacement ( ADR ) prosthesis to treat degenerative cervical spine disease at 2 adjacent levels compared with anterior cervical discectomy and fusion ( ACDF ) . METHODS A prospect i ve , r and omized , controlled , multicenter FDA -approved clinical trial was conducted at 30 US centers , comparing the low-profile titanium ceramic composite-based Prestige LP ADR ( n = 209 ) at 2 levels with ACDF ( n = 188 ) . Clinical and radiographic evaluations were completed preoperatively , intraoperatively , and at regular postoperative intervals to 84 months . The primary end point was overall success , a composite variable that included key safety and efficacy considerations . RESULTS At 84 months , the Prestige LP ADR demonstrated statistical superiority over fusion for overall success ( observed rate 78.6 % vs 62.7 % ; posterior probability of superiority [ PPS ] = 99.8 % ) , Neck Disability Index success ( 87.0 % vs 75.6 % ; PPS = 99.3 % ) , and neurological success ( 91.6 % vs 82.1 % ; PPS = 99.0 % ) . All other study effectiveness measures were at least noninferior for ADR compared with ACDF . There was no statistically significant difference in the overall rate of implant-related or implant/surgical procedure-related adverse events up to 84 months ( 26.6 % and 27.7 % , respectively ) . However , the Prestige LP group had fewer serious ( Grade 3 or 4 ) implant- or implant/surgical procedure-related adverse events ( 3.2 % vs 7.2 % , log hazard ratio [ LHR ] and 95 % Bayesian credible interval [ 95 % BCI ] -1.19 [ -2.29 to -0.15 ] ) . Patients in the Prestige LP group also underwent statistically significantly fewer second surgical procedures at the index levels ( 4.2 % ) than the fusion group ( 14.7 % ) ( LHR -1.29 [ 95 % BCI -2.12 to -0.46 ] ) . Angular range of motion at superior- and inferior-treated levels on average was maintained in the Prestige LP ADR group to 84 months . CONCLUSIONS The low-profile artificial cervical disc in this study , Prestige LP , implanted at 2 adjacent levels , maintains improved clinical outcomes and segmental motion 84 months after surgery and is a safe and effective alternative to fusion . Clinical trial registration no. : NCT00637156 ( clinical trials.gov ) Introduction There is increasing interest in the role of cervical total disc replacement ( TDR ) as an alternative to anterior cervical discectomy and fusion ( ACDF ) . Multiple prospect i ve r and omized studies with minimum 2 year follow-up have shown TDR to be at least as safe and effective as ACDF in treating symptomatic degenerative disc disease at a single level . The purpose of this study was to compare outcomes of cervical TDR using the Mobi-C ® with ACDF at 5-year follow-up . Methods This prospect i ve , r and omized , controlled trial was conducted as a Food and Drug Administration regulated Investigational Device Exemption trial across 23 centers with 245 patients r and omized ( 2:1 ) to receive TDR with Mobi-C ® Cervical Disc Prosthesis or ACDF with anterior plate and allograft . Outcome assessment s included a composite overall success score , Neck Disability Index ( NDI ) , visual analog scales ( VAS ) assessing neck and arm pain , Short Form-12 ( SF-12 ) health survey , patient satisfaction , major complications , subsequent surgery , segmental range of motion , and adjacent segment degeneration . Results The 60-month follow-up rate was 85.5 % for the TDR group and 78.9 % for the ACDF group . The composite overall success was 61.9 % with TDR vs. 52.2 % with ACDF , demonstrating statistical non-inferiority . Improvements in NDI , VAS neck and arm pain , and SF-12 scores were similar between groups and were maintained from earlier follow-up through 60 months . There was no significant difference between TDR and ACDF in adverse events or major complications . Range of motion was maintained with TDR through 60 months . Device-related subsequent surgeries ( TDR : 3.0 % , ACDF : 11.1 % , p<0.02 ) and adjacent segment degeneration at the superior level ( TDR : 37.1 % , ACDF : 54.7 % , p<0.03 ) were significantly lower for TDR patients . Conclusions Five-year results demonstrate the safety and efficacy of TDR with the Mobi-C as a viable alternative to ACDF with the potential advantage of lower rates of reoperation and adjacent segment degeneration , in the treatment of one-level symptomatic cervical degenerative disc disease . Clinical Relevance This prospect i ve , r and omized study with 5-year follow-up adds to the existing literature indicating that cervical TDR is a viable alternative to ACDF in appropriately selected patients . Level of Evidence This is a Level I study Disc prostheses have been design ed to restore and maintain cervical segmental motion and reduce the accelerated degeneration of the adjacent level . There is no knowledge about the reaction of the neighboured asymptomatic segments after implantation of prostheses or fusion . The effects of these procedures to segmental movement of the uninvolved vertebrae have not been subjected to studies so far . The objective of this study was to compare the segmental motion following cervical disc replacement versus fusion and the correlation to the clinical outcome . Another aim was to compare the segmental motion of the asymptomatic segments above the treated ones and to compare both with Roentgen stereometric analysis ( RSA ) including the asymptomatic segments . 20 patients with one-level cervical radiculopathy scheduled for surgery were r and omized to arthroplasty ( 10 patients , study group ) or anterior cervical discectomy and fusion ( 10 patients , control group ) . Clinical results were evaluated using Visual Analogue Scale and Neck Disability Index . RSA was performed immediately postoperative , after 6 and 12 months . The adjacent segment showed a significantly higher segmental motion in all three-dimensional axes in comparison to the segment treated with prostheses ( P < 0.05 ) . In the fusion group the segmental motion of the adjacent segment was significantly higher in all three-dimensional axes ( P < 0.05 ) at each examination time . When the adjacent level of both groups is compared , the fusion group could show a higher segmental motion in all three-dimensional axes , but without significant difference ( P > 0.05 ) 1 year after surgery . Regarding the clinical results , there was no significant difference in pain relief between both groups ( P > 0.05 ) . In conclusion , the adjacent segment could show a higher segmental motion , when compared with the segment either treated with prostheses or fusion . There was no significant difference in segmental motion adjacent to prosthesis or fusion . Clinical results did also show no significant difference in pain relief between both groups Study Design . Prospect i ve , multicenter , r and omized clinical trial . Objective . To evaluate the long-term safety and effectiveness of the PCM Cervical Disc compared with anterior cervical discectomy and fusion ( ACDF ) in treatment of patients with symptomatic single-level degenerative spondylosis between C3–C4 and C7–T1 with or without prior cervical fusion . Summary of Background Data . The 2-year results of the PCM Cervical Disc trial have been reported previously . The current study reports the long-term results of the same trial . Methods . Patients with single-level cervical spondylosis and radiculopathy with or without myelopathy unresponsive to nonoperative treatment were enrolled . The per protocol patient sample at 5 years included 293 patients ( 163 PCM , 130 ACDF ) . Adverse events and secondary surgical procedures are reported on the cohorts through current follow-up , which include 110 patients ( 68 PCM , 42 ACDF ) at 7 years . Results . At 5 years postoperative , all patient-reported outcomes —neck and arm pain visual analogue scale score , neck disability index , and general health ( 36-Item Short Form Health Survey physical and mental component scores : physical component summary , mental component summary ) —were significantly improved from baselines in both groups , and mean scores were significantly better in the PCM group for neck disability index ( P = 0.001 ) , neck pain ( P = 0.002 ) , general health ( Pphysical component summary = 0.014 ; Pmental component summary = 0.004 ) , and patient satisfaction ( P = 0.005 ) . PCM patients trended toward fewer 2- to 7-year device-related serious adverse events ( 1/214 , 0.5 % PCM ; 2/190 , 1.1 % ACDF ) and secondary surgical procedures ( 7/211 , 3.3 % PCM ; 14/290 , 7.6 % ACDF ) . Adjacent-level degeneration was radiographically more frequent after ACDF ( 33.1 % PCM , 50.9 % ACDF ; P = 0.006 ) and was the primary indication for the increase in late-term secondary surgical procedures after ACDF . Conclusion . The long-term results show good clinical outcomes after ACDF and PCM arthroplasty . PCM patients showed greater improvement in neck disability index and neck pain scores with a lower rate of radiographical adjacent-level degeneration and a trend toward fewer secondary surgical procedures . These data support PCM arthroplasty to be a viable and sustainable alternative to ACDF . Level of Evidence : AIMS In order to evaluate the effectiveness of the Mobi-C implant in cervical disc degeneration , a r and omised study was conducted , comparing the Mobi-C prosthesis arthroplasty with anterior cervical disc fusion ( ACDF ) in patients with single level cervical spondylosis . PATIENTS AND METHODS From January 2008 to July 2009 , 99 patients were enrolled and r and omly divided into two groups , those having a Mobi-C implant ( n = 51 ; 30 men , 21 women ) and those undergoing ACDF ( n = 48 ; 28 men , 20 women).The patients were followed up for five years , with the primary outcomes being the Japanese Orthopaedic Association score , visual analogue scale for pain and the incidence of further surgery . The secondary outcomes were the Neck Disability Index and range of movement ( ROM ) of the treated segment . RESULTS The incidence of further surgery was found to be statistically significant between the two groups ( p = 0.49 ) , with seven ACDF patients requiring further surgery and only one Mobi-C patient requiring re-operation . There were significant differences ( p < 0.001 ) between the two groups in the ROM of the treated segment . However , both Mobi-C surgery and ACDF surgery were effective in improving the patient 's clinical symptoms . TAKE HOME MESSAGE Mobi-C implant surgery is a safe alternative to ACDF surgery in cervical disc degeneration . Cite this article : Bone Joint J 2016;98-B:829 - 3 Study Design : Prospect i ve clinical study . Objective : To evaluate the factors that would predispose a patient to heterotopic ossification ( HO ) formation after cervical arthroplasty . Summary of Background Data : HO after arthroplasty is one of the complications of cervical total disk replacement ( TDR ) . However , the predisposing factors and pathophysiology of HO have not been precisely described . Material s and Methods : We prospect ively enrolled and followed up 23 patients , who received single-level arthroplasty with ProDisc-C , for 5 years after the operation . The patients who developed grade 3 or 4 HO were classified into the “ high- grade HO group , ” whereas the patients with grade 0 , 1 , or 2 HO were classified into the “ low- grade HO group . ” We compared the postoperative changes in the range of motion ( ROM ) and height of the functional segmental unit ( FSU ) of the implantation segments between the 2 groups . Results : The mean differences in height and ROM of the FSU were 2.59±1.42 mm and 6.7±3.2 degrees in the high- grade HO group , and 0.87±0.72 mm and 3.1±2.8 degrees in the low- grade HO group . The mean differences in height and ROM of the FSU were significantly higher in the high- grade HO group than in the low- grade HO group ( P<0.05 ) . After cervical arthroplasty , the height of the FSU and ROM of the implantation segments were significantly increased in the high- grade HO group compared with the low- grade HO group . Conclusions : Overcorrection of the height of the FSU and increase in the ROM of the implantation segment may influence the formation of HOs after cervical arthroplasty OBJECTIVE The authors compared the efficacy and safety of arthroplasty using the Prestige LP cervical disc with those of anterior cervical discectomy and fusion ( ACDF ) for the treatment of degenerative disc disease ( DDD ) at 2 adjacent levels . METHODS Patients from 30 investigational sites were r and omized to 1 of 2 groups : investigational patients ( 209 ) underwent arthroplasty using a Prestige LP artificial disc , and control patients ( 188 ) underwent ACDF with a cortical ring allograft and anterior cervical plate . Patients were evaluated preoperatively , intraoperatively , and at 1.5 , 3 , 6 , 12 , and 24 months postoperatively . Efficacy and safety outcomes were measured according to the Neck Disability Index ( NDI ) , Numeric Rating Scales for neck and arm pain , 36-Item Short-Form Health Survey ( SF-36 ) , gait abnormality , disc height , range of motion ( investigational ) or fusion ( control ) , adverse events ( AEs ) , additional surgeries , and neurological status . Treatment was considered an overall success when all 4 of the following criteria were met : 1 ) NDI score improvement of ≥ 15 points over the preoperative score , 2 ) maintenance or improvement in neurological status compared with preoperatively , 3 ) no serious AE caused by the implant or by the implant and surgical procedure , and 4 ) no additional surgery ( supplemental fixation , revision , or nonelective implant removal ) . Independent statisticians performed Bayesian statistical analyses . RESULTS The 24-month rates of overall success were 81.4 % for the investigational group and 69.4 % for the control group . The posterior mean for overall success in the investigational group exceeded that in the control group by 0.112 ( 95 % highest posterior density interval = 0.023 to 0.201 ) with a posterior probability of 1 for noninferiority and 0.993 for superiority , demonstrating the superiority of the investigational group for overall success . Noninferiority of the investigational group was demonstrated for all individual components of overall success and individual effectiveness end points , except for the SF-36 Mental Component Summary . The investigational group was superior to the control group for NDI success . The proportion of patients experiencing any AE was 93.3 % ( 195/209 ) in the investigational group and 92.0 % ( 173/188 ) in the control group , which were not statistically different . The rate of patients who reported any serious AE ( Grade 3 or 4 ) was significantly higher in the control group ( 90 [ 47.9 % ] of 188 ) than in the investigational group ( 72 [ 34.4 % ] of 209 ) with a posterior probability of superiority of 0.996 . Radiographic success was achieved in 51.0 % ( 100/196 ) of the investigational patients ( maintenance of motion without evidence of bridging bone ) and 82.1 % ( 119/145 ) of the control patients ( fusion ) . At 24 months , heterotopic ossification was identified in 27.8 % ( 55/198 ) of the superior levels and 36.4 % ( 72/198 ) of the inferior levels of investigational patients . CONCLUSIONS Arthroplasty with the Prestige LP cervical disc is as effective and safe as ACDF for the treatment of cervical DDD at 2 contiguous levels and is an alternative treatment for intractable radiculopathy or myelopathy at 2 adjacent levels . Clinical trial registration no. : NCT00637156 ( clinical trials.gov ) BACKGROUND CONTEXT To date , most reports on the incidence of adverse events ( AEs ) in spine surgery have been retrospective and dependent on data abstract ion from hospital-based administrative data bases . To our knowledge , there have been no previous rigorously performed prospect i ve analysis of all AEs occurring in the entire population of patients presenting to an academic quaternary referral center . PURPOSE To determine the mortality and true incidence and severity of morbidity ( major and minor , medical and surgical ) in adults undergoing complex spinal surgery , both trauma and elective , in a quaternary referral center . To examine the influence of the introduction of a dedicated weekly multidisciplinary rounds , and a formal abstract ion tool , on the recording of this prospect i ve perioperative morbidity data . To examine the validity and inter- and intraobserver reliability of a dedicated Spine AdVerse Events Severity system , version 2 ( SAVES V2 ) AE abstract ion tool . STUDY DESIGN Ours is an academic quaternary referral center serving a population of 4.5 million people . Beginning in April 2008 , a spine-specific AE-recording instrument , entitled SAVES V2 , was introduced at our center for reporting , categorization , and classification of AEs . The use of this system remains an ongoing prospect i ve study . PATIENT SAMPLE All adult patients admitted to the spine service of a quaternary referral center for a 12-month period . OUTCOME MEASURES A validity and an inter- and intraobserver reliability examination of the SAVES V2 system , as used at our institution . Morbidity and inhospital deaths , unplanned second surgeries during index admission , wound infections requiring reoperation , and readmissions during the same calendar year . We also examined in detail all intraoperative and nonsurgical postoperative AEs , as well as hospital length of stay ( LOS ) . METHODS Data on all patients undergoing surgery over a 12-month period were prospect ively collected using a perioperative morbidity abstract ion tool at weekly dedicated mortality and morbidity rounds . This tool allows identification of each specific AE and grade s the severity . Before the introduction of this system , and using the hospital inpatient data base , our documented perioperative morbidity rate ( major and minor , medical and surgical ) was 23 % . Diagnosis , operative data , hospital data , major and minor complications both medical and surgical , and deaths were recorded . RESULTS One hundred percent of all patients discharged from the unit had complete data available for analysis . Nine hundred forty-two patients with an age range of 16 to 90 years ( mean , 54 years ; mode , 38 years ) were identified . There were 552 males and 390 females . Around 58.5 % of patients had undergone elective surgery . Thirty percent of patients were American Spinal Injury Association class D or worse on admission . The average LOS was 13.5 days ( range , 1 - 221 days ) . Eight hundred twenty-two ( 87 % ) patients had at least one documented complication . Thirty-nine percent of these adversely affected hospital LOS . There were 14 mortalities during the study period . The rate of intraoperative surgical complication was 10.5 % ( 4.5 % incidental durotomy and 1.9 % hardware malposition requiring revision and 2.2 % blood loss > 2 L ) . The incidence of postoperative complication was 73.5 % ( wound complications , 13.5 % ; delerium , 8 % ; pneumonia , 7 % ; neuropathic pain , 5 % ; dysphagia , 4.5 % ; and neurological deterioration , 3 % ) . CONCLUSIONS Major spinal surgery in the adult is associated with a high incidence of intra- and postoperative complications . We identified a very high rate of previously unrecognized postoperative complications , which adversely affect LOS . Without strict adherence to a prospect i ve data collection system , the true complexity of this surgery may be greatly underestimated OBJECT The purpose of this study was to evaluate the safety and effectiveness of 2-level total disc replacement ( TDR ) using a Mobi-C cervical artificial disc at 48 months ' follow-up . METHODS A prospect i ve r and omized , US FDA investigational device exemption pivotal trial of the Mobi-C cervical artificial disc was conducted at 24 centers in the U.S. Three hundred thirty patients with degenerative disc disease were r and omized and treated with cervical total disc replacement ( 225 patients ) or the control treatment , anterior cervical discectomy and fusion ( ACDF ) ( 105 patients ) . Patients were followed up at regular intervals for 4 years after surgery . RESULTS At 48 months , both groups demonstrated improvement in clinical outcome measures and a comparable safety profile . Data were available for 202 TDR patients and 89 ACDF patients in calculation of the primary endpoint . TDR patients had statistically significantly greater improvement than ACDF patients for the following outcome measures compared with baseline : Neck Disability Index scores , 12-Item Short Form Health Survey Physical Component Summary scores , patient satisfaction , and overall success . ACDF patients experienced higher subsequent surgery rates and displayed a higher rate of adjacent-segment degeneration as seen on radiographs . Overall , TDR patients maintained segmental range of motion through 48 months with no device failure . CONCLUSIONS Four-year results from this study continue to support TDR as a safe , effective , and statistically superior alternative to ACDF for the treatment of degenerative disc disease at 2 contiguous cervical levels . Clinical trial registration no. : NCT00389597 ( clinical trials.gov ) BACKGROUND CONTEXT Several previous studies comparing artificial disc replacement ( ADR ) and fusion have been conducted with cautiously positive results in favor of ADR . This study is not , in contrast to most previous studies , an investigational device exemption study required by the Food and Drug Administration for approval to market the product in the United States . This study was partially funded with unrestricted institutional research grants by the company marketing the artificial disc used in this study . PURPOSE To compare outcomes between the concepts of an artificial disc to treatment with anterior cervical decompression and fusion ( ACDF ) and to register complications associated to the two treatments during a follow-up time of 2 years . STUDY DESIGN / SETTING This is a r and omized controlled multicenter trial , including three spine centers in Sweden . PATIENT SAMPLE The study included patients seeking care for cervical radiculopathy who fulfilled inclusion criteria . In total , 153 patients were included . OUTCOME MEASURES Self- assessment with Neck Disability Index ( NDI ) as a primary outcome variable and EQ-5D and visual analog scale as secondary outcome variables . METHODS Patients were r and omly allocated to either treatment with the Depuy Discover artificial disc or fusion with iliac crest bone graft and plating . R and omization was blinded to both patient and caregivers until time for implantation . Adverse events , complications , and revision surgery were registered as well as loss of follow-up . RESULTS Data were available in 137 ( 91 % ) of the included and initially treated patients . Both groups improved significantly after surgery . NDI changed from 63.1 to 39.8 in an intention-to-treat analysis . No statistically significant difference between the ADR and the ACDF groups could be demonstrated with NDI values of 39.1 and 40.1 , respectively . Nor in secondary outcome measures ( EQ-5D and visual analog scale ) could any statistically significant differences be demonstrated between the groups . Nine patients in the ADR group and three in the fusion group underwent secondary surgery because of various reasons . Two patients in each group underwent secondary surgery because of adjacent segment pathology . Complication rates were not statistically significant between groups . CONCLUSIONS Artificial disc replacement did not result in better outcome compared to fusion measured with NDI 2 years after surgery Study Design . Prospect i ve , multicenter , r and omized Food and Drug Administration approved investigational device exemption clinical trial . Objective . To evaluate the safety and effectiveness of the PCM Cervical Disc compared with anterior cervical discectomy and fusion ( ACDF ) in the treatment of patients with degenerative spondylosis and neurological symptoms at 1 level between C3–C4 and C7–T1 . Summary of Background Data . Cervical disc arthroplasty in the treatment of symptomatic cervical spondylosis has been studied in other series . The PCM Cervical Disc is a nonconstrained motion-sparing alternative to ACDF . Methods . Patients 18 to 65 years of age with single-level symptomatic cervical spondylosis with radiculopathy and /or myelopathy unresponsive to nonoperative treatment were enrolled , including patients with prior nonadjacent or adjacent single-level fusions . The per- protocol patient sample at 2 years included 342 patients ( 189 PCM , 153 ACDF ) . Longitudinal outcomes were comparatively evaluated . Results . At 2 years postoperatively , clinical measures —neck and arm pain visual analogue scale , Neck Disability Index ( NDI ) , SF-36 , and neurological status — were significantly improved from preoperative baselines in both groups . Mean NDI score at 2 years was significantly lower in PCM group ( P = 0.029 ) . There were no statistical differences between groups in rates of surgery-related serious adverse events ( 5.6 % PCM , 7.4 % ACDF ) or secondary surgical procedures ( 5.2 % PCM , 5.4 % ACDF ) . Patients with PCM reported lower dysphagia scores ( 8.8/100 vs. 12.1/100 ; P = 0.045 ) and higher patient satisfaction ( 82.8/100 vs. 81.4/100 ) . Overall success , a composite endpoint including minimum 20 % NDI improvement , no major complications , no neurological worsening , no secondary surgical procedures , and meeting radiographical criteria of motion for PCM and fusion for ACDF , was significantly greater in the PCM group ( 75.1 % vs. 64.9 % ; P = 0.020 ) . Conclusion . The treatment of symptomatic single-level cervical spondylosis with PCM achieves clinical outcomes that are at least equivalent to ACDF while maintaining motion . At 2 years , patients with PCM had lower NDI scores , statistically lower rate of prolonged dysphagia , greater patient satisfaction , and superior overall success . Level of Evidence : OBJECT The authors assess the long-term safety and efficacy of cervical disc replacement with the Prestige Cervical Disc in a prospect i ve , r and omized , multicenter trial at 7 years of follow-up . METHODS At 31 investigational sites , 541 patients with single-level cervical disc disease with radiculopathy were r and omized to 1 of 2 treatment groups : 276 investigational group patients underwent anterior cervical discectomy and arthroplasty with the Prestige disc , and 265 control group patients underwent anterior cervical discectomy and fusion . Clinical outcomes included Neck Disability Index , the 36-Item Short-Form Health Survey , and neck and arm pain scores . Radiographs were assessed for angle of motion and fusion . Clinical and radiographic outcomes were evaluated preoperatively , intraoperatively , and at 1.5 , 3 , 6 , 12 , 24 , 36 , 60 , and 84 months . RESULTS Of the 541 patients treated , 395 patients ( 73 % ; 212 investigational and 183 control patients ) completed 7 years of clinical follow-up . Significant improvements achieved by 1.5 months in both groups were sustained at 7 years . In the investigational group , mean Neck Disability Index improvements from preoperative scores were 38.2 and 37.5 at 60 and 84 months , respectively . In the control group , the corresponding means were 33.8 and 31.9 . The differences between the investigational and control groups at the 60-month and 84-month periods were significant ( p = 0.014 and 0.002 , respectively ) . The overall rates of maintenance or improvement in neurological status in the investigational group were significantly higher : 92.2 % and 88.2 % at 60 months and 84 months , respectively , compared with 85.7 % and 79.7 % in the control group ( p = 0.017 and 0.011 , respectively ) . At 84 months , the percentage of working patients in the investigational group was 73.9 % , and in the control group , 73.1 % . Postoperatively , the implant effectively maintained average angular motion of 6.67 ° at 60 months and 6.75 ° at 84 months . Cumulative rates for surgery at the index level were lower ( p < 0.001 ) in the investigational group ( 11 [ 4.8 % ] of 276 ) when compared with the control group ( 29 [ 13.7 % ] of 265 ) ( based on life-table method ) , and there were statistical differences between the investigational and control groups with specific regard to the rate of subsequent revision and supplemental fixation surgical procedures . Rates for additional surgical procedures that involved adjacent levels were lower in the investigational group than in the control group ( 11 [ 4.6 % ] of 276 vs. 24 [ 11.9 % ] of 265 , respectively ) . CONCLUSIONS Cervical disc arthroplasty has the potential for preserving motion at the operated level while providing biomechanical stability and global neck mobility and may result in a reduction in adjacent-segment degeneration . The Prestige Cervical Disc maintains improved clinical outcomes and segmental motion after implantation at 7-year follow-up . Clinical trial registration no. NCT00642876 ( Clinical Trials.gov ) Study Design : A prospect i ve r and omized and controlled study of 30 patients with 2 noncontiguous levels of cervical spondylosis . Objective : To compare the clinical outcome between zero-profile devices and artificial cervical disks for noncontiguous cervical spondylosis . Summary of Background Data : Noncontiguous cervical spondylosis is an especial degenerative disease of the cervical spine . Some controversy exists over the choice of surgical procedure and fusion levels for it because of the viewpoint that the stress at levels adjacent to a fusion mass will increase . The increased stress will lead to the adjacent segment degeneration ( ASD ) . According to the viewpoint , the intermediate segment will bear more stress after both superior and inferior segments ’ fusion . Cervical disk arthroplasty is an alternative to fusion because of its motion-preserving . Few comparative studies have been conducted on arthrodesis with zero-prolife devices and arthroplasty with artificial cervical disks for noncontiguous cervical spondylosis . Methods : Thirty patients with 2 noncontiguous levels of cervical spondylosis were enrolled and assigned to either group A ( receiving arthroplasty using artificial cervical disks ) and group Z ( receiving arthrodesis using zero-profile devices ) . The clinical outcomes were assessed by the mean operative time , blood loss , Japanese Orthopedic Association ( JOA ) score , Neck Dysfunction Index ( NDI ) , cervical lordosis , fusion rate , and complications . Results : The mean follow-up was 32.4 months . There were no significant differences between the 2 groups in the blood loss , JOA score , NDI score , and cervical lordosis except operative time . The mean operative time of group A was shorter than that of group Z. Both the 2 groups demonstrated a significant increase in JOA score , NDI score , and cervical lordosis . The fusion rate was 100 % at 12 months postoperatively in group Z. There was no significant difference between the 2 groups in complications except the ASD . Three patients had radiologic ASD at the final follow-up in group Z , and none in group A. Conclusions : Both zero-prolife devices and artificial cervical disks are generally effective and safe in the treatment of 2 noncontiguous levels of cervical spondylosis . However , in view of occurrence of the radiologic ASD and operative time , we prefer to artificial cervical disks if indications are well controlled Purpose Total cervical artificial disc replacement ( TDR ) simulates normal disc structure , thus avoiding the drawbacks of anterior cervical decompression and fusion ( ACDF ) . This prospect i ve , r and omized , controlled and multicentre study aim ed to evaluate clinical and radiographic outcomes by comparing cervical disc replacement using Mobi-C disc prostheses with ACDF . Methods This prospect i ve , r and omized , controlled and multicentre study consisted of 111 patients undergoing single-level Mobi-C disc prosthesis replacement ( TDR group , n = 55 ) or ACDF ( n = 56 ) from February 2008 to November 2009 at 11 medical centres across China . Patients were assessed before surgery , at seven days postoperation and one , three , six , 12 , 24 , 36 and 48 months postoperation . Clinical and neurological outcome was determined by measuring the Japanese Orthopaedic Association ( JOA ) scores , visual analogue scale ( VAS ) and Neck Disability Index ( NDI ) . Static and dynamic radiographs were obtained of the cervical curvature , the functional spinal unit ( FSU ) angle and range of motion ( ROM ) of the cervical spine , FSU angle and treated and adjacent segments . Results A total of 111 patients were included and r and omly assigned to either Mobi-C disc prosthesis replacement or ACDF . JOA , VAS and NDI showed statistically significant improvements 48 months after surgery ( P < 0.05 ) . ROM , FSU angle , treated segment and adjacent segments in the Mobi-C group were not significantly different before and after replacement ( p > 0.05 ) . ROM in the ACDF group was significantly reduced at one month and remained so throughout the follow-up . By 48-months , more ACDF patients required secondary surgery ( four of 56 patients ) . Conclusions Although ACDF may increase the risk of additional surgery , clinical outcomes indicated that both Mobi-C artificial cervical disc replacement and ACDF were reliable . Radiographic data showed that ROM of the cervical spine , FSU angle and treated and adjacent segments were relatively better reconstructed and maintained in the Mobi-C group compared with those in the ACDF group Background The current st and ard of care for cervical myopathy is anterior discectomy and fusion ( ACDF ) . Although well tolerated in the short term , this treatment might ultimately result in progressive degeneration of adjacent motion segments . Artificial disc arthroplasty offers the theoretical advantage of preservation of motion at the operative level with consequent stress reduction at adjacent levels . Questions / purpose sWe compared function , radiographic measures , and incidence of complications at 3-year followup after cervical disc arthroplasty with the Bryan ® prosthesis and ACDF in patients with cervical myelopathy . Patients and Methods Eighty-three patients with cervical myelopathy were r and omized to undergo arthroplasty with implantation of a Bryan ® cervical disc prosthesis ( n = 41 ) or ACDF ( n = 42 ) . Patients were assessed preoperatively to 3 years postoperatively using the modified Odom ’s criteria , Japanese Orthopaedic Association scale , SF-36 , and Neck Disability Index . ROM , stability , and subsidence of the prostheses were evaluated radiographically . Results Patients who received the Bryan ® prosthesis scored significantly better in three of the four functional assessment methods used ( Japanese Orthopaedic Association scale , SF-36 , and Neck Disability Index ) . ROM was retained by the patients in the Bryan ® group but not in the patients in the ACDF group . Patients in the Bryan ® group had fewer complications , primarily because dysphagia occurred in only one patient in the Bryan ® group but in seven patients in the ACDF group . Other complications included pseudarthrosis in three patients in the ACDF group and one patient had spontaneous fusion , one had deep vein thrombosis , and one had heterotopic ossification in the Bryan ® group . Conclusions Bryan ® cervical disc arthroplasty appears reliable and effective in the treatment of cervical myelopathy . Level of Evidence Level II , therapeutic study . See the Guidelines for Authors for a complete description of the levels of evidence OBJECT Cervical total disc replacement ( CTDR ) represents a relatively novel procedure intended to address some of the shortcomings associated with anterior cervical discectomy and fusion ( ACDF ) by preserving motion at the treated level . This prospect i ve , r and omized , multicenter study evaluates the safety and efficacy of a new metal-on-metal CTDR implant ( Kineflex|C ) by comparing it with ACDF in the treatment of single-level spondylosis with radiculopathy . METHODS The study was a prospect i ve , r and omized US FDA Investigational Device Exemption ( IDE ) pivotal trial conducted at 21 centers across the US . The primary clinical outcome measures included the Neck Disability Index ( NDI ) , visual analog scale ( VAS ) scores , and a composite measure of clinical success . Patients were r and omized to CTDR using the Kineflex|C ( SpinalMotion , Inc. ) cervical artificial disc or ACDF using structural allograft and an anterior plate . RESULTS A total of 269 patients were enrolled and r and omly assigned to either CTDR ( 136 patients ) or to ACDF ( 133 patients ) . There were no significant differences between the CTDR and ACDF groups when comparing operative time , blood loss , length of hospital stay , or the reoperation rate at the index level . The overall success rate was significantly greater in the CTDR group ( 85 % ) compared with the ACDF group ( 71 % ) ( p = 0.05 ) . In both groups , the mean NDI scores improved significantly by 6 weeks after surgery and remained significantly improved throughout the 24-month follow-up ( p < 0.0001 ) . Similarly , the VAS pain scores improved significantly by 6 weeks and remained significantly improved through the 24-month follow-up ( p < 0.0001 ) . The range of motion ( ROM ) in the CTDR group decreased at 3 months but was significantly greater than the preoperative mean at 12- and 24-month follow-up . The ROM in the ACDF group was significantly reduced by 3 months and remained so throughout the follow-up . Adjacent-level degeneration was also evaluated in both groups from preoperatively to 2-year follow-up and was classified as none , mild , moderate , or severe . Preoperatively , there were no significant differences between groups when evaluating the different levels of adjacent-level degeneration . At the 2-year follow-up , there were significantly more patients in the ACDF group with severe adjacent-level radiographic changes ( p < 0.0001 ) . However , there were no significant differences between groups in adjacent-level reoperation rate ( 7.6 % for the Kineflex|C group and 6.1 % for the ACDF group ) . CONCLUSIONS Cervical total disc replacement allows for neural decompression and clinical results comparable to ACDF . Kineflex|C was associated with a significantly greater overall success rate than fusion while maintaining motion at the index level . Furthermore , there were significantly fewer Kineflex|C patients showing severe adjacent-level radiographic changes at the 2-year follow-up . These results from a prospect i ve , r and omized study support that Kineflex|C CTDR is a viable alternative to ACDF in select patients with cervical radiculopathy Study Design . Prospect i ve , r and omized , controlled , multicenter clinical trial . Objective . To compare outcomes of cervical disc arthroplasty with those of anterior cervical decompression and fusion ( ACDF ) in a Chinese population . Summary of Background Data . Cervical disc arthroplasty has been found to be superior to ACDF for maintaining range of motion ( ROM ) at the index spinal segment and possibly will avoid abnormal stress to adjacent segments . Methods . A total of 120 patients from 3 large hospitals in China were r and omly assigned to treatment with cervical disc arthroplasty ( n = 60 ) using the BRYAN prosthesis or ACDF ( n = 60 ) and were observed postoperatively for 24 months . Results . The 2 groups had similar preoperative demographics and baseline characteristics including ROM , neck disability index , and visual analogue scale for neck and arm pain . The total disc replacement ( TDR ) group had a significantly longer operation time than the ACDF group ( P < 0.001 ) . Outcome data obtained after 24 months revealed a significant difference between the groups in mean change from baseline in ROM at the index level ( P < 0.001 ) ; ROM was maintained in the TDR group but reduced in the ACDF group . There were no significant between-group differences in the baseline changes in neck disability index or visual analogue scale scores for pain . One patient in the TDR group and 4 patients in the ACDF group required reoperations . Conclusion . At 24 months after surgery , the cervical disc prosthesis yielded good clinical results while maintaining ROM at the index level . Cervical disc arthroplasty appears to be a viable alternative to ACDF OBJECTIVE The purpose of this study was to report the outcome of a study of 2-level cervical total disc replacement ( Mobi-C ) versus anterior cervical discectomy and fusion ( ACDF ) . Although the long-term outcome of single-level disc replacement has been extensively described , there have not been previous reports of the 5-year outcome of 2-level cervical disc replacement . METHODS This study reports the 5-year results of a prospect i ve , r and omized US FDA investigational device exemption ( IDE ) study conducted at 24 centers in patients with 2-level , contiguous , cervical spondylosis . Clinical outcomes at up to 60 months were evaluated , including vali date d outcome measures , incidence of reoperation , and adverse events . The complete study data and methodology were critically review ed by 3 independent surgeon authors without affiliation with the IDE study or financial or institutional bias toward the study sponsor . RESULTS A total of 225 patients received the Mobi-C cervical total disc replacement device and 105 patients received ACDF . The Mobi-C and ACDF follow-up rates were 90.7 % and 86.7 % , respectively ( p = 0.39 ) , at 60 months . There was significant improvement in all outcome scores relative to baseline at all time points . The Mobi-C patients had significantly more improvement than ACDF patients in terms of Neck Disability Index score , SF-12 Physical Component Summary , and overall satisfaction with treatment at 60 months . The reoperation rate was significantly lower with Mobi-C ( 4 % ) versus ACDF ( 16 % ) . There were no significant differences in the adverse event rate between groups . CONCLUSIONS Both cervical total disc replacement and ACDF significantly improved general and disease-specific measures compared with baseline . However , there was significantly greater improvement in general and disease-specific outcome measures and a lower rate of reoperation in the 2-level disc replacement patients versus ACDF control patients . Clinical trial registration no. NCT00389597 ( clinical trials.gov ) OBJECTIVE Cervical total disc replacement ( TDR ) has been shown in a number of prospect i ve clinical studies to be a viable treatment alternative to anterior cervical discectomy and fusion ( ACDF ) for the treatment of symptomatic degenerative disc disease . In addition to preserving motion , evidence suggests that cervical TDR may result in a lower incidence of subsequent surgical intervention than treatment with fusion . The goal of this study was to evaluate subsequent surgery rates up to 5 years in patients treated with TDR or ACDF at 1 or 2 contiguous levels between C-3 and C-7 . METHODS This was a prospect i ve , multicenter , r and omized , unblinded clinical trial . Patients with symptomatic degenerative disc disease were enrolled to receive 1- or 2-level treatment with either TDR as the investigational device or ACDF as the control treatment . There were 260 patients in the 1-level study ( 179 TDR and 81 ACDF patients ) and 339 patients in the 2-level study ( 234 TDR and 105 ACDF patients ) . RESULTS At 5 years , the occurrence of subsequent surgical intervention was significantly higher among ACDF patients for 1-level ( TDR , 4.5 % [ 8/179 ] ; ACDF , 17.3 % [ 14/81 ] ; p = 0.0012 ) and 2-level ( TDR , 7.3 % [ 17/234 ] ; ACDF , 21.0 % [ 22/105 ] , p = 0.0007 ) treatment . The TDR group demonstrated significantly fewer index- and adjacent-level subsequent surgeries in both the 1- and 2-level cohorts . CONCLUSIONS Five-year results showed treatment with cervical TDR to result in a significantly lower rate of subsequent surgical intervention than treatment with ACDF for both 1 and 2 levels of treatment . Clinical trial registration no. : NCT00389597 ( clinical trials.gov ) |
11,927 | 17,970,862 | RESULTS The strongest evidence from scientifically rigorous evaluations exists for a positive effect on some academic outcomes from school health programs for asthmatic children that incorporate health education and parental involvement .
Strong evidence also exists for a lack of negative effects of physical education programs on academic outcomes .
Limited evidence from scientifically rigorous evaluations support the effect of nutrition services , health services , and mental health programs , but no such evidence is found in the literature to support the effect of staff health promotion programs or school environment interventions on academic outcomes .
However , school health programs hold promise for improving academic outcomes for children | BACKGROUND Few evaluations of school health programs measure academic outcomes .
K-12 education needs evidence for academic achievement to implement school programs .
This article presents a systematic review of the literature to examine evidence that school health programs aligned with the Coordinated School Health Program ( CSHP ) model improve academic success . | Hunger during school may prevent children in developing countries from benefiting from education . Although many countries have implemented school feeding programs , few programs have been rigorously evaluated . We conducted a r and omized , controlled trial of giving breakfast to undernourished and adequately nourished children . The undernourished group comprised 407 children in grade s 2 - 5 in 16 rural Jamaican schools ( weights-for-age < or = -1 SD of the National Center for Health Statistics references ) and the adequately nourished group comprised 407 children matched for school and class ( weights-for-age > -1 SD ) . Both groups were stratified by class and school , then r and omly assigned to breakfast or control groups . After the initial measurements , breakfast was provided every school day for 1 school year . Children in the control group were given one-quarter of an orange and the same amount of attention as children in the breakfast group . All children had their heights and weights measured and were given the Wide Range Achievement Test before and after the intervention . School attendance was taken from the schools ' registers . Compared with the control group , height , weight , and attendance improved significantly in the breakfast group . Both groups made poor progress in Wide Range Achievement Test scores . Younger children in the breakfast group improved in arithmetic . There was no effect of nutritional group on the response to breakfast . In conclusion , the provision of a school breakfast produced small benefits in children 's nutritional status , school attendance , and achievement . Greater improvements may occur in more undernourished population s ; however , the massive problem of poor achievement levels requires integrated programs including health and educational inputs as well as school meals OBJECTIVE To examine the long-term effects of an intervention combining teacher training , parent education , and social competence training for children during the elementary grade s on adolescent health-risk behaviors at age 18 years . DESIGN Nonr and omized controlled trial with follow-up 6 years after intervention . SETTING Public elementary schools serving high-crime areas in Seattle , Wash. PARTICIPANTS Of the fifth- grade students enrolled in participating schools , 643 ( 76 % ) were given written parental consent for the longitudinal study and 598 ( 93 % ) were followed up and interviewed at age 18 years . INTERVENTIONS A full intervention provided in grade s 1 through 6 of 5 days of in-service training for teachers each intervention year , developmentally appropriate parenting classes offered to parents when children were in grade s 1 through 3 and 5 through 6 , and developmentally adjusted social competence training for children in grade s 1 and 6 . A late intervention , provided in grade s 5 and 6 only , paralleled the full intervention at these grade s. MAIN OUTCOME MEASURES Self-reported violent and nonviolent crime , substance use , sexual activity , pregnancy , bonding to school , school achievement , grade repetition and school dropout , suspension and /or expulsion , and school misbehavior ; delinquency charges from court records ; grade point average ; California Achievement Test scores : and disciplinary action reports from school records . RESULTS Fewer students receiving full intervention than control students reported violent delinquent acts ( 48.3 % vs 59.7 % ; P=.04 ) , heavy drinking ( 15.4 % vs 25.6 % ; P=.04 ) , sexual intercourse ( 72.1 % vs 83.0 % ; P=.02 ) , having multiple sex partners ( 49.7 % vs 61.5 % ; P=.04 ) , and pregnancy or causing pregnancy ( 17.1 % vs 26.4 % ; P=.06 ) by age 18 years . The full intervention student group reported more commitment ( P=.03 ) and attachment ( P=.006 ) to school , better academic achievement ( P=.01 ) , and less school misbehavior ( P=.02 ) than control students . Late intervention in grade s 5 and 6 only did not significantly affect health-risk behaviors in adolescence . CONCLUSIONS A package of interventions with teachers , parents , and children provided throughout the elementary grade s can have enduring effects in reducing violent behavior , heavy drinking , and sexual intercourse by age 18 years among multiethnic urban children . Results are consistent with the theoretical model guiding the intervention and support efforts to reduce health-risk behaviors through universal interventions in selected communities or schools serving high-crime neighborhoods This study evaluated the effect of Students for Peace , a multi-component violence-prevention intervention , on reducing aggressive behaviors among students of eight middle schools r and omly assigned into intervention or control conditions . The intervention , based on Social Cognitive Theory , included the formation of a School Health Promotion Council , training of peer mediators and peer helpers , training of teachers in conflict resolution , a violence-prevention curriculum , and newsletters for parents . All students were evaluated in the spring of 1994 , 1995 and 1996 ( approximately 9000 students per evaluation ) . Sixth grade rs in 1994 were followed through seventh grade in 1995 or eighth grade in 1996 or both ( n = 2246 ) . Cohort and cross-sectional evaluations indicated little to no intervention effect in reducing aggressive behaviors , fights at school , injuries due to fighting , missing classes because of feeling unsafe at school or being threatened to be hurt . For all variables , the strongest predictors of violence in eighth grade were violence in sixth grade and low academic performance . Although ideal and frequently recommended , the holistic approach to prevention in schools in which teachers , administrators and staff model peaceful conflict resolution is difficult to implement , and , in this case , proved ineffective . The Students for Peace experience suggests that interventions begin prior to middle school , explore social environmental intervention strategies , and involve parents and community members OBJECTIVE To examine the long-term effects of the Seattle Social Development Project intervention in promoting positive adult functioning and preventing mental health problems , crime , and substance use ( including tobacco , alcohol , and other drugs ) at 21 years of age . DESIGN This nonr and omized controlled trial followed up participants to 21 years of age , 9 years after the intervention ended . We compared the following 3 intervention conditions : a full 6-year intervention ( grade s 1 through 6 ) ; a late 2-year intervention ( grade s 5 and 6 only ) ; and a no-treatment control condition . SETTING Eighteen public elementary schools serving diverse neighborhoods , including high-crime neighborhoods , of Seattle , Wash. PARTICIPANTS A sex-balanced , multiethnic sample of 605 participants across the 3 conditions who completed interviews at 21 years of age ( 94 % of the original sample in these conditions ) . INTERVENTIONS Teacher training in classroom instruction and management , child social and emotional skill development , and parent training . MAIN OUTCOME MEASURES Self-reports of functioning in school and work , emotional and mental health , and crime and substance use at 21 years of age and official court records . RESULTS Broad significant effects on functioning in school and work and on emotional and mental health were found . Fewer significant effects on crime and substance use were found at 21 years of age . Most outcomes had a consistent dose effect , with the strongest effects in subjects in the full-intervention group and effects in the late-intervention group between those in the full-intervention and control groups . CONCLUSIONS A theory-guided preventive intervention that strengthened teaching and parenting practice s and taught children interpersonal skills during the elementary grade s had wide-ranging beneficial effects on functioning in early adulthood The effects of a 2-year health-related school physical education program on st and ardized academic achievement scores was assessed in 759 children who completed Metropolitan Achievement Tests before and after the program . Schools were r and omly assigned to condition : ( a ) Specialists taught the Sports , Play , and Active Recreation for Kids curriculum ; ( b ) classroom teachers were trained to implement the curriculum ; and ( c ) controls continued their usual programs . The Trained Teacher condition was superior to Control on Language , Reading , and Basic Battery . The Specialist condition was superior to Control on Reading , but inferior on Language . Despite devoting twice as many minutes per week to physical education as Controls , the health-related physical education program did not interfere with academic achievement . Health-related physical education may have favorable effects on students ' academic achievement STUDY OBJECTIVE This study assessed the impact of a comprehensive school-based asthma program on symptoms , grade s , and school absences in children , and parents ' asthma management practice s. DESIGN R and omized controlled trial . SETTING Fourteen elementary schools in low-income neighborhoods in Detroit , MI . PARTICIPANTS Eight hundred thirty-five children with asthma in grade s 2 through 5 and their parents . INTERVENTION The intervention entailed six components for children , their parents , classmates , and school personnel to encourage and enable disease management . MEASUREMENTS AND RESULTS Parents completed telephone interviews and the schools provided data at baseline and 24 months after intervention . At follow-up , treatment children with persistent disease had significant declines in both daytime ( 14 % fewer , p < 0.0001 ) and nighttime ( 14 % fewer , p < 0.0001 ) symptoms . Among children with both mild intermittent and persistent disease , those in the treatment group had 17 % fewer daytime symptoms ( p < 0.0001 ) but 40 % more nighttime symptoms . Treatment children had higher grade s for science ( p < 0.02 ) but not reading , mathematics , or physical education . No differences in school absences for all causes between groups were noted in school records . However , parents of treatment group children reported fewer absences attributable to asthma in the previous 3 months ( 34 % fewer , p < 0.0001 ) and 12 months ( 8 % fewer , p < 0.05 ) . Parents of treatment children had higher scores ( 2.19 greater , p = 0.02 ) on an asthma management index . The program may have stimulated attention to symptoms at night by parents of children with mild intermittent disease . Overall , the intervention provided significant benefits , particularly for children with persistent asthma The authors examined the effectiveness of a school-based prevention program on reducing binge drinking in a sample of minority , inner-city , middle-school students . Rates of binge drinking were compared among youth who received the program beginning in the 7th grade ( n = 1,713 ) and a control group ( n = 1,328 ) that did not . The prevention program had protective effects in terms of binge drinking at the 1-year ( 8th grade ) and 2-year ( 9th grade ) follow-up assessment s. The proportion of binge drinkers was over 50 % lower in the intervention group relative to the control group at the follow-up assessment s. There were also several significant program effects on proximal drinking variables , including drinking knowledge , pro-drinking attitudes , and peer drinking norms . These findings indicate that a school-based drug abuse prevention approach previously found to be effective among White youth significantly reduced binge drinking among urban minority youth A six-year , school-based prevention program , which modified classroom teacher practice s , offered parent training , and provided child social skills training , was evaluated for its effects on school failure , drug abuse , and delinquency among low-income urban children . Compared to a low-income control group , children in the intervention group showed enhanced school commitment and class participation . The girls in the group also evidence d lower rates of substance use initiation , while the boys exhibited increased social and school work skills Objectives . This study evaluated the long-term effectiveness of Safer Choices , a theory-based , multi-component educational program design ed to reduce sexual risk behaviors and increase protective behaviors in preventing HIV , other STDs , and pregnancy among high school students . Methods . The study used a r and omized controlled trial involving 20 high schools in California and Texas . A cohort of 3869 ninth- grade students was tracked for 31 months from fall semester 1993 ( baseline ) to spring semester 1996 ( 31-month follow-up ) . Data were collected using self-report surveys administered by trained data collectors . Response rate at 31-month follow-up was 79 % . Results . Safer Choices had its greatest effect on measures involving condom use . The program reduced the frequency of intercourse without a condom during the three months prior to the survey , reduced the number of sexual partners with whom students had intercourse without a condom , and increased use of condoms and other protection against pregnancy at last intercourse . Safer Choices also improved 7 of 13 psychosocial variables , many related to condom use , but did not have a significant effect upon rates of sexual initiation . Conclusions . The Safer Choices program was effective in reducing important risk behaviors for HIV , other STDs , and pregnancy and in enhancing most psychosocial determinants of such behavior OBJECTIVES An earlier report described desirable 1-month follow-up effects of the Safe Date s program on psychological , physical , and sexual dating violence . Mediators of the program-behavior relationship also were identified . The present report describes the 1-year follow-up effects of the Safe Date s program . METHODS Fourteen schools were in the r and omized experiment . Data were gathered by question naires in schools before program activities and 1 year after the program ended . RESULTS The short-term behavioral effects had disappeared at 1 year , but effects on mediating variables such as dating violence norms , conflict management skills , and awareness of community services for dating violence were maintained . CONCLUSIONS The findings are considered in the context of why program effects might have decayed and the possible role of boosters for effect maintenance OBJECTIVE This prospect i ve study is focused on the characteristics leading to alcohol use disorders in early adulthood among a cohort of black children . The principal aim of this work is to examine the impact of educational attainment , school dropout and early school adaptation on the development of alcohol abuse and dependence in adulthood . METHOD From a population that consisted of 1,242 first grade rs in 1966 - 67 , a total of 953 were interviewed at age 32 - 33 about their current alcohol and drug use , educational attainment , employment and family situation . RESULTS Diagnoses of alcohol abuse and dependence were defined according to DSM-III-R criteria result ing in identification of 13.5 % as having a lifetime alcohol use disorder . Early predictions of an alcohol use disorder in adulthood included early reports of underachievement in first grade by the child 's teacher , dropping out of high school , whether the family set definite rules about school during adolescence , and how often the adolescent worked on homework with his/her family . CONCLUSIONS The results suggest that educational achievement and some early adaptive behaviors in school are associated with risk for alcohol use disorders . The public health importance of the findings are discussed |
11,928 | 24,022,428 | Statins have little or no beneficial effects on mortality or cardiovascular events and uncertain adverse effects in adults treated with dialysis despite clinical ly relevant reductions in serum cholesterol levels | BACKGROUND People with advanced kidney disease treated with dialysis experience mortality rates from cardiovascular disease that are substantially higher than for the general population .
Studies that have assessed the benefits of statins ( HMG CoA reductase inhibitors ) report conflicting conclusions for people on dialysis and existing meta-analyses have not had sufficient power to determine whether the effects of statins vary with severity of kidney disease .
Recently , additional data for the effects of statins in dialysis patients have become available .
This is an up date of a review first published in 2004 and last up date d in 2009 .
OBJECTIVES To assess the benefits and harms of statin use in adults who require dialysis ( haemodialysis or peritoneal dialysis ) . | BACKGROUND Although patients with chronic kidney disease ( CKD ) are at increased risk of cardiovascular disease ( CVD ) , the roles of lipid-modifying therapies in decreasing CVD risk are unclear . Our aim is to compare the effects of statin and fibrate therapy on arterial function as a risk marker of CVD . STUDY DESIGN Double-blind , r and omized , placebo-controlled , parallel-group study . SETTING & PARTICIPANTS Ambulatory patients with stages 3 to 5 CKD . INTERVENTION 6 weeks of atorvastatin , 40 mg/d , or gemfibrozil , 600 mg twice daily , with placebo . OUTCOMES & MEASUREMENTS Primary outcome was arterial function assessed by means of endothelial-dependent flow-mediated dilatation ( FMD ) and small-artery compliance ( C2 ) . Secondary outcomes included endothelial-independent glyceryl trinitrate-mediated dilatation ( GTNMD ) , large-artery compliance ( C1 ) , and levels of lipids , lipoproteins , and oxidized low-density lipoprotein , as well as markers of insulin resistance and inflammation . RESULTS Compared with placebo , atorvastatin significantly decreased low-density lipoprotein ( -52 % ) , triglyceride ( -30 % ) , and oxidized low-density lipoprotein levels ( -41 % ; P < 0.0001 ) . Gemfibrozil significantly decreased triglyceride levels ( -40 % ) and increased high-density lipoprotein levels ( + 20 % ; P < 0.0001 ) . Neither atorvastatin nor gemfibrozil had a significant effect on markers of insulin resistance or inflammation . There was no significant change in FMD , GTNMD , or C1 with either atorvastatin or gemfibrozil . There was improvement in C2 with atorvastatin ( + 1.1 mL/mm Hg x 100 ) compared with placebo ( P = 0.024 ) , but not with gemfibrozil compared with placebo . LIMITATIONS Small sample size leading to inadequate power , short duration of therapy , and use of a heterogeneous group of patients with CKD and dialysis patients . CONCLUSION In patients with advanced CKD , atorvastatin is associated with improvement in dyslipidemia and small-artery stiffness , but not endothelial function . Gemfibrozil improves dyslipidemia , but has no effect on arterial function Background Patients with end-stage renal disease ( ESRD ) are at high risk of cardiovascular events . Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population . In contrast to patients with normal renal function , the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospect i ve r and omised trials . A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis : an Assessment of survival and cardiovascular events ( AURORA ) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis . Methods More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been r and omised ( 1:1 ) , irrespective of baseline lipid levels , to treatment with rosuvastatin 10 mg or placebo . The primary study endpoint is the time to a major cardiovascular event ( first occurrence of cardiovascular death , non-fatal myocardial infa rct ion or non-fatal stroke ) . Secondary endpoints include all-cause mortality , major cardiovascular event-free survival time , time to cardiovascular death , time to non-cardiovascular death , cardiovascular interventions , tolerability of treatment and health economic costs per life-year saved . Study medication will be given until 620 subjects have experienced a major cardiovascular event . Conclusion Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this exp and ing population Statins have multiple effects , including anti-inflammatory actions , lowering C-reactive protein levels , and reducing coronary events . We performed a post hoc analysis of the r and omized placebo-controlled 4D Study that had evaluated the efficacy and safety of atorvastatin in 1255 patients with type 2 diabetes mellitus who were on maintenance hemodialysis . Here we determined the relationship between atorvastatin treatment , C-reactive protein , and the outcome of patients who had pre-specified and adjudicated endpoints of all-cause mortality , composite vascular endpoint , myocardial infa rct ion , sudden death , and stroke . Atorvastatin had no significant effect on the risk of composite vascular endpoint or death relative to placebo in any quartile of baseline C-reactive protein . These baseline levels were not significantly different between the treated and placebo group and remained stable at 6 months on atorvastatin but significantly increased in those patients on placebo . All of the patients with baseline C-reactive protein in the fourth quartile had a significantly increased risk of deaths and in composite vascular endpoint compared to patients in the first quartile . The mean value of two consecutive C-reactive protein measurements was associated with significant increases in the risk of sudden death , stroke , all-cause mortality and composite vascular endpoint . Our results show that C-reactive protein was highly predictive of outcome , but atorvastatin treatment was not associated with reduced relative risks in the composite vascular endpoint or mortality in patients on hemodialysis with or without inflammation Background The high incidence of cardiovascular disease in patients with end stage renal disease ( ESRD ) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range . As online hemodiafiltration ( HDF ) removes these molecules more effectively than st and ard hemodialysis ( HD ) , it has been suggested that online HDF improves survival and cardiovascular outcome . Thus far , no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available . Therefore , the CONvective TRAnsport STudy ( CONTRAST ) has been initiated . Methods CONTRAST is a Dutch multi-center r and omised controlled trial . In this trial , approximately 800 chronic hemodialysis patients will be r and omised between online HDF and low-flux HD , and followed for three years . The primary endpoint is all cause mortality . The main secondary outcome variables are fatal and non-fatal cardiovascular events . Conclusion The study is design ed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to st and ard HD The efficacy , tolerability and safety of simvastatin in the treatment of hyperlipemia in uremic patients undergoing hemodialysis were evaluated in 6 patients ; a further 6 patients were treated with placebo and represented the control group . All patients treated completed the study . No clinical or laboratory side-effects were noted during the entire period of observation . Simvastatin caused a significant 26 % reduction in total cholesterol , a 36 % reduction in LDL cholesterol and a 28 % reduction in triglycerides ; HDL cholesterol and Apolipoprotein A increased by 19 % and 12 % respectively Summary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infa rct ion , ischaemic stroke , and the need for coronary revascularisation in people without kidney disease , but its effects in people with moderate-to-severe kidney disease are uncertain . The SHARP trial aim ed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients . Methods This r and omised double-blind trial included 9270 patients with chronic kidney disease ( 3023 on dialysis and 6247 not ) with no known history of myocardial infa rct ion or coronary revascularisation . Patients were r and omly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo . The key prespecified outcome was first major atherosclerotic event ( non-fatal myocardial infa rct ion or coronary death , non-haemorrhagic stroke , or any arterial revascularisation procedure ) . All analyses were by intention to treat . This trial is registered at Clinical Trials.gov , NCT00125593 , and IS RCT N54137607 . Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo . Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L ( SE 0·02 ; with about two-thirds compliance ) during a median follow-up of 4·9 years and produced a 17 % proportional reduction in major atherosclerotic events ( 526 [ 11·3 % ] simvastatin plus ezetimibe vs 619 [ 13·4 % ] placebo ; rate ratio [ RR ] 0·83 , 95 % CI 0·74–0·94 ; log-rank p=0·0021 ) . Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infa rct ion or died from coronary heart disease ( 213 [ 4·6 % ] vs 230 [ 5·0 % ] ; RR 0·92 , 95 % CI 0·76–1·11 ; p=0·37 ) and there were significant reductions in non-haemorrhagic stroke ( 131 [ 2·8 % ] vs 174 [ 3·8 % ] ; RR 0·75 , 95 % CI 0·60–0·94 ; p=0·01 ) and arterial revascularisation procedures ( 284 [ 6·1 % ] vs 352 [ 7·6 % ] ; RR 0·79 , 95 % CI 0·68–0·93 ; p=0·0036 ) . After weighting for subgroup-specific reductions in LDL cholesterol , there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined , and , in particular , they were similar in patients on dialysis and those who were not . The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination ( 9 [ 0·2 % ] vs 5 [ 0·1 % ] ) . There was no evidence of excess risks of hepatitis ( 21 [ 0·5 % ] vs 18 [ 0·4 % ] ) , gallstones ( 106 [ 2·3 % ] vs 106 [ 2·3 % ] ) , or cancer ( 438 [ 9·4 % ] vs 439 [ 9·5 % ] , p=0·89 ) and there was no significant excess of death from any non-vascular cause ( 668 [ 14·4 % ] vs 612 [ 13·2 % ] , p=0·13 ) . Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease . Funding Merck/Schering-Plough Pharmaceuticals ; Australian National Health and Medical Research Council ; British Heart Foundation ; UK Medical Research Council BACKGROUND Cardiovascular disease as a result of accelerated atherogenesis is common in patients with end-stage renal disease ( ESRD ) . Dyslipidemia may be a major contributor in this process and can be influenced by lipid-lowering drugs ( statins ) . Moreover , statins may exhibit additional inhibitory effects on the atherogenesis , such as a modulation of the immune system as triggered by oxidatively modified LDL and a reduction of the inflammatory marker C-reactive protein ( CRP ) . METHODS We evaluated in a single-blind r and omized trial of 28 ESRD patients on hemodialysis , the dose-depending effects of both atorvastatin and simvastatin on lipids , lipoproteins , LDL particle heterogeneity , high sensitive-CRP , and markers of in vivo LDL oxidation . RESULTS Both statin therapies significantly lowered total plasma cholesterol and LDL-cholesterol concentrations to the same extent , whereas reduction in the concentrations of triglyceride-rich particles was less pronounced . Furthermore , statin therapy reduced LDL cholesterol in all LDL subfractions , without altering the overall LDL particle density . After both statins plasma hs-CRP concentrations were not significantly reduced ; parameters of in vivo LDL oxidation ( plasma ox-LDL concentration and the oxidation level of isolated LDL ) , were significantly decreased . Autoantibodies against ox-LDL , however , did not change during this trial period . CONCLUSIONS These results show that atorvastatin and simvastatin exhibit comparable favourable effects on lipid profiles in ESRD . Moreover , the reduction of in vivo oxidatively modified LDL as shown in this ESRD population , may indicate that these statins exhibit favourable effects on oxidative stress in vivo Objective . There have been no endpoint studies with statins for patients with severe renal failure . The purpose of this prospect i ve , open , r and omized , controlled study was to investigate whether atorvastatin ( 10 mg/day ) would alter cardiovascular endpoints and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 ( creatinine clearance < 30 ml/min ) . Material and methods . The study subjects comprised 143 patients who were r and omized either to placebo ( controls ; n=73 ; mean age 69.5 years ) or to treatment with atorvastatin ( n=70 ; mean age 67.9 years ) . The patients included were either non-dialysis ( n=33 ) , haemodialysis ( n=97 ) or peritoneal dialysis ( n=13 ) patients . Analysis focused on the primary endpoints of all-cause mortality , non-lethal acute myocardial infa rct ion , coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty . Statistical analysis for endpoint data was mainly by intention-to-treat . Results . Primary endpoints occurred in 74 % of the subjects . There was no difference in outcome between the control and atorvastatin groups . The 5-year endpoint-free survival rate from study entry was ≈20 % . Atorvastatin was withdrawn in ≈20 % of patients due to unacceptable side-effects . In the atorvastatin group , low-density lipoprotein ( LDL ) cholesterol was reduced by 35 % at 1 month and then sustained . The controls showed a progressive reduction in LDL cholesterol until 36 months . Conclusions . Although atorvastatin reduced total and LDL cholesterol effectively it was not beneficial regarding the long-term outcomes of cardiovascular endpoints or survival . In contrast to other patient groups , patients with severe chronic kidney disease , especially those on dialysis , seem to derive limited benefit from this lower dose of atorvastatin Objective . To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease ( CKD ) stages 4 and 5 and a glomerular filtration rate of < 30 ml/min . Material and methods . This was an open , prospect i ve , r and omized study . A total of 143 patients were included : 73 were controls and 70 were prescribed 10 mg/day of atorvastatin . As efficacy variables , total cholesterol , low-density lipoprotein ( LDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol and triglyceride levels were determined at the start of the study and at 1 , 3 , 6 , 12 , 18 , 24 , 30 and 36 months . Results . The follow-up period was a mean of 20±14.4 months ( range 1–36 months ) for those on atorvastatin versus 22±12.7 months ( range 0.5–36 months ) for the controls . Compared with baseline values , patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 ( 5.8 vs 4.4 mmol/l ; −23 % ; p<0.001 ) , of LDL cholesterol at Month 36 ( 3.6 vs 2.2 mmol/l ; −35 % ; p<0.001 ) and of triglycerides at Months 24 ( 2.5 vs 1.9 mmol/l ) and 36 ( 2.5 vs 1.8 mmol/l ) . The controls had significantly reduced levels of total cholesterol at Month 36 ( p<0.21 ) and of LDL cholesterol at Months 30 and 36 . Compared with the controls , the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1–30 . Fifteen patients ( 21 % ) stopped taking their medication as they could not tolerate the side-effects , the most frequent complaints being gastrointestinal discomfort and headache . Conclusion . Although the medication caused no severe adverse events , we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified BACKGROUND AND OBJECTIVES In hemodialysis , applicable guidelines recommend regular electrocardiogram ( ECG ) recordings . However , respective systematic evaluations are absent . Thus , the authors investigated whether routine ECG findings add prognostic information to st and ard risk assessment in hemodialysis . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The relationship between nine common baseline ECG variables and a combined cardiovascular endpoint ( CVE ; cardiac death , myocardial infa rct ion , stroke ) , sudden death , stroke , MI , and all-cause death in 1253 patients from the German Diabetes and Dialysis Study was evaluated . All patients were on maintenance hemodialysis , had type 2 diabetes mellitus , and received r and omized treatment with atorvastatin or placebo . RESULTS During 4 yr of follow-up ( March 1998 to March 2004 ) , 469 patients reached the CVE , and 617 died . After adjustment for demographics , comorbidities , and biomarkers in multivariate analysis , patients presenting without sinus rhythm were 89 % more likely to die , and the risk of CVE and stroke increased by 75 % and 164 % , respectively , compared with patients with preserved sinus rhythm . Left ventricular hypertrophy was associated with > 2-fold increase in the risk of stroke and a 60 % increase in the risk of sudden death . CONCLUSIONS In hemodialysis patients with type 2 diabetes mellitus , the absence of sinus rhythm is a risk indicator for CVE , stroke , and all-cause death , and left ventricular hypertrophy is associated with stroke and sudden death . Thus , routine ECG recording adds prognostic information to st and ard risk assessment BACKGROUND Patients with end-stage renal disease commonly present with an atherogenic lipid profile characterized by the accumulation of triglyceride-rich , apoprotein B-containing " remnant " lipoproteins , small dense low-density lipoprotein , and low levels of high-density lipoprotein . They are at increased cardiovascular risk and may benefit from drastic lipid-lowering treatment with atorvastatin , a potent , broadacting lipid regulator . This study aims to assess the effects of atorvastatin on the lipid profile in hemodialysis patients , to determine wether atorvastatin is also effective at lowering lipid levels in this particular high-risk subgroup . METHODS In this r and omized , placebo-controlled , double-blind study in hemodialysis patients with hypercholesterolemia ( n = 42 , mean total cholesterol 243 + /- 33 mg/dl ( 6.3 + /- 0.8 mmol/l ) ) , the efficacy of 4-weekly increasing doses of atorvastatin ( 10 - 40 mg daily ) was investigated . Lipids and apoproteins were measured in plasma and isolated lipoprotein fractions . RESULTS Mean total cholesterol and low-density lipoprotein cholesterol progressively decreased with increasing doses of atorvastatin ( total cholesterol -33 % , low-density lipoprotein cholesterol -43 % after 12 weeks ) , while high-density lipoprotein cholesterol remained unchanged . Plasma levels of apoprotein B and apoprotein E were also significantly reduced by atorvastatin 10 mg , while up-titration to 20 and 40 mg daily provided additional benefits by lowering triglycerides and apoprotein C-III . At week 12 , the fraction of small dense low-density lipoprotein was significantly reduced from 23 % - 18 % , and apoprotein B-containing intermediate-density lipoproteins were no longer detectable . CONCLUSION In conclusion , atorvastatin not only treated hypercholesterolemia but also favorably affected the uremic lipid profile in patients on hemodialysis . Atorvastatin 4-weekly dose escalation up to 40 mg daily was well-tolerated . Further prospect i ve studies are needed to evaluate the impact of this improved lipid profile on morbidity and mortality A r and omised trial of simvastatin and enalapril in patients with chronic renal failure on dialysis : effects on serum lipoprotein concentrations and left ventricular mass . Left ventricular hypertrophy and abnormalities of lipoprotein metabolism are both possible contributors to the high risk of cardiovascular death in patients with chronic renal failure on dialysis . We investigated the effects of simvastatin on lipid and lipoprotein concentrations and the effects of enalapril on left ventricular mass in 107 patients receiving haemodialysis or continuous ambulatory peritoneal dialysis . Patients were r and omised in a factorial design to receive simvastatin ( 10 mg daily ) or placebo and enalapril ( 2.5 - 5 mg daily ) or placebo . During follow-up , there was a significant excess of patients withdrawn from enalapril because of hypotension ( 2p = 0.002 ) , and after 6 months only 55 % of those assigned enalapril were still on treatment . From baseline to 6 months , there were no statistically significant differences in left ventricular mass or left ventricular dimensions between patients assigned enalapril and those assigned placebo . Among the patients assigned simvastatin , total cholesterol was reduced by 13 % ( 2p = 0.001 ) , LDL cholesterol was reduced by 17 % ( 2p = 0.003 ) and apolipoprotein B was reduced by 12 % ( 2p = 0.005 ) compared to patients assigned placebo . There were borderline significant ( 2p = 0.05 to 0.08 ) reductions in VLDL cholesterol , total triglyceride and VLDL triglycerides of 26 % , 12 % and 17 % respectively . Large-scale trials are now required to determine whether reductions in lipid and lipoprotein concentrations confer a reduction in coronary heart disease morbidity and mortality in patients on dialysis Hyperphosphatemia is highly prevalent among patients with end-stage renal disease ( ESRD ) and is associated with increased mortality risk in hemodialysis ( HD ) patients . The mechanism through which this mortality risk is mediated is unclear . Data from two national r and om sample s of HD patients ( n = 12,833 ) was used to test the hypothesis that elevated serum PO(4 ) contributes mainly to cardiac causes of death . During a 2-yr follow-up , the cause-specific relative risk ( RR ) of death for patients was analyzed separately for several categories of cause of death , including coronary artery disease ( CAD ) , sudden death , and other cardiac causes , cerebrovascular and infection . Cox regression models were fit for each of the eight cause of death categories , adjusting for patient demographics and non-cardiovascular comorbid conditions . Time at risk for each cause-specific model was censored at death that result ed from any of the other causes . Higher mortality risk was seen for patients in the high PO(4 ) group ( > 6.5mg/dl ) compared with the lower PO(4 ) group ( < or = 6.5mg/dl ) for death result ing from CAD ( RR 1.41 ; P < 0.0005 ) , sudden death ( RR 1.20 ; P < 0.01 ) , infection ( RR 1.20 ; P < 0.05 ) , and unknown causes ( RR 1.25 ; P < 0.05 ) . Patients in the high PO(4 ) group also had non-significantly increased RR of death from other cardiac and cerebrovascular causes of death . The RR of sudden death was also strongly associated with elevated Ca x PO(4 ) product ( RR 1.07 per 10 mg(2)/dl(2 ) ; P < 0.005 ) and serum parathyroid hormone levels greater than 495 pg/ml ( RR 1.25 ; P < 0.05 ) . This study identifies strong relationships between elevated serum PO(4 ) , Ca x PO(4 ) product , and parathyroid hormone and cardiac causes of death in HD patients , especially deaths result ing from CAD and sudden death . More vigorous measures to reduce the prevalence of these factors in HD patients may result in improved survival BACKGROUND Statins and angiotensin receptor blockers ( ARBs ) are known to improve vascular dysfunction in patients with chronic kidney disease . However , these effects have been inconsistent in dialysis patients . Moreover , it is currently unknown whether adding statins to ARBs improves vascular dysfunction better than ARB monotherapy in these patients . METHODS We conducted a prospect i ve open r and omized trial to investigate the effects of statin add-on to ARB on vascular protection in 124 nondiabetic patients undergoing peritoneal dialysis ( PD ) . Initially , all patients received 80 mg/day of valsartan for 6 months . Excluding 10 patients who dropped out during this period , patients were r and omly assigned to continue ARB treatment alone ( n = 57 ) or to receive 10 mg/day of rosuvastatin ( n = 57 ) added to ARB for the next 6 months . To assess vascular function , endothelium-dependent vasodilation and arterial stiffness were determined by brachial artery flow-mediated dilation ( FMD ) and brachial-ankle pulse wave velocity ( baPWV ) , respectively . RESULTS Compared to baseline values , ARB treatment for the first 6 months significantly improved FMD% ( 2.97 ± 2.64 to 3.57 ± 2.58 % , P < 0.001 ) . In addition , there was a small but significant decrease in baPWV during this period ( 1691.5 ± 276.3 to 1635.0 ± 278.6 cm/s , P = 0.048 ) . After r and omization , add-on treatment further improved FMD% ( 3.57 ± 2.73 to 4.24 ± 2.77 % , P = 0.003 ) , whereas ARB monotherapy did not ( P = 0.02 for between-group difference ) . Further slight improvement in baPWV ( 1617.0 ± 280.9 to 1528.9 ± 266.8 cm/s , P = 0.021 ) was observed only in the combined treatment group ( P = 0.28 for between-group difference ) . CONCLUSIONS Adding a statin to the ARB was of some help in improving vascular dysfunction more effectively than ARB monotherapy in nondiabetic PD patients . However , whether such limited improvements can lead to better clinical outcomes requires further investigation BACKGROUND Arterial stiffness assessed by pulse wave velocity ( PWV ) predicts all-cause and cardiovascular mortality in diabetic patients with end-stage renal disease . We studied the preventive effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor , fluvastatin , on arterial PWV values in this population . METHODS Twenty-two patients with normal serum lipid levels received fluvastatin ( 20 mg/day p.o . ) or a placebo for 6 months . Their serum lipid levels , serum levels of C-reactive protein ( CRP ) , arterial PWV , and ankle brachial indexes ( ABI ) were determined before , and 3 and 6 months after taking the medication to evaluate arterial stiffness . RESULTS At the beginning of the follow-up , there were no differences in age , blood pressure , body mass index , serum haemoglobin A1c level , serum CRP level , serum lipid levels , PWV or ABI between the placebo- ( n=10 ) and the fluvastatin-treated patients ( n=12 ) . After 6 months , the PWV and the serum oxidized low-density lipoprotein cholesterol ( LDL-C ) level increased significantly ( from 1969+/-140 to 2326+/-190 cm/s and 70.4+/-13.8 to 91.8+/-15.5 U/l , respectively ) in the placebo-treated patients . However , the fluvastatin group had a significantly reduced PWV ( from 1991+/-162 to 1709+/-134 cm/s ) , oxidized LDL-C serum levels ( from 89.0+/-9.6 to 73.0+/-5.8 U/l ) and CRP serum levels ( from 0.97+/-0.32 to 0.26+/-0.16 mg/dl ) compared with those in the placebo group . CONCLUSIONS Long-term administration of fluvastatin prevents further worsening of arterial biomechanics in haemodialysis patients with type 2 diabetes mellitus , even in the presence of serum lipid levels in the normal range We compared the lipid-lowering effects of simvastatin , a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor , and gemfibrozil , a fibric acid derivative , in 22 continuous ambulatory peritoneal dialysis patients whose serum total cholesterol and /or triglyceride levels were > or = 220 mg/dL after a st and ard diet for six months . The study group was first treated with gemfibrozil ( 600 mg/b.i.d . ) for three months ( stage 1 ) . After a wash-out period of two months , during which no treatment was given , all of the patients became hyperlipidemic again and , therefore , were given simvastatin ( 10 mg/day ) for three months ( stage 2 ) , which was followed by another two-month wash-out period . A control group , which served to evaluate the natural progression of pharmacologically untreated dyslipidemia , was followed during the same period . Blood determinations of triglyceride , total cholesterol , and high-density lipoprotein ( HDL ) cholesterol were performed after each step . Low-density lipoprotein ( LDL ) cholesterol and HDL ratio were calculated from the measured values . Both gemfibrozil and simvastatin improved all parameters of the lipid profile , but the effect of simvastatin was better than that of gemfibrozil ( -69 vs -39 mg/dL for triglyceride and -95 vs -64 mg/dL for cholesterol ) , while their actions on LDL and HDL cholesterol were of equal magnitude . Two months after discontinuation of simvastatin , significant decreases of total cholesterol ( -46 mg/dL ) and triglyceride ( -60 mg/dL ) were still present , while these values had returned to pretreatment levels after stopping gemfibrozil . The HDL ratio remained markedlyhigher ( p < 0.05 ) during the wash-out period after simvastatin , while it decreased to pretreatment values after gemfibrozil was stopped . The lipid profile of the control group did not change during the follow-up . Both drugs were well tolerated , and no serious side effects occurred The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-mediated lowering of serum cholesterol has been associated with a significant reduction in cardiovascular morbidity and mortality . Recent studies suggest that additional non-lipid lowering effects ( eg , endothelial stabilization , anti-inflammatory , antithrombogenic ) may be important in modulating their effectiveness . Dyslipidemia is common in end-stage renal disease ( ESRD ) , and hemodialysis patients have increased cardiovascular morbidity and mortality . Cerivastatin , a new statin with powerful low-density lipoprotein-cholesterol ( LDL-C ) lowering capabilities , possesses some unique non-LDL-C-mediated properties that may contribute to a reduction of coronary events in the patient with ESRD . The primary objective of this multicenter multinational study of 1,054 hemodialysis patients is to compare 2 years of treatment with cerivastatin ( 0.4 mg/d ) versus placebo on the composite clinical event rate of myocardial infa rct ion , sudden cardiac death , ischemic stroke , and the need for coronary arterial bypass graft ( CABG ) or percutaneous transluminal coronary angioplasty ( PTCA ) procedures in these patients . Changes in lipids , inflammatory proteins including heat stable C-reactive protein ( hsCRP ) , interleukin-6 ( IL-6 ) , oncostatin-M , intracellular adhesion molecule-1 ( ICAM-1 ) and monocyte-chemoattractant protein-1 ( MCP-1 ) , as well as markers of cardiac muscle pathology , such as troponin I and troponin T , will be assessed in a subset of patients . This study is the first of its kind to assess the effect of a statin on the reduction of cardiovascular morbidity and mortality in an incident hemodialysis population . It will determine whether treatment with cerivastatin can effectively reduce the significant cardiovascular morbidity and mortality Patients with type 2 diabetes on dialysis are at a substantially increased risk of cardiovascular and cerebrovascular diseases . Dyslipidemia characterized by moderately elevated low-density lipoprotein cholesterol and high triglycerides and low high-density lipoprotein cholesterol levels is common in this population . We hypothesized that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors would reduce vascular morbidity and mortality in this patient group . The ‘ Deutsche Diabetes Dialyse Studie ’ ( 4D study ) is a prospect i ve , r and omized , double-blind study involving 178 dialysis centers throughout Germany . Between March 1998 and October 2002 , 1,255 patients were r and omized to either atorvastatin 20 mg or placebo ; 677 men and 578 women , aged 30–83 years , have been enrolled . The study will be terminated as soon as the predefined number of 424 patients with primary combined end points ( i.e. , cardiovascular death , nonfatal myocardial infa rct ion , or fatal/nonfatal stroke ) will have occurred . The total cohort had the following characteristics at baseline : the mean age was 65.7 years , 54 % were men , 89 % had a history of hypertension , 21 % had coronary artery disease , 17.8 % had a history of stroke or a transient ischemic attack , and 45 % suffered from peripheral arterial disease . The mean time interval between the diagnosis of diabetes and the onset of dialysis was 17.4 years . On average , the patients were on hemodialysis for 8.3 months . Mean lipid and lipoprotein levels were : total cholesterol 219 ± 43 mg/dl , low-density lipoprotein cholesterol 126 ± 30 mg/dl , high-density lipoprotein cholesterol 36 ± 13 mg/dl , and triglycerides 264 ± 167 mg/dl . The results of the study will provide important information on the efficacy and safety of atorvastatin to support its use in patients with an impaired renal function who are at a high risk of vascular morbidity and mortality A r and omized , placebo-controlled trial in diabetic patients receiving hemodialysis showed no effect of atorvastatin on a composite cardiovascular endpoint , but analysis of the component cardiac endpoints suggested that atorvastatin may significantly reduce risk . Because the AURORA ( A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis : An Assessment of Survival and Cardiovascular Events ) trial included patients with and without diabetes , we conducted a post hoc analysis to determine whether rosuvastatin might reduce the risk of cardiac events in diabetic patients receiving hemodialysis . Among the 731 participants with diabetes , traditional risk factors such as LDL-C , smoking , and BP did not associate with cardiac events ( cardiac death and nonfatal myocardial infa rct ion ) . At baseline , only age and high-sensitivity C-reactive protein were independent risk factors for cardiac events . Assignment to rosuvastatin associated with a nonsignificant 16.2 % reduction in risk for the AURORA trial 's composite primary endpoint of cardiac death , nonfatal MI , or fatal or nonfatal stroke ( HR 0.84 ; 95 % CI 0.65 to 1.07 ) . There was no difference in overall stroke , but the rosuvastatin group had more hemorrhagic strokes than the placebo group ( 12 versus two strokes , respectively ; HR , 5.21 ; 95 % CI 1.17 to 23.27 ) . Rosuvastatin treatment significantly reduced the rates of cardiac events by 32 % among patients with diabetes ( HR 0.68 ; 95 % CI 0.51 to 0.90 ) . In conclusion , among hemodialysis patients with diabetes mellitus , rosuvastatin might reduce the risk of fatal and nonfatal cardiac events BACKGROUND AND OBJECTIVES Patients undergoing maintenance hemodialysis are at high cardiovascular risk . Lowering LDL-cholesterol with statins reduces the incidence rate of cardiovascular events in patients with chronic kidney disease . In contrast , two r and omized , prospect i ve , placebo-controlled trials have been completed in hemodialysis patients that showed no significant effects of statins on cardiovascular outcomes . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A post hoc analysis was conducted of the 4D ( Die Deutsche Diabetes Dialyze ) study to investigate whether LDL-cholesterol at baseline is predictive of cardiovascular events and whether the effect of atorvastatin on clinical outcomes depends on LDL-cholesterol at baseline . RESULTS High concentrations of LDL-cholesterol by tendency increased the risks of cardiac endpoints and all-cause mortality . Concordantly , atorvastatin significantly reduced the rates of adverse outcomes in the highest quartile of LDL-cholesterol ( ≥145 mg/dl , 3.76 mmol/L ) . The hazard ratios and 95 % confidence intervals were 0.69 ( 0.48 to 1.00 ) for the composite primary endpoint , 0.58 ( 0.34 to 0.99 ) for cardiac death , 0.48 ( 0.25 to 0.94 ) for sudden cardiac death , 0.62 ( 0.33 to 1.17 ) for nonfatal myocardial infa rct ion , 0.68 ( 0.47 to 0.98 ) for all cardiac events combined , and 0.72 ( 0.52 to 0.99 ) for death from all causes , respectively . No such decrease was seen in any of the other quartiles of LDL-cholesterol at baseline . CONCLUSIONS In patients with type 2 diabetes mellitus undergoing hemodialysis , atorvastatin significantly reduces the risk of fatal and nonfatal cardiac events and death from any cause if pretreatment LDL-cholesterol is > 145 mg/dl ( 3.76 mmol/L ) Background : Dialysis patients have many underlying traditional and nontraditional risk factors that may predispose them to a high prevalence of cardiovascular disease . The effects of statins ( eg , atorvastatin ) on altering nontraditional lipoprotein measures in dialysis patients have not been extensively investigated . Objective : To evaluate the efficacy of atorvastatin compared with a control group in inducing changes in lipoprotein(a ) [ Lp(a ) ] , apolipoprotein ( Apo ) A-1 , Apo-B , and fibrinogen levels , as well as the conventional lipoprotein profile , in hemodialysis patients over 36 weeks ; secondary objectives were to assess changes in C-reactive protein , albumin , and safety measures . Methods : Forty-five hemodialysis patients with low-density lipoprotein cholesterol ( LDL-C ) levels greater than 100 mg/dL were r and omized to parallel groups : atorvastatin ( n = 19 ) or no treatment ( n = 26 ) . The atorvastatin dose was titrated from 10 mg to achieve an LDL-C goal of 100 mg/dL or less and therapy was continued for 36 weeks . Biochemical and lipoprotein laboratory tests for efficacy outcomes were obtained at baseline , 12 weeks , and 36 weeks . Results : The atorvastatin group exhibited clinical ly significant reductions ( mean ± SD ) compared with controls in total cholesterol ( –21.7 ± 41.7 vs –3.2 ± 40.0 mg/dL , respectively ; p = 0.017 ) and LDL-C ( –13.1 ± 32.0 vs –1.1 ± 38.4 mg/dL. respectively ; p = 0.056 ) levels , as well as Lp(a ) ( –10.6 ± 27 vs 3.5 ± 17.8 mg/dL , respectively ; p = 0.046 ) . Statistical analyses included analysis of variance on ranked measures for multivariable modeling and paired t-test to determine changes in efficacy measures between baseline and 36 weeks within groups . Conclusions : Atorvastatin was safe and effective in reducing Lp(a ) , total cholesterol , and LDL-C levels . Given the prevalence of atherosclerosis in hemodialysis patients , therapy aim ed at reducing traditional and nontraditional risk factors may be beneficial 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 BACKGROUND Plasma cholesteryl ester transfer activity is increased in patients with chronic renal failure on dialysis who have elevated levels of apolipoprotein B (apoB)-containing lipoproteins . Simvastatin , a 3-hydroxy-3-methylglutaryl coenzyme A ( HMG CoA ) reductase inhibitor , reduces levels of these lipoproteins but the effect of treatment on cholesteryl ester transfer activity in patients on dialysis remains to be determined . METHODS We measured serum newly synthesized cholesteryl ester transfer ( NCET ) activity , lecithin : cholesterol acyltransferase ( LCAT ) activity and serum lipid , lipoprotein and apolipoprotein concentrations before and immediately after 6 months treatment with simvastatin ( 10 mg daily , n = 24 ) or placebo ( n = 29 ) in 53 patients with chronic renal failure receiving haemodialysis or continuous ambulatory peritoneal dialysis ( CAPD ) . RESULTS Simvastatin therapy significantly reduced serum cholesterol , LDL cholesterol , apoB concentrations , and both NCET ( P = 0.001 ) and LCAT ( P = 0.012 ) rates . The decrease in NCET activity was correlated significantly with the corresponding decrease in apoB concentration ( r = 0.715 , P < 0.001 ) and LCAT activity ( r = 0.715 , P < 0.001 ) during simvastatin therapy and was no longer significant when apoB concentration ( P = 0.14 ) or LCAT activity ( P = 0.07 ) were controlled . CONCLUSIONS These data show that simvastatin therapy reduces serum NCET rates , and suggest that this may be linked to the concomitant decrease in levels of apoB-containing lipoproteins which are acceptors of transferred cholesteryl esters , and to the decrease in serum LCAT rates in patients with chronic renal failure with treatment Elevated plasma intermediate density lipoprotein ( IDL ) is one of the features of uremic dyslipidemia which is potentially atherogenic . We examined the effects of pravastatin , an HMG-CoA reductase inhibitor , on IDL levels as well as other lipoprotein parameters in 19 uremic patients treated with hemodialysis ( HD , n = 11 ) or continuous ambulatory peritoneal dialysis ( CAPD , n = 8) . The patients were administered 5 mg/day pravastatin for the initial 4 weeks and 10 mg/day for the subsequent 12 weeks . In the analysis of the total subjects , IDL-cholesterol was reduced by 31 % as well as low density lipoprotein (LDL)-cholesterol . Cholesterol in very low density lipoprotein ( VLDL ) also decreased whereas that in high density lipoprotein ( HDL ) did not . Significant decrease of serum triglycerides was due mainly to reduced IDL- and LDL-triglycerides . Apolipoprotein ( apo ) A-I did not change , whereas apo A-II , B , C-II , C-III , E , and B/A-I ratio were significantly lowered . Pravastatin did not affect measured activity of lecithin : cholesterol acyltransferase , post-heparin plasma lipoprotein lipase or hepatic triglyceride lipase . HD and CAPD patients responded almost equally to the treatment . IDL elevation was present independent of serum total cholesterol , and it was lowered by pravastatin even in non-hypercholesterolemic subjects . There was no critical adverse effect besides transient and asymptomatic increase of serum creatine kinase level . We conclude that pravastatin can be a safe and effective approach to the management of dyslipidemia in uremic patients who have an elevated level of IDL INTRODUCTION . This study was conducted to determine the effect of statins on the serum levels of interleukin-6 ( IL-6 ) , low-density lipoprotein cholesterol ( LDLC ) , and high-sensitivity C-reactive protein ( HSCPR ) . MATERIAL S AND METHODS . This r and omized clinical trial was carried out on 95 hemodialysis patients divided into three groups of atorvastatin , 10 mg ; simvastatin , 20 mg ; and lovastatin , 40 mg , daily , administered for 2 months . Levels of serum HSCRP , IL-6 , and LDLC were all measured before and after the study period . RESULTS . At baseline , 59 % of the hemodialysis patients presented with elevated HSCRP , 46.3 % them had increased IL-6 , and 26.3 % had an increased LDLC level . The three drugs were capable to lower the level of HSCRP , among which atorvastatin had the highest effect size ( 41.8 % reduction , P = .001 ) . Lovastatin stood in the next ( 37.6 % reduction , P = .02 ) , while HSCRP reduction was not significant in the simvastatin group ( 25 % reduction , P = .14 ) . Neither of the drugs significantly reduced IL-6 levels . Effects of atorvastatin and simvastatin on the LDLC levels were significant , while lovastatin had a marginal effect . CONCLUSIONS . Use of statins result ed in CRP reduction in patients on hemodialysis . Atorvastatin was much more effective than lovastatin , while CRP reduction was not significant by simvastatin . However , simvastatin had the greatest impact on LDLC . None of these drugs could reduce IL-6 levels within 2 months BACKGROUND Dyslipoproteinaemia is an important risk factor for cardiovascular disease in uraemic patients on continuous ambulatory peritoneal dialysis ( CAPD ) . Lovastatin is an HMG Coenzyme A reductase inhibitor which is useful in treating non-uraemic patients with hypercholesterolaemia . AIMS We conducted a single blind cross-over study versus placebo in 10 CAPD patients to examine the effect of lovastatin ( 20 - 40 mg ) on the serum lipid profile and its safety in uraemic patients . METHODS Treatment phases were of eight weeks ' duration . Each four weeks ' measurements were made of serum total cholesterol ( TC ) , triglyceride ( TG ) , HDL-cholesterol ( HDL-C ) , LDL-cholesterol ( LDL-C ) , VLDL-cholesterol ( VLDL-C ) , Apolipoprotein A1 & B ( Apo A1 & Apo B ) and Lipoprotein ( a ) . After eight weeks , lovastatin significantly reduced TC by 29 % from 6.7 + /- 0.3 ( mean + /- S.E.M. ) to 4.8 + /- 0.1 mmol/L , LDL-C by 41 % from 4.6 + /- 0.3 to 2.7 + /- 0.1 mmol/L and Apo B by 32 % from 116 + /- 7 to 78 + /- 3 mg/dl ( p < 0.01 ) . HDL-C increased by 8 % from 1.2 + /- 0.1 to 1.3 + /- 0.2 mmol/L after eight weeks ' therapy ( p < 0.05 ) . TG decreased by 18 % from 1.9 + /- 0.4 to 1.6 + /- 0.3 mmol/L ( p < 0.05 ) . There was no significant difference in changes of other lipid profiles between placebo and drug . No adverse effects of the drug were noted during treatment and the liver function and muscle enzymes were not significantly altered by either drug therapy or placebo . RESULTS Lovastatin appears to be a safe and useful drug in effectively treating dyslipoproteinaemia in CAPD patients Coronary artery disease is the most important cause of morbidity and mortality in patients with end-stage renal failure ( RF ) . Hypercholesterolemia is an important risk factor for coronary heart disease . Patients with chronic renal failure ( CRF ) have difficulties in compliance with their care and treatment . Intermittent simvastatin treatment may help to increase compliance and can be a treatment alternative in patients with CRF at risk of coronary artery disease . We investigated the effects of simvastatin and compared intermittent with continuous simvastatin treatment in hypercholesterolamic patients with CRF . The study group included 40 of 422 CRF patients on dialysis in our clinic . The inclusion criterion was low density lipoprotein cholesterol ( LDL-C ) of 130 mg/dL or more . Twenty patients received simvastatin 10 mg/day ( continuous group ) and 20 patients received simvastatin 20 mg three times a week ( only dialysis days- intermittent group ) for four months . Nineteen patients served as controls and they were given a prescribed diet only . Total cholesterol ( TC ) and LDL-C decreased markedly in patients receiving intermittent and continuous simvastatin compared to controls . Continuous simvastatin decreased TC by 23 % ( P < 0.001 ) and LDL-C by 39 % ( P < 0.001 ) . Intermittent simvastatin decreased TC by 26 % ( P < 0.001 ) and LDL-C by 40 % ( P < 0.001 ) . The atherogenic index ratios in both the continuous and intermittent groups ( TC/High density lipoprotein-cholesterol ( HDL-C ) and LDL-C/HDL-C ) decreased significantly . There was no significant difference in patient compliance between the two groups . Intermittent simvastatin is as effective and reliable as continuous simvastatin treatment and can be an alternative treatment in hypercholesterolemic patients on dialysis BACKGROUND The increase in serum C-reactive protein ( CRP ) levels is an independent determinant of cardiovascular events in long-term hemodialysis ( HD ) patients . Recently , statins have shown anti-inflammatory properties in addition to their lipid-lowering effect . METHODS We design ed a 6-month , prospect i ve , r and omized , controlled study to assess the safety and efficacy of atorvastatin in reducing serum CRP levels in long-term HD patients . Patients on HD therapy for at least 6 months , with autologous vascular access , were included . Patients presenting with illnesses and /or use of drugs that may affect CRP levels were excluded . After r and omization , group A included 16 patients treated with atorvastatin ( 10 mg/d orally ) , and group B included 17 patients treated with placebo . Body mass index , Kt/V , normalized protein catabolic rate , mean blood pressure , and levels of hemoglobin , serum CRP , albumin , creatinine , lipids , and enzymes were recorded at baseline and after 6 months . RESULTS Qualitative/quantitative parameters were homogeneous between the groups at baseline . In group A , median serum CRP levels decreased from 9 mg/L ( range , 5 to 22 mg/L ) at baseline to 5 mg/L ( range , 3 to 16 mg/L ) after 6 months ( P = 0.004 ) . In group B , values were 8 mg/L ( range , 4 to 14 mg/L ) at baseline and 7 mg/L ( range , 3 to 17 mg/L ) after 6 months ( P = 0.98 ) . Serum CRP levels were lower in group A than group B at month-4 ( 5 mg/L ; range , 3 to 11 mg/L versus 7 mg/L ; range , 3 to 10 mg/L , respectively ; P = 0.054 ) and month-6 evaluations ( 5 mg/L ; range , 3 to 16 mg/L versus 7 mg/L ; range , 3 to 17 mg/L , respectively ; P = 0.060 ) . After 6 months , only in group A was there a significant decrease in serum cholesterol levels ( P = 0.041 ) and a significant increase in serum albumin levels ( P = 0.004 ) . Enzyme levels were stable during the study in both groups . CONCLUSION Administration of atorvastatin is safe in patients on long-term HD therapy and , in addition to its beneficial effects on lipid levels , induces a significant decrease in serum CRP levels , with a consequential increase in serum albumin levels The therapeutic effects of simvastatin on hyperlipidemia and its protective effects on residual renal function ( RRF ) in continuous ambulatory peritoneal dialysis ( CAPD ) patients with hyperlipidemia were observed . Forty-seven CAPD patients were r and omly divided into two groups , the treatment group and control group . The treatments of two groups were the same except that the treatment group patients were additionally given simvastatin 20 mg.d-1 . The results were that , after 12-week treatment , the total cholesterol ( TC ) , triglyceride ( TG ) , low density lipoprotein ( LDL ) , and apoprotein B100 ( ApoB100 ) in the treatment group significantly decreased , but high density lipoprotein ( HDL ) and apoprotein A1 ( ApoA1 ) significantly increased compared with the control group ( all P < 0.05 ) ; one year later , RRF of patients of both groups all decreased but there was no significant difference between them . The results suggest that simvastatin can effectively normalize lipidemia , but has no protective effect on RRF in CAPD patients STUDY OBJECTIVES To determine the effects of atorvastatin on low-density lipoprotein cholesterol ( LDL ) particle size and C-reactive protein ( CRP ) concentrations in patients undergoing long-term hemodialysis . Another objective was to compare the effects of atorvastatin on lipoprotein profiles as determined by direct versus indirect assessment of lipoprotein composition . DESIGN R and omized , parallel-group sub study . SETTING Two university-affiliated outpatient hemodialysis centers . PATIENTS Nineteen patients with LDL levels above 100 mg/dl and with at least two cardiovascular risk factors . INTERVENTION Patients were r and omized in a 1:1 ratio to atorvastatin 10 mg/day or no treatment ( control ) for 20 weeks . MEASUREMENTS AND MAIN RESULTS We compared the differences between LDL particle size and CRP levels at baseline and 20 weeks in the atorvastatin versus control groups . Baseline demographic characteristics were similar between the two groups . Atorvastatin therapy was associated with no change in mean LDL particle size ( p=0.23 ) and with a 90 % decrease in mean CRP level ( p=0.52 ) . When evaluated by st and ard chemical analysis , atorvastatin therapy reduced total cholesterol levels by 29 % ( p=0.025 ) and result ed in nonsignificant reductions in LDL , high-density lipoprotein cholesterol , and triglyceride levels . Treatment with atorvastatin was not associated with significant changes in lipoprotein profile as determined by nuclear magnetic resonance ( NMR ) spectroscopy . CONCLUSION Treatment with atorvastatin did not affect LDL particle size but was associated with a sizable , yet nonsignificant , reduction in CRP concentrations . The drug had variable effects on lipoprotein concentrations as determined by chemical and NMR analytical methods . A larger study is necessary to provide definitive information on the effects of atorvastatin on LDL phenotype and CRP in patients with kidney disease Patients with end-stage renal failure are a high-risk group for atherosclerotic cardiovascular disease and commonly have dyslipidemia as a major factor . Dietary manipulation is the recommended first line of therapy for reducing lipid levels in people with normal renal function ; however , complex dietary requirements of dialysis-treated patients with end-stage renal failure impose significant constraints . In this study , we evaluated the effect of trying to comply with established lipid-lowering recommendations superimposed on our normally prescribed dialysis diet over 14 weeks in stable subjects treated with either hemodialysis ( HD ) or chronic peritoneal dialysis ( PD ) . Of 306 dialysis patients screened , 75 subjects were enrolled ; 8 subjects did not complete the study . In the remainder , HD subjects ( n = 41 ) decreased saturated fat intakes by 18 % overall and cholesterol intakes by 16 % . This was associated with a decrease in total cholesterol levels from 232 + /- 8 to 209 + /- 4 mg/dL ( mean + /- SEM ; P = 0.007 ) and low-density lipoprotein cholesterol levels from 147 + /- 4 to 131 + /- 4 mg/dL ( P = 0.009 ) . However , energy intakes decreased by almost 10 % . There were no statistically significant changes in PD patients ( n = 26 ) . Only 24.4 % of HD ( 10 of 41 patients ) and 15.4 % of PD patients ( 4 of 26 patients ) normalized their lipid levels . Considerable problems were encountered in maintaining compliance with the modified dialysis diets . This study shows that if adhered to , properly constructed dialysis diets are close to optimal lipid-lowering recommendations . Further dietary manipulation is difficult , leads to little benefit in the majority , and is accompanied by added problems of adherence . We conclude that the vast majority of dyslipidemic patients with end-stage renal failure require pharmacological therapy BACKGROUND Our purpose was to evaluate the efficacy and safety of atorvastatin , a potent cholesterol- and triglyceride-lowering agent , in peritoneal dialysis patients with dyslipidaemia . METHODS Peritoneal dialysis patients with hypercholesterolaemia were treated for 4 months with atorvastatin at a starting dose of 10 mg . The dose could be increased to 20 or 40 mg in order to achieve the following targets : plasma LDL-cholesterol of 130 mg/dl for primary prevention of coronary heart disease , plasma LDL cholesterol of 100 mg/dl for secondary prevention , and plasma triglycerides of 200 mg/dl . Plasma lipid profile and liver and muscle enzyme levels were assessed at baseline and then monthly during treatment . RESULTS Thirty-one patients with hypercholesterolaemia were included ( 16 males and 15 females ; mean age 57+/-16 years ; mean duration of peritoneal dialysis 27+/-17 months ) . Nineteen of the patients also had hypertriglyceridaemia and seven had diabetes . Twenty patients had no coronary history ( primary prevention ) , whereas nine had experienced a coronary event ( secondary prevention ) . In the primary and the secondary prevention patients , mean LDL-cholesterol levels ( mg/dl ) decreased significantly by 42 and 46 % from 204+/-23 to 119+/-27 ( P<0 . 001 ) and 198+/-37 to 104+/-21 ( P<0.001 ) , and mean triglyceride levels ( mg/dl ) decreased by 37 and 26 % from 289+/-132 to 186+/-92 ( P<0.001 ) and 201+/-62 to 150+/-54 ( P<0.001 respectively ) . Nineteen primary prevention and seven secondary prevention patients achieved the LDL-cholesterol target . The triglyceride target was achieved by 15 of the 19 hypertriglyceridaemic patients . Two patients stopped treatment ( one because of gastrointestinal disturbances , the other because of an allergic skin reaction ) . After 4 months , there were no changes in enzyme levels . CONCLUSION Atorvastatin is an effective and safe lipid-lowering agent for peritoneal dialysis patients with mixed dyslipidaemia The efficacy of lovastatin and simvastatin , competitive inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A reductase , was investigated in 40 hemodialysis ( HD ) patients displaying hypercholesterolemia and moderate hypertriglyceridemia ( selection of 40 patients required screening of 700 hemodialysis patients ) . After a four-week placebo period , lovastatin or simvastatin was administered to two groups of 20 patients in increasing doses over a period of three months . Thirty-six patients completed the study . Lovastatin ( 1st month 20 mg ; 2nd and 3rd months 40 mg day-1 ) and simvastatin ( 1st month 10 mg , 2nd month 20 mg and 3rd month 40 mg day-1 ) reduced total serum cholesterol from 280.3 + /- 9.4 to 213.0 + /- 6.7 ( -24 % ) and 295.0 + /- 12.2 to 202.3 + /- 8.9 mg/dl ( -31.4 % ) , LDL cholesterol from 161.9 + /- 10.7 to 112.1 + /- 7.9 ( -30.8 % ) and 181.8 + /- 14.7 to 107.4 + /- 8.1 mg/dl ( -40.9 % ) , as well as apolipoprotein B ( apo B ) from 116.0 + /- 6.6 to 83.3 + /- 3.7 ( -28.2 % ) and 134.4 + /- 8.2 to 84.1 + /- 5.3 mg/dl ( -37.4 % ) , respectively . Furthermore , the ratio of LDL apo B/LDL cholesterol increased significantly ( 0.63 + /- 0.02 vs. 0.71 + /- 0.05 and 0.63 + /- 0.02 vs. 0.66 + /- 0.02 , respectively ) . Another remarkable effect was the reduction of cholesterol concentration in VLDL ( 72.4 + /- 8.9 vs. 47.3 + /- 6.8 [ lovastatin ] and 78.3 + /- 11.1 vs. 50.7 + /- 8.8 mg/dl [ simvastatin ] , respectively ) . Therefore , the ratio of triglycerides/cholesterol in VLDL increased ( 3.2 + /- 0.2 vs. 3.8 + /- 0.3 and 3.2 + /- 0.2 vs. 4.0 + /- 0.2 , respectively ) , indicating VLDL formation poor in cholesterol and rich in triglycerides . ( ABSTRACT TRUNCATED AT 250 WORDS Background : Cardiovascular disease ( CVD ) is the leading cause of death in patients with end-stage renal disease ( ESRD ) . Aims : AURORA ( A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis : an Assessment of survival and cardiovascular events ) is the first large-scale international trial to assess the effects of statins on cardiovascular outcomes in patients with ESRD on chronic haemodialysis . Preliminary baseline data from the r and omised population are presented . Methods : A total of 2,775 patients from 280 centres in 25 countries were r and omised into the study . Patients aged 50–80 years on regular chronic haemodialysis for at least 3 months before screening were eligible for inclusion . They were r and omised 1:1 to receive either rosuvastatin 10 mg or placebo daily and assessed throughout the study . Results : The mean age at baseline was 64 years . Most patients were male ( 62 % ) and 85 % were white . The median time since commencing renal replacement was 32 months . Mean total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) levels were 4.53 mmol/l ( 175 mg/dl ) and 2.57 mmol/l ( 99 mg/dl ) , respectively . Conclusion : Results from the AURORA trial will impact on the current guidelines and use of statins in this patient population OBJECTIVES The objective of this study was to examine the effects of treatment with atorvastatin , alpha-tocopherol and the combination of both , on lipoproteins and oxidative stress in dialysis patients . DESIGN AND SETTING This double-blind r and omised placebo-controlled trial was performed at the dialysis department of a non-university hospital . SUBJECTS , INTERVENTION AND MEASUREMENTS : A total of 44 clinical ly stable , non-diabetic patients on dialysis therapy ( 23 on haemo- and 21 on peritoneal-dialysis ) without manifest cardiovascular disease were included in this study . They were r and omised for treatment during a period of 12 weeks with 40 mg atorvastatin + placebo alpha-tocopherol ( group 1 ) once daily , 800 IU alpha-tocopherol + placebo atorvastatin once daily ( group 2 ) , 40 mg atorvastatin + 800 IU alpha-tocopherol once daily ( group 3 ) , or placebo atorvastatin + placebo alpha-tocopherol once daily ( group 4 ) . Assessment of lipid profile and oxidative stress was performed at the start of the study and after 12 weeks of treatment . RESULTS Treatment with atorvastatin reduced total cholesterol , triglycerides ( TG ) , low-density lipoprotein ( LDL ) cholesterol , apolipoprotein B ( apoB ) and levels of oxidised LDL ( oxLDL ) with 30 - 43 % . It had no influence on LDL oxidisability . Additional supplementation with alpha-tocopherol had no effect on lipid profile and oxLDL levels but decreased in vitro LDL oxidisability . No side-effects were observed . CONCLUSIONS Treatment with atorvastatin is effective in lowering plasma total cholesterol , TG , LDL , apoB and oxLDL in a population of stable dialysis patients and might therefore be an effective tool in improving the poor cardiovascular outcome in these patients . Supplementation of alpha-tocopherol to atorvastatin had beneficial effects on in vitro LDL oxidisability and might therefore be of additional value . Further research on the clinical effects of treatment with atorvastatin in combination with alpha-tocopherol is necessary BACKGROUND Simvastatin , a 3-hydroxy 3-methylglutaryl co-enzyme A ( HMG-CoA ) reductase inhibitor , is used widely for treatment of hypercholesterolemia . Simvastatin may be a suitable treatment for dyslipidemia in hemodialysis ( HD ) patients . However , investigation of the side-effects and safety of long-term administration of simvastatin to HD patients has been limited . In this study , we investigated the effects and safety of simvastatin and its effects on lipoprotein metabolism in hypercholesterolemic patients on HD . METHODS Simvastatin was administered at a dosage of 5 mg/day for 24 weeks to 38 HD patients with high serum total cholesterol ( TC ) levels ( 200 mg/dl ) or low high-density lipoprotein cholesterol ( HDL-C ) levels ( 35 mg/dl ) . Every four weeks , serum lipids , apolipoprotein , lipoprotein ( a ) [ Lp(a ) ] and malondialdehyde ( MDA ) levels were measured . In addition , lipid levels were determined in each lipoprotein fraction separated by ultracentrifugation . RESULTS After 24 weeks of simvastatin administration , TC significantly decreased by 25.7 % , and low-density lipoprotein cholesterol ( LDL-C ) was significantly decreased by 33.6 % . Triglyceride ( TG ) and HDL-C showed no significant changes . Apolipoprotein ( apo ) B significantly decreased by 24.5 % and apo E by 30.0 % . No significant changes were observed in the other apolipoproteins . MDA was also significantly decreased , whereas Lp(a ) was not significantly altered . In the lipoprotein fractions , very LDL cholesterol ( VLDL-C ) , intermediate-density lipoprotein cholesterol ( IDL-C ) , LDL1 cholesterol ( LDL1-C ) , and LDL2 cholesterol ( LDL2-C ) showed significant decreases . No particular side-effects were observed during the 12 months of simvastatin administration . CONCLUSIONS These results suggest that simvastatin appears to be safe and effective in HD patients with hypercholesterolemia BACKGROUND Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk . However , a benefit of statins in such patients who are undergoing hemodialysis has not been proved . METHODS We conducted an international , multicenter , r and omized , double-blind , prospect i ve trial involving 2776 patients , 50 to 80 years of age , who were undergoing maintenance hemodialysis . We r and omly assigned patients to receive rosuvastatin , 10 mg daily , or placebo . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . Secondary end points included death from all causes and individual cardiac and vascular events . RESULTS After 3 months , the mean reduction in low-density lipoprotein ( LDL ) cholesterol levels was 43 % in patients receiving rosuvastatin , from a mean baseline level of 100 mg per deciliter ( 2.6 mmol per liter ) . During a median follow-up period of 3.8 years , 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point ( 9.2 and 9.5 events per 100 patient-years , respectively ; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group , 0.96 ; 95 % confidence interval [ CI ] , 0.84 to 1.11 ; P=0.59 ) . Rosuvastatin had no effect on individual components of the primary end point . There was also no significant effect on all-cause mortality ( 13.5 vs. 14.0 events per 100 patient-years ; hazard ratio , 0.96 ; 95 % CI , 0.86 to 1.07 ; P=0.51 ) . CONCLUSIONS In patients undergoing hemodialysis , the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . ( Clinical Trials.gov number , NCT00240331 . UNLABELLED BACKGROUND . : Patients with end-stage renal disease ( ESRD ) suffer from markedly higher rates of cardiovascular disease than the general population . Although therapy with 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors ( " statins " ) has been demonstrated to reduce the mortality from cardiovascular disease in patients without ESRD , only 10 % of patients on dialysis are treated with these medications by day 60 of ESRD . We determined whether the use of statins is associated with a reduction in cardiovascular-specific death and total mortality in ESRD patients . METHODS Data were analyzed from the U.S. Renal Data System Dialysis Morbidity and Mortality Wave-2 study , a cohort of r and omly selected patients who were initiating dialysis in 1996 . Information about the use of statins as well as other baseline characteristics was abstract ed from the patients ' dialysis records by dialysis personnel . Cox proportional hazards models were developed to determine the association between use of statins at baseline and subsequent risk of mortality , with adjustment for known mortality risk factors . RESULTS Follow-up data were available for 3716 patients through July 1998 . At baseline , 362 ( 9.7 % ) of patients were using statins . These patients had a mortality rate of 143/1000 person-years , compared with a rate of 202/1000 person-years for patients not using statins . Statin use was independently associated with a reduced risk of total mortality [ relative risk (RR)=0.68 , 95 % confidence interval (CI)=0.54 , 0.87 ] as well as cardiovascular-specific mortality ( RR=0.64 , 95 % CI=0.45 , 0.91 ) . In contrast , the use of fibrates was not associated with reduced mortality ( RR=1.29 ) . CONCLUSIONS Statin use was associated with a reduction in cardiovascular-specific death and total mortality in patients on dialysis Objective . Increased serum pro-inflammatory cytokine levels are associated with an increased mortality rate in end-stage renal disease ( ESRD ) patients . Statins decrease cardiovascular mortality and serum C-reactive protein ( CRP ) levels in hemodialysis patients . As the anti-inflammatory effect of statins has not previously been studied in peritoneal dialysis ( PD ) patients with a non-inflammatory status , we wanted to investigate the anti-inflammatory effect of simvastatin in these patients . Material and methods . Forty-eight PD patients were r and omly allocated to either simvastatin treatment ( n=25 ) or placebo ( n=23 ) . Patients in the active-treatment group received simvastatin 20mg/day for 1 month . At baseline and after 1 month of treatment , blood sample s were drawn and high-sensitivity CRP , interleukin-6 , tumor necrosis factor (TNF)-α and plasma lipid profiles were determined . These parameters were compared between the groups at baseline and at the end of the study period . Results . Twenty-five subjects in the treatment group and 20 in the placebo group completed the study . Three patients in the placebo group were excluded from the study due to the occurrence of bacterial peritonitis during the study period . Clinical characteristics and baseline parameters were similar in both groups . Serum total and low-density lipoprotein cholesterol levels , and triglyceride and serum TNF-α levels decreased significantly compared to baseline in the treatment group ; there were no corresponding differences in the placebo group . Conclusions . Simvastatin decreased the serum TNF-α level in PD patients with a non-inflammatory status . A decrease in the TNF-α level could be one of the possible mechanisms of the anti-atherogeneic effect of simvastatin . We suggest that different treatment strategies aim ed at decreasing serum cytokine levels could be evaluated to decrease cardiovascular morbidity and mortality in the dialysis population A 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor is recommended in hemodialysis ( HD ) patients with hypercholesterolemia to improve their lipid profiles . We evaluated effects of simvastatin on markers for inflammation , oxidative stress , and coagulation in HD patients . Sixty-two maintenance HD patients with serum cholesterol levels of 200 mg/dL or greater were r and omly assigned to the treatment group ( n = 31 ; 8 men , 23 women ; age , 63 + /- 11 years ) and administered simvastatin , 20 mg/d , for 8 weeks or to the control group ( n = 31 ; 10 men , 21 women ; age , 60 + /- 12 years ) . We measured cholesterol , albumin , high-sensitivity C-reactive protein ( hs-CRP ) , malondialdehyde ( MDA ; an index of lipid peroxidation ) , and D-dimer ( a marker of intravascular coagulation ) in blood at baseline and again at 8 weeks . Fifty-eight of 62 patients completed the study . In the control group , total cholesterol , serum albumin , hs-CRP , MDA , and D-dimer levels did not change . In the treatment group , simvastatin administration for 8 weeks significantly reduced total cholesterol levels from 232 + /- 25 to 165 + /- 39 mg/dL ( P < 0.001 ) and hs-CRP levels from a median of 0.23 mg/dL ( range , 0.05 to 1.63 mg/dL ) to 0.12 mg/dL ( range , < 0.006 to 1.45 mg/dL ; P < 0.01 ) , whereas it increased serum albumin levels from 3.4 + /- 0.3 to 3.6 + /- 0.4 g/dL ( P < 0.001 ) . Administration of simvastatin did not affect MDA and D-dimer levels . These results suggest that in addition to the lipid-lowering effect , simvastatin had an antiinflammatory effect in HD patients . Considering that atherosclerosis is inflammation of the vascular wall , simvastatin may have a beneficial effect on cardiovascular disease , in part because it alleviates inflammation Objective : To study the quality of the information provided to and the procedure for obtaining the consent of chronically ill patients participating in a clinical trial . All patients included in a clinical trial concerning a lipid‐lowering treatment over a 1‐year period were asked to participate in the present research ethical study . Material and Methods : Patients ( n=55 ) on hemodialysis or in a prerenal state were selected . About 2 weeks after being recruited , the patients received a question naire concerning different aspects of the information provided . None of those responsible for providing information and obtaining consent were aware of the research ethical study in advance . Results : A total of 44 patients answered the question naire ( response rate 80 % ) . All but one participant perceived the information provided as being very good or fairly good . None felt that they had been forced to participate in the trial . A total of 12 patients stated that they had delegated the decision making to their doctor . Compared to the younger patients , elderly participants more often stated that they had only been informed orally ( p=0.027 ) . Those who stated that they were only informed orally tended to let the doctor decide whether or not they should participate in the trial . Conclusions : The study indicates that , compared to younger patients , elderly patients tended to be informed about the trial only orally and were also inclined to let the doctor decide whether or not they should participate . Providing information both orally and in writing and providing sufficient time for consideration may improve the informed consent process for severely ill patients BACKGROUND Evaluating the effects of decreasing low-density lipoprotein ( LDL ) cholesterol levels requires large r and omized trials . In preparation for such a trial , we assessed the biochemical efficacy , safety , and tolerability of adding ezetimibe , 10 mg/d , to simvastatin , 20 mg/d , as initial therapy for such patients . METHODS Two hundred three patients ( 152 predialysis patients with creatinine levels > or = 1.7 mg/dL [ > or = 150 micromol/L ] , 18 patients on peritoneal dialysis therapy , and 33 patients on hemodialysis therapy ) were r and omly assigned to the administration of simvastatin , 20 mg/d , plus ezetimibe , 10 mg/d ; or simvastatin , 20 mg , plus placebo ezetimibe daily . RESULTS After 6 months , allocation to simvastatin monotherapy was associated with a 31-mg/dL ( 0.8-mmol/L ) decrease in nonfasting LDL cholesterol levels compared with baseline . Allocation to simvastatin plus ezetimibe produced an additional 18-mg/dL ( 0.47-mmol/L ) decrease in LDL cholesterol level , representing an incremental 21 % reduction over that achieved with simvastatin monotherapy ( P < 0.0001 ) . There were no statistically significant effects of the addition of ezetimibe to simvastatin on triglyceride or high-density lipoprotein cholesterol levels . Ezetimibe was not associated with an excess risk of abnormal liver function test results or of elevated creatine kinase levels and did not impair absorption of fat-soluble vitamins . There were no serious adverse events caused by study treatment . CONCLUSION This 6-month study shows that the addition of ezetimibe to simvastatin , 20 mg/d , as initial therapy for patients with chronic kidney disease was well tolerated and produced an additional 21 % decrease in LDL cholesterol levels . The clinical efficacy and safety of combination therapy in this population are now being assessed in a large r and omized trial BACKGROUND In the general population , C-reactive protein ( CRP ) in addition to low-density lipoprotein ( LDL ) cholesterol level is useful in predicting cardiovascular events . In hemodialysis patients , the additive value is unknown . The association between LDL cholesterol level and outcome previously was suggested to be inverse and confounded by inflammation . STUDY DESIGN Prospect i ve cohort study . SETTING & PARTICIPANTS 1,255 hemodialysis patients with type 2 diabetes mellitus r and omly assigned to atorvastatin versus placebo in the German Diabetes Dialysis Study . PREDICTORS Baseline LDL cholesterol level . OUTCOMES & MEASUREMENTS Combined vascular end point ( cardiac death , myocardial infa rct ion , and stroke ) , mortality , myocardial infa rct ion , sudden death , and stroke . RESULTS During 4 years , 465 combined vascular events , 612 deaths , 160 sudden deaths , 200 myocardial infa rct ions , and 99 strokes occurred . Median LDL cholesterol level was 123 mg/dL. LDL cholesterol level ( millimoles per liter and quartiles ) was not predictive of outcome . This was analyzed further in patients with and without inflammation . In patients with inflammation ( CRP level > 5 mg/L ) , the adjusted relative risk of combined vascular events was 29 % greater compared with those without inflammation and a low LDL cholesterol level ( LDL cholesterol < or = 123 mg/dL ) . This was irrespective of whether LDL cholesterol level was low or high ( hazard ratio [ HR ] for LDL < 123 mg/dL [ HR ( for LDL < or = 123 mg/dL ) ] , 1.29 , with 95 % confidence interval [ CI ] , 0.98 to 1.70 ; HR(LDL>123 mg/dL ) , 1.29 , with 95 % CI , 0.99 to 1.69 ) . Similar results were found for all-cause death ( HR(LDL < or = 123 mg/dL ) , 1.47 [ 95 % CI , 1.16 to 1.86 ] ; HR(LDL>123 mg/dL ) , 1.48 [ 95 % CI , 1.16 to 1.88 ] ) , sudden death ( HR(LDL < or = 123 mg/dL ) , 1.98 [ 95 % CI , 1.23 to 3.20 ] ; HR(LDL>123 mg/dL ) , 1.66 [ 95 % CI , 1.01 to 2.75 ] ) , and myocardial infa rct ion ( HR(LDL < or = 123 mg/dL ) , 1.74 [ 95 % CI , 1.14 to 2.66 ] ; HR(LDL>123 mg/dL ) , 1.54 [ 95 % CI , 0.99 to 2.38 ] ) . In patients without inflammation , the respective risks did not differ significantly between patients with varying LDL cholesterol levels . However , there was a trend toward an increased risk of myocardial infa rct ion ( HR(LDL>123 mg/dL ) , 1.45 [ 95 % CI , 0.95 to 2.21 ] ) in patients with high compared with low LDL cholesterol levels . P values for the interaction between CRP and LDL cholesterol levels were 0.9 ( composite vascular end point ) , 0.5 ( mortality ) , 0.9 ( sudden death ) , 0.09 ( stroke ) , and 0.2 ( myocardial infa rct ion ) . LIMITATIONS Selected patient cohort , post hoc analysis . CONCLUSION Because CRP level more than LDL cholesterol level determined outcome , the value of regular LDL cholesterol measurements in long-term hemodialysis patients with type 2 diabetes needs re assessment In chronic renal failure hypertriglyceridemia is a well-known complication that persists during hemodialysis treatment : it may be one of the major risk factor for cardiovascular death in these patients . We studied the effects of two lipid lowering drugs ; simvastatin ( 20 mg/day for six months ) and probucol ( 500 mg/day for six months ) , on lipid profile in 12 hemodialysis patients . Simvastatin therapy reduced plasma total cholesterol by 26 % ( p > 0.002 ) , LDL-cholesterol by 36 % ( p > 0.002 ) and triglycerides by 28 % ( p > 0.05 ) : plasma HDL-cholesterol and apo-A were raised , but not significantly . Probucol therapy decreased plasma triglycerides by 38 % ( p > 0.05 ) , total cholesterol by 15 % and LDL-cholesterol by 19 % : plasma HDL-cholesterol and apo-A were decreased but not significantly . No side effects occurred with either drug . These data suggest that in hemodialysis patients both simvastatin and probucol profoundly affect the lipid profile , as well as the triglyceride levels BACKGROUND We prospect ively tested the prediction power of homocysteinemia for all-cause and cardiovascular outcomes in a cohort of 175 hemodialysis patients followed for 29 + /- 12 months . METHODS Survival analysis was performed by the Cox 's proportional hazard model and data were expressed as hazard ratio and 95 % confidence interval ( CI ) . RESULTS During the follow-up period 51 patients died , 31 of them ( 61 % ) of cardiovascular causes and 16 patients developed non-fatal atherothrombotic complications . Plasma total homocysteine was an independent predictor of cardiovascular mortality ( P=0.01 ) . Combined analysis of fatal and non-fatal atherothrombotic events showed that homocysteine was a strong and independent predictor of these outcomes because the risk of these events was 8.2 times higher ( 95 % CI 1.9 to 32.2 ) in patients in the third homocysteine tertile than in those in the first tertile ( P=0.005 ) . CONCLUSIONS There is a clear association between hyperhomocysteinemia and incident cardiovascular mortality and atherothrombotic events in hemodialysis patients . Intervention studies are needed to determine whether the accumulation of this substance has a causal role in the pathogenesis of cardiovascular damage in patients undergoing hemodialysis BACKGROUND Patients on regular hemodialysis present high cardiovascular mortality . Uremic dyslipidemia and inflammation take part in the etiology of atherosclerosis . Rosuvastatin calcium has not been studied in patients on dialysis to date . We sought to evaluate the results of rosuvastatin therapy regarding lipids , lipoproteins and a marker of inflammation in hemodialysis patients . METHODS In a double-blind r and omized placebo-controlled trial , 59 patients on hemodialysis ( 31 in the placebo group , and 28 taking rosuvastatin 10 mg/day ) were followed for 3 months . Lipids , lipoproteins and high-sensitivity C-reactive protein ( hs-CRP ) were measured at baseline , 30 days and 3 months . RESULTS In the rosuvastatin group , there was a significant decrease from baseline to the study end in total cholesterol ( 163+/-53 mg/dL to 142+/-43 mg/dL ; p<0.05 ) , in LDL cholesterol ( 90+/-39 mg/dL to 69+/-32 mg/dL ; p<0.05 ) and in non-HDL cholesterol ( 121+/-46 mg/dL to 99+/-39 mg/dL ; p<0.05 ) . In the placebo group , no significant decrease was observed . High-sensitivity CRP was lower in the rosuvastatin than in the placebo group at 3 months ( p<0.01 ) . CONCLUSIONS Rosuvastatin calcium at 10 mg/day was effective in lowering total cholesterol , LDL cholesterol , non-HDL cholesterol and hs-CRP in hemodialysis patients BACKGROUND Accelerated atherosclerosis result ing in an abnormally high incidence of coronary and cerebrovascular occlusive accidents has been repeatedly reported in dialysis patients , but incidence and risk factors of such complications in chronic renal failure ( CRF ) predialysis patients are debated . METHODS We prospect ively assessed the incidence of first myocardial and cerebral infa rct ion episodes in a cohort of 147 CRF patients ( 99 male ) followed from January 1985 to December 1994 . Relevant clinical and laboratory risk factors for atherogenesis were determined at yearly intervals . They included blood pressure , smoking , blood lipids , fibrinogen , and homocysteine which were compared in patients with ( CVA+ ) or without ( CVA- ) occurrence of cardiovascular ( CV ) atherosclerotic accidents . RESULTS Incidence of CV accidents was nearly three times higher in CRF patients than in the French general population in both genders . In particular , incidence of myocardial infa rct ion in male patients aged 45 - 55 , 55 - 65 and > 65 years was 7.6 , 18.2 , and 27.8/1000 patient-years , respectively , compared to 3.4 , 8.9 , and 10.4/1000 subject-years in the general population . Although age and degree of renal failure at onset of CV events or at end of follow-up did not differ between CVA+ and CVA- groups , cigarette smoking ( 24.5 [ SD 24.3 ] vs 8.2 [ 14.7 ] pack-years , P < 0.0001 ) and systolic blood pressure ( 159 [ 19 ] vs 148 [ 19 ] mmHg , P < 0.001 ) were markedly higher in CVA+ patients . Similarly , mean plasma HDL-cholesterol was lower , whereas LDL-cholesterol , triglycerides , apoB , Lp(a ) , fibrinogen , and homocysteine levels all were significantly higher in CVA+ than in CVA- patients . Multivariate Cox analysis identified cigarette smoking , systolic pressure , HDL cholesterol , and fibrinogen as independent risk factors for developing CV accidents . CONCLUSIONS Incidence of atherosclerotic CV complications is abnormally high in predialysis CRF patients , suggesting that the uraemic state per se is associated with atherogenesis . As several of the identified clinical and metabolic risk factors for such accidents are potentially remediable by specific therapeutic interventions , prophylactic measures should be initiated long before start of renal replacement therapy According to the concept of apolipoprotein (apo)-defined lipoproteins , apoA-I-containing lipoproteins consist of two subclasses referred to as lipoprotein A-I ( LpA-I ) and lipoprotein A-I : A-II ( LpA-I : A-II ) , and apoB-containing lipoproteins of five subclasses , namely lipoprotein B ( LpB ) , lipoprotein B : C ( LpB : C ) , lipoprotein B : E ( LpB : E ) , lipoprotein B : C : E ( LpB : C : E ) , and lipoprotein A-II : B : C : D : E ( LpA-II : B : C : D : E ) . The purpose of this study was to determine the levels of apoA-I- and apoB-containing lipoprotein subclasses before and after fluvastatin treatment of patients with chronic renal insufficiency . ApoA-I- and apoB-containing lipoprotein subclasses were measured in 15 patients with chronic renal failure and 15 asymptomatic subjects . The effect of fluvastatin on lipoprotein subclasses was determined in a r and omized , double-blind , placebo-controlled , two-way , treatment period crossover study . Patients were administered fluvastatin 40 mg/day or placebo during 8 weeks in a r and omized order . Patients were characterized by significantly higher levels of LpB ( P < 0.001 ) , LpB : C ( P < 0.001 ) , and LpB : E ( P < 0.05 ) , and slightly higher levels of LpB : C : E and LpA-II : B : C : D : E than controls . The levels of LpA-I : A-II were significantly lower ( P < 0.01 ) in patients than controls . Fluvastatin treatment reduced all apoB-containing subclasses , but only the reduced level of LpB subclass was statistically significant ( P < 0.02 ) . The levels of LpA-I and LpA-I : A-II were not affected . Fluvastatin treatment reduced and normalized LpB and LpB : E subclasses . Although slightly reduced , the levels of markedly atherogenic LpB : C subclass were not normalized . The potential role of LpB : C on the progression of coronary artery disease in chronic renal insufficiency remains to be determined in future studies We conducted a single , blinded cross-over placebo versus lovastatin study on 10 continuous ambulatory peritoneal dialysis ( CAPD ) patients with dyslipoproteinemia who failed to respond to diet control . They were given 8 weeks of lovastatin ( 20–40 mg ) and placebo , respectively . After 8 weeks of lovastatin treatment , total cholesterol was significantly reduced by 28.6 % ( 6.68±0.26 mmol/L , mean±SEM , to 4.77±0.12 , p<0.01 ) ; low-density lipoprotein cholesterol by 40.5 % ( 4.57±0.27 mmol/L to 2.72±0.09 , p<0.01 ) ; apolipoprotein B by 32.4 % ( 115.9±6.99 mg/dL to 78.3±2.9 mg/dL , p<0.01 ) ; and triglyceride by 17.8 % ( 1.92±0.38 mmol/L to 1.58±0.32 , p<0.05 ) . Simultaneously high-density lipoprotein cholesterol increased by 7.6 % from 1.24±0.13 mmol/L to 1.34±0.16 , p<0.05 . There were no significant changes in other lipid profiles between placebo and drug treatment . No significant adverse effects were observed with lovastatin treatment . Lovastatin appears to be effective in treating dyslipoproteinemia in CAPD patients BACKGROUND Individuals with chronic renal disease are at high risk of cardiovascular morbidity and mortality , and therefore the management of dyslipidemia is particularly important in this patient population . This double-blind r and omized study investigated the efficacy and safety of the 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor , atorvastatin , in continuous ambulatory peritoneal dialysis ( CAPD ) patients with dyslipidemia . METHODS Following a two- to four-week baseline period , patients with low-density lipoprotein (LDL)-cholesterol > or = 3.5 mmol/L ( 135 mg/dL ) were r and omized to receive either atorvastatin 10 mg ( N = 82 ) or placebo ( N = 95 ) for 16 weeks . If LDL-cholesterol remained > or = 3.5 mmol/L , the dose of atorvastatin was titrated to 20 mg and 40 mg after four and eight weeks , respectively . RESULTS After four weeks a significantly greater proportion of patients receiving atorvastatin 10 mg had achieved the LDL-cholesterol goal < or = 3.5 mmol/L compared with patients receiving placebo ( 85.4 % vs. 16.0 % ; P < or = 0.001 ) . The statistically significant difference between the two groups was maintained at week 8 and week 16 ( P < or = 0.001 at both time points ) . At week 16 , patients receiving atorvastatin had significantly greater reductions from baseline in LDL-cholesterol , total cholesterol , triglycerides and total cholesterol : HDL-cholesterol ratio ( all P = 0.0001 ) , and a significantly greater increase from baseline in HDL-cholesterol ( P = 0.001 ) than patients receiving placebo . The overall adverse event profile for atorvastatin was similar to that observed with placebo . CONCLUSIONS Atorvastatin was effective in achieving target LDL-cholesterol levels in a high proportion of the dyslipidemic CAPD patients studied at doses that are well tolerated Dyslipidemia is universal but hypercholesterolemia per se is present in around 50 % of dialysis patients . Although dietary therapy is of benefit in some , the majority require drug therapy . We compared the efficacy and safety of simvastatin plus an optimized lipid-lowering dialysis diet with placebo plus diet in a r and omized , double-blind trial stratified for dialysis modality . Patients treated with hemodialysis ( HD ) or continuous ambulatory peritoneal dialysis ( CAPD ) for at least 9 months and with serum non-high-density lipoprotein ( HDL ) cholesterol greater than 135 mg/dL , low-density lipoprotein ( LDL ) greater than 116 mg/dL , and triglyceride less than 600 mg/dL after a 6-week dietary treatment phase and an 8-week diet plus placebo run-in phase , were enrolled in the 24-week double-blind treatment phase . Fifty-seven patients ( 16 men , 41 women , median age 63 years , range 22 - 75 yr ) were r and omized 2:1 to diet plus 5 mg/day simvastatin ( n = 38 : 22 HD , 16 CAPD ) or diet plus placebo ( n = 19 : 12 HD , 7 CAPD ) for 24 weeks . Dose was doubled bimonthly ( maximum 20 mg/day ) if non-HDL cholesterol was greater than 135 mg/dL. Forty-two patients ( 73.7 % ) completed the trial . Comparing baseline and 24 weeks , simvastatin ( median 10 mg/day ) was significantly more effective than placebo in reducing serum non-HDL cholesterol concentrations . For HD , the median percentage changes for total cholesterol ( TC ) ( simvastatin versus placebo ) were -21.4 % and -12.1 % ( P = 0.011 ) , respectively ; for LDL cholesterol , -33.0 % and -8.8 % ( P = 0.023 ) ; for non-HDL cholesterol , -25.2 % and -14.0 % ( P = 0.008 ) ; and for TC : HDL , -17.65 % and -1.67 % ( P = 0.008 ) . For CAPD , changes for TC were -22.1 % and -1.5 % ( P = 0.003 ) , respectively ; for LDL , -36.4 % and 0.0 % ( P = 0.001 ) ; for non-HDL cholesterol , -24.9 % and -3.6 % ( P = 0.002 ) ; and for TC : HDL ratio , -21.49 % and + 9.74 % ( P = 0.045 ) . Changes with CAPD in apolipoprotein ( Apo ) A1 were -4.7 % and + 4.0 % ( P = 0.031 ) ; and for ApoB , -19.9 % and + 2.6 % , respectively ( P = 0.031 ) . There were no significant changes in ApoA1 or ApoB with HD . Compared with placebo , triglyceride levels fell 10.2 % with HD and 6.2 % with CAPD . HDL cholesterol was unchanged with HD but rose 8.5 % with CAPD . These trends , however , did not reach statistical significance ( P > 0.05 ) . There was no effect on Lp ( a ) . The incidence of clinical and laboratory adverse experiences were not increased in the simvastatin-treated patients compared with placebo . Simvastatin appears to be a safe and effective treatment for the reduction of serum non-HDL cholesterol levels in both HD and , particularly , CAPD patients Chronic renal insufficiency is characterized by specific abnormalities in lipoprotein metabolism , affecting both apolipoprotein A ( apo A)- and apo B-containing lipoproteins . To evaluate the effects of fluvastatin , a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor , on renal dyslipoproteinemia , we performed a r and omized , double-blind , placebo-controlled , two-way , period cross-over study . Study patients were administered fluvastatin , 40 mg/d , or placebo during 8 weeks in r and omized order . Forty-five nonnephrotic patients ( 28 men , 17 women ) without diabetes with moderate to advanced chronic renal insufficiency participated in the study . Their mean age was 56.4 + /- 11.0 years . Glomerular filtration rate ranged from 12 to 44 mL/min/1.73 m2 of body surface area ( mean , 27.5 + /- 10.5 mL/min/1.73 m2 ) . Fluvastatin treatment result ed in significant reductions in the primary outcome variables low-density lipoprotein cholesterol ( LDL-C ; -26 % ; P < 0.001 ) , apo B ( -21 % ; P < 0.001 ) , and lipoprotein B complex ( Lp-Bc ) ( -14 % ; P < 0.01 ) . There were statistically significant differences between fluvastatin and placebo treatment for the secondary outcome variables total cholesterol ( -19 % ) , triglycerides ( TGs ; -13 % ) , VLDL-C ( -13 % ) , apo E ( -13 % ) , and Lp-B ( -22 % ) . There was no treatment effect on high-density lipoprotein cholesterol or lipoprotein(a ) . Fluvastatin treatment was well tolerated , with no serious adverse events during the study . In conclusion , fluvastatin treatment was well tolerated in patients with moderately advanced renal insufficiency and led to a significant reduction in cholesterol-rich , but to a lesser extent in TG-rich , apo B-containing lipoproteins . It remains to be clarified whether these positive changes in lipoprotein profile also will result in attenuation of the atherosclerotic process in these patients , as well as beneficially affect the progression of chronic renal failure |
11,929 | 25,699,212 | The general positive effect trend suggests individuals taking mineral derivatives during cancer therapies are less likely to experience peak OM than those without . | Objectives .
Oral mucositis ( mouth ulcers ) is a cancer therapy side effect .
Costly treatment interventions are often neglected in favor of cost-effective agents .
This review assessed the general efficacy of mineral derivatives ( a cost-effective agent ) in alleviating oral mucositis ( OM ) during cancer therapy compared to the st and ard care , or placebo-including a decision tree to aide healthcare workers . | Background and the Purpose of the Study Patients undergoing high-dose chemotherapy for hematological malignancies are susceptible to development of oral mucositis , and no effective modality has been reported for its prophylaxis and treatment . The aim of this study was to evaluate the effectiveness of zinc mouthwash on chemotherapy-induced oral mucositis lesions . Methods In this double-blind r and omized trial , patients under chemotherapy for acute leukemia were divided into two test and control groups of 15 patients each . The groups were homogeneous with respect to medical history , tumor characteristics , and therapeutic details . The test group received 10ml 0.2 % zinc sulfate mouthwash , and the control group received 10ml 0.2 % chlorhexidine gluconate mouthwash , twice a day for a period of two weeks . Spijkervet scale was used to grade the severity of mucositis at every other week during eight weeks . The severity scores were analyzed with repeated measure ANOVA using SPSS 13.0 computer software . Results Mean severity scores were generally lower in the test group compared to the controls at all four time intervals evaluated ; but only , the differences in weeks of 2 and 3 were statistically significant ( P=0.025 ) . Conclusion Zinc mouthwash used in conjunction with chemotherapy may reduce the severity of oral mucositis lesions in patients with leukaemia The purpose of this study was to evaluate the effect of oral zinc sulfate in the prevention of chemotherapy‐induced mucositis in patients undergoing hematopoietic stem‐cell transplantation ( HSCT ) . This study was a double‐blind , r and omized , placebo‐controlled design , with 60 patients undergoing HSCT , divided proportionally in experimental group who received zinc sulfate , and in placebo group . They all had received high‐dose chemotherapy conditioning regimen for allogenic transplantation . Oral mucositis assessed was based on World Health Organization ( WHO ) oral mucositis scale . There were no significant differences in the development of mucositis between the two groups . Severity of mucositis was not significantly different between the two groups either . The same result was obtained regarding the duration of mucositis . Zinc sulfate did not show any significant adverse effects in experimental group . In conclusion , Zinc sulfate did not have any clinical benefits in prevention or reduction of severity , and duration of high‐dose chemotherapy‐induced mucositis in patients undergoing HSCT . Copyright © 2011 John Wiley & Sons , Oral mucositis ( OM ) is a complication of high-dose chemotherapy ( HDC ) followed by hematopoietic SCT ( HSCT ) with few effective treatments . Selenium has a cytoprotective role via the glutathione peroxidase ( Glu . Px ) enzyme and prevents chemotherapy-induced toxicities . We performed a double‐blind , r and omized , placebo-controlled study to evaluate the efficacy of selenium on the prevention of OM in 77 patients with leukemia , undergoing allogeneic HSCT . Thirty-seven patients received oral selenium tablets ( 200 mcg twice daily ) from the starting day of HDC to 14 days after transplantation . OM was evaluated daily for 21 days after transplantation according to World Health Organization oral toxicity scale . The incidence of severe OM ( grade s 3–4 ) was significantly lower in the selenium group ( 10.8 % vs 35.1 % , P<0.05 ) . We noted that the duration of objective OM ( grade s 2–4 ) , excluding patient ’s self-declaration ( grade 1 ) , was significantly shorter in the selenium group ( 3.6±1.84 vs 5.3±2.2 days , P=0.014 ) . Significant elevations in serum selenium level and plasma Glu . Px activity were observed 7 and 14 days after transplantation compared with baseline in the selenium group . We conclude that selenium can reduce the duration and severity of OM after HDC . Clinical trial.org ID : NCT01432873 PURPOSE To determine the effect of oral zinc sulphate supplementation on radiation-induced oropharyngeal mucositis in patients with head- and -neck cancer . MATERIAL S AND METHODS Thirty patients with head- and -neck cancer were r and omly assigned to receive either zinc sulfate or placebo . Primary tumors were localized in the larynx in 14 patients , in the nasopharynx in 4 , in the oral cavity in 4 , in a salivary gl and in 1 , in the maxillary sinus in 1 , in neck nodes ( lymphoma presenting primarily ) in 3 and in neck metastases from an unknown primary in 3 . In the placebo group , 3 patients were excluded ; 1 patient died during treatment , 1 left the study , and 1 did not come to the 6 week control visit . The patients were treated with telecobalt radiotherapy at conventional fractionation ( 2 Gy/fraction , five fractions weekly , for 20 - 35 fractions within 4 - 7 weeks ) . The median radiation dose was 6400 cGy ( 4000 - 7000 cGy ) . Oral mucositis was assessed by two independent physicians , experts in radiation oncology , using the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring criteria . RESULTS In the zinc sulfate group , Grade 3 - 4 mucositis was not detected in any patient ; Grade 0 mucositis was detected in 2 , and Grade 1 in 8 , and Grade 2 in 5 patients . In the placebo group , Grade 2 mucositis was detected in 4 and Grade 3 in 8 patients . We observed that the degree of mucositis in the patients in the zinc sulfate group was significantly lower than that in the placebo group ( p < 0.05 ) . Confluent mucositis developed earlier in the placebo group than in the zinc sulfate group after the onset of treatment ( p < 0.05 ) and started to improve sooner in the zinc sulfate group than in the placebo group ( p < 0.05 ) . CONCLUSIONS Zinc sulfate is beneficial in decreasing the severity of radiation-induced mucositis and oral discomfort . These results should be confirmed by additional evaluation in r and omized studies with a larger number of patients Objectives Mucosal damage is an important and debilitating side effect when treating head and neck cancer patients with (chemo-)radiation . The aim of this r and omized clinical trial was to investigate whether the addition of a neutral , supersaturated , calcium phosphate ( CP ) mouth rinse benefits the severity and duration of acute mucositis in head and neck cancer patients treated with (chemo)radiation . Material s and methods A total of 60 patients with malignant neoplasms of the head and neck receiving (chemo)radiation were included in this study . Fifty-eight patients were r and omized into two treatment arms : a control group receiving st and ard of care ( n = 31 ) and a study group receiving st and ard of care + daily CP mouth rinses ( n = 27 ) starting on the first day of (chemo-)radiation . Oral mucositis and dysphagia were assessed twice a week using the National Cancer Institute common toxicity criteria scale version 3 , oral pain was scored with a visual analogue scale . Results No significant difference in grade III mucositis ( 59 vs. 71 % ; p = 0.25 ) and dysphagia ( 33 vs. 42 % , p = 0.39 ) was observed between the study group compared to the control group . Also no significant difference in time until development of peak mucositis ( 28.6 vs. 28.7 days ; p = 0.48 ) , duration of peak mucositis ( 22.7 vs. 24.6 days ; p = 0.31 ) , recuperation of peak dysphagia ( 20.5 vs 24.2 days ; p = 0.13 ) and occurrence of severe pain ( 56 vs. 52 % , p = 0.5 ) . Conclusion In this r and omized study , the addition of CP mouth rinse to st and ard of care did not improve the frequency , duration or severity of the most common acute toxicities during and early after (chemo)radiation . There is currently no evidence supporting its st and ard use in daily practice Purpose Of patients undergoing allogeneic hematopoietic stem cell transplantation ( HSCT ) , 75 % or more experience oral mucositis , a painful acute complication that can delay discharge , interrupt treatment , and threaten life . To evaluate the efficacy of a supersaturated calcium phosphate rinse ( SCPR ) , we compared it with customary care — topical mouth solutions — on measures of severity and consequent interventions and complications . Methods In this r and omized controlled trial , 40 patients undergoing allogeneic HSCT were r and omized : 20 to SCPR four times daily and 20 to solutions made with salvia leaf extract , iodine-povidine , and fluconazole . Treatment extended from initiation of conditioning treatment until the granulocyte count was ≥0.2 g/L. Mucositis severity was measured daily by a hematologist according to a World Health Organization ( WHO ) scale and self-assessed by patients . Need for interventions [ analgesics , total parenteral nutrition ( TPN ) , and granulocyte colony-stimulating factor ] and complications ( acute graft-versus-host disease and infections ) were also assessed . Results In comparison with the control group , the SCPR group had significantly lower mean measures of WHO oral toxicity ( 0.9 vs. 1.8 ; P = 0.02 ) , disease course ( 3.2 vs. 7.1 days ; P = 0.02 ) , and peak mouth pain ( 0.85 vs. 1.75 ; P = 0.005 ) . Analgesic need was significantly shorter ( 1.1 vs. 3.4 days ; P = 0.047 ) and the need for TPN significantly lower ( 0 vs. 6 patients ; P = 0.02 ; 0 vs. 1.9 mean days ; P = 0.009 ) . Measures of complications were lower in the SCPR group , but not significantly so . Trial limitations include the impracticality of achieving double blinding with agents so different in appearance and in preadministration preparation . Conclusions Compared with the control group , the SCPR group had significantly lower mean measures of oral toxicity , peak mouth pain , and disease course duration . These results warrant confirmation in controlled , multicenter , r and omized trials The purpose of this study was to determine the effect of zinc supplementation on radiation-induced mucositis in patients with nasopharyngeal carcinoma ( NPC ) and those with oral cancers ( OC ) . A total of 100 patients with head and neck cancers engaged in a r and omized double blind study . All participants were placed into two r and omized groups ( experimental and control ) . The experimental group received a st and ard dose of zinc supplements , and the control group was given a placebo . Subgroup analyses were performed between 40 NPC and 43 OC patients . It was found that patients with OC in the control group developed Grade 2 and Grade 3 mucositis sooner than those in the experimental group . However , the benefits were not found to extend to patients with NPC . The results indicated that zinc supplementation prescribed in conjunction with radiotherapy postponed the development of severe mucositis solely for patients with OC . The pretreatment oral mucosa condition and areca chewing habit might account for such discrepancy Changes in the microflora on oral carcinoma surfaces may lead to both local and systemic infections , which may complicate the morbidity of the patient suffering from oral malignant neoplasms . Thus , anticancer therapy , irradiation , chemotherapy or surgery impairs the defence mechanism of the oral mucosa and is accompanied by proliferation of the mucosal biofilm with overgrowth of yeast and bacteria . This study investigates the inhibition of the biofilm present on the surface of oral squamous cell carcinomas . Biofilm sample s were obtained from the central surface ( 1 cm2 ) of each lesion in 10 patients ( eight male , two female ; mean age : 47.6 years ; SD + /- 7.6 ) before any antibiotherapy or tumour treatment . Patients were r and omly divided into two groups and were rinsed with Meridol mouthrinse ( amine fluoride ) or placebo ( saline solution ) for 7 days . Sample s were repeatedly taken from the same site after rinsing . Sample s were transported in pre-reduced brain heart infusion broth and cultured within 1 h of removal , using aerobic and anaerobic complete and selective media . Total aerobic and anaerobic counts were determined and isolated bacteria were identified . The median counts of colony forming units ( CFU/ml ) after rinsing with Meridol were significantly lower for both aerobes and anaerobes than before rinsing with Meridol . ( For aerobes before rinsing : 1.35 x 10(6 ) , after rinsing : 7.55 x 10(5 ) ; p = 0.025 ; for anaerobes before rinsing : 1.39 x 10(6 ) , after rinsing : 7.15 x 10(5 ) ; p = 0.011 . Rinsing with placebo : no significant difference was found . Aerobe median counts before rinsing : 1.17 x 10(6 ) , after rinsing : 1.03 x 10(5 ) , and for anaerobes : before rinsing 1.75 x 10(6 ) , after rinsing : 1.51 x 10(6 ) ; p > 0.05 [ Wilcoxon test ] . ) It was concluded that 7-days ( three times a day ) Meridol rinsing significantly reduced the surface biofilm of oral carcinoma compared to rinsing with placebo . Clinical examination indicated no irritation of the mucosa . The mouthrinse was well tolerated by the patients , who commented on a reduction in burning sensation and bad breath . Besides routine oral hygiene , rinsing itself could reduce patient morbidity . The findings of the present study indicate that in addition to any other oral focus , the lesion itself , when ulcerated , should receive direct antimicrobial treatment so as to reduce patient morbidity and enhance quality of life Oral mucositis is frequent but serious adverse event associated with radiotherapy or radiochemotherapy in head and neck cancer severely impairs health‐related quality of life , leading to poor prognosis due to discontinuation of the therapy . Although a number of compounds have been tested for prophylaxis of oral mucositis , few of them are satisfactory . We investigated the effect of polaprezinc ( zinc L‐carnosine ) , a gastric mucosal protective drug , on radiochemotherapy‐induced oral mucositis , pain , xerostomia and taste disturbance in patients with head and neck cancer . Patients were r and omly assigned to receive polaprezinc ( n = 16 ) or azulene oral rinse as the control ( n = 15 ) . The incidence rates of mucositis , pain , xerostomia and taste disturbance were all markedly lower in polaprezinc group than in control . Moreover , the use of analgesics was significantly ( p = 0.003 ) less frequent and the amount of food intake was significantly ( p = 0.002 ) higher in polaprezinc group than in control . On the other h and , tumor response rate in patients with neoadjuvant radiochemotherapy was not significantly affected by polaprezinc , in which the response rate ( complete plus partial response ) was 88 % for polaprezinc and 92 % for control ( p = 1.000 ) . Therefore , it is highly assumable that polaprezinc is potentially useful for prevention of oral mucositis and improvement of quality of life without reducing the tumor response OBJECTIVE To determine the efficacy of zinc sulfate supplementation in reducing ofradiation-induced oral mucositis and pharyngitis in head and neck cancer patients . MATERIAL AND METHOD One hundred forty four head and neck patients were enrolled in a r and omized , double-blind , placebo-controlled trial . Patients who received radiation therapy alone or postoperative radiation therapy were eligible . Radiation therapy used conventional fractionation with 1.8 to 2.0 Gy perfraction , to total doses of 50 to 70 Gy over five to seven weeks . Drug and identically appearing placebo were self-administered 50 mg ( 10 cc ) per meal , three times a day at mealtime . The zinc sulfate and placebo were administered beginning on the first day of radiation , and continued daily including weekends until radiation was completed Patients were evaluated before radiation , weekly during radiation and at the first month after completion of radiation . RESULTS The baseline characteristics of patients , tumor , and treatment were not significantly different between the two groups . There were no statistically significant differences between the two treatment groups in frequency of patients experiencing greater than or equal to grade 2 oral mucositis and pharyngitis at each week during radiation and at the first month after completion of radiation . Six patients ( 17 % ) in the zinc sulfate and ten patients ( 23 % ) in placebo group developed grade 3 oral mucositis , which was not significantly different . Twenty-two patients ( 32 % ) in the zinc sulfate and nineteen patients ( 27 % ) in the placebo group developed grade 3 pharyngitis , which was not signifiibantly different . However there was no observation of grade 4 oral mucositis and pharyngitis in either group . Nausea and vomiting were mostly of mild degree . Adverse events were not statistically significant different between the two groups . CONCLUSION It was concluded that zinc sulfate administered during head and neck radiation therapy produced no significant benefit in relieving radiation-induced oral mucositis and pharyngitis with acceptable side effects OBJECTIVE Oral mucositis ( OM ) is an unresolved problem among patients treated with a high-dose therapy supported by hematopoietic stem cell transplantation ( HSCT ) . We tested the ability of supersaturated calcium phosphate mouth rinse ( Caphosol ) to ameliorate oral mucosal injury induced by a conditioning regimen . PATIENTS AND METHODS Thirty-two patients with hematologic malignancies were treated with Caphosol to prevent OM during HSCT procedures . The conditioning regimens for 16 patients were BGNU 300 mg/m2 , day 6 ; ARA-C 200 mg/m2 daily , days 5 , 4 , 3 , 2 ; VP-16 200 mg/m2 daily , days 5 , 4 , 3 , 2 ; L-PAM 140 mg/m2 , day 1 ( BEAM ) and for 16 patients , MEL 200 ( non-Hodgkin 's lymphoma ) . A control group was composed of 24 consecutive patients , who had been treated with HSCT before Caphosol was available . The source of the graft was autologous peripheral blood . RESULTS Among patients treated with Caphosol no one had to receive total parenteral nutrition . Among the BEAM group no one experienced III to IV degree OM compared with 40 % of the control group . The median OM duration was 2.25 days versus controls of 8.6 , ( P<.001 ) ; only one patient received opioids versus 100 % of controls . In the MEL 200 group , 93.7 % of patients developed 0 to II degree OM vs 94 % of the control group ( P=.74 ) with median duration of 1 , 73 days versus 2.42 for the controls ( P=.73 ) . In both control and Caphosol cohorts one patient received opioids . CONCLUSION Caphosol may reduce the incidence , severity , and duration of oral mucositis and decrease the number of days with painkillers among patients treated with a BEAM but not a Mel 200 regimen AIMS The present study was done to assess the effect of three alcohol-free mouthwashes on radiation-induced oral mucositis in patients with head and neck malignancies . MATERIAL S AND METHODS Eighty patients with head and neck malignancies , scheduled to undergo curative radiotherapy , were r and omly assigned to receive one of the three alcohol-free test mouthwashes ( 0.12 % chlorhexidine , 1 % povidone-iodine , or salt/soda ) or a control . The patients were instructed to rinse with 10 ml of the mouthwash , twice a day , for a period of 6 weeks . Mucositis was assessed at baseline and at weekly intervals during radiation therapy , using the World Health Organization criteria for grading of mucositis . The baseline demography of the four groups was matched for age , sex , stage of cancer , and whether the patient had cancer of oral or extraoral regions . A post hoc test for repeated measures was used to find the difference of mean mucositis scores between the groups at various week intervals . RESULTS Among the 76 patients who completed the study , patients in the povidone-iodine group had significantly lower mucositis scores when compared to the control group from the first week of radiotherapy . Their scores were also significantly lower when compared to the salt/soda and chlorhexidine groups from the fourth and fifth week , respectively , after radiotherapy . CONCLUSIONS This study demonstrates that use of alcohol-free povidone-iodine mouthwash can reduce the severity and delay the onset of oral mucositis due to antineoplastic radiotherapy Summary : Oral mucositis is a complication common to many cancer therapies and produces considerable pain and morbidity . The present study reports a double-blind , prospect i ve , r and omized clinical trial testing the efficacy of a calcium phosphate mouth rinse ( Caphosol ® ) with fluoride treatments vs a st and ard regimen of fluoride rinsing and placebo tray treatments in 95 patients undergoing hematopoietic stem cell transplantation ( HSCT ) . The days and severity of mucositis were prospect ively evaluated . There were statistically significant decreases in days of mucositis ( 3.72 vs 7.22 P=0.001 ) , duration of pain ( 2.86 vs 7.67 , P=0.0001 ) , dose of morphine ( 34.54 mg vs 122.78 mg ) , days of morphine ( 1.26 vs 4.02 , P=0.0001 ) and days to the onset of engraftment ANC ( absolute neurotrophil count)>200 mm3 ( 11.12 vs 12.56 ) in the Caphosol ® and fluoride treatment group vs fluoride-rinse group , respectively . Caphosol ® , a neutral , supersaturated , Ca2+/PO43− mouth rinse , used in combination with topical fluoride treatments , is superior to fluoride rinse alone in reducing the frequency , intensity and duration of oral mucositis in patients undergoing HSCT Antimicrobial solutions are widely used in the nursing care of chemotherapy induced oral mucositis ( OM ) . There is little evidence , however , supporting their use for reducing mucosal damage . In our study , 132 patients were r and omized to use normal saline ( n=65 ) or povidone-iodine diluted 1:100 ( n=67 ) mouthwashes for OM prophylaxis and treatment after high-dose chemotherapy comprising BEAM or HD-L-PAM followed by autologous peripheral stem cell transplantation . The study groups were well balanced in respect of age , sex , chemotherapy and the number of CD34 + cells in the graft . No significant difference was found between the groups in respect of OM characteristics , fever of unknown origin ( FUO ) and other infections . The antimicrobial solution was less tolerable for patients . OM occurred significantly more often in females than in males ( 86 % vs 60 % , P=0.0016 ) and was worse and of longer duration . The mechanical effect of mouthwashes might have a certain importance in FUO prevention . When indicating oral rinses , the patient ’s individual preference and tolerance of solutions offered should be considered In pediatric oncology , chemotherapyor radiotherapy-induced oral mucositis ( OM ) is accompanied by decreased oral intake , pain , analgesics use , and hospital admission [ 1 , 2 ] . Moreover , OM is correlated with an increased risk of sepsis [ 3 , 4 ] . Recently , Caphosol , a supersaturated CaPO4 mouth rinse , became available to prevent or treat mucositis [ 5 ] . Papas et al. demonstrated Caphosol to have a beneficial prophylactic effect in adult hematopoietic stem cell transplantation ( HSCT ) patients , but evidence in pediatric patients is lacking [ 6 ] . We studied whether Caphosol can be used to treat OM in a prospect i ve r and omized study BACKGROUND Oral mucositis is a serious complication of chemotherapy that results in painful debilitating inflammation , necessitating the administration of analgesics . There is no cure for mucositis . Some studies have evaluated the effect of zinc sulfate on mucositis . The present study aims to evaluate the effect of oral zinc sulfate on prevention of mucositis , xerostomia , and pain induced by chemotherapy . METHODS This double-blind , r and omized controlled trial was carried out on 50 adult patients who underwent chemotherapy during 2008 - 2009 . Patients were divided in two groups . Patients in the intervention group were administered three , 220 mg zinc sulfate capsules daily until the end of their chemotherapy treatment . Patients in the placebo group received three placebo capsules daily , which were similar in shape , taste , and color to the zinc sulfate capsules . Data were analyzed by SPSS version 17 software , using the independent sample s t-test , Mann-Whitney U and Friedman tests . RESULTS The incidence of grade 3 mucositis was lower in the zinc sulfate group . In the first follow up , grade 3 mucositis was detected in 10 % of patients . In the placebo group , grade 3 mucositis was seen in 46.6 % of patients . By the fourth follow up , grade 3 mucositis was detected in 3.33 % of patients in the intervention group and in 20 % of patient in the placebo group . At the end of the study there was no grade 3 mucositis detected in the zinc sulfate group , whereas there were 3.57 % of patients in the placebo group with grade 3 mucositis . The results also showed that zinc sulfate decreased the effects of xerostomia and pain in patients under chemotherapy treatment . CONCLUSION It can be concluded that zinc sulfate might decrease the intensity of mucositis PURPOSE To determine whether zinc supplementation can accelerate the healing of mucositis and dermatitis after radiotherapy . METHODS AND MATERIAL S In this double-blind study , patients were placed into two r and omized groups ( experimental and control ) of 50 patients each . The groups were homogeneous with respect to medical history , tumor characteristics , and therapeutic details . The experimental group received a st and ard dose of a zinc supplement , and the control group was given a placebo . RESULTS Patients in the control group developed Grade 2 mucositis and dermatitis earlier and sooner than patients in the experimental group . There was also a significant difference in the development of Grade 3 mucositis and dermatitis between the two groups . Patients in the experimental group were found to have milder mucositis and dermatitis . Zinc supplementation did not show much benefit in those patients receiving concurrent chemotherapy or make a substantial impact on weight changes . CONCLUSIONS Zinc supplementation used in conjunction with radiotherapy could postpone the development of severe mucositis and dermatitis for patients with cancers of the head and neck . Zinc supplementation can also alleviate the degree of mucositis and dermatitis . The impact of zinc on tumor growth and patient survival is under further investigation BACKGROUND The aim of this study was to examine the effect of magnesium supplementation on nephrotoxicity accompanying st and ard cisplatin-based chemotherapy in patients with epithelial ovarian cancer ( EOC ) . PATIENTS AND METHODS A double-blind , placebo-controlled , r and omised study was conducted in which study arm magnesium sulphate ( 5 g ) was administered before each course of st and ard chemotherapy with paclitaxel ( 135 mg/m(2)/24 h ) plus cisplatin ( 75 mg/m(2 ) ) every 3 weeks in patients with EOC . Magnesium subcarbonate ( 500 mg ) , three times per day orally , was administered during the treatment intervals . The control arm was administered a placebo instead of both magnesium salts . Magnesium serum levels ( sMg ) and GFR markers : serum levels of creatinine ( sCr ) , Cockroft-Gault ( ClCG ) and Modification Diet of Renal Disease ( MDRD ) formulae were recorded before each cycle , and 3 weeks after the sixth course . RESULTS 41 EOC patients were r and omised and 40 were eligible . sMg varied significantly between the supplemented and placebo groups ( p<0.0001 ) . The control group showed a significantly greater decrease of GFR assessed by : sCr ( p=0.0069 ) , ClCG ( p=0.0077 ) and MDRD ( p=0.032 ) formulae compared with the magnesium supplemented group . CONCLUSIONS These results demonstrate the nephroprotective effect of magnesium supplementation during chemotherapy with cisplatin OBJECTIVE The substitution of selenium activates the selenium-dependent enzyme glutathione peroxidase , which is important for scavenging free radicals . To date , only limited data are available about the clinical impact of selenium regarding the toxicities due to free radical producing therapies , e.g. irradiation or chemotherapy , and therefore the objective of this study was to investigate the clinical impact of selenium in such therapies . PATIENTS AND METHODS 39 patients ( 8 female , 31 male ) with advanced head and neck cancer were included in a r and omised phase II study . The mean age was 63.52+/-9.31 years . Tumour localizations : oral cavity 15 patients , oropharynx 19 patients , hypopharynx 5 patients , carcinoma of unknown primary 1 patient . Group A ( n=22 ) received 500 microg sodium selenite on the days of radiotherapy and 300 microg sodium selenite on days without radiotherapy . Group B ( 17 ) was irradiated without any selenium substitution . Both groups were well balanced according to age , gender , localization and stage of the tumour . The RTOG grade of radiation-associated toxicities was evaluated once per week . RESULTS The following serious toxicities were observed ( group A vs. group B ) : dysphagia 22.7 % vs. 35.3 % , loss of taste 22.7 % vs. 47.1 % , dry mouth 22.7 % vs. 23.5 % , and stomatitis 36.4 % vs. 23.5 % . A statistical trend ( Fisher 's exact test ) was only seen for the loss of taste ( p=0.172 ) . The weekly patient analysis ( Student 's t-test ) showed a significant reduction of dysphagia in the selenium group ( Group 1 ) at the last week of irradiation . CONCLUSION This small r and omised trial showed limited effects of selenium in the prevention of ageusia ( loss of taste ) and dysphagia due to radiotherapy of head and neck cancer We aim ed to investigate the effect of zinc supplementation on oropharyngeal infections in immunocompromised patients . Thirty patients receiving radiotherapy for head and neck cancer received 150 mg/day zinc or placebo , orally , during radiotherapy and for a further 6 weeks . None received antibiotics during this period . Oropharyngeal sample s were collected 1 day before the first course and 1 day after the last course of radiotherapy , and 1 week and 6 weeks after radiotherapy . Sample s were cultured and pathogens identified using microbial diagnostic and gas chromatography methods . Coagulase-positive and -negative staphylococci , group A β-haemolytic streptococci , Streptococcus pneumoniae , and C and ida species were detected in both groups , but some infections , especially with C and ida species and staphylococci , were prevented by zinc supplementation . We therefore suggest use of low-dose antibiotics and oral zinc supplementation in patients with these infections . No effects of zinc supplementation were observed on group A β-haemolytic streptococci and Streptococcus pneumoniae , making it essential to start antimicrobial chemotherapy before radiotherapy |
11,930 | 21,964,941 | SARA and ICARS were the best studied and vali date d so far , and their reliability sustain their use .
Ataxia and non-ataxia scores will probably provide a better view of the overall disability in long-term trials and studies of natural history . | We aim ed to perform a comprehensive systematic review of the existing ataxia scales . | BACKGROUND AND PURPOSE A pilot study of high dose coenzyme Q(10 ) ( CoQ(10))/vitamin E therapy in Friedreich 's ataxia ( FRDA ) patients result ed in significant clinical improvements in most patients . This study investigated the potential for this treatment to modify clinical progression in FRDA in a r and omized double blind trial . METHODS Fifty FRDA patients were r and omly divided into high or low dose CoQ(10)/ vitamin E groups . The change in International Co-operative Ataxia Ratings Scale ( ICARS ) was assessed over 2 years as the primary end-point . A post hoc analysis was made using cross-sectional data . RESULTS At baseline serum CoQ(10 ) and vitamin E levels were significantly decreased in the FRDA patients ( P < 0.001 ) . During the trial CoQ(10 ) and vitamin E levels significantly increased in both groups ( P < 0.01 ) . The primary and secondary end-points were not significantly different between the therapy groups . When compared to cross-sectional data 49 % of all patients demonstrated improved ICARS scores . This responder group had significantly lower baseline serum CoQ(10 ) levels . CONCLUSIONS A high proportion of FRDA patients have a decreased serum CoQ(10 ) level which was the best predictor of a positive clinical response to CoQ(10)/vitamin E therapy . Low and high dose CoQ(10)/vitamin E therapies were equally effective in improving ICARS scores Background : Friedreich ’s ataxia ( FRDA ) , the most common genetic cause of ataxia , is characterised by progressive neurodegeneration and cardiomyopathy . Initial treatments are likely to slow progression rather than reverse morbidity . An appropriate and sensitive scale to measure disease progress is critical to detect the benefit of treatments . Objective : To compare the Friedreich Ataxia Rating Scale ( FARS ) with other scales proposed as outcome measures for FRDA . Methods : 76 participants were assessed with the FARS and the International Cooperative Ataxia Rating Scale ( ICARS ) and 72 of these participants were also assessed with the Functional Independence Measure and the Modified Barthel Index . 43 participants had repeat measures at an interval of 12 months . Sensitivity and responsiveness were assessed using the effect size for each measure and the sample size required for a placebo-controlled clinical trial . Results : The FARS showed a high correlation with the other three measures . A significant change in the score over 12 months was detected by the FARS , the International Cooperative Ataxia Rating Scale and the Functional Independence Measure . The FARS had the greatest effect size and requires fewer patients for an equivalently powered study . Conclusions : Of the scales assessed , the FARS is the best to use in clinical trials of FRDA . This is based on effect size , and power calculations that show that fewer participants are required to demonstrate the same effect of an intervention . Further work is required to develop more sensitive and responsive instruments Objective : To examine the potential validity of performance measures and examination-based scales in Friedreich ataxia ( FA ) by examining their correlation with disease characteristics . Methods : The authors assessed the properties of a c and i date clinical outcome measure , the Friedreich Ataxia Rating Scale ( FARS ) , and simple performance measures ( 9-hole peg test , the timed 25-foot walk , PATA test , and low-contrast letter acuity ) in 155 patients with FA from six institutions , and correlated the scores with disease duration , functional disability , activity of daily living scores , age , and shorter GAA repeat length to assess whether these measures capture the severity of neurologic dysfunction in FA . Results : Scores for the FARS and performance measures correlated significantly with functional disability , activities of daily living scores , and disease duration , showing that these measures meet essential criteria for construct validity for measuring the progressive nature of FA . In addition , the FARS and transformed performance measures scores were predicted by age and shorter GAA repeat length in linear regression models accounting for sex and testing site . Correlations between performance measures were moderate in magnitude , suggesting that each test captures separate yet related dimensions of neurologic function in FA and that a composite measure might better predict disease status . Composite measures created using cohort means and st and ard deviations predicted disease status better than or equal to single performance measures or examination-based measures . Conclusions : The Friedreich Ataxia Rating Scale , performance measures , and performance measure composites provide valid assessment s of disease progression in Friedreich ataxia Background : The pleiotropic effects of riluzole may antagonize common mechanisms underlying chronic cerebellar ataxia , a debilitating and untreatable consequence of various diseases . Methods : In a r and omized , double-blind , placebo-controlled pilot trial , 40 patients presenting with cerebellar ataxias of different etiologies were r and omly assigned to riluzole ( 100 mg/day ) or placebo for 8 weeks . The following outcome measures were compared : proportion of patients with a decrease of at least 5 points in the International Cooperative Ataxia Rating Scale ( ICARS ) total score after 4 and 8 weeks compared with the baseline score ; mean changes from the baseline to posttreatment ICARS ( total score and subscores at 8 weeks ) ; and occurrence of adverse events . Results : Riluzole and placebo groups did not differ in baseline characteristics . The number of patients with a 5-point ICARS drop was significantly higher in the riluzole group than in the placebo group after 4 weeks ( 9/19 vs 1/19 ; odds ratio [ OR ] = 16.2 ; 95 % confidence interval [ CI ] 1.8–147.1 ) and 8 weeks ( 13/19 vs 1/19 ; OR = 39.0 ; 95 % CI 4.2–364.2 ) . The mean change in the riluzole group ICARS after treatment revealed a decrease ( p < 0.001 ) in the total score ( −7.05 [ 4.96 ] vs 0.16 [ 2.65 ] ) and major subscores ( −2.11 [ 2.75 ] vs 0.68 [ 1.94 ] for static function , −4.11 [ 2.96 ] vs 0.37 [ 2.0 ] for kinetic function , and −0.74 [ 0.81 ] vs 0.05 [ 0.40 ] for dysarthria ) . Sporadic , mild adverse events occurred . Conclusions : These findings indicate the potential effectiveness of riluzole as symptomatic therapy in diverse forms of cerebellar ataxia . Classification of evidence : This study provides Class I evidence that riluzole reduces , by at least 5 points , the ICARS score in patients with a wide range of disorders that cause cerebellar ataxia ( risk difference 63.2 % , 95 % CI 33.5%–79.9 % ) OBJECTIVE To assess the efficacy of idebenone on neurological function in patients with Friedreich ataxia . DESIGN R and omized , double-blind , placebo-controlled intervention trial . SETTING Children 's Hospital of Philadelphia and the University of California at Los Angeles . PARTICIPANTS Seventy ambulatory pediatric patients ( age , 8 - 18 years ) with a baseline International Cooperative Ataxia Rating Scale ( ICARS ) score of 10 to 54 . INTERVENTIONS Participants were r and omized into 1 of 3 treatment arms : 450 or 900 mg of idebenone per day ( in those with a body weight < or = or > 45 kg , respectively ; n = 22 ) ; 1350 or 2250 mg of idebenone per day ( n = 24 ) ; or placebo ( n = 24 ) . MAIN OUTCOME MEASURES Mean change from baseline to week 24 in ICARS score was the primary efficacy variable . Mean change in Friedreich Ataxia Rating Scale ( FARS ) score , performance measures , and activities of daily living were the secondary efficacy variables . RESULTS Patients who received idebenone improved by 2.5 points on mean ICARS score compared with baseline , while patients in the placebo group improved by 1.3 points . Patients who took idebenone also improved by 1.6 points on the FARS , while patients taking placebo declined by 0.6 points . For both end points , the difference between the idebenone and placebo groups was not statistically different . CONCLUSIONS Idebenone did not significantly alter neurological function in Friedreich ataxia during the 6-month study . Larger studies of longer duration may be needed to assess the therapeutic potential of drug c and i date s on neurological function in Friedreich ataxia . Trial Registration clinical trials.gov Identifier : NCT00537680 Objective – To preliminarily compare the efficacy of pregabalin with that of placebo on the cerebellar signs caused by cortical cerebellar atrophy ( CCA ) . A deficiency of gamma‐aminobutyric acid ( GABA ) has been described in the cerebellum in CCA , and pregabalin has been shown to enhance GABA release in rat hippocampus BACKGROUND Olivopontocerebellar atrophy ( OPCA ) is a chronic neurodegenerative disease with symptoms of cerebellar ataxia , parkinsonism , autonomic disturbances and ophthalmoplegia . Buspirone , a 5-HT1(A ) agonist could constitute a symptomatic improvement in cerebellar dysfunction whereas estrogen has been investigated for neuroprotection . We conducted an open-labeled pilot trial to assess the efficacy of estrogen with buspirone treatment . PATIENTS AND METHODS Eighteen patients ( 7 male and 11 female ) with OPCA were r and omized into the buspirone ( 15 mg/day , n=9 ) , or the combined treatment group ( estrogen , 0.625 mg/d plus buspirone , n=9 ) . For the clinical rating , International Cooperative Ataxia Rating Scale ( ICARS ) was used and dysarthria , gaze evoked nystagmus , finger to nose , pronation-supination alternating movement , knee-tibia test , and gait speed were evaluated for 12 months . RESULTS Buspirone-treated group showed improvements in finger to nose and pronation-supination alternating movement test ( p=0.046 and p=0.025 , respectively ) . The combination group ( Estrogen+buspirone ) , however , showed no improvement in cerebellar sub-scales compared to the baseline . CONCLUSIONS Buspirone treatment showed feasible efficacies for OPCA , while the combined treatment of estrogen and buspirone failed to improve , suggesting estrogen may not have further benefit in cerebellar dysfunction Abstract . The aim of this study was to assess the efficacy and the safety of ondansetron administered orally in patients with a cerebellar disorder . The study was a r and omised , multi-center , double-blind trial . The patients were r and omised either to oral ondansetron 8 mg or to placebo twice daily for seven days . Cerebellar dysfunction was quantified before and after treatment using the International Cooperative Ataxia Rating Scale ( ICARS ) . We performed a global analysis ( total scores ) , we analysed by subscores ( 4 subscores : oculomotor , speech , kinetic , postural ) and subgroups ( 4 subgroups : Cerebellar Cortical Atrophy ( CCA ) , Multiple Systemic Atrophy ( MSA ) , Familial Cerebellar Degeneration ( FCD ) and miscellaneous cerebellar disorders ) , and we also performed an analysis by individual test items . We investigated whether ondansetron and placebo had different effects upon ICARS total scores and subscores in the 4 subgroups considered together or separately . For p values < 0.05 , we subsequently applied the Mann-Whitney test to compare ondansetron and placebo effect for each individual item . We evaluated 45 of the 46 patients included . No effect was found in global analysis . We found no difference in the analysis of the ICARS subscores . Concerning the individual test items , there was a significant difference between the placebo and ondansetron for the finger-to-nose test ( p = 0.049 ) , the Heel-to-Knee test ( HK ) ; ( p = 0.03 ) , the Body Sway Eyes Closed ( p = 0.017 ) and the Body Sway Eyes Open ( BSEO ) ; ( p = 0.014 ) . There was no significant difference for tremor in upper limbs ( p = 0.32 ) or for gait ( p = 0.49 ) . The Mann-Whitney test showed a greater effect of ondansetron than placebo for BSEO in miscellaneous disorders ( p = 0.013 ) and for HK in FCD ( p = 0.036 ) , but ondansetron was deleterious for HK in CCA ( p = 0.019 ) . Our study showed no effect of oral ondansetron on global cerebellar dysfunction . The analysis by subgroups showed that the oral form of ondansetron ( a ) is deleterious for coordination in patients with CCA , ( b ) has no effect upon tremor in upper limbs , and ( c ) has a mild effect upon posture and coordination in lower limbs in some subgroups of ataxic diseases BACKGROUND Friedreich 's ataxia ( FA ) is a progressive , multisystem , degenerative disorder caused by a reduction in frataxin . Loss of frataxin results in mitochondrial dysfunction and oxidative damage in patients and model systems . Previous studies have indicated that the antioxidant idebenone ( 5 mg/kg daily ) reduces cardiac hypertrophy , but definite improvement in neurological function has not been shown . METHODS 48 genetically confirmed FA patients , aged 9 - 17 years , were enrolled in a 6-month , r and omised , double-blind , placebo-controlled study . The patients received placebo or one of three doses of idebenone ( approximately 5 mg/kg , 15 mg/kg , and 45 mg/kg ) , stratified by body weight . The primary endpoint was change from baseline in urinary 8-hydroxy-2'-deoxyguanosine ( 8OH2'dG ) , a marker of oxidative DNA damage . Secondary endpoints included changes in the international cooperative ataxia rating scale ( ICARS ) , the FA rating scale ( FARS ) , and a survey of activities of daily living ( ADL ) . This study is registered with Clinical Trials.gov , number NCT00229632 . FINDINGS Idebenone was generally well tolerated with similar numbers of adverse events in each group . One child receiving high-dose idebenone developed neutropenia after 6 months , which resolved after discontinuation of treatment . 8OH2'dG concentrations were not increased , and did not significantly change with idebenone treatment . Whereas an overall analysis did not show a significant difference in ICARS , FARS , or ADL total scores , there were indications of a dose-dependent response in the ICARS score . A second , pre-specified analysis , excluding patients who required wheelchair assistance , showed a significant improvement in ICARS ( Bonferroni p=0.03 ) and suggested a dose-related response in ICARS , FARS , and ADL scores . INTERPRETATION Treatment with higher doses of idebenone was generally well tolerated and associated with improvement in neurological function and ADL in patients with FA . The degree of improvement correlated with the dose of idebenone , suggesting that higher doses may be necessary to have a beneficial effect on neurological function Spinocerebellar ataxia 3 is an untreatable CAG repeat expansion disorder whose natural history is not completely understood . Our aims were to describe the progression of neurological manifestations in a long-term cohort of spinocerebellar ataxia 3 , and to verify if CAG exp and ed repeat , gender , and age at onset were associated with the rate of progression . Patients entered the study between 1998 and 2005 and were seen until 2007 . On each visit , the vali date d NESSCA scale , an inventory of 18 neurological manifestations , was applied . Scores observed in each year of disease duration produced a Growth Curve , which was analyzed through the r and om coefficients model . Scores obtained in some individual items were described through multi-state Markov models . One hundred fifty-six patients ( 78 families ) were recruited ; 28 were lost , and 23 died . Mean ( sd ) ages at onset and at baseline were 32.8 ( 10.6 ) and 40.7 ( 12.8 ) years ; median ( range ) exp and ed CAGn was 74 ( 67–85 ) . Three hundred fifteen NESSCA evaluations were performed , comprising disease duration s from zero to 34 years . The 105 patients who completed the study were seen over 5 ( sd = 2.4 ) years at intervals of 2.5 ( sd = 1.5 ) years . The trajectory of NESSCA obtained for the overall group increased by 1.26 points per year . This slope increased by 0.15 points per each additional CAG in the exp and ed repeat ( p < 0.0002 ) and decreased by 0.03 points per each additional year of age at onset ( p = 0.005 ) . NESSCA worsened steadily , producing linear trajectories , which were faster among patients with longer exp and ed repeats ( > 74 ) and with lower ages at onset ( < 34 years ) BACKGROUND Responsive ataxia rating scales are essential for determining outcome measures in clinical trials . METHODS We evaluated the responsiveness over time of the composite cerebellar functional severity score , a quantitative score measuring cerebellar ataxia in 133 patients with autosomal dominant cerebellar ataxias ( ADCA ) , which were prospect ively evaluated at inclusion and after one-year of follow-up . A more responsive tool was developed , the Cerebellar Functional Severity score writing , incorporating the writing test at dominant h and to the Cerebellar Functional Severity score . RESULTS Within the one-year follow-up period , the Cerebellar Functional Severity score and its writing version increased significantly and the Scale for the Assessment and Rating of Ataxia decreased significantly reflecting increased severity of the cerebellar symptoms . The Cerebellar Functional Severity score writing responsiveness was best in genotypes SCA1 , 2 , and 3 compared with the other genotypes ( effect size = 0.196 , st and ardized response mean ( SRM ) = 0.624 versus effect size = -0.051 , SRM = -0.150 ) . The Cerebellar Functional Severity score writing used as an outcome measure would require only 163 SCA1 , 2 , or 3 patients per group in a two-arm interventional trial for a 50 % reduction in progression and 80 % of power . DISCUSSION Our study demonstrates that the Cerebellar Functional Severity score and Cerebellar Functional Severity score writing are responsive quantitative scores for evaluating sensitivity to change in ADCA patients and can be used as outcome measures in clinical trials , especially when targeting genotypes SCA1 , 2 and 3 Objective : To evaluate the usefulness of functional measures in patients with spinocerebellar ataxia ( SCA ) . Methods : We assessed three functional measures —8 m walking time ( 8MW ) , 9-hole peg test ( 9HPT ) , and PATA repetition rate — in 412 patients with autosomal dominant SCA ( genotypes 1 , 2 , 3 , and 6 ) in a multicenter trial . Results : While PATA rate was normally distributed ( mean/median 21.7/20.5 per 10 s ) , the performance times for 8MW ( mean/median 10.8/7.5 s ) or 9HPT ( mean/median 47.2/35.0 s in dominant , 52.2/37.9 s in nondominant h and ) were markedly skewed . Possible learning effects were small and likely clinical ly irrelevant . A composite functional index ( SCAFI ) was formed after appropriate transformation of subtest results . The Z-scores of each subtest correlated well with the Scale for the Assessment and Rating of Ataxia ( SARA ) , the Unified Huntington 's disease Rating Scale functional assessment , and disease duration . Correlations for SCAFI with each of these parameters were stronger ( Pearson r = −0.441 to −0.869 ) than for each subtest alone . Furthermore , SCAFI showed a linear decline over the whole range of disease severity , while 9HPT and 8MW had floor effects with respect to SARA . Analysis of possible confounders showed no effect of genotype or study site and only minor effects of age for 8MW . Conclusion : The proposed functional measures and their composite SCAFI have favorable properties to assess patients with spinocerebellar ataxia The objective of this paper was to assess the phenotypic variance in patients with the Fragile X-associated Tremor Ataxia Syndrome ( FXTAS ) and to further eluci date genotype – phenotype correlations in the illness . A second goal was to generate hypotheses regarding symptom progression based on careful histories in our sample that can now be tested in ongoing longitudinal studies . The variability of clinical signs and symptom progression in FXTAS complicates our underst and ing of its phenotype and presents a series of problems in clinical trial design . Similarly , pre-motor and non-motor symptoms have not been adequately explored to answer outst and ing questions regarding genotype – phenotype associations in FXTAS . This was a cross-sectional study of FMR1 premutation carriers from known fragile X syndrome pedigrees . We report on the first 50 subjects who have completed a full neurologic evaluation and a brain MRI . Subjects were selected on the basis of motor symptoms or abnormal results ( > 1 SD ) on a quantitative instrument design ed to detect mild tremor and ataxia ( CATSYS 1994 ) . A neuropsychological battery included the WAIS-III , COWA , and WCST . Statistical analysis used ANOVA and Fisher ’s exact test with p < 0.05 . All FMR1 premutation carriers were men of mean age 65 ± 7 years . According to the diagnostic criteria of Jacquemont et al. ( Am J Hum Genet 72(4):869–878 , 2003 ) , 21 subjects met criteria for definite FXTAS , 10 for probable , 9 for possible , and 10 were indeterminate . Duration of motor symptoms was significantly longer in the definitive group ( 8.6 ± 6 ) compared to the other groups ( p < 0.01 ) . The presentations in 40 subjects , excluding the indeterminate group , included : tremor 24 , ataxia 5 , memory symptoms 3 , parkinsonism 2 , and torticollis 1 . The data suggest at least two dominant phenotypic presentations : ( a ) a tremor-dominant subtype in which the onset of ataxia is delayed ; ( b ) a second in which ataxia is the dominant presentation from the outset . In both subtypes , once ataxia emerges it tends to track frontal cognitive changes ( p < 0.01 ) . The data support the view that FXTAS is a late-life neurodegenerative disorder with involvement of motor , non-motor , and cognitive systems . The results suggest at least two presentations with tremor- and ataxia-predominant phenotypes . In both , global cognitive decline appears to track ataxia . Prospect i ve longitudinal studies are needed to vali date this proposed evolution of FXTAS and its relevance to future clinical trials design The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple-System-Atrophy Parkinson-type ( MSA-P ) . Sixty-three patients were r and omized to minocycline 200 mg/d ( n = 32 ) or a matching placebo ( n = 31 ) . The primary outcome variable was the change in the value of the motor score of the Unified Multiple-System-Atrophy Rating-Scale ( UMSARSII ) from baseline to 48 weeks . Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified-Parkinson's-Disease Rating-Scale ( UPDRS ) . Health-related quality of life ( HrQoL ) was assessed using the EQ-5D and SF-12 . " Progression rate " was assumed to be reflected in the change in motor function over 48 weeks . At 24 weeks and 48 weeks of follow-up , there was a significant deterioration in motor scores in both groups , but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups , i.e. " progression rate " was considered to be similar in both treatment arms . HrQoL did not differ among the two treatment arms . In a small subgroup of patients ( n = 8 ; minocycline = 3 , placebo = 5)[(11)C](R)-PK11195-PET was performed . The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group ( P = 0.07 ) and in two of them individually showed decreased [11C](R)-PK11195 binding actually decreased . These preliminary PET- data suggest that minocycline may interfere with microglial activation . The relevance of this observation requires further investigation . This prospect i ve , 48 week , r and omized , double-blind , multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function Friedreich ataxia ( FA ) , the most common form of degenerative ataxia , is thought to be caused by respiratory deficiency due to mitochondrial iron accumulation and oxidative stress . Idebenone , a free-radical scavenger , protects mitochondrial function in in vitro models of FA . In a placebo-controlled crossover trial we studied the effect of idebenone on respiratory function in nine ambulant FA patients . (31)P magnetic resonance spectroscopy demonstrated mitochondrial impairment in vivo in skeletal muscle of all FA patients , but no recovery with idebenone . No effects were seen in clinical scores . Echocardiography did not confirm a preliminary study reporting improvement of FA-associated cardiomyopathy with idebenone The disease-specific Unified Multiple System Atrophy Rating Scale ( UMSARS ) has been developed recently and vali date d for assessing disease severity in multiple system atrophy ( MSA ) . Here , we aim ed at ( 1 ) assessing rates of disease progression in MSA and ( 2 ) validating UMSARS for sensitivity to change over time . Impairment was assessed at two time points 12 months apart using UMSARS Part I ( historical review ) , UMSARS Part II ( motor examination ) , as well as measures of global disease severity , including UMSARS Part IV , Hoehn and Yahr ( HY ) Parkinson 's disease staging , Schwab Engl and Activities of Daily Living ( SE ADL ) , and a three-point global Severity Scale ( SS3 ) . Fifty patients ( male : female ratio , 1:0.9 ; possible MSA , 16 % ; probable MSA , 84 % ; MSA-parkinsonian , 58 % ; MSA-cerebellar , 42 % ) were assessed twice with an interval of 12.3 months . UMSARS II scores progressed by 57.3 % ( P<0.0001 ) and UMSARS I scores by 35.6 % ( P<0.0001 ) in relation to the respective baseline scores with no differences between motor subtypes , diagnostic categories and gender . Significant inverse correlations between ( 1 ) UMSARS I or UMSARS II progression and ( 2 ) baseline disability measures ( i.e. , the respective UMSARS or SS3 scores ) and disease duration were found . Furthermore , the increases in HY staging , SE ADL and SS3 correlated significantly with UMSARS I , UMSARS II , and UMSARS IV progression . This report is the first prospect i ve study showing rapid annual UMSARS rates of decline in MSA . Our data contribute to the ongoing validation process of UMSARS , and they facilitate the planning and implementation of future neuroprotective intervention trials To determine whether treatment with branched-chain amino acids ( BCAA ) can improve the condition of patients with ataxia , a double-blind crossover study of BCAA therapy was performed in 16 patients with spinocerebellar degeneration ( SCD ) . The patients were treated with BCAA in oral doses of 1.5 , 3.0 , or 6.0 g or with placebo daily for 4 weeks in each study phase . The order of treatment phases ( placebo or BCAA ) was assigned r and omly . An International Cooperative Ataxia Rating Scale ( ICARS ) was used to quantify the severity of symptoms of SCD . The mean ICARS score improved significantly with BCAA treatment compared with the mean pretreatment score ( p<0.01 ) . In addition , the improvement in the mean global ICARS score was significant in the middle-dose group compared with that in the placebo group ( p<0.02 ) . The estimated improvement in kinetic functions compared with pretreatment ( p<0.01 ) was significant after treatment with BCAA , 1.5 and 3.0 g. All of the responders manifested predominantly cerebellar symptoms , especially those with spinocerebellar ataxia type 6 ( SCA6 ) . Thus , treatment with BCAA may be effective in patients with the cerebellar form of SCD Although ataxia is the most distressing manifestation of Machado-Joseph disease ( MJD ) , little is known about its natural history . Therefore , we prospect ively followed a cohort of patients with MJD for 13 months to characterize the progression of ataxia and identify its contributory factors . The international cooperative ataxia rating scale ( ICARS ) was used to estimate severity of ataxia at baseline and at follow-up . Thirty-four patients were enrolled in the study , 22 of whom were men . Mean age at onset of the disease was 34.7 years and length of exp and ed CAG repeat was 66 . Mean ICARS scores at baseline was 37.6 and at follow-up was 42.7 ( P < 0.001 ) . Multivariate analysis did not find significant association of progression of disease and age at disease onset , length of exp and ed ( CAG ) , or duration of disease |
11,931 | 20,923,922 | Nevertheless , indirect evidence supports the observation that deficits in quality of care are contributing to higher than expected mortality in those with severe mental illness ( SMI ) and schizophrenia .
The quality of medical treatment provided to those with cardiac conditions and comorbid schizophrenia is often suboptimal and may be linked with avoidable excess mortality . | We have previously documented inequalities in the quality of medical care provided to those with mental ill health but the implication s for mortality are unclear .
We aim ed to test whether disparities in medical treatment of cardiovascular conditions , specifically receipt of medical procedures and receipt of prescribed medication , are linked with elevated rates of mortality in people with schizophrenia and severe mental illness . | CONTEXT The prevalence of medical disorders is high among substance abuse patients , yet medical services are seldom provided in coordination with substance abuse treatment . OBJECTIVE To examine differences in treatment outcomes and costs between integrated and independent models of medical and substance abuse care as well as the effect of integrated care in a subgroup of patients with substance abuse-related medical conditions ( SAMCs ) . DESIGN R and omized controlled trial conducted between April 1997 and December 1998 . SETTING AND PATIENTS Adult men and women ( n = 592 ) who were admitted to a large health maintenance organization chemical dependency program in Sacramento , Calif. INTERVENTIONS Patients were r and omly assigned to receive treatment through an integrated model , in which primary health care was included within the addiction treatment program ( n = 285 ) , or an independent treatment-as-usual model , in which primary care and substance abuse treatment were provided separately ( n = 307 ) . Both programs were group based and lasted 8 weeks , with 10 months of aftercare available . MAIN OUTCOME MEASURES Abstinence outcomes , treatment utilization , and costs 6 months after r and omization . RESULTS Both groups showed improvement on all drug and alcohol measures . Overall , there were no differences in total abstinence rates between the integrated care and independent care groups ( 68 % vs 63 % , P = .18 ) . For patients without SAMCs , there were also no differences in abstinence rates ( integrated care , 66 % vs independent care , 73 % ; P = .23 ) and there was a slight but nonsignificant trend of higher costs for the integrated care group ( $ 367.96 vs $ 324.09 , P = .19 ) . However , patients with SAMCs ( n = 341 ) were more likely to be abstinent in the integrated care group than the independent care group ( 69 % vs 55 % , P = .006 ; odds ratio [ OR ] , 1.90 ; 95 % confidence interval [ CI ] , 1.22 - 2.97 ) . This was true for both those with medical ( OR , 3.38 ; 95 % CI , 1.68 - 6.80 ) and psychiatric ( OR , 2.10 ; 95 % CI , 1.04 - 4.25 ) SAMCs . Patients with SAMCs had a slight but nonsignificant trend of higher costs in the integrated care group ( $ 470.81 vs $ 427.95 , P = .14 ) . The incremental cost-effectiveness ratio per additional abstinent patient with an SAMC in the integrated care group was $ 1581 . CONCLUSIONS Individuals with SAMCs benefit from integrated medical and substance abuse treatment , and such an approach can be cost-effective . These findings are relevant given the high prevalence and cost of medical conditions among substance abuse patients , new developments in medications for addiction , and recent legislation on parity of substance abuse with other medical benefits Objective : The objective of this study was to determine if receipt of revascularization was similar among commercially insured adults with mental disorders compared with people without mental disorders . Methods : This was a retrospective analysis of a 100 % sample of Blue Cross/Blue Shield of Iowa administrative cl aims data , 1996 to 2001 . Logistic regression was used to calculate unadjusted and adjusted odds ratios ( OR ) for receipt of angioplasty ( PTCA ) and bypass graft surgery ( CABG ) within 30 days of discharge . Results : A total of 3368 adults , aged 18 to 64 years , were hospitalized for myocardial infa rct ion ( MI ) and 40 % ( n = 1342 ) had a mental disorder . Subjects with mental disorders were more likely to be younger , female , urban residents , and to have increased cardiovascular and medical comorbidity . They were similarly likely as subjects without mental disorders to have received PTCA ( OR , 1.10 ; 95 % confidence interval [ CI ] , 0.95–1.29 ) and CABG ( OR , 0.89 ; 95 % CI , 0.71–1.11 ) in analyses adjusted for demographic and clinical characteristics . Revascularization rates did not differ by mental disorder type , with few exceptions . Conclusions : Receipt of revascularization was similar for patients with and without mental disorders . Our results may differ from previous findings as a result of the younger population studied and increased comorbidity in people with mental disorders , which may have result ed in a contraindication for surgical intervention . Conversely , the increased burden of comorbidity could suggest that these patients should have received PTCA at higher rates because of the better prognosis associated with revascularization as compared with medical management . Prospect i ve analyses with review of clinical data and behavioral risk factors are necessary to determine why some patients with mental illness may be less likely to receive cardiac interventions . MI = myocardial infa rct ion ; CVD = cardiovascular disease ; MHD = mental health disorders ; PTCA = percutaneous transluminal coronary angioplasty ; CABG = coronary artery bypass graft surgery ; CPT = Common Procedural Terminology ; ICD = International Classification of Diseases ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ; OR = odds ratio ; COPD = chronic obstructive pulmonary disease ; CI = confidence interval Abstract BACKGROUND : Persons with persistent mental illness are at risk for failure to receive medical services . In order to deliver appropriate preventive and primary care for this population , it is important to determine which chronic medical conditions are most common . OBJECTIVE : We examined chronic medical comorbidity in persons with schizophrenia using vali date d method ologies . DESIGN : Retrospective analysis of longitudinal administrative cl aims data from Wellmark Blue Cross/Blue Shield of Iowa . PARTICIPANTS : Subjects with schizophrenia or schizoaffective disorder ( N=1,074 ) , and controls ( N=726,262 ) who filed at least 1 cl aim for medical services , 1996 to 2001 . MEASUREMENTS : Case subjects had schizophrenia as the most clinical ly predominant psychotic disorder , based on psychiatric hospitalization , psychiatrist diagnoses , and outpatient care . Controls had no cl aims for any psychiatric comorbidity . Using a modified version of the Elixhauser Comorbidity Index , inpatient and outpatient cl aims were used to determine the prevalence of 46 common medical conditions . Odds ratios ( ORs ) were adjusted for age , gender , residence , and nonmental health care utilization using logistic regression . RESULTS : Subjects with schizophrenia were significantly more likely to have 1 or more chronic conditions compared with controls . Adjusted OR ( 95 % confidence interval [ CI ] ) were 2.62 ( 2.09 to 3.28 ) for hypothyrodisim , 1.88 ( 1.51 to 2.32 ) for chronic obstructive pulmonary disease , 2.11 ( 1.36 to 3.28 ) for diabetes with complications , 7.54 ( 3.55 to 15.99 ) for hepatitis C , 4.21 ( 3.25 to 5.44 ) for fluid/electrolyte disorders , and 2.77 ( 2.23 to 3.44 ) for nicotine abuse/dependence . CONCLUSIONS : Schizophrenia is associated with substantial chronic medical burden . Familiarity with conditions affecting persons with schizophrenia may assist programs aim ed at providing medical care for the mentally ill Background / Objective .Somatic health care utilization was studied among individuals with serious mental illness who were receiving community-based psychiatric services . Research Design .Cross-sectional study . SubjectsA total of 200 out patients , 100 with schizophrenia and 100 with affective disorder , were recruited from r and omly selected sample s receiving care at two psychiatric centers . Measures . Patients were interviewed using questions from national health surveys . Multiple logistic regression analyses were used to compare responses from each sample to those of matched subsets of individuals from the general population . Results .The psychiatric sample s were more likely to report receiving some medical care services in the past year than were individuals in the general population including having visited a general medical doctor ( Odds ratio , schizophrenia sample = 2.04 ; Odds ratio , affective disorder sample = 2.37 ) and having a complete physical examination ( Odds ratio , schizophrenia sample = 2.69 ; Odds ratio , affective disorder sample = 1.74 ) . However , our sample s were less likely to receive routine dental care ( Odds ratio , schizophrenia sample = 0.46 ; Odds ratio , affective disorder sample = 0.60 ) . Perceived barriers to receiving medical care were reported significantly more often by the patient groups than the comparison groups ( Odds ratios > 3 ) . Conclusions . General health services are widely utilized by individuals with serious mental illness who are in outpatient psychiatric care . Dental services remain underutilized , however , and there is a high rate of perceived barriers to receiving medical care in this population OBJECTIVE In this secondary data analysis of Primary Care Research in Substance Abuse and Mental Health for the Elderly ( PRIMSe ) study , we hypothesized that older minorities who receive mental health services integrated in primary care setting s would have greater service use and better mental health outcomes than older minorities referred to community services . METHOD We identified 2,022 ( 48 % minorities ) primary care patients 65 years and older , who met study inclusion criteria and had either alcohol misuse , depression , and /or anxiety . They were r and omized to receive treatment for these disorders in the primary care clinic or to a brokerage case management model that linked patients to community-based services . Service use and clinical outcomes were collected at baseline , three months and six months post r and omization on all participants . RESULTS Access to and participation in mental health /substance abuse services was greater in the integrated model than in referral ; there were no treatment by ethnicity effects . There were no treatment effects for any of the clinical outcomes ; Whites and older minorities in both integrated and referral groups failed to show clinical ly significant improvement in symptoms and physical functioning at 6 months . CONCLUSIONS While providing services in primary care results in better access to and use of these services , accessing these services is not enough for assuring adequate clinical outcomes We determined whether patients with serious mental illness ( SMI ) were less likely than non-SMI to self-report having a medical condition that was recorded in their medical record . We included all patients from the VA National Psychosis Registry diagnosed with SMI and a r and om sample of non-SMI patients in fiscal year 1999 who completed the Large Health Survey of Veteran Enrollees ( N = 35,837 ) . Among patients with diagnoses for any of 11 conditions recorded in administrative data , we evaluated whether patients reported having that same condition in the survey , using multivariable logistic regression and generalized estimating equations . Among patients diagnosed with a given condition , those with SMI were less likely to report being told by providers that they had seven of the 11 conditions examined : heart disease ( OR = 0.68 , p < 0.001 ) , arthritis ( OR = 0.79 , p < 0.001 ) , cancer ( OR = 0.69 , p < 0.001 ) , diabetes ( OR = 0.79 , p < 0.001 ) , back pain ( OR = 0.81 , p < 0.001 ) , congestive heart failure ( OR = 0.71 , p < 0.001 ) , and hypertension ( OR = 0.77 , p < 0.001 ) . Patients with SMI were less aware of co-occurring medical conditions OBJECTIVE The aim of this study was to examine patterns of use of general medical services among persons with a severe and persistent mental illness enrolled in Medicaid from 1996 to 1998 . METHODS A total of 669 persons with a severe and persistent mental illness were identified by using statewide clinical criteria . A three-year data base of Medicaid cl aims was developed to examine service use . The main outcome measures were use of outpatient services for a general medical problem , use of dental and vision services , and use of screening tests for women . Service use was examined by primary psychiatric diagnosis ( schizophrenic , affective , paranoid , and anxiety disorders ) , and analyses controlled for the presence of a chronic medical condition , age , race , and sex . RESULTS This study found high levels of service use for outpatient services but very low levels for primary and preventive services . Although 78 percent of persons with a schizophrenic disorder had an office-based visit during the three-year period , all persons with an anxiety disorder had such a visit . Sixty-nine percent of persons with a schizophrenic disorder had at least one emergency department visit , whereas 83 percent of those with an anxiety disorder had such a visit . Dental and vision visits and the use of mammograms and pap tests followed the same pattern ; persons with a schizophrenic disorder had fewer visits and had less overall use than the other diagnostic groups . The use patterns across the four groups were significantly different in outpatient service use , dental and vision service use , and screening tests for women . Compared with persons with a schizophrenic disorder , those with an anxiety disorder were more likely to have had an office-based visit and to have received vision services , those with a paranoid disorder were more likely to have used dental services or received a mammogram , and those with an affective disorder were more likely to have had a pap test . CONCLUSION Although this group of Medicaid patients with severe and persistent mental illness had access to providers , they received an unacceptably low level of preventive care . Use of health services for general medical problems differed somewhat by primary psychiatric illness OBJECTIVE To identify patient characteristics and health care experiences associated with primary care linkage after alcohol or drug detoxification . DATA SOURCES / STUDY SETTING Primary data collected over two years . Subjects were adults without primary medical care , in an urban residential detoxification program . STUDY DESIGN A prospect i ve cohort study in the context of a r and omized trial of a linkage intervention , and an expansion of Medicaid benefits . DATA COLLECTION / EXTRACTION METHODS Data were collected by interview assessment of predisposing , enabling , and illness variables . Linkage was defined as self-report of at least one visit with a primary care clinician during follow-up . PRINCIPAL FINDINGS Of 400 subjects , 63 percent linked with primary medical care . In a multivariable model adjusting for r and omization assignment , predisposing , enabling , and illness variables , women , those with no recent incarceration , those with support for abstinence by family or friends , and those who had visited a medical clinic or physician recently were significantly more likely to link with primary care . Those with health insurance during follow-up were also more likely to link . Recent mental health or addictions treatment utilization and health status were not associated with linkage . CONCLUSIONS A substantial proportion of adults with addictions do not link with primary medical care . These data suggest that efforts could be focused on those least likely to link , that contacts with mental health and addictions treatment providers are underutilized opportunities for these efforts , and that health policy changes such as exp and ing health insurance benefits may improve entry of substance-dependent patients into primary medical care |
11,932 | 20,557,999 | Studies evaluating pain thresholds and nociceptive flexion reflex indicated the opposite when simply averaged across studies ; however , weighted analyses of threshold found more efficient DNIC in males .
Gender differences in DNIC effect depend on both the experimental methodology and the modes of measurement of the effect | Over the last decade , extensive research has demonstrated sex differences in pain perception and modulation .
Several factors have been proposed to account for the differences observed between men and women , including pain modulation through diffuse noxious inhibitory controls ( DNIC ) .
Studies investigating sex differences in DNIC have shown mixed results , with some reporting decreased DNIC effect in women compared with men , while others found no difference in DNIC between the sexes .
Additional studies have investigated DNIC in both sexes without focusing on sex differences .
This systematic review aim ed to answer the following question : " In humans of reproductive age without chronic pain , are women more likely than men to have decreased Diffuse Noxious Inhibitory Controls ? " | & NA ; The purpose of the present study was to determine whether gender differences exist in the forebrain cerebral activation patterns of the brain during pain perception . Accordingly , positron emission tomography ( PET ) with intravenous injection of H2 15O was used to detect increases in regional cerebral blood flow ( rCBF ) in normal right‐h and ed male and female subjects as they discriminated differences in the intensity of innocuous and noxious heat stimuli applied to the left forearm . Each subject was instructed in magnitude estimation based on a scale for which 0 indicated ‘ no heat sensation ’ ; 7 , ‘ just barely painful ’ and 10 , ‘ just barely tolerable ’ . Thermal stimuli were 40 ° C or 50 ° C heat , applied with a thermode as repetitive 5‐s contacts to the volar forearm . Both male and female subjects rated the 40 ° C stimuli as warm but not painful and the 50 ° C stimuli as painful but females rated the 50 ° C stimuli as significantly more intense than did the males ( P=0.0052 ) . Both genders showed a bilateral activation of premotor cortex in addition to the activation of a number of contralateral structures , including the posterior insula , anterior cingulate cortex and the cerebellar vermis , during heat pain . However , females had significantly greater activation of the contralateral prefrontal cortex when compared to the males by direct image subtraction . Volume of interest comparison ( t‐statistic ) also suggested greater activation of the contralateral insula and thalamus in the females ( P<0.05 ) . These pain‐related differences in brain activation may be attributed to gender , perceived pain intensity , or to both factors OBJECTIVE To determine the prevalence and characteristics of fibromyalgia in the general population . METHODS A r and om sample of 3,006 persons in Wichita , KS , were characterized according to the presence of no pain , non-widespread pain , and widespread pain . A sub sample of 391 persons , including 193 with widespread pain , were examined and interviewed in detail . RESULTS The prevalence of fibromyalgia was 2.0 % ( 95 % confidence interval [ 95 % CI ] 1.4 , 2.7 ) for both sexes , 3.4 % ( 95 % CI 2.3 , 4.6 ) for women , and 0.5 % ( 95 % CI 0.0 , 1.0 ) for men . The prevalence of the syndrome increased with age , with highest values attained between 60 and 79 years ( > 7.0 % in women ) . Demographic , psychological , dolorimetry , and symptom factors were associated with fibromyalgia . CONCLUSION Fibromyalgia is common in the population , and occurs often in older persons . Characteristic features of fibromyalgia -- pain threshold and symptoms -- are similar in community and clinic population s , but overall severity , pain , and functional disability are more severe in the clinic population UNLABELLED Pain catastrophizing is among the most robust predictors of pain outcomes , and a disruption in endogenous pain-inhibitory systems is 1 potential mechanism that may account for increased pain among individuals who report higher pain catastrophizing . Pain catastrophizing may negatively influence diffuse noxious inhibitory controls ( DNIC ) , a measure of endogenous pain inhibition , through complex anatomical circuitry linking cortical responses to pain with processes that modulate pain . The current study examined whether DNIC mediated the relationship between catastrophizing and pain among 35 healthy young adults and examined the moderating effects of sex to determine whether the magnitude or direction of associations differed among men and women . DNIC was assessed using pressure pain thresholds on the forearm before and during a cold pressor task . Using bias-corrected bootstrapped confidence intervals , results showed that diminished DNIC was a significant partial mediator of the relation between greater pain-related catastrophizing and more severe pain ratings . Participant sex moderated these associations ; higher catastrophizing predicted lower DNIC for men and women , however , the effect of catastrophizing on pain ratings was partially mediated by DNIC for women only . These findings further support the primary role of pain catastrophizing in modulation of pain outcomes . PERSPECTIVE These findings support the hypothesis that the heightened pain reported by individuals higher in pain catastrophizing may be related to a disruption in the endogenous modulation of pain , operationalized by assessing DNIC . Whether interventions that reduce pain catastrophizing affect pain outcomes via effects on DNIC is in need of investigation In this study we tested the hypothesis that hypoalgesia in individuals at risk for hypertension is related to enhanced activation of supraspinal pain modulation systems . Supraspinal inhibition of pain signals was assessed using a diffuse noxious inhibitory control paradigm , in which a noxious conditioning stimulus was used to suppress pain in response to a noxious test stimulus applied to a remote area of the body . Specifically , the nociceptive flexion reflex ( NFR ) was assessed in 113 healthy young adults before , during , and after exposure to forearm tourniquet ischemia . Consistent with previous evidence of hypoalgesia in individuals at risk for hypertension , offspring of hypertensive individuals exhibited significantly higher NFR thresholds than offspring of normotensive persons . Although NFR activity was significantly decreased in all participants during concomitant application of forearm ischemia , the degree of attenuation of NFR activity was not significantly different as a function of risk for hypertension We present the first prevalence study of specific headache entities using the operational diagnostic criteria of the International Headache Society . One thous and 25 - 64 year old men and women , who lived in the western part of Copenhagen County were r and omly drawn from the Danish National Central Person Registry . All subjects were invited to a general health examination focusing on headache and including : a self-administered question naire concerning sociodemographic variables , a structured headache interview and a general physical and neurological examination . The participation rate was 76 % . Information about 79 % of the non- participants showed a slightly differing headache prevalence which was not quantitatively important . The following results in participants are therefore representative of the total sample . The lifetime prevalences of headache ( including anybody with any form of headache ) , migraine , and tension-type headache were 93 , 8 and 69 % in men ; and 99 , 25 and 88 % in women . The point prevalence of headache was 11 % in men and 22 % in women . Prevalence of migraine in the previous year was 6 % in men and 15 % in women and the corresponding prevalences of tension-type headache were 63 and 86 % . Differences according to sex were significant with a male : female ratio of 1:3 in migraine , and 4:5 in tension-type headache . The prevalence of tension-type headache decreased with increasing age , whereas migraine showed no correlation to age within the studied age interval . Headache disorders are extremely prevalent and represent a major health problem , which merits increased attention Objective Sex differences in pain sensitivity and stress reactivity have been well documented . Little is known about the role of the endogenous opioid system in these differences . This study was conducted to compare adrenocortical , pain sensitivity , and blood pressure responses to opioid blockade using naltrexone in men and women . Methods Twenty-six participants completed 2 sessions during which placebo or 50 mg of naltrexone was administered , using a double-blind , counterbalanced design . Thermal pain threshold and heat tolerance were assessed . Participants also rated pain during a 90-second cold pressor test ( CPT ) and completed the McGill Pain Question naire ( MPQ ) after each pain challenge . Blood and saliva sample s and cardiovascular and mood measures were obtained throughout the sessions . Results Plasma cortisol , adrenocorticotropin , beta endorphin , prolactin , and salivary cortisol levels increased similarly in men and women after naltrexone administration compared with placebo . Women reported more pain during both pain procedures and had lower thermal pain tolerance . In response to naltrexone , women exhibited reduced blood pressure responses and reduced MPQ pain ratings after CPT . No effects of naltrexone on these measures were found in men . Conclusions Although men and women exhibited similar hormonal responses to opioid receptor blockade , women reported less pain and showed smaller blood pressure responses during CPT . Results suggest differential effects of the endogenous opioid system on pain perception and blood pressure in men and women 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 & NA ; The aim of this study was to investigate the effects of diffuse noxious inhibitory controls ( DNICs ) on the temporal summation of the nociceptive flexion reflex ( RIII reflex ) in humans . Recordings were obtained from 36 healthy adults ( 16 M , 20 F ) , and the area and temporal summation threshold ( TST ) of the RIII reflex were measured . The subjective intensity of the painful sensation was rated on an 11‐point visual analogue scale ( VAS ) . Neurophysiological and VAS measurements were recorded after activation of DNICs by means of the cold pressor test ( CPT ) , which involved immersing the h and in cold water ( 2–4 ° C ) . A slight significant lower TST was found in the females versus the males . In all the subjects , the CPT induced a significant TST increase and RIII area reduction compared with the control session . The VAS results paralleled those of the RIII reflex area and TST . During the CPT , a significant difference in the percentage TST increase emerged between females and males , being lower in the former . Similarly , we found a significantly lower percentage reduction of the RIII area in women than in men during the CPT . To summarize , activation of DNICs through the CPT significantly increased the TST of the RIII reflex in healthy subjects . This inhibitory effect was gender‐specific . Whereas other findings are based on psychophysical evaluations , the results of this experimental study provide an objective neurophysiological demonstration that DNICs attenuate temporal summation in humans and confirm the presence of significant differences in pain modulation mechanisms between men and women & NA ; Little is known about sex differences in the temporal pattern of descending inhibitory mechanisms , such as descending noxious inhibitory control ( DNIC ) . Sex differences in temporal characteristics of DNIC were investigated by measuring pressure pain thresholds ( PPTs ) over time in the trapezius muscles ( local pain areas ) and the posterolateral neck muscles ( referred pain areas ) following repeated bilateral injection of hypertonic versus isotonic saline into both trapezius muscles . Ten females and 11 males received two consecutive bilateral injections , with 15 min interval , of either 5.8 % hypertonic saline ( 0.5 ml in each side for each bilateral injection ) or isotonic saline as a control in a r and omized manner . Following hypertonic saline injection , the maximal pain intensities of the first and second bilateral injections were significantly higher in females than in males . The PPTs in the trapezius muscles were significantly lower in females than in males . Significantly higher PPTs ( hypoalgesia ) in men than in women were shown 15 min after the first bilateral injection , and 7.5 and 15 min after the second bilateral injection in the referred pain areas . Importantly , the second bilateral injection failed to further increase the PPTs for both sexes . These results showed that there were sex differences in temporal characteristics of descending inhibition with long‐lasting hypoalgesia in men than in women . Repeated noxious muscular stimuli may inhibit further build‐up of DNIC , which may reflect a mechanism of plasticity of the descending inhibitory systems following recurrent nociceptive barrage for both sexes & NA ; The aims of this study were to investigate possible sex differences in ( a ) intraoral pain evoked by topical application of capsaicin to the gingiva , and ( b ) the modulation of this pain by diffuse noxious inhibitory controls ( DNIC ) . Three groups with a total of fifty‐four healthy volunteers ( 20 men , 20 women using oral contraceptives ( W+OC ) , 14 women not using ( W−OC ) ) completed the study . In two sessions , intraoral pain was evoked by topical application of 30 μL 5 % capsaicin to the gingiva . Conditioning stimuli were applied with three min h and immersion in ice water in one session and 30 ° C water ( control ) in another session . The capsaicin‐evoked pain and the water‐evoked pain were evaluated by the participants on visual analogue scales ( VAS ) . No main effects of group in capsaicin‐evoked pain ( P>0.062 ) or water‐evoked pain ( P>0.149 ) were found . There was a significant group x time interaction ( P<0.001 ) with W+OC reporting lower capsaicin‐evoked pain scores than W−OC in the early phase ( 2–3 min ) and lower pain scores than men in the later phase ( 5–11 min ) . The degree of modulation by DNIC did not differ between groups ( P=0.636 ) . In conclusion , for a superficial type of intraoral pain , only minor sex differences were found in pain intensity and no differences in the degree of endogenous modulation by DNIC . Female sex and the use of OC may not consistently be associated with higher sensitivity to pain |
11,933 | 23,996,457 | No significant differences were found between psychostimulants and placebo for any of the studied efficacy outcomes .
Results of this review do not support the use of psychostimulant medications at the tested doses as a replacement therapy for amphetamine abuse or dependence . | BACKGROUND Amphetamine dependence is a public health problem with medical , psychiatric , cognitive , legal and socioeconomic consequences .
To date , no pharmacological treatment has been approved for this disorder , and psychotherapy remains the mainstay of treatment .
In recent years , psychostimulants have been investigated as a possible replacement therapy .
OBJECTIVES To evaluate the efficacy and safety of psychostimulant medications for amphetamine abuse or dependence .
The influences of type of drug , type of dependence , comorbid disorders , clinical trial risk of bias and publication of data were also studied . | AIM Modafinil was tested for efficacy in decreasing use in methamphetamine-dependent participants , compared to placebo . METHODS This was a r and omized , double-blind , placebo-controlled study , with 12 weeks of treatment and a 4-week follow-up . Eight outpatient substance abuse treatment clinics participated in the study . There were 210 treatment-seekers r and omized , who all had a DSM-IV diagnosis of methamphetamine dependence ; 68 participants to placebo , 72 to modafinil 200 mg , and 70 to modafinil 400 mg , taken once daily on awakening . Participants came to the clinic three times per week for assessment s , urine drug screens , and group psychotherapy . The primary outcome measure was a methamphetamine non-use week , which required all the week 's qualitative urine drug screens to be negative for methamphetamine . RESULTS Regression analysis showed no significant difference between either modafinil group ( 200 or 400 mg ) or placebo in change in weekly percentage having a methamphetamine non-use week over the 12-week treatment period ( p=0.53 ) . Similarly , a number of secondary outcomes did not show significant effects of modafinil . However , an ad-hoc analysis of medication compliance , by urinalysis for modafinil and its metabolite , did find a significant difference in maximum duration of abstinence ( 23 days vs. 10 days , p=0.003 ) , between those having the top quartile of compliance ( > 85 % of urines were positive for modafinil , N=36 ) , and the lower three quartiles of modafinil 200 and 400 mg groups ( N=106 ) . CONCLUSIONS Although these data suggest that modafinil , plus group behavioral therapy , was not effective for decreasing methamphetamine use , the study is probably inconclusive because of inadequate compliance with taking medication The safety and tolerability of modafinil ( 400 mg/day , n = 14 ) and mirtazapine ( 60 mg/day , n = 13 ) in inpatient methamphetamine withdrawal treatment were compared to a historical comparison group receiving treatment as usual ( pericyazine , 2.5 - 10 mg/day , n = 22 ) . Modafinil and mirtazapine were well tolerated , producing minimal positive subjective effects and no discontinuation effects in this open-label study . Side effects were mild and transient . Aches and pains were most commonly reported by participants receiving mirtazapine , whereas headache was reported by modafinil-treated participants . Modafinil-treated participants had a milder withdrawal syndrome as measured by the Amphetamine Cessation Symptom Assessment and less sleep disturbance in comparison to mirtazapine . Pericyazine was associated with a more severe withdrawal syndrome in comparison to mirtazapine and modafinil . Both modafinil and mirtazapine were safe and well tolerated in methamphetamine withdrawal treatment . However , these early findings of efficacy in symptom amelioration should be replicated in an adequately powered , r and omized , placebo-controlled double-blind design AIM To investigate the safety and efficacy of once-daily supervised oral administration of sustained-release dexamphetamine in people dependent on methamphetamine . DESIGN R and omized , double-blind , placebo-controlled trial . PARTICIPANTS Forty-nine methamphetamine-dependent drug users from Drug and Alcohol Services South Australia ( DASSA ) clinics . INTERVENTION Participants were assigned r and omly to receive up to 110 mg/day sustained-release dexamphetamine ( n = 23 ) or placebo ( n = 26 ) for a maximum of 12 weeks , with gradual reduction of the study medication over an additional 4 weeks . Medication was taken daily under pharmacist supervision . MEASUREMENTS Primary outcome measures included treatment retention , measures of methamphetamine consumption ( self-report and hair analysis ) , degree of methamphetamine dependence and severity of methamphetamine withdrawal . Hair sample s were analysed for methamphetamine using liquid chromatography-mass spectrometry . FINDINGS Treatment retention was significantly different between groups , with those who received dexamphetamine remaining in treatment for an average of 86.3 days compared with 48.6 days for those receiving placebo ( P = 0.014 ) . There were significant reductions in self-reported methamphetamine use between baseline and follow-up within each group ( P < 0.0001 ) , with a trend to a greater reduction among the dexamphetamine group ( P = 0.086 ) . Based on hair analysis , there was a significant decrease in methamphetamine concentration for both groups ( P < 0.0001 ) . At follow-up , degree of methamphetamine dependence was significantly lower in the dexamphetamine group ( P = 0.042 ) . Dexamphetamine maintenance was not associated with serious adverse events . CONCLUSIONS The results of this preliminary study have demonstrated that a maintenance pharmacotherapy programme of daily sustained-release amphetamine dispensing under pharmacist supervision is both feasible and safe . The increased retention in the dexamphetamine group , together with the general decreases in methamphetamine use , degree of dependence and withdrawal symptom severity , provide preliminary evidence that this may be an efficacious treatment option for methamphetamine dependence OBJECTIVE To compare bupropion to placebo for reducing methamphetamine ( MA ) use , increasing retention , and reducing the severity of depressive symptoms and MA-cravings . A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants . METHODS Following a 2-week , non-medication baseline screening period , 73 treatment-seeking MA dependent participants were r and omly assigned to bupropion sustained release ( 150 mg twice daily ; N=36 ) or placebo ( twice daily ; N=37 ) for 12-weeks under double-blind conditions . Participants attended clinic thrice weekly to provide urine sample s analyzed for MA-metabolite , to complete research measures and assessment s , and to receive contingency management and weekly cognitive behavioral therapy sessions . RESULTS There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens , for reducing the severity of depressive symptoms or MA-cravings , or on study retention . In a post hoc analysis , there was a statistically significant effect of bupropion treatment on MA use among participants with lighter ( 0 - 2 MA-positive urines ) , but not heavier ( 3 - 6 MA-positive urines ) MA use during baseline ( OR=2.81 , 95 % CI=1.61 - 4.93 , p<0.001 for MA-free week with bupropion among light users ) . Bupropion treatment was also associated with significantly reduced cigarette smoking , by almost five cigarettes per day ( p=0.0002 ) . CONCLUSION Bupropion was no more effective than placebo in reducing MA use in planned analyses , though bupropion did reduce cigarette smoking . Post hoc findings of an effect for bupropion among baseline light , but not heavy , MA users suggests further evaluation of bupropion for light-MA users is warranted The efficacy of stimulant treatment in patients with substance use disorders and comorbid attention deficit hyperactivity disorder ( ADHD ) has been tested for cocaine and alcohol dependence but so far no studies have been conducted in amphetamine dependent individuals . The present trial was a pilot study aim ing to test the feasibility of treating amphetamine dependent patients with comorbid ADHD with central stimulant medication . The study was a double-blind , placebo controlled trial with parallel groups design comparing the efficacy of a fixed dose ( 72 mg ) of OROS methylpheni date ( MPH ) with placebo ( PL ) in reducing ADHD symptoms in currently abstinent adults with amphetamine dependence and ADHD . Twenty-four treatment seeking patients who met the DSM IV criteria for amphetamine dependence and ADHD were r and omized to MPH/PL . The trial was conducted at an outpatient facility with twice weekly visits , measuring ADHD symptoms and drug use . Patients rated their ADHD symptoms on a weekly basis and provided supervised urine specimens for drug toxicology twice weekly . All patients participated in weekly sessions of a skills training programme . Both the groups significantly reduced their self-rated ADHD symptoms during the 12-week treatment but there was no difference between the two treatment arms . Drug use , both measured by urine toxicology and self-report did not differ between the groups . No difference was found between the two groups with regards to craving for amphetamine or in retention in treatment . Larger studies with higher doses combined with individual dosage and longer follow-up periods are warranted Methamphetamine is a highly addictive stimulant and long-term exposure leads to reductions in dopamine . One therapeutic strategy is to develop and test compounds that normalize dopamine . The primary aim of this study was to determine the safety of modafinil treatment during methamphetamine exposure in a controlled clinical setting . Methamphetamine-dependent volunteers ( N=13 ) , who were not seeking treatment , were r and omized to receive either modafinil ( 200 mg , PO ) or matching placebo over three days ( Days 1 - 3 or Days 8 - 10 ) . On Day 1 , subjects were r and omized to modafinil or placebo in the morning , and then 3 and 6h later received infusions of methamphetamine ( 0 and 30 mg , i.v . ) , after which cardiovascular and subjective effects were assessed . On Day 3 , participants completed i.v . self-administration sessions during which they made 10 choices for low doses of methamphetamine ( 3 mg , i.v . ) or saline . Days 4 - 7 were used as a washout period . On Day 8 participants were assigned to the alternate study medication ( placebo or modafinil ) , and the same testing procedures were repeated through Day 10 . The data reveal that modafinil treatment was well-tolerated and not associated with increased incidence of adverse events . In general , modafinil reduced by approximately 25 % ratings of methamphetamine-induced " Any Drug Effect " , " High " , and " Want Methamphetamine " , and reduced total number of choices for methamphetamine and monetary value of methamphetamine , though none of these measures reached statistical significance . Given these encouraging , though non-significant trends , the primary conclusion is that it appears safe to proceed with modafinil in further clinical evaluations of therapeutic efficacy AIM To examine the safety and efficacy of modafinil ( 200 mg/day ) compared to placebo in the treatment of methamphetamine dependence and to examine predictors of post-treatment outcome . PARTICIPANTS AND DESIGN Eighty methamphetamine-dependent subjects in Sydney , Australia were allocated r and omly to modafinil ( 200 mg/day ) ( n = 38 ) or placebo ( n = 42 ) under double-blind conditions for 10 weeks with a further 12 weeks post-treatment follow-up . MEASURES Comprehensive drug use data ( urine specimens and self-report ) and other health and psychosocial data were collected weekly during treatment and research interviews at baseline , week 10 and week 22 . RESULTS Treatment retention and medication adherence were equivalent between groups . There were no differences in methamphetamine abstinence , craving or severity of dependence . Medication-compliant subjects tended to provide more methamphetamine-negative urine sample s over the 10-week treatment period ( P = 0.07 ) . Outcomes were better for methamphetamine-dependent subjects with no other substance dependence and those who accessed counselling . There were statistically significant reductions in systolic blood pressure ( P = 0.03 ) and weight gain ( P = 0.05 ) in modafinil-compliant subjects compared to placebo . There were no medication-related serious adverse events . Adverse events were generally mild and consistent with known pharmacological effects . CONCLUSIONS Modafinil demonstrated promise in reducing methamphetamine use in selected methamphetamine-dependent patients . The study findings support definitive trials of modafinil in larger multi-site trials OBJECTIVE Problems related to illegal amphetamine use have become a major public health issue in many developed countries . To date , evidence on the effectiveness of psychosocial treatments has remained modest , and no pharmacotherapy has proven effective for amphetamine dependence . METHOD Individuals meeting DSM-IV criteria for intravenous amphetamine dependence ( N=53 ) were r and omly assigned to receive aripiprazole ( 15 mg/day ) , slow-release methylpheni date ( 54 mg/day ) , or placebo for 20 weeks . The study was terminated prematurely due to unexpected results of interim analysis . An intention-to-treat analysis was used . The primary outcome measure was the proportion of amphetamine-positive urine sample s. RESULTS Patients allocated to aripiprazole had significantly more amphetamine-positive urine sample s than patients in the placebo group ( odds ratio=3.77 , 95 % CI=1.55 - 9.18 ) , whereas patients who received methylpheni date had significantly fewer amphetamine-positive urine sample s than patients who had received placebo ( odds ratio=0.46 , 95 % CI=0.26 - 0.81 ) . CONCLUSIONS Methylpheni date is an effective treatment for reducing intravenous drug use in patients with severe amphetamine dependence BACKGROUND Two clinical trials have shown efficacy for bupropion in treating methamphetamine ( MA ) dependence among those with moderate baseline MA use . However , treatment response is highly variable and it is unclear what duration of treatment is necessary to determine if maintaining the treatment course is indicated or if discontinuation or augmentation is appropriate . The present study assessed the relationship among early bupropion treatment response for moderate MA users and end-of-treatment ( EOT ) abstinence . These data provide estimates of the duration of treatment and the degree of responsiveness required to persist in bupropion treatment . METHODS Participants with moderate baseline MA use in the bupropion condition of two r and omized double-blind placebo controlled trials were included . The relationship between early treatment response and EOT outcomes was assessed with Receiver Operating Characteristic ( ROC ) curves . RESULTS With thrice weekly urine drug testing , excellent predictive power was established in the first two weeks of treatment . The inability to achieve at least three MA negative sample s in the first two weeks is associated with greater than 90 % likelihood of treatment failure . More closely approximating clinical setting s , once-weekly testing featured reliable predictive power within three weeks , suggesting that the failure to produce at least two clean sample s in the first three weekly visits confers high risk of treatment failure . DISCUSSION The findings provide preliminary evidence to guide clinical decisions for moderate MA users receiving bupropion . The results are consistent with data from the smoking cessation literature and may highlight the importance of early response in addiction treatment Bupropion is an antidepressant with stimulant properties , which inhibits the reuptake of dopamine ( DA ) and norepinepherine , and is purported to enhance DA neurotransmission . Bupropion is considered an appealing c and i date medication for the treatment of methamphetamine dependence . The current laboratory study was set forth to assess the impact of bupropion treatment on the subjective effects produced by methamphetamine in the laboratory . We also assessed the effects of bupropion treatment on craving elicited by exposure to videotaped methamphetamine cues . A total of 26 participants were enrolled and 20 completed the entire study ( n=10 placebo and n=10 bupropion , parallel groups design ) . Bupropion treatment was associated with reduced ratings of ‘ any drug effect ’ ( p<0.02 ) , and ‘ high ’ ( p<0.02 ) following methamphetamine administration . There was also a significant bupropion-by-cue exposure interaction on General Craving Scale total score ( p<0.002 ) , and on the Behavioral Intention subscale ( p<0.001 ) . Overall , the data reveal that bupropion reduced acute methamphetamine-induced subjective effects and reduced cue-induced craving . Importantly , these data provide a rationale for the evaluation of bupropion in the treatment of methamphetamine dependence Bupropion was tested for efficacy in increasing weeks of abstinence in methamphetamine-dependent patients , compared to placebo . This was a double-blind placebo-controlled study , with 12 weeks of treatment and a 30-day follow-up . Five outpatient substance abuse treatment clinics located west of the Mississippi participated in the study . One hundred and fifty-one treatment-seekers with DSM-IV diagnosis of methamphetamine dependence were consented and enrolled . Seventy-two participants were r and omized to placebo and 79 to sustained-release bupropion 150 mg twice daily . Patients were asked to come to the clinic three times per week for assessment s , urine drug screens , and 90-min group psychotherapy . The primary outcome was the change in proportion of participants having a methamphetamine-free week . Secondary outcomes included : urine for quantitative methamphetamine , self-report of methamphetamine use , subgroup analyses of balancing factors and comorbid conditions , addiction severity , craving , risk behaviors for HIV , and use of other substances . The generalized estimating equation regression analysis showed that , overall , the difference between bupropion and placebo groups in the probability of a non-use week over the 12-week treatment period was not statistically significant ( p=0.09 ) . Mixed model regression was used to allow adjustment for baseline factors in addition to those measured ( site , gender , level of baseline use , and level of symptoms of depression ) . This subgroup analysis showed that bupropion had a significant effect compared to placebo , among male patients who had a lower level of methamphetamine use at baseline ( p<0.0001 ) . Comorbid depression and attention-deficit/hyperactivity disorder did not change the outcome . These data suggest that bupropion , in combination with behavioral group therapy , was effective for increasing the number of weeks of abstinence in participants with low-to-moderate methamphetamine dependence , mainly male patients , regardless of their comorbid condition INTRODUCTION AND AIMS To examine the cost-effectiveness of modafinil ( 200 mg daily ) plus counselling compared with placebo for the treatment of psychostimulant dependence . DESIGN AND METHODS Cost and outcome data were collected alongside two r and omised controlled trials of modafinil 200 mg daily over 10 weeks for methamphetamine ( n = 74 ) and cocaine dependence ( n = 8) , respectively . Incremental cost-effectiveness ratios representing the additional costs to achieve a given outcome were calculated for both the change in the number of stimulant-free days and quality -adjusted life years 12 weeks post-treatment . RESULTS The incremental cost-effectiveness ratio indicated that it would cost an additional $ AUD79 to achieve an extra stimulant-free day with modafinil compared with placebo . This result was not statistically significant , but appeared to be a robust estimate after sensitivity analysis . Counselling , whether received within program or from other services , improved the cost-effectiveness of modafinil relative to placebo . DISCUSSION AND CONCLUSIONS Strategies to improve the uptake of counselling are recommended as cost-effective Objective : To determine whether actively using , methamphetamine (meth)-dependent men who have sex with men ( MSM ) could be enrolled and retained in a pharmacologic intervention trial , and the degree to which participants would adhere to study procedures , including medication adherence . Study design : Phase II r and omized , double-blind trial of bupropion vs. placebo . Methods : Thirty meth-dependent , sexually active MSM were r and omized to receive daily bupropion XL 300 mg or placebo for 12 weeks . Participants received weekly substance use counseling , provided weekly urine specimens , and completed monthly audio-computer assisted self-interview ( ACASI ) behavioral risk assessment s. Adherence was measured by medication event monitoring systems ( MEMS ) caps ( the number of distinct MEMS cap openings divided by the number of expected doses ) and self-report . Results : Ninety percent completed the trial : 89 % of monthly ACASIs were completed , 81 % of study visits were attended , and 81 % of urine sample s were collected . Adherence by MEMS cap was 60 % and by self-report was 81 % and did not differ significantly by treatment assignment . The median number of positive urine sample s was 5.5 out of a possible 11 ( 50 % ) . Participants in both arms reported similar declines in the median number of sex partners ( P = 0.52 ) . No serious adverse events occurred and there were no significant differences in adverse events by treatment assignment ( P = 0.11 ) . Conclusions : It is feasible to enroll and retain actively using , meth-dependent MSM in a pharmacologic intervention . Bupropion was well tolerated . Study participation and retention rates were high , however , study drug medication adherence was only moderate . Findings support a larger trial with improved adherence support to evaluate the efficacy of bupropion and other pharmacologic interventions for meth dependence in this population AIMS There are no studies directly comparing self-administration of methamphetamine and d-amphetamine by humans . This study compared intranasal methamphetamine- and d-amphetamine self-administration and characterized the mood , performance and physiological effects produced by the drugs . DESIGN A r and omized , double-blind , placebo-controlled , cross-over study . SETTING An out-patient research unit at the New York State Psychiatric Institute . PARTICIPANTS Male recreational methamphetamine users ( n = 13 ) . MEASUREMENTS Five 2-day blocks of sessions were conducted . On the first day of each block , participants ' sample d ' a single methamphetamine or d-amphetamine dose ( 0 , 12 , 50 mg/70 kg ) and a monetary reinforcer ( $ 5 or $ 20 ) . Amphetamine plasma levels , cardiovascular , mood , and psychomotor performance effects were assessed before drug administration and repeatedly thereafter . On the second day of each block , participants chose between the sample d reinforcers ( drug or money ) . FINDINGS There were no significant differences between the drugs on the majority of measures . Under the $ 5 condition , both amphetamines increased self-administration dose-dependently , with 41 % drug choices overall . Under the $ 20 condition , only 17 % drug options were selected . Both drugs increased cardiovascular activity and ' positive ' mood , although methamphetamine produced more prominent effects on some measures ( e.g. heart rate and ratings of ' high ' ) . CONCLUSIONS Methamphetamine and d-amphetamines appear to produce a similar dose-related profile of effects in humans , which supports their equivalence for abuse potential Sixty treatment‐seeking individuals with methamphetamine ( MA ) dependence entered a r and omized , placebo‐controlled , double‐blind clinical trial of oral dextroamphetamine ( d‐AMP ) as a replacement therapy for MA dependence . The subjects took 60 mg sustained‐release d‐AMP for 8 weeks , during which time they received eight 50‐min sessions of individual psychotherapy . Adverse events and urine toxicology for MA were assessed two times a week . There were no serious adverse events . Urine sample s containing < 1,000 ng/ml of MA were classified as negative for MA . The MA‐negative scores in the d‐AMP group ( 3.1 ± SD 4.6 ) were no higher than those in the placebo group ( 3.3 ± SD 5.3 ; P > 0.05 ) . However , withdrawal and craving scores were significantly lower in the d‐AMP group ( P < 0.05 for both ) . Although subjects taking d‐AMP did not reduce their use of MA , the significant reductions observed in withdrawal and craving scores in this group support the need for further exploration of d‐AMP as a pharmacologic intervention for MA dependence , possibly at higher doses AIMS To test the feasibility of conducting a definitive r and omized controlled trial of dexamphetamine substitution for amphetamine dependent people and provide preliminary data . DESIGN An open , two-group pre-post r and omized controlled trial . PARTICIPANTS Forty-one long-term , dependent amphetamine users seeking treatment . INTERVENTION Twenty subjects were offered weekly counselling . Twenty-one subjects were , in addition , prescribed up to 60 mg dexamphetamine daily . MEASUREMENTS Immunoassay and mass spectrometric urinalysis techniques were used to identify the presence of amphetamine and methylamphetamine in urine . The Opiate Treatment Index and Severity of Dependence Scale were used to collect pre- and post-self-report data . Subjects were screened using the Composite International Diagnostic Interview . FINDINGS Reduced street amphetamine use and amphetamine dependence was observed both in subjects prescribed dexamphetamine and subjects receiving counselling only . Treatment subjects appeared more likely to attend counselling . CONCLUSIONS A definitive r and omized controlled trial of dexamphetamine substitution using the techniques and instruments piloted in this study is feasible . Users appeared to be attracted and retained in substitution treatment . The intervention also appeared to be acceptable to clinicians Relatively little is known about the impact of drug court treatment programs for methamphetamine ( MA ) dependence . This article examines treatment performance among a sub sample of 287 MA-dependent adults who participated in the Methamphetamine Treatment Project from 1999 to 2001 . To gain a preliminary indication of MA users ' response to drug court intervention , we compared a group of 57 MA-dependent participants treated in outpatient treatment within the context of a drug court to a group of comparable MA-dependent individuals treated in outpatient treatment but not supervised by a drug court ( n = 230 ) . Analyses reveal that drug court participation was associated with better rates of engagement , retention , completion , and abstinence , compared to outpatient treatment without drug court supervision . Six- and 12-month outcome analyses indicated that participants who were enrolled in drug court intervention used MA significantly less frequently . These findings suggest that drug court supervision coupled with treatment may improve the outcomes of MA-dependent offenders beyond that seen from treatment alone Five central ly acting sympathomimetic amines , d‐amphetamine , d‐methamphetamine , ephedrine , phenmetrazine , and methylpheni date , were studied in man . All of these agents increased blood pressure and respiratory rate , produced similar types of subiective changes , and increased the excretion of epinephrine . With regard to these parameters , there was a high concordance between estimates of their relative potencies . The concordance between the potency estimates for the different parameters suggests , but does not prove , that these five agents share a common mode of central action . Further , if the peripheral modes of action as eluci date d by animal studies are true for man , this study suggests that it is unlikely that their central actions in man are a consequence of the release of norepinephrine in the brain Modafinil is indicated for the management of excessive daytime sleepiness ; however , recent studies have examined a broad range of potential uses . Given that clinical uses of modafinil may be exp and ing , this study compared modafinil and d-amphetamine effects on subjective and performance measures . Across 11 sessions , 11 healthy adults were tested after oral doses of placebo ( 5 sessions ) , modafinil ( 1.75 mg/kg , 3.50 mg/kg , or 7.00 mg/kg ) , and d-amphetamine ( 0.035 mg/kg , 0.070 mg/kg , 0.140 mg/kg ) under double-blind , r and omized conditions . Assessment s of cognitive performance and subjective effects were completed before drug administration , 30 min after drug administration , and at hourly intervals after drug administration for 5 hr . Modafinil increased ratings on the Amphetamine and Morphine Benzedrine Group scales of the Addiction Research Center Inventory ( ARCI ) and increased ratings on the Vigor and Total Positive scales of the Profile of Mood States . d-Amphetamine increased visual analog ratings of feeling stimulated and liking the drug and increased ratings on the Morphine Benzedrine Group scale of the ARCI . Both medications significantly reduced visual analog scale ratings of feeling sleepy , and modafinil decreased ratings on the ARCI Pentobarbital-Chlorpromazine-Alcohol Group scale . Both medications sustained performance that deteriorated across time on the Sternberg Number Recognition Test . Modafinil also enhanced performance rate on the Digit-Symbol Substitution Task above baseline levels and increased response rate on the Repeated Acquisition of Response Sequences Task . These results suggest that modafinil engenders alerting effects and increases performance in healthy non-sleep-deprived individuals comparable with that of d-amphetamine Clinical lore dictates that craving drives the compulsive use of drugs and alcohol - the core feature of substance dependence . Yet limited research has yielded mixed results , suggesting that craving is neither necessary nor sufficient for continued use or relapse to addictive substances . To investigate the role of craving in compulsive methamphetamine use , 31 men and women in treatment for methamphetamine dependence were asked to indicate , once each week for 12 weeks , the severity of craving that they had experienced during the previous 24 h , using a 100-mm visual analog scale . In a prospect i ve , repeated- measures , within-subject analysis , craving intensity significantly predicted methamphetamine use in the week immediately following each craving report . Craving remained a highly significant predictor in multivariate models controlling for pharmacological intervention , and for methamphetamine use during the prior week . Craving scores that preceded use were 2.7 times higher than scores that preceded abstinence . Risk of subsequent use was 2.5 times greater for scores in the upper half of the scale relative to scores in the lower half . The results obtained demonstrate that , while craving alone may be neither necessary nor sufficient to explain substance addiction , when measured prospect ively in a carefully- design ed study craving emerges as a salient predictive factor in continued methamphetamine use for patients in treatment for methamphetamine dependence OBJECTIVE To compare modafinil to placebo for reducing methamphetamine ( MA ) use , improving retention , and reducing depressive symptoms and MA cravings . Rates of adverse events and cigarette smoking with modafinil versus placebo were also compared . METHODS Following a 2-week , non-medication lead-in period , 71 treatment-seeking MA-dependent participants were r and omly assigned to modafinil ( 400 mg once daily ; N=34 ) or placebo ( once daily ; N=37 ) for 12 weeks under double-blind conditions . Participants attended clinic thrice-weekly to provide urine sample s analyzed for MA-metabolite , to complete research assessment s , and to receive contingency management and weekly cognitive behavioral therapy ( CBT ) sessions . RESULTS There were no statistically significant effects for modafinil on MA use , retention , depressive symptoms , or MA cravings in pre-planned analyses . Outcomes for retention and MA use favored modafinil in a post hoc analysis among participants with low CBT attendance and among participants with baseline high-frequency of MA use ( MA use on > 18 of past 30 days ) , but did not reach statistical significance in these small subgroups . Modafinil was safe and well tolerated and did not increase cigarette smoking . CONCLUSIONS Modafinil was no more effective than placebo at 400 mg daily in a general sample of MA users . A post hoc analysis showing a trend favoring modafinil among subgroups with baseline high-frequency MA use and low CBT attendance suggests that further evaluation of modafinil in MA users is warranted INTRODUCTION AND AIMS Cigarette smoking occurs frequently among individuals with methamphetamine ( MA ) dependence . Pre clinical and clinical evidence has suggested that the common co-abuse of MA and cigarettes represents a pharmacologically meaningful pattern . METHODS The present study is a secondary analysis of a r and omised , placebo-controlled trial of bupropion treatment for MA dependence ( bupropion n = 36 ; placebo n = 37 ) . A hierarchical logistic modelling approach assessed the efficacy of bupropion for reducing MA use separately among smokers and non-smokers . Among smokers , relations between cigarettes smoked and MA use were assessed . RESULTS Smoking status did not affect treatment responsiveness in either the bupropion condition or the placebo condition . In the placebo condition , increased cigarette use was associated with an increased probability of MA use during the same time period . This effect was not observed in the bupropion condition . DISCUSSION AND CONCLUSIONS Initial smoking status did not impact treatment outcomes . Among smokers , results suggest that bupropion may dissociate cigarette and MA use . The effect was modest and a precise pharmacological mechanism remains elusive . Cholinergic systems may be relevant for MA use outcomes . Future studies should continue to assess the role of smoking in MA treatment outcomes Although some individuals who abuse methamphetamine have considerable cognitive deficits , no prior studies have examined whether neurocognitive functioning is associated with outcome of treatment for methamphetamine dependence . In an outpatient clinical trial of bupropion combined with cognitive behavioral therapy and contingency management ( Shoptaw , S. , Heinzerling , K.G. , Rotheram-Fuller , E. , Steward , T. , Wang , J. , Swanson , A.N. , De La Garza , R. , Newton , T. , Ling , W. , 2008 . R and omized , placebo-controlled trial of bupropion for the treatment of methamphetamine dependence . Drug Alcohol Depend 96 , 222 - 232 . ) , 60 methamphetamine-dependent adults completed three tests of reaction time and working memory at baseline . Other variables that were collected at baseline included measures of drug use , mood/psychiatric functioning , employment , social context , legal status , and medical status . We evaluated the relative predictive value of all baseline measures for treatment outcome using Classification and Regression Trees ( CART ; Breiman , L. , Friedman , J.H. , Olshen , R.A. , Stone , C.J. , 1984 . Classification and Regression Trees . Wadsworth , Belmont , CA . ) , a nonparametric statistical technique that produces easily interpretable decision rules for classifying subjects that are particularly useful in clinical setting s. Outcome measures were whether or not a participant completed the trial and whether or not most urine tests showed abstinence from methamphetamine abuse . Urine-verified methamphetamine abuse at the beginning of the study was the strongest predictor of treatment outcome ; two psychosocial measures ( e.g. , nicotine dependence and Global Assessment of Functioning ) also offered some predictive value . A few reaction time and working memory variables were related to treatment outcome , but these cognitive measures did not significantly aid prediction after adjusting for methamphetamine usage at the beginning of the study . On the basis of these findings , we recommend that research groups seeking to identify new predictors of treatment outcome compare the predictors to methamphetamine usage variables to assure that unique predictive power is attained |
11,934 | 10,908,406 | This systematic review of r and omized trials shows that both impact and non-impact exercise have a positive effect at the lumbar spine in pre- and postmenopausal women .
Impact exercise probably has a positive effect at the femoral neck . | Abstract .
Studies of the effect of exercise programs on bone mass appear inconsistent .
Our objective was to systematic ally review and meta-analyze r and omized trials of the effect of exercise on bone mass in pre- and postmenopausal women . | In 1987 I contributed a commentary that seriously evaluated the method ologic quality of studies promulgating the assumption that exercise has a role in the prevention of osteoporosis [ l ] . Along with a more comprehensive review published separately in 1989 121 , that commentary recommended r and omized controlled trials to confirm the well-recognized association between above average levels of physical activity and higher bone mineral density ( BMD ) [ l-4 ] . A recent literature search revealed eight reports published since 1989 that utilized a r and omized study design to determine the potential effects of various types of exercise interventions on BMD 15 - 121 . These studies had equivocal results ; some showed mild positive effects but others showed virtually no effect of exercise on BMD ( Table 1 ) . What is most disturbing about these studies is the generalIy high level of subject attrition reported . Indeed , subject dropout rates ranged from 4 % to 50 % . Five of the studies had attrition rates above 20 % ( Table 1 ) . Such high levels of attrition have serious implication s for analyzing and interpreting the results of these trials . In fact , not a single study presented a valid intention-to-treat ( ITT ) analysis to adjust statistically for significant subject attrition . Interestingly , a recent position statement on exercise and osteoporosis made no mention of this problem , its potential impact on the results of r and omized trials , or its statistical implication s 1131 . As articulated by a working group of the American Statistical Association , ITT analysis includes all r and omized subjects in the groups to which they were r and omly assigned , regardless of their compliance to the intervention and regardless of subsequent withdrawal from treatment or deviation from the protocol 1141 . ITT requires that all subjects initially r and omized into the study be included in the primary test statistics . Because this type of analysis may require imputation of data , its consequences can be profound in studies with attrition rates as high as many of these exercise studies . Some study reports stated that withdrawal rates were similar between groups ill ] , that reasons for withdrawal were not study related [ 9,11 ] , or that dropouts were not dissimilar to subjects who remained in the study on selected baseline variables 1121 . While these findings may To assess the effect of an exercise intervention using a weighted vest on perceived health status and bone density in older persons , we enrolled 36 seniors in a r and omized controlled trial . The vest-use group met weekly for 1 h for a low level exercise class . They wore a weighted vest during the class and as tolerated at home . The discussion controls met for 1 h weekly . At baseline and follow-up ( 20 weeks ) , subjects completed a question naire that incuded the 20 item MOS Short-Form Health Survey , Multidimensional Health Locus of Control Scale , and Philadelphia Geriatric Center Morale Scale , and bone density was measured by dual energy X-ray absorptiometry . Subjects also completed daily activity diaries . Subjects in the vest group reported a statistically significant dicrease in bodily pain , improved physical functioning , and increased internal health locus of control . Bone density increased by 1 % in the vest group and decreased by 0.6 % in the controls ( p=0.12 ) . We conclude that our exercise intervention had a positive effect on some measures of perceived health in older persons The objectives of this study were to evaluate ( 1 ) the effect of spinal muscle strengthening by loading exercises on the bone mineral density ( BMD ) of the spine , and ( 2 ) the effect of upper extremity loading exercises on the BMD of the midradius and femur in healthy , premenopausal women . The study design was a r and omized , controlled trial of 3 years ' duration . Ninety-six healthy , premenopausal , white women aged 30 - 40 years participated ; 67 completed the study . All subjects were in good health ( normal menses ) and were active , but not athletic ( that is , not involved in a regular sport activity ) . Subjects were r and omized to an exercise or control group . The exercise group performed a supervised , non-strenuous , weight-lifting exercise program . Exercise performance was supervised once a week at the medical facility . In addition , the subjects performed the exercises twice a week on their own . Dietary calcium intake was to be maintained at 1,500 mg/day in both groups . Bone density was measured at the lumbar spine and hip with dual-energy X-ray absorptiometry at 0 , 1 , and 3 years . BMD of the midradius was measured with single photon absorptiometry . Measurements of muscle strength were obtained at baseline and every 3 months for 3 years . Maximal oxygen uptake was measured , and the level of physical activity was recorded . Compliance with the exercise program was excellent during the first year of the study , but decreased thereafter . At the end of 3 years , subject withdrawal was about 34 % from the exercise group and about 22 % from the control group ( total subject withdrawal was about 30 % ) . Muscle strength in the exercise group increased significantly at all involved skeletal sites ( p values all < 0.001 ) . There was a modest positive correlation between the BMD of Ward 's triangle with spinal flexor strength ( r = 0.32 , p = 0.008 ) and with grip strength ( r = 0.38 , p = 0.001 ) . Comparing study groups , we found no significant effect of the loading and nonstrenuous strengthening exercises in the exercise group or free physical activity group ( our control group ) on BMD at the spine , hip , or midradius measurement sites . In active , but not athletic premenopausal women , additional moderate weight-lifting exercises showed no significant effect on BMD Summary The purpose of this study was to determine the optimal intensity of exercise necessary to prevent the postmenopausal bone loss on the basis of anaerobic threshold ( AT ) . Thirty-three postmenopausal women were r and omized to control ( group C : n=12 ) or two exercise groups ( group H and group M ) . All women performed a treadmill exercise test , and the AT was measured by expired gas analysis . The exercise regimen consisted mainly of walking at a speed that kept the exercise heart rate above the AT ( group H : n=12 ) or below the AT ( group M : n=9 ) . Exercise was performed for 30 minutes , three times a week for 7 months . The bone mineral density ( BMD ) of the lumbar vertebrae was measured using dual energy X-ray absorptiometry . The BMD level in group C decreased by 1.7±2.7 % , but there was a significant increase of 1.1±2.9 % in group H. In group M there was a decrease of 1.0±3.1 % which did not differ from group C. In group C , serum osteocalcin and urinary hydroxyproline excretion were significantly increased , but no changes were seen in either of the exercise groups . Urinary calcium significantly decreased in the exercise groups . We conclude that short-term ( 7 months ) exercise with intensity above the AT is safe and effective in preventing postmenopausal bone loss OBJECTIVE The purpose of the study was to determine the effect of six months of heavy resistance training ( weightlifting ) on the bone density of premenopausal women . EXPERIMENTAL DESIGN A 6-month prospect i ve design with r and om assignment to groups . SETTING Measurements of bone mineral density ( BMD ) were obtained from the Radiology Clinic at North Carolina Memorial Hospital . Exercise sessions were completed in the Physical Education Department facilities at the University of North Carolina , Chapel Hill , NC . PARTICIPANTS Thirty-five premenopausal women , 40 - 50 years of age , were r and omly assigned to either a resistance training ( RT ) and sedentary control ( CON ) group . The study finished with 12 women exercising and 14 in the control group . INTERVENTION The resistance training consisted of three days per week of high-intensity weightlifting specifically design ed to place strain on the spine and hips . MEASURES Bone density of the lumbar vertebrae , femoral neck , and distal radius , were determined prior to and at the end of the exercise program using dual energy X-ray absorptiometry ( DEXA ) . RESULTS Resistance-training produced strength gains : overhead press = 125 % , leg press = 86 % , and calf raises = 91 % ( p < 0.001 ) . RT tended to increased lumbar BMD 1.03 % , while the CON decreased 0.36 % ( p = 0.072 ) . Both groups lost radial BMD ( CON = -0.45 % ; RT = -1.04 % ) . Both groups gained femoral neck BMD ( CON = 1.26 % ; RT = 1.22 % ) . CONCLUSIONS These results suggest that even a short-term weight training program can either maintain or improve the BMD of the femoral neck and lumbar vertebrae in premenopausal women A substantial body of cross-sectional data and a smaller number of intervention trials generally justify optimism that regular physical activity benefits the skeleton . We conducted an 8 month controlled exercise trial in a group of healthy college women ( mean age = 19.9 years ) who were r and omly assigned to a control group or to progressive training in jogging or weight lifting . We measured the following variables : bone mineral density ( BMD ) of the spine ( L2 - 4 ) and right proximal femur using dual-energy x-ray absorptiometry , dynamic muscle strength using the 1-RM method , and endurance performance using the 1.5 mile walk/run field test . A total of 31 women completed the 8 month study . For women completing the study , compliance , defined as the percentage of workout sessions attended , was 97 % for the runners ( range 90 - 100 % ) and 92 % ( range 88 - 100 % ) for the weight trainers . Body weight increased by approximately 2 kg in all groups ( p less than 0.05 ) . Weight training was associated with significant increases ( p less than 0.01 ) in muscle strength in all muscle groups . Improvement ranged from 10 % for the deep back to 54 % for the leg . No significant changes in strength scores were observed in the control or running groups . Aerobic performance improved only in the running group ( 16 % , p less than 0.01 ) . Lumbar BMD increased ( p less than 0.05 ) in both runners ( 1.3 + /- 1.6 % ) and weight trainers ( 1.2 + /- 1.8 % ) . These results did not differ from each other but were both significantly greater than results in control subjects , in whom bone mineral did not change . ( ABSTRACT TRUNCATED AT 250 WORDS A r and omized controlled trial was carried out to determine whether calcium supplementation and load-bearing exercise can increase or maintain bone mass in the elderly . Fifty Chinese women , aged 62–92 years , living in a hostel for the elderly in Hong Kong were r and omized to enter one of four treatment groups : ( I ) calcium supplementation of 800 mg ( as calcium lactate gluconate ) daily ; ( II ) load-bearing exercise four times a week plus a daily placebo tablet ; ( III ) calcium supplementation daily and load-bearing exercise four times a week ; ( IV ) a placebo tablet daily . The interventions went on for 10 months . The bone mineral density ( BMD ) was measured at three sites in the hip ( femoral neck , Ward 's triangle and intertrochanteric area ) and the L2–4 level of the spine . The percentage change in BMD in 10 months was used as the main outcome measurement . The parathyroid hormone level and indices of bone metabolism were also measured before and after 10 months of intervention . The BMD at Ward 's triangle and the intertrochanteric area increased significantly in subjects on calcium supplement ( p<0.05 ) , but there was no significant change at the spine and femoral neck . Exercise had no effect on bone loss at any site . However , the results of two-way analysis of variance showed a significant joint effect of calcium supplements and exercise at the femoral neck ( p<0.05 ) , but not at the other sites . The parathyroid hormone levels fell significantly in subjects on calcium supplements (p<0.01).Calcium supplement in the form of calcium lactate gluconate was adequately absorbed in elderly Chinese women with a calcium intake of less than 300 mg per day . It was effective in reducing bone loss at the hip , and there may be interaction effects with exercise in maintaining bone density The effect of two structured exercise programmes on the bone mass of 48 healthy postmenopausal white women aged 50 - 62 was studied after one year . Volunteers were r and omised to group 1 ( control ) , group 2 ( aerobic exercise ) , or group 3 ( aerobic and strengthening exercises ) . Before and after the training programme each subject had evaluations of bone mass ( determined by neutron activation analysis and expressed as calcium bone index ) and maximum oxygen uptake attained on a multistage exercise treadmill test . After one year both exercise groups had higher levels of fitness and greater bone mass than controls . Mean values ( 2 SEM ) for changes in the calcium bone index were -0.011 ( 0.037 ) , 0.039 ( 0.035 ) , and 0.066 ( 0.036 ) for groups 1 , 2 , and 3 , respectively . Analysis of variance on the observed data and analysis of covariance adjusting changes to the initial mean value for the whole group showed significant differences between each exercise group and the controls but no difference between the exercise groups themselves . Both exercise groups showed a significant improvement in maximum oxygen uptake . This study suggests that exercise may modify bone loss in healthy postmenopausal women OBJECTIVE to evaluate the effects of brisk walking on bone mineral density in women who had suffered an upper limb fracture . DESIGN r and omized placebo-controlled trial . Assessment s of bone mineral density were made before and at 1 and 2 years after intervention . St and ardized and vali date d measures of physical capacity , self-rated health status and falls were used . SETTING district general hospital outpatient department . SUBJECTS 165 women drawn from local accident and emergency departments with a history of fracture of an upper limb in the previous 2 years . Women were r and omly allocated to intervention ( self-paced brisk walking ) or placebo ( upper limb exercises ) groups . INTERVENTION both groups were seen at 3-monthly intervals to assess progress , measure physical capacity and maintain enthusiasm . The brisk-walking group were instructed to progressively increase the amount and speed of walking in a manner that suited them . The upper limb exercise placebo group were asked to carry out a series of exercises design ed to improve flexibility and fine h and movements , appropriate for a past history of upper limb fracture . RESULTS drop-outs from both intervention and placebo groups were substantial ( 41 % ) , although there were no significant differences in bone mineral density , physical capacity or health status between drop-outs and participants . At 2 years , among those completing the trial , bone mineral density at the femoral neck had fallen in the placebo group to a greater extent than in the brisk-walking group [ mean net difference between intervention and placebo groups 0.019 g/cm2 , 95 % confidence interval ( CI ) -0.0026 to + 0.041 g/cm2 , P = 0.056 ] . Lumbar spine bone mineral density had increased to a similar extent ( + 0.017 g/cm2 ) in both groups . The cumulative risk of falls was higher in the brisk-walking group ( excess risk of 15 per 100 person-years , 95 % CI 1.4 - 29 per 100 person-years , P < 0.05 ) . There were no significant differences in clinical or spinal x-ray fracture risk or self-rated health status between intervention and placebo groups . CONCLUSION the promotion of exercise through brisk-walking advice given by nursing staff may have a small , but clinical ly important , impact on bone mineral density but is associated with an increased risk of falls . Self-paced brisk walking is difficult to evaluate in r and omized controlled trials because of drop-outs , placebo group exercise , limited compliance and lack of st and ardization of the duration and intensity of walking . Further work is needed to evaluate the best means of safely achieving increased activity levels in different groups , such as older women and those at high risk of fractures Previous research suggests that physical activity may have a beneficial effect on bone mineral density ( BMD ) in women . This relationship was explored in a 2-year , r and omized , intervention trial investigating the efficacy of exercise and calcium supplementation on increasing peak bone mass in young women . One hundred and twenty-seven subjects ( ages of 20 - 35 years ) were r and omly assigned either to an exercise program that contained both aerobics and weight training components or to a stretching program . Calcium supplementation ( up to 1500 mg/day including dietary intake ) or placebo was given in a double-blinded design to all subjects . Spinal trabecular BMD was determined using quantitative computed tomography ( QCT ) . Spinal integral , femoral neck , and trochanteric BMD were measured by dual X-ray absorptiometry ( DXA ) and calcaneal BMD by single photon absorptiometry ( SPA ) . Fitness variables included maximal aerobic capacity ( VO2max ) , and isokinetic muscle performance of the trunk and thigh . Measurements were made at baseline , 1 year , and 2 years . Sixty-three subjects ( 32 exercise , 31 stretching ) completed the study , and all the measured bone parameters indicated a positive influence of the exercise intervention . There were significant positive differences in BMD between the exercise and stretching groups for spinal trabecular ( 2.5 % ) , femoral neck ( 2.4 % ) , femoral trochanteric ( 2.3 % ) , and calcaneal ( 6.4 % ) measurements . The exercise group demonstrated a significant gain in BMD for spinal integral ( 1.3 + /- 2.8 % , p < 0.02 ) , femoral trochanteric ( 2.6 + /- 6.1 % , p < 0.05 ) , and calcaneal ( 5.6 + /- 5.1 , p < 0.01 ) measurements . In contrast to exercise , the calcium intervention had no positive effect on any of the bone parameters . In regard to fitness parameters , the exercise group completed the study with significant gains in VO2max and isokinetic ( peak torque ) values for the knee flexion and extension and trunk extension . This study indicates that over a 2-year period , a combined regimen of aerobics and weight training has beneficial effects on BMD and fitness parameters in young women . However , the addition of daily calcium supplementation does not add significant benefit to the intervention OBJECTIVE To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women . DESIGN R and omized controlled trial of 1-year duration . SETTING Exercise laboratory at Tufts University , Boston , Mass. POPULATION Forty postmenopausal white women , 50 to 70 years of age , participated in the study ; 39 women completed the study . The subjects were sedentary and estrogen-deplete . INTERVENTIONS High-intensity strength training exercises 2 days per week using five different exercises ( n = 20 ) vs untreated controls ( n = 19 ) . MAIN OUTCOME MEASURES Dual energy x-ray absorptiometry for bone status , one repetition maximum for muscle strength , 24-hour urinary creatinine for muscle mass , and backward t and em walk for dynamic balance . RESULTS Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005 + /- 0.039 g/cm2 ( 0.9 % + /- 4.5 % ) ( mean + /- SD ) and 0.009 + /- 0.033 g/cm2 ( 1.0 % + /- 3.6 % ) , respectively , in the strength-trained women and decreased by -0.022 + /- 0.035 g/cm2 ( -2.5 % + /- 3.8 % ) and -0.019 + /- 0.035 g/cm2 ( -1.8 % + /- 3.5 % ) , respectively , in the controls ( P = .02 and .04 ) . Total body bone mineral content was preserved in the strength-trained women ( + 2.0 + /- 68 g ; 0.0 % + /- 3.0 % ) and tended to decrease in the controls ( -33 + 77 g ; -1.2 % + /- 3.4 % , P = .12 ) . Muscle mass , muscle strength , and dynamic balance increased in the strength-trained women and decreased in the controls ( P = .03 to < .001 ) . CONCLUSIONS High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass , strength , and balance in postmenopausal women This study was undertaken to examine the effect of estrogen replacement therapy alone and estrogen replacement therapy plus variable-resistance weight training on the bone mineral content of surgically menopausal women . A total of 20 surgically menopausal women were r and omized and treated with either 0.625 mg conjugated estrogen daily or the same dose of estrogen plus a closely monitored exercise program involving the use of Nautilus muscle strengthening/endurance equipment . After 1 year 's observation , the bone mineral density ( BMD ) of the spine determined by dual-photon absorptiometry increased in the exercising subjects by 8.3 + /- 5.3 % ( p = 0.004 ) , 95 % confidence limits ( CL ) 3.9 - 12.8 % ; the group with estrogen replacement therapy alone maintained their BMD : 1.5 + /- 12.4 % ( p = 0.36 ; 95 % CL = -6.9 - 9.8 % ) . The total body BMD of the exercising group increased by 2.1 + /- 1.5 % ( p = 0.003 ; 95 % CL = 0.8 - 3.3 % ) ; the nonexercising women had a nonsignificant 0.6 + /- 2.9 % change ( p = 0.30 ; 95 % CL = -1.4 - 2.5 % ) . A significant increase of 4.1 + /- 4.3 % ( p = 0.01 ; 95 % CL = 0.8 - 7.4 % ) in the radial midshaft BMD of the exercising group was found ; the estrogen alone group recorded a nonsignificant change of -0.3 + /- 3.1 % ( p = 0.33 ; 95 % CL = -1.7 - 2.4 % ) . The results of this study suggest that variable-resistance training in estrogen-replete women adds bone to both the axial and appendicular skeleton Summary On the premise that bone response to exercise is locally controlled [ 1 ] , we conducted a r and omized trial to evaluate the effects of a 1-year training of psoas muscles ( treatment group : TG ) versus a 1-year training of deltoid muscles ( control group : CG ) on the lumbar trabecular bone mineral density ( TBMD ) . TBMD was measured with computed tomography scan . Seventy-eight subjects were included and 67 completed the study . Intention to treat analysis revealed no significant change in TBMD from 0 to 12 months . Data analysis in the 67 remaining women , including both assiduous and nonassiduous subjects , revealed greater bone loss in CG than in TG although the difference was not significant . Similar analysis in a subgroup of subjects who performed the exercises assiduously ( TG : n = 23 , CG : n = 26 ) showed that the mean bone loss of all four vertebrae from 0 to 12 months was significantly greater in the CG ( −8.87 ± 12.75 mg/cm3 , mean ± SD ) than in the TG ( 0.14 ± 11.21 mg/cm3 , mean ± SD , P = 0.01 ) . These results suggest that continuous 1-year psoas training can prevent lumbar bone loss in postmenopausal women and support the hypothesis of local action of physical activity The purpose of this study was to determine the effects of a 12-month resistance training program , of two different intensities , on bone mineral density ( BMD ) in healthy , older women . Twenty-six Caucasian women ( aged 65 - 79 years ) completed the study . Subjects were r and omly assigned to one of three groups : high-intensity ( HI ; n = 8) , low-intensity ( LI ; n = 7 ) , and control ( CON ; n = 11 ) . The active groups performed 10 exercises , 3 days/week under supervision . Exercise intensity was maintained at 80 % of one-repetition maximum ( 1-RM ) for the HI groups , and at 40 % 1-RM for the LI group . The volume of work was maintained constant between the two groups by assigning the LI group twice as many repetitions for each exercise . Maximal muscular strength and BMD of the lumbar spine and total hip were measured at baseline and at 12 months . Strength was evaluated using the 1-RM method , and BMD was determined by dual-energy X-ray absorptiometry . Exercise session attendance was similar for the two groups ( 81.0 % HI ; 76.8 % LI ) . Muscular strength improved in the exercisers compared with the CON group ( p < or = 0.05 ) . Percentage change in lumbar spine BMD was 0.7 + /- 1.9 % , 0.5 + /- 2.4 % , and -0.1 + /- 2.3 % for the HI , LI , and CON groups , respectively . Percentage change in total hip BMD was 0.8 + /- 2.3 % ( HI ) , 1.0 + /- 1.7 % ( LI ) , and 0.9 + /- 1.3 % ( CON ) . Group differences in BMD change were not significant ( p > 0.05 ) . These findings suggest that high-intensity and low-intensity resistance training regimens effectively increase muscular strength , but not lumbar spine or total hip BMD , in healthy , older women The etiology of age-related bone loss is unclear but both lack of exercise and dietary calcium deficiency have been implicated in its causation . This 2-year r and omized placebo-controlled study was design ed to examine the effects of increased dietary calcium and exercise in 168 women who were more than 10 years postmenopausal . The subjects were r and omized into one of 4 groups : placebo , milk powder containing 1 g of calcium , calcium tablets 1 g/night , and calcium tablets 1 g/night and an exercise regimen . The exercise group aim ed to undertake 4 h of extra weight-bearing exercise per week and were undertaking 10 % more activity than other groups at 2 years . Bone mineral density at the lumbar spine , three hip sites , and two sites of the tibia close to the ankle joint were measured at 6 month intervals . Dietary intake was evaluated by a weighed food record , exercise was evaluated by an exercise diary , and blood and urine sample s were obtained to examine effects on calcium homeostasis . Individual data points were compared using repeated measures ANOVA and least squares regression . Calcium supplementation by either the calcium tablets or the milk powder result ed in cessation of bone loss at the intertrochanteric hip site ( placebo , calcium tablets , calcium and exercise , milk powder -0.81 , + 0.17 , + 0.23 , and + 0.07 % per year , respectively ; p < 0.05 for all supplementation groups compared with placebo ) with similar results at the trochanteric hip site . The calcium and exercise group had less bone loss at the femoral neck site when compared with calcium supplementation alone ( placebo , calcium tablets , calcium and exercise , milk powder -0.67 , -0.18 , + 0.28 , and -0.18 % per year , respectively ; p < 0.05 for calcium and exercise compared with calcium alone ) . There was a significant reduction in the rate of bone loss at the ultradistal site of the tibia ( placebo , calcium tablets , calcium and exercise , milk powder -2.5 , -1.6 , -1.0 , and -1.5 % per year , respectively ; p < 0.05 for all supplementation groups compared with placebo ) . There was no significant bone loss at the spine site in any group . ( ABSTRACT TRUNCATED AT 250 WORDS The effects of brief daily exercise on bone mineral density ( BMD ) were assessed in a r and omized controlled trial in 44 healthy postmenopausal women using weight-bearing exercise in a regimen adapted from osteogenic protocol s reported in animal studies . BMD was assessed masked using dual energy X-ray absorptiometry at 0 , 6 , and 12 months . The sites assessed were the proximal femur ( neck , Ward 's triangle , and trochanter ) and the lateral spine ( L2 - 3 ) to assess the effects of the exercise , and the radius ( ultradistal and 33 % distal ) as a marker for systemic effects . The test group was required to perform 50 " heel drops " daily at home ( raising the body weight onto the toes and then letting it drop to the floor keeping the knees and hips extended ) and to attend a weekly class of mixed exercises , which included some high-impact activity . The control group also attended a weekly exercise class run by the same teacher , which included only low-impact activity , and did flexibility exercises at home daily . The ground reaction forces ( as a ratio of body weight ) during heel drops were 2.5 to 3.0 N/N , with a rate of rise of 50 - 100 kN/sec . A patient with an instrumented femoral implant allowed comparison of compressive axial forces in the shaft of the proximal femur with the ground reaction forces , and these appeared to be transmitted undamped to the shaft of the femur . Initial analysis of BMD in the women showed no significant increases after 12 months of exercise at any site in either group , and the groups did not differ significantly from each other in this respect . Proximity to menopause was not associated with rapid bone loss , and in those who were more than 6 years postmenopausal , there was evidence for a maintenance effect of the exercise in the test group . Compliance ( 83 % ) and increases in leg extensor power ( 15 % ) were similar in both groups , and when they were combined , BMD was maintained at the trochanter but fell significantly at the radius ( p < 0.001 ) OBJECTIVES To determine the effects of up to 14 months of aerobic exercise on measures of bone density in older adults . DESIGN R and omized controlled trial with subjects assigned to either an aerobic exercise condition , non-aerobic yoga , or a wait list non-exercise control group for 4 months . Aerobic fitness and bone density were evaluated in all subjects at baseline ( Time 1 ) and after 4 months ( Time 2 ) . A semi-crossover design was utilized with all subjects completing 4 months of aerobic exercise , followed by another evaluation ( Time 3 ) . All subjects were then given the option of 6 additional months of aerobic exercise , after which they had a fourth evaluation ( Time 4 ) . SETTING An outpatient exercise rehabilitation facility at a large , major medical center . SUBJECTS One-hundred-one healthy men ( n = 50 ) and women ( n = 51 ) over age 60 ( Mean age = 67.0 ) , recruited from the community . INTERVENTION The exercise program included stretching , cycle ergometry , and walking three times per week for 60 minutes throughout the course of the study . OUTCOME MEASURES Aerobic fitness ( VO2max ) as assessed by cycle ergometry , and bone density ( bone mineral content ) measured by single photon absorptiometry . RESULTS Subjects achieved a 10%-15 % increase in VO2max after 4 months of exercise training , and 1%-6 % further improvement with additional training . Aerobic fitness was associated with significant increases in bone density in men , but not women , who maintained aerobic exercise for 14 months One hundred and seventy-nine women aged 60–85 years ( mean age 71.6 years , SD 5.3 years ) were r and omly recruited from the community to participate in a 12-month r and omized controlled trial to determine whether a program of twice-weekly structured exercise has beneficial effects on three factors associated with osteoporotic fractures : quadriceps strength , postural sway and bone density . At initial testing , there were no significant differences in the strength , sway and bone density measures ( assessed at the hip and lumbar spine ) between the exerciser and control groups . The exercise classes included strengthening , coordination and balance exercises , and approximately 35 min of each class comprised weight-bearing exercise . The mean number of classes attended for the 68 exercisers who completed the program was 59.8 of the 82 classes ( 72.9 % ) . At the completion of the trial , the intervention group showed significant improvements in quadriceps strength and sway but not bone mineral density when compared with the control group . Indices of fracture risk , indicated by ( i ) the sum of st and ard score results and ( ii ) the sum of quartile grade s of the femoral neck bone density , sway and strength measures , decreased significantly in the exercisers at the end of the trial compared with the controls . In conclusion , the program of general aerobic exercise may have reduced overall fracture risk , even though it did not significantly increase bone density . Further long-term studies are required that include acceptable weight-loaded exercises to determine optimal programs for reducing fracture risk factors by improving bone density as well as strength and balance The effects of 52 weeks resistance training at one of two exercise intensities on thigh muscle strength , fiber cross-sectional area ( CSA ) , and tissue composition were studied in healthy 65 - 79-year-old women . Subjects were assigned to either a control ( CO ) , high-intensity ( HI ) or low-intensity ( LO ) training group . Exercise regimens consisted of three sets of leg press , knee extension , and knee flexion exercises , 3 days/week , at either 80 % of one-repetition maximum ( 1-RM ) for seven repetitions ( HI ) or 40 % of 1-RM for 14 repetitions ( LO ) . Dynamic muscle strength was evaluated by 1-RM , thigh lean tissue mass ( LTM ) , fat mass , and bone mineral density ( BMD , g/cm2 ) by dual energy X-ray absorptiometry , and fiber CSA of vastus lateralis m. by histomorphometry . Muscle strength increased , on average ( + /- SEM ) , by 59.4 + /- 7.9 % and 41.5 + /- 7.9 % for HI and LO , respectively , compared to 1.3 + /- 4.8 % in CO ( P = 0.0001 ) . Type I fiber CSA increased over time ( P < 0.05 ) in both exercise groups , with a trend for increased type II area ( HI , P = 0.06 ; LO , P = 0.11 ) . There was no significant effect of either exercise program on thigh tissue composition , except for BMD at the 1/3 site ( middle third of the femur ) , where LO and CO groups experienced a decline ( P < 0.05 ) of -2.2 + /- 0.5 % and -1.8 + /- 0.6 % , respectively , while HI maintained BMD ( + 1.0 + /- 1.0 % ) . Both training programs produced significant gains in thigh muscle strength , which were associated with fiber hypertrophy , although these did not translate into appreciable alterations in thigh tissue composition This 1 year study examined the effect of high impact and low impact activities on bone mineral density ( BMD ) at the lumbar vertebrae ( L2-L4 ) in healthy , sedentary , early postmenopausal women . Fifteen subjects whose postmenopausal status was verified by the blood levels of follicle stimulating hormone ( FSH ) and estradiol were chosen . These subjects were tested on the following variables : BMD via dual photon absorptiometry , heart rate response to the Balke treadmill test , percent fat via skinfolds , and a 3-d dietary analysis . Subjects were matched and then assigned r and omly to one of three groups : ( a ) a control nonexercising group , ( b ) a low impact exercise group , and ( c ) a high impact exercise group . The control nonexercising group experienced a significant linear decrease in BMD during the study ( F = 12.63 , P = 0.002 ) . Both the low and high impact exercise groups maintained BMD during the study ( F = 0.04 , P = 0.85 ; F = 1.08 , P = 0.31 , respectively ) . The difference in BMD between the low impact and the high impact exercise groups was not significant ( F = 0.36 , P = 0.55 ) . In conclusion , 20 min of moderate intensity low impact or high impact exercise 3 d.wk-1 for 1 yr is effective in maintaining BMD in early postmenopausal women A considerable increase in muscle strength and bone mass can be achieved in young adults through athletic exercise programs . We studied a less dem and ing nonloading exercise program for the back extensor muscles in postmenopausal women who were not on estrogen therapy . We r and omly assigned 65 healthy Caucasian women without evidence of or risk factors for osteoporosis into an exercise group and a control group . The strength of the back extensor muscles and bone mineral density of the lumbar spine were measured at baseline and every 6 months for 2 years . In addition , a physical activity score was determined . Compliance was assessed by regular interviews and review of diaries . During the 2-year study , the mean rates of bone loss in the two groups were not statistically different . The strength of the back extensor muscles increased in both groups but significantly more ( P = 0.002 ) in the exercise group . We conclude that postmenopausal bone loss is unaffected by a modest exercise program despite an increase in muscle strength . Nonloading muscle exercise may be ineffective in retarding vertebral bone loss in ambulatory , healthy postmenopausal women We conducted a 2-year ( 42 weeks of consecutive training in each year , separated by 10 weeks of testing and vacation time ) r and omized , controlled trial of weight training in 142 healthy male and female subjects , aged 60 to 80 years . Measurements included dynamic strength , symptom-limited endurance in cycling , treadmill walking and stair climbing , muscle size , and bone mineral density and content of the lumbar spine and whole body . One hundred and thirteen subjects completed the study ( 57 exercise , 56 control ) , with a mean attendance of 85 % among the exercisers . Muscle strength was unchanged in the control subjects but increased ( collapsed across age and gender ) from 32 % ( leg press ) to 90 % ( military press ) in the exercisers . Symptom-limited endurance in cycling , treadmill walking , and stair climbing increased in the exercisers by ( mean + /- SE ) 6.2 + /- 0.8 % , 29.2 + /- 7.3 % , and 57 + /- 12 % , respectively ; the only change in the controls was an unanticipated 33 % increase in stair climbing performance during the first year . These values were unchanged in the controls . Cross-sectional area of the knee extensors increased by 8.7 + /- 0.9 % in the trained subjects and was unchanged in controls . Measures of whole body , lumbar spine bone mineral density , and lumbar spine bone mineral content were unchanged in the exercisers , but whole body bone mineral content decreased by 1 % . In contrast , there were small increases ( < 4.0 % ) in bone mineral density among the controls . Long-term weight training proved to be a safe and well-tolerated mode of exercise for the elderly . Increased strength was associated with muscle hypertrophy in each year , and with increased endurance in cycling , walking , and stair climbing . There were no changes in bone mineral density but a small reduction in whole body bone mineral content BACKGROUND Osteoporotic fractures among the elderly are common , and without preventive measures the burden of these fractures on health-care systems will increase further . The purpose of this r and omised controlled study was to evaluate , in premenopausal women , the effects of high-impact loading on several determinants osteoporotic fractures . METHODS 98 healthy , sedentary female volunteers aged 35 - 45 years were r and omly assigned to either a training ( n = 49 ) or a control group ( n = 49 ) . Progressive high-impact exercises were done three times per week for 18 months . We measured bone mineral density ( BMD ) in specific axial and lower-limb sites , by dual-energy X-ray absorptiometry , at baseline and after 12 and 18 months . Maximum isometric strength , muscular and cardiovascular performance , and dynamic balance were also assessed . FINDINGS BMD at the femoral neck , a weightbearing site , increased significantly more in the training group ( mean 1.6 % [ 95 % CI 0.8 - 2.4 ] ) than in the control group ( 0.6 % [ -0.2 to 1.4 ] , p = 0.006 ) . By contrast , at non-weightbearing sites , such as the distal radius , there was no significant difference between the training and control groups ( -1.5 % [ -2.7 to -0.3 ] vs -0.7 % [ -1.9 to -0.5 ] , p = 0.60 ) . In the training group there was a significant improvement in vertical jump and predicted oxygen consumption per min at maximum exercise compared with controls . INTERPRETATION High-impact exercises that load bones with a rapidly rising force profile in versatile movements improve skeletal integrity , muscular performance , and dynamic balance in premenopausal women . If done on a regular basis , this type of exercise may help decrease the risk of osteoporotic fractures in later life . Long-term studies are required to show whether these 18-month results can be translated into long-term benefit Summary This report deals with the analysis of data from a 3-year clinical trial on the effect of walking on postmenopausal bone loss . Two hundred fifty-five women , with an average age of 57 at entry , were r and omized into two groups , a walking and a control group . Bone measures in the shaft of the radius were carried out with a CT scanner in search of generalized skeletal effects rather than effects localized to the bones of the leg . Although bone density losses were comparable in the two r and omized groups , changes in the crosssectional area of the radius were significantly greater in the walkers with high grip strength ( > 25 Kg ) than in the controls with comparable high grip strength which corresponded to the upper half range of the grip-strength distribution . It is concluded that the moderate activity of walking exerted systemically positive effects on the radius which , within the protocol of the study , could be substantiated only when synergized with inherent muscle strength Studies of the effects of different exercise programmes on bone in postmenopausal women have produced different conclusions , but few have targeted elderly women specifically.1 We report a controlled trial of weight bearing exercise in this clinical ly important population . The study was approved by the local ethics committee . We recruited volunteers by advertising in the local press . After excluding subjects with conditions or drug treatment likely to affect bone , we r and omly allocated 118 volunteers ( mean age 64.5 ( range 60 - 73 ) years ) to either a group taking calcium supplementation ( 1000 mg calcium daily , as calcium carbonate ) or to an exercise group taking the same calcium supplementation . We monitored compliance with calcium by a tablet count every six months . We asked volunteers in the calcium group taking exercise to attend the University of Dundee 's exercise class for people aged over 60 three times weekly for each of three 10 It is considered that skeletal mass in humans may respond to loading or the number of loading cycles . The aim of this study was to examine the effect of a 1 year progressive resistance training program on the bone mass of 56 postmenopausal women . Assignment was by block r and omization to one of two resistance training groups : a strength trained group ( 3 x 8 repetition maximum ) or an endurance group ( 3 x 20 repetition maximum ) . The resistance exercises were selected to stress the ipsilateral forearm and hip region . The exercising side was r and omly assigned with one side exercised while the alternate side acted as the nonexercise control . Bone mineral density ( BMD ) was measured every 3 months at the radial forearm and four hip sites using the Hologic QDR 2000 bone densitometer . A linear regression function was fitted for each individual 's bone density results , and the slope was compared for the exercise and control side using paired t-tests . The bone mass increase with the strength regimen was significantly greater at the trochanteric hip site ( control -0.6 + /- 2.2 % , exercise 1.7 + /- 4.1 % , p < 0.01 ) , at the intertrochanteric hip site ( control -0.1 + /- 2.1 % , exercise 1.5 + /- 3.0 % , p < 0.05 ) , Ward 's triangle ( control 0.8 + /- 5.2 % , exercise 2.3 + /- 4.0 % , p < 0.05 ) , and at the ultradistal radial site ( control -1.4 + /- 2.3 % , exercise 2.4 + /- 4.3 % , p < 0.01 ) . There was no significant increase in BMD with the endurance regimen except at the radius midsite ( control -1.0 + /- 2.3 % , exercise 0.1 + /- 1.4 % , p < 0.01 ) . In both the endurance and the strength group , muscle strength , tested by a one-repetition maximum ( 1RM ) test , increased significantly for all 10 exercises ( p < 0.01 ) and to a similar degree in the two groups . In the strength group but not the endurance group there were significant correlations between the slope of the change in BMD and the percentage increase in strength as follows : trochanter with leg press ; intertrochanter with leg press ( p < 0.05 ) ; and Ward 's triangle with hip extension and hip adduction ( p < 0.05 ) . Thus these results support the notion of a site-specific response of bone to maximal loading from resistance exercise in that although the trochanter and intertrochanter bone density was elevated by the resistance exercises undertaken , there was no effect on the femoral neck value . Postmenopausal bone mass can be significantly increased by a strength regimen that uses high-load low repetitions but not by an endurance regimen that uses low-load high repetitions . We conclude that the peak load is more important than the number of loading cycles in increasing bone mass in early postmenopausal women Healthy premenopausal women were r and omized into control and test groups ; both exercised weekly in class and daily at home for a year . The test class did intermittent high-impact exercise ; the control class did low-impact exercise . Bone density was assessed blind using dual energy X-ray absorptiometry at the femur ( neck , Ward 's triangle and trochanter ) and at the lumbar spine ( antero-posterior L1–4 ) on entry into the study , and again after 6 months ( n=27 ) and 12 months ( n=19 ) . At 6 months the test group ( n=14 ) showed a significant increase of 3.4 % in trochanteric bone density ( p=0.01 ) and this was significantly different from control ( p=0.05 ) . In the second 6 months the control group was crossed over to high-impact exercise and showed a significant increase of 4.1 % in trochanteric density ( n=7 ) while the original group maintained their improvement relative to baseline The purpose of this study was to determine the effect of a 1-year trunk resistive exercise program on bone mineral density at the lumbar spine and hip in postmenopausal women . Forty-nine subjects were divided into exercise and control groups . Dual photon absorptiometry was used to measure bone mineral density and the Muscle Examination and Exercise Dosimeter 3000 system was used to assess trunk muscle strength . Resistive exercise target levels for the exercise group were based on the results of the trunk muscle strength tests . The exercise group performed 3 sets of 10 repetitions for each of the sit-up , prone trunk extension , and double leg flexion exercises . The subjects were seen once per month and performed the exercises a minimum of three times per week . The bone mineral density and strength tests were done at baseline , at 6 months and at 12 months . The results of the study showed that 1 ) the dual photon absorptiometry method and the Muscle Examination and Exercise Dosimeter 3000 system were highly reliable in measuring bone mineral density and trunk muscle strength , respectively ; and 2 ) no significant differences were found between the exercise and control groups at lumbar vertebrae L2 , L3 , L4 , L2-L4 , and the femoral neck , Ward 's triangle , and trochanteric region of the proximal femur at baseline , 6-month , and 12-month evaluation sessions To evaluate the efficacy of therapeutic exercises in the prevention of bone loss , 146 untrained healthy postmenopausal women were prospect ively controlled for ( mean + /- SD ) 3.0 + /- 1.3 yr . Eighty-two subjects aged ( mean + /- SD ) 61.5 + /- 6.1 yr participated in an exercise program ( group 1 ) and sixty-four aged ( mean + /- SD ) 59.1 + /- 7.4 yr served as controls ( group 2 ) . Periodically during the study period , we measured women 's bone density at two forearm sites and recorded their physical activities . Because bone loss differed insignificantly between the groups , group 1 was retrospectively subdivided into group 1a ( regular exercise ) and group 1b ( nonregular exercise ) . The results showed that only 39 women ( 48 percent ) of group 1 ( group 1a ) performed the exercise program regularly for the prescribed time . Regression slopes of forearm bone density ( distal and proximal scans ) v time were significantly less negative ( P < 0.05 ) in group 1a ( distal , -0.3 percent and proximal , -0.7 percent per year ) than in group 1b ( distal , -1.8 percent and proximal -1.6 percent per year ) or group 2 ( distal , -1.7 percent and proximal , -1.9 percent per year ) . We conclude that in untrained elderly women , poor compliance with regular physical activities is a main factor , explaining the lack of response to exercise treatment in prevention of osteoporosis |
11,935 | 31,775,786 | Conclusion This systematic review and meta- analysis revealed that schizophrenia and other psychotic disorders are highly prevalent among homeless people , indicating an urgent need for studies to help develop better mechanisms of prevention , detection as well as treatment of those disorders among homeless people | Background Schizophrenia and other psychotic disorders constitute a huge global burden of disease and they are major contributors to disability as well as premature mortality among homeless people .
This systematic review and meta- analysis aim ed to estimate the pooled prevalence of schizophrenia and other psychotic disorders among homeless people . | INTRODUCTION AND AIMS Homelessness is associated with increased prevalence of mental health disorders , substance use disorders and mental health/substance use disorder comorbidity in the United States of America . Gay , bisexual and other men who have sex with men ( MSM ) living in the United States are at increased risk for homelessness , and have also evidence d elevated mental health and substance use disorder prevalence relative to their non-MSM male counterparts . DESIGN AND METHODS Secondary analysis of data from a r and omised controlled trial estimating the diagnostic prevalence of substance use/mental health disorder comorbidity among a sample of homeless , substance-dependent MSM ( DSM-IV verified ; n = 131 ) . RESULTS The most prevalent substance use/mental health disorder comorbidities were stimulant dependence comorbid with at least one depressive disorder ( 28 % ) , alcohol dependence comorbid with at least one depressive disorder ( 26 % ) and stimulant dependence comorbid with antisocial personality disorder ( 25 % ) . DISCUSSION AND CONCLUSIONS Diagnostic depression and antisocial personality disorder both demonstrated high rates of prevalence among homeless , substance-dependent ( particularly stimulant and alcohol dependent ) MSM . [ Fletcher JB , Reback CJ . Mental health disorders among homeless , substance-dependent men who have sex with men . Drug Alcohol Rev 2016;36:555 - 559 ] Metholodogy This study examined the prevalence and correlates of mental illness in homeless people in Hong Kong and explored the barriers preventing their access to health care . Ninety-seven Cantonese-speaking Chinese who were homeless during the study period were selected at r and om from the records of the three organisations serving the homeless population . The response rate was 69 % . Seventeen subjects could not give valid consent due to their poor mental state , so their responses were excluded from the data analysis . A psychiatrist administered the Structured Clinical Interview for DSM-IV Axis-I disorders ( SCID-I ) and the Mini -Mental State Examination . Consensus diagnoses for subjects who could not complete the SCID-I were established by three independent psychiatrists . Findings The point prevalence of mental illness was 56 % . Seventy-one percent of the subjects had a lifetime history of mental illness , 30 % had a mood disorder , 25 % had an alcohol use disorder , 25 % had a substance use disorder , 10 % had a psychotic disorder , 10 % had an anxiety disorder and 6 % had dementia . Forty-one percent of the subjects with mental illness had undergone a previous psychiatric assessment . Only 13 % of the subjects with mental illness were receiving psychiatric care at the time of interview . The prevalence of psychotic disorders , dementia and the rate of under treatment are hugely underestimated , as a significant proportion ( 18 % ) of the subjects initially selected were too ill to give consent to join the study . Conclusion The low treatment rate and the presence of this severely ill and unreached group of homeless people reflect the fact that the current mode of service delivery is failing to support the most severely ill homeless individuals BACKGROUND Very little is known about the mental health of homeless women . The present study is one of the first to focus on psychiatric diagnosis and comorbidity in a population of homeless women systematic ally interviewed with a structured instrument . METHOD Three hundred homeless women r and omly selected from St. Louis shelters were interviewed using the Diagnostic Interview Schedule ( DIS ) . RESULTS The population of homeless women in St. Louis is predominantly young adult , single , and black ; most have young children and average nearly a high school education . Schizophrenia and bipolar affective disorder account for only a small portion of the mental illness in these women . Nearly one in three has a history of substance abuse , with drug abuse being more prevalent than alcoholism . One third of the sample met lifetime criteria for posttraumatic stress disorder . One fourth of the women have received inpatient psychiatric care , and the majority with a nonsubstance Axis I diagnosis have received some mental health treatment . CONCLUSION Although major mental illness is overrepresented among these homeless women , the majority do not suffer from major mental illness . Despite the severity of the stressors these women face , the large numbers escaping psychiatric disorders speak to their resilience and to the likelihood that important factors other than mental illness contribute to their homelessness . Future studies to examine positive outcomes and investigate protective factors might provide a valuable source of information on coping with the stresses associated with homelessness and point to more effective interventions Introduction Quality assessment of included studies is an important component of systematic review s. Objective The authors investigated inter-rater and test – retest reliability for quality assessment s conducted by inexperienced student raters . Design Student raters received a training session on quality assessment using the Jadad Scale for r and omised controlled trials and the Newcastle – Ottawa Scale ( NOS ) for observational studies . Raters were r and omly assigned into five pairs and they each independently rated the quality of 13–20 articles . These articles were drawn from a pool of 78 papers examining cognitive impairment following electroconvulsive therapy to treat major depressive disorder . The articles were r and omly distributed to the raters . Two months later , each rater re-assessed the quality of half of their assigned articles . Setting McMaster Integrative Neuroscience Discovery and Study Program . Participants 10 students taking McMaster Integrative Neuroscience Discovery and Study Program courses . Main outcome measures The authors measured inter-rater reliability using κ and the intraclass correlation coefficient type 2,1 or ICC(2,1 ) . The authors measured test – retest reliability using ICC(2,1 ) . Results Inter-rater reliability varied by scale question . For the six-item Jadad Scale , question -specific κs ranged from 0.13 ( 95 % CI −0.11 to 0.37 ) to 0.56 ( 95 % CI 0.29 to 0.83 ) . The ranges were −0.14 ( 95 % CI −0.28 to 0.00 ) to 0.39 ( 95 % CI −0.02 to 0.81 ) for the NOS cohort and −0.20 ( 95 % CI −0.49 to 0.09 ) to 1.00 ( 95 % CI 1.00 to 1.00 ) for the NOS case – control . For overall scores on the six-item Jadad Scale , ICC(2,1)s for inter-rater and test – retest reliability ( accounting for systematic differences between raters ) were 0.32 ( 95 % CI 0.08 to 0.52 ) and 0.55 ( 95 % CI 0.41 to 0.67 ) , respectively . Corresponding ICC(2,1)s for the NOS cohort were −0.19 ( 95 % CI −0.67 to 0.35 ) and 0.62 ( 95 % CI 0.25 to 0.83 ) , and for the NOS case – control , the ICC(2,1)s were 0.46 ( 95 % CI −0.13 to 0.92 ) and 0.83 ( 95 % CI 0.48 to 0.95 ) . Conclusions Inter-rater reliability was generally poor to fair and test – retest reliability was fair to excellent . A pilot rating phase following rater training may be one way to improve agreement Background : Homelessness is a growing problem in the cities of the western world , and homeless people have a plethora of mental health and social difficulties . These are , nevertheless , difficult to evaluate epidemiologically . Method : In this paper we present a population survey using the Composite International Diagnostic Interview ( CIDI ) conducted in the city of Paris in winter 1996 on a representative sample of 838 homeless people . Night shelters as well as food kitchens were r and omly sample d , and the mean response rate was around 65 % . Results : The sample was relatively young and predominantly male ( 85 % ) . Forty percent were born outside France , 96 % had worked at some time , and one-third reported no re sources at all . The lifetime prevalence of psychiatric disorders was 57.9 % , while the 1-year prevalence was 29.1 % . For definite psychotic disorders , prevalence was 16 % ( lifetime ) and 6 % ( 1-year ) . Generally , this Parisian homeless population had some access to care : in the preceding 6 months 57.7 % of them had been medically attended and 14.2 % of these had been hospitalised . The survey was cross-sectional , and did not evaluate regular access to care or the quality of care . Conclusions : The implication s for health and social systems are discussed in the light of comparisons with European and North American data Objective : To determine whether the prevalence of schizophrenia among the homeless population of Edinburgh resident in hostels has changed between 1966 and 1992 . Design : Comparison of two cross sectional surveys . Setting s -- Hostels for homeless people in Edinburgh . Subjects -- In 1966 a r and om sample of 98 residents of three common lodging houses . In 1992 a r and om sample of 198 residents of nine hostels . Main outcome measure -- Prevalence of schizophrenia . Results : The prevalence of schizophrenia in 1992 was 12/136 ( 9 % ) compared with 20/79 ( 25 % ) in 1966 ( odds ratio 0.29 ; 95 % confidence interval 0.13 to 0.62 ; P=0.001 ) . Adjustment for confounding by age , current hostel , and duration of unemployment by means of logistic regression produced an adjusted odds ratio of 0.22 ( 0.08 to 0.58 ) . Conclusions : The prevalence of schizophrenia was lower in 1992 even after other changes in the population resident in hostels occurring between 1966 and 1992 were taken into account . The findings are not consistent with an increase in the prevalence of schizophrenia among homeless people despite a 66 % reduction in adult psychiatric beds in the region during 1966 - 92 Objective : International studies indicate high prevalence rates of post-traumatic stress disorder within homeless population s. In Australia , studies indicate high rates of trauma among homeless adults , yet post-traumatic stress disorder has not been investigated in homeless Australian adults . The primary aim of this project was to determine the prevalence of post-traumatic stress disorder among homeless adults in Sydney . Further , another aim of the study was to determine whether the onset of post-traumatic stress disorder preceded the first episode of homelessness or was a consequence of homelessness . Method : The sample consisted of 70 homeless men and women aged 18–73 years , who were r and omly sample d through eight homeless services . A computer-assisted face-to-face structured clinical interview was conducted with each participant . Lifetime prevalence of post-traumatic stress disorder was determined via the Composite International Diagnostic Interview . Results : The majority of the sample had experienced at least one traumatic event in their lifetime ( 98 % ) . Indeed , the mean number of traumas per person was six . The 12 month prevalence of post-traumatic stress disorder was higher among homeless adults in Sydney in comparison to the Australian general population ( 41 % vs 1.5 % ) . But 79 % of the sample had a lifetime prevalence of post-traumatic stress . In 59 % of cases , the onset of post-traumatic stress disorder preceded the age of the first reported homeless episode . Conclusions : Homeless adults in Sydney frequently experience trauma and post-traumatic stress disorder . The study found that trauma and post-traumatic stress disorder more often precede homelessness , but re-victimization is common . These findings highlight the high mental health needs among homeless people and have implication s for services for homeless people A study of homeless people in Baltimore , Md , focused on their health and other characteristics , with special emphasis on their needs for services . In the first stage , 298 men and 230 women were r and omly selected from the missions , shelters , and jail in Baltimore to respond to a baseline interview that provided extensive sociodemographic and health-related data . In the second stage , a sub sample of 203 subjects was r and omly selected from the baseline survey respondents to have systematic psychiatric and physical examinations . Data are presented from both stages . Data from the first stage demonstrate , among other things , the high levels of disaffiliation of this population and their heavy involvement in substance abuse . Data from the clinical examinations demonstrate the high prevalence of mental illnesses and other psychiatric disorders and of a wide range of physical disorders and confirm the high prevalence of alcohol abuse disorders . The high rates of comorbidity of these conditions is demonstrated and data are provided on the subjects ' needs for mental health and substance abuse services Purpose Previous cross-sectional studies have indicated that homeless individuals may present with high rates of suicidal ideation , which are strongly associated with completed suicide . We conducted the first known longitudinal study of suicidal ideation in the homeless . Methods We used data collected over 24 months in the Vancouver At Home project ( N = 497 ) , comprised two r and omized-controlled trials of housing interventions for homeless individuals with mental disorders . Presence of suicidal ideation was determined using the Colorado symptom index . Results Suicidal ideation significantly decreased over time [ odds ratio ( OR ) = 0.31 at 24 months , 95 % confidence interval ( CI ) 0.21–0.46 ] . Baseline diagnoses of mood ( OR = 2.18 , 95 % CI 1.48–3.21 ) and anxiety disorders ( OR = 2.05 , 95 % CI 1.42–2.97 ) , as well as depressive mood ( OR = 2.52 , 95 % CI 1.90–3.33 ) , use of any substance ( OR = 1.59 , 95 % CI 1.09–2.32 ) , and polysubstance use ( OR = 1.90 , 95 % CI 1.40–2.60 ) were significantly associated with suicidal ideation in the multivariate model . Baseline diagnosis of a psychotic disorder ( protective effect ) , daily substance use , intravenous drug use , recent arrest , multiple physical illnesses and history of traumatic brain injury were significantly associated with suicidal ideation in the unadjusted model only . Conclusions Interventions targeting depressive symptoms and substance use could help decrease suicide risk in homeless individuals . Mental health services need to be tailored to address the complex needs of socially marginalized individuals . Trial registration Current controlled trials : IS RCT N57595077 ( Vancouver At Home study : Housing First plus Assertive Community Treatment versus congregate housing plus supports versus treatment as usual ) and IS RCT N66721740 ( Vancouver At Home study : Housing first plus intensive case management versus treatment as usual ) . Assigned 9 Oct. 2012 Background Homelessness is an increas- ing problem among subjects with severe mental illnesses and little is known about the characteristics of homeless subjects with psychosis using emergency psychiatric services . The aims of the present study were to assess the frequency of psychotic disorders among subjects attending a psychiatric emergency service and to explore the clinical and demographic characteristics of these subjects and the management proposed by the emergency staff . Methods All homeless patients ( n = 104 ) consecutively attending a psychiatric emergency service were included over a 6-month period . Patients were categorised according to ICD-10 diagnoses as presenting with psychotic disorder ( schizophrenia and other non-affective psychotic disorders ) versus other disorders . A r and om sample of matched non-homeless controls ( n = 71 ) was included over the same period . Results Nearly one out of three homeless subjects ( 32.7 % ) presented with a psychotic disorder , a higher proportion than that found in non-homeless subjects ( 15.7 % ) . Compared to non-homeless subjects with psychosis , homeless subjects with psychosis were more likely to be male and to present with drug use disorder . The likelihood of being hospitalised after attending the psychiatric emergency services did not significantly differ between the two groups . Compared to homeless subjects with other psychiatric disorders , homeless subjects with psychosis were more likely to be single , to have a history of psychiatric hospitalisation and presented less frequently with anxiety or depressive symptoms motivating admission . Conclusion Most homeless subjects with psychosis attending a psychiatric emergency service were already identified as suffering from a severe mental illness , suggesting that homelessness was a consequence of a break in contact with mental health services . Since homelessness is incompatible with the adequate management of psychosis , strategies have to be developed in mental health organisations in combination with outside partnerships , to drastically reduce the frequency of this condition in subjects with psychosis The present study is a r and om , systematic study of 900 homeless subjects in St. Louis that describes violence in their lives , both in terms of victimization , by specific violent traumatic events , and victimizing with recognized aggressive behaviors . Many subjects had experienced a traumatic event , and post-traumatic stress disorder was very common . Substance abuse and other Axis I disorders were associated with a history of a traumatic event . The majority of men and a substantial proportion of women also had a history of physically aggressive behaviors , often beginning in childhood . Aggressive adult behavior was associated with substance abuse and major depression . The aggressive behaviors usually pre date d homelessness , and about half continued after the individual had become homeless . Therefore , it is seen that violence is very much a part of the lives of the homeless , and it seems to be part of a broader picture of problems associated with risk for and experience of homelessness |
11,936 | 32,122,288 | Regarding intra-arterial treatment , the symptomatic intracerebral hemorrhage and post-procedural recanalization rates were comparable between the two groups , although the posterior circulation stroke group had a higher mortality risk and lower tendency for a favorable functional outcome .
CONCLUSIONS Safety and efficacy of thrombolysis in posterior circulation stroke depends on involvement of large vessel occlusion and reperfusion modality such that intravenous thrombolytics is more effective and safer than in anterior circulation stroke ; the safety and efficacy of intra-arterial treatment is comparable or lower than anterior circulation stroke . | BACKGROUND It remains unclear whether thrombolysis outcomes can be influenced by the affected vascular territory ( i.e. anterior circulation stroke vs. posterior circulation stroke ) in stroke patients owing to the lack of r and omized controlled trials .
AIMS Using multiple comprehensive data bases , we search ed for observational studies of the safety and efficacy of intravenous thrombolytics and intra-arterial treatment with or without intravenous thrombolytics in accordance with the affected vascular territory . | Background and Purpose — Intravenous thrombolysis is an approved treatment for anterior ( ACS ) and posterior ( PCS ) circulation stroke . However , no r and omized controlled trial has investigated safety and efficacy of intravenous thrombolysis according to stroke territory , although PCS is assumed to differ from ACS in many ways . We aim ed to compare the safety and clinical outcome of intravenous thrombolysis applied to patients with PCS and ACS . Methods — Prospect ively collected data of 883 consecutive patients with acute ischemic stroke ( 788 ACS , 95 PCS ) treated with intravenous thrombolysis in 3 Swiss stroke centers were analyzed . Presenting characteristics , symptomatic intracranial hemorrhage , mortality , and favorable outcome ( modified Rankin scale 0 or 1 ) at 3 months were compared between patients with PCS and ACS . Results — As compared with patients with ACS , those with PCS were younger ( mean age , 63 versus 67 years , P=0.012 ) and had a lower mean baseline National Institutes of Health Stroke Scale score ( 9 versus 12 , P<0.001 ) . Patients with PCS less often had symptomatic intracranial hemorrhage ( 0 % versus 5 % , P=0.026 ) and had more often a favorable outcome ( 66 % versus 47 % , P<0.001 ) . Mortality was similar in the 2 groups ( PCS , 9 % ; ACS , 13 % ; P=0.243 ) . After multivariable adjustment , PCS was an independent predictor of lower symptomatic intracranial hemorrhage frequency ( P=0.001 ) , whereas stroke territory was not associated either with favorable outcome ( P=0.177 ) or with mortality ( P=0.251 ) . Conclusions — Our study suggests that PCS is associated with a lower risk of symptomatic intracranial hemorrhage after intravenous thrombolysis as compared with ACS , whereas favorable outcome and mortality were similar in the 2 stroke territories Background and Purpose — Early reperfusion is a predictor of good outcome in acute ischemic stroke . We investigated whether middle cerebral artery ( MCA ) occlusions have a better clinical outcome and proportion of recanalization compared with internal carotid artery ( ICA ) occlusion after st and ard treatment with intravenous ( IV ) tissue plasminogen activator ( tPA ) . Patients — In a retrospective analysis of our prospect i ve stroke data base between January 7 , 1998 , and January 30 , 2002 , we identified 36 consecutive patients who were treated with IV tPA within 3 hours after symptom onset of a stroke in the distribution of a documented ICA or MCA occlusion . The National Institutes of Health Stroke Scale ( NIHSS ) score was recorded before tPA , at 24 hours , 3 days , and 3 months after stroke . Three-month outcome was recorded by modified Rankin scale . Magnetic resonance angiography or computed tomographic angiography was obtained before tPA . The presence of recanalization was assessed by transcranial Doppler and /or magnetic resonance angiography within 3 days after stroke onset . Results — Nineteen patients had MCA occlusion , and 17 had ICA-plus-MCA occlusion before tPA . Although there was no difference in age and NIHSS at day 0 between the 2 groups , the MCA group had a lower day 3 NIHSS score compared with the ICA group ( P = 0.006 ) in an ANCOVA . In addition , patients who had a MCA occlusion had lower day 1 and 3 NIHSS scores compared with the ICA group ( P = 0.04 and P = 0.03 , respectively ; Wilcoxon rank sum ) . Similarly , NIHSS was significantly lower in patients who recanalized on days 1 and 3 ( P = 0.004 and P = 0.003 respectively , Wilcoxon rank sum ) . When we adjusted for NIHSS score at day 0 in an ANCOVA , the adjusted mean was lower in the group that recanalized compared with the group that did not recanalize ( P < 0.001 ) . There was a significant difference between the proportion of recanalization in the MCA group ( 15 of 17 recanalized , 88 % ) at 3 days after tPA compared with that of the ICA group ( 5 of 16 recanalized , 31%;P = 0.001 , Fisher exact test ) . The 3-month modified Rankin scale was not different between the 2 groups . Conclusions — Despite comparable age and NIHSS scores before IV tPA , MCA occlusions have lower day 1 and 3 NIHSS scores and higher proportion of recanalization compared with ICA occlusions . A combined IV/intra-arterial or mechanical thrombolysis may be needed to achieve early recanalization in ICA occlusions Background and Purpose — Thrombolytic therapy is licensed for use in highly selected patients with acute ischemic stroke . We aim ed to model the health economic impact of limited use of thrombolytic therapy and to assess whether it was likely to be cost-effective when used more widely in the UK National Health Service ( NHS ) . Methods — The authors formed a discussion panel to develop the decision- analysis model of acute stroke care . It consisted of Markov state-transition processes , with probabilities of different health states determined by certain key variables . The range of estimates of efficacy of recombinant tissue plasminogen activator ( rt-PA ) was taken from an up date to a Cochrane systematic review of r and omized trials of thrombolysis . Data on outcome after stroke were taken from our hospital-based stroke register , supplemented by data derived from relevant literature sources . Results — The model suggested that compared with st and ard care , if eligible patients were treated with rt-PA up to 6 hours , there was a 78 % probability of a gain in quality -adjusted survival during the first year , at a cost of £ 13 581 per quality -adjusted life-year ( QALY ) gained . Over a lifetime , rt-PA was associated with cost-savings of £ 96 565 per QALY . However , the estimates were imprecise and highly susceptible to the assumptions used in the economic model ; under several plausible assumptions , rt-PA was much less cost-effective than st and ard care , and under others , a great deal more cost-effective . Conclusions — The estimates of effectiveness and cost-effectiveness were imprecise . Although the benefits appeared promising , the data did not support the widespread use of thrombolytic therapy outside the terms of the current restricted license in routine clinical practice in the NHS . There is a case for new large-scale r and omized trials comparing thrombolytic therapy with control up to 6 hours to determine more precisely the effects of rt-PA on short-term and long-term survival and its cost-effectiveness when used in a wider range of patients BACKGROUND Trials of endovascular therapy for ischemic stroke have produced variable results . We conducted this study to test whether more advanced imaging selection , recently developed devices , and earlier intervention improve outcomes . METHODS We r and omly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR ( Flow Restoration ) stent retriever or to continue receiving alteplase alone . All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic ( CT ) perfusion imaging . The co primary outcomes were reperfusion at 24 hours and early neurologic improvement ( ≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3 ) . Secondary outcomes included the functional score on the modified Rankin scale at 90 days . RESULTS The trial was stopped early because of efficacy after 70 patients had undergone r and omization ( 35 patients in each group ) . The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group ( median , 100 % vs. 37 % ; P<0.001 ) . Endovascular therapy , initiated at a median of 210 minutes after the onset of stroke , increased early neurologic improvement at 3 days ( 80 % vs. 37 % , P=0.002 ) and improved the functional outcome at 90 days , with more patients achieving functional independence ( score of 0 to 2 on the modified Rankin scale , 71 % vs. 40 % ; P=0.01 ) . There were no significant differences in rates of death or symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging , early thrombectomy with the Solitaire FR stent retriever , as compared with alteplase alone , improved reperfusion , early neurologic recovery , and functional outcome . ( Funded by the Australian National Health and Medical Research Council and others ; EXTEND-IA Clinical Trials.gov number , NCT01492725 , and Australian New Zeal and Clinical Trials Registry number , ACTRN12611000969965 . ) BACKGROUND Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation , less than 40 % regain functional independence when treated with intravenous tissue plasminogen activator ( t-PA ) alone . Thrombectomy with the use of a stent retriever , in addition to intravenous t-PA , increases reperfusion rates and may improve long-term functional outcome . METHODS We r and omly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone ( control group ) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset ( intervention group ) . Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions . The primary outcome was the severity of global disability at 90 days , as assessed by means of the modified Rankin scale ( with scores ranging from 0 [ no symptoms ] to 6 [ death ] ) . RESULTS The study was stopped early because of efficacy . At 39 centers , 196 patients underwent r and omization ( 98 patients in each group ) . In the intervention group , the median time from qualifying imaging to groin puncture was 57 minutes , and the rate of substantial reperfusion at the end of the procedure was 88 % . Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale ( P<0.001 ) . The rate of functional independence ( modified Rankin scale score , 0 to 2 ) was higher in the intervention group than in the control group ( 60 % vs. 35 % , P<0.001 ) . There were no significant between-group differences in 90-day mortality ( 9 % vs. 12 % , P=0.50 ) or symptomatic intracranial hemorrhage ( 0 % vs. 3 % , P=0.12 ) . CONCLUSIONS In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation , thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days . ( Funded by Covidien ; SWIFT PRIME Clinical Trials.gov number , NCT01657461 . ) Background and Purpose — The frequent use of a longer time window for recanalization therapy in patients with basilar artery occlusion ( BAO ) in daily practice is not supported by any scientific evidence . We investigated the relationship between time to recanalization therapy and functional outcome in BAO with data from the Basilar Artery International Cooperation Study ( BASICS ) . Methods — BASICS is a prospect i ve multicenter registry of patients ( n=619 ) with radiologically confirmed BAO . We analyzed patients receiving intravenous thrombolysis or intra-arterial treatment . Patients were divided into 4 groups based on the interval between estimated time of BAO and start of recanalization therapy : ⩽3 hours ( n=134 ) , > 3 to ⩽6 hours ( n=151 ) , > 6 to ⩽9 hours ( n=56 ) , and > 9 hours ( n=68 ) . Primary outcome measure was poor functional outcome ( modified Rankin scale score 4–6 ) after 1 month . We calculated adjusted risk ratios with 95 % CIs using Poisson regression analyses with the ⩽3 hours group as the reference group . Results — Patients had an increased risk of poor functional outcome as time to recanalization therapy became longer ( ⩽3 hours : 62 % ; > 3 to ⩽6 hours : 67 % [ adjusted risk ratio , 1.06 ; 0.91–1.25 ] ; > 6 to ⩽9 hours : 77 % [ adjusted risk ratio , 1.26 ; 1.06–1.51 ] ; > 9 hours : 85 % [ adjusted risk ratio , 1.47 ; 1.26–1.72 ] ) . Conclusions — Early recanalization therapy in patients with BAO is associated with a more favorable outcome with a significant increased chance of a poor outcome when recanalization therapy is started > 6 hours after estimated time of BAO BACKGROUND Among patients with a proximal vessel occlusion in the anterior circulation , 60 to 80 % of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment . We evaluated rapid endovascular treatment in addition to st and ard care in patients with acute ischemic stroke with a small infa rct core , a proximal intracranial arterial occlusion , and moderate-to-good collateral circulation . METHODS We r and omly assigned participants to receive st and ard care ( control group ) or st and ard care plus endovascular treatment with the use of available thrombectomy devices ( intervention group ) . Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset . Patients with a large infa rct core or poor collateral circulation on computed tomography ( CT ) and CT angiography were excluded . Workflow times were measured against predetermined targets . The primary outcome was the score on the modified Rankin scale ( range , 0 [ no symptoms ] to 6 [ death ] ) at 90 days . A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care ( shift analysis ) . RESULTS The trial was stopped early because of efficacy . At 22 centers worldwide , 316 participants were enrolled , of whom 238 received intravenous alteplase ( 120 in the intervention group and 118 in the control group ) . In the intervention group , the median time from study CT of the head to first reperfusion was 84 minutes . The rate of functional independence ( 90-day modified Rankin score of 0 to 2 ) was increased with the intervention ( 53.0 % , vs. 29.3 % in the control group ; P<0.001 ) . The primary outcome favored the intervention ( common odds ratio , 2.6 ; 95 % confidence interval , 1.7 to 3.8 ; P<0.001 ) , and the intervention was associated with reduced mortality ( 10.4 % , vs. 19.0 % in the control group ; P=0.04 ) . Symptomatic intracerebral hemorrhage occurred in 3.6 % of participants in intervention group and 2.7 % of participants in control group ( P=0.75 ) . CONCLUSIONS Among patients with acute ischemic stroke with a proximal vessel occlusion , a small infa rct core , and moderate-to-good collateral circulation , rapid endovascular treatment improved functional outcomes and reduced mortality . ( Funded by Covidien and others ; ESCAPE Clinical Trials.gov number , NCT01778335 . ) BACKGROUND In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion , intraarterial treatment is highly effective for emergency revascularization . However , proof of a beneficial effect on functional outcome is lacking . METHODS We r and omly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone . Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset . The primary outcome was the modified Rankin scale score at 90 days ; this categorical scale measures functional outcome , with scores ranging from 0 ( no symptoms ) to 6 ( death ) . The treatment effect was estimated with ordinal logistic regression as a common odds ratio , adjusted for prespecified prognostic factors . The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores , as compared with usual care alone ( shift analysis ) . RESULTS We enrolled 500 patients at 16 medical centers in The Netherl and s ( 233 assigned to intraarterial treatment and 267 to usual care alone ) . The mean age was 65 years ( range , 23 to 96 ) , and 445 patients ( 89.0 % ) were treated with intravenous alteplase before r and omization . Retrievable stents were used in 190 of the 233 patients ( 81.5 % ) assigned to intraarterial treatment . The adjusted common odds ratio was 1.67 ( 95 % confidence interval [ CI ] , 1.21 to 2.30 ) . There was an absolute difference of 13.5 percentage points ( 95 % CI , 5.9 to 21.2 ) in the rate of functional independence ( modified Rankin score , 0 to 2 ) in favor of the intervention ( 32.6 % vs. 19.1 % ) . There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation , intraarterial treatment administered within 6 hours after stroke onset was effective and safe . ( Funded by the Dutch Heart Foundation and others ; MR CLEAN Netherl and s Trial Registry number , NTR1804 , and Current Controlled Trials number , IS RCT N10888758 . ) Background and purpose The benefits of mechanical thrombectomy ( MT ) in basilar artery occlusions ( BAO ) have not been explored in recent clinical trials . We compared outcomes and procedural complications of MT in BAO with anterior circulation occlusions . Methods Data from the Madrid Stroke Network multicenter prospect i ve registry were analyzed , including baseline characteristics , procedure times , procedural complications , symptomatic intracranial hemorrhage ( SICH ) , modified Rankin Scale ( mRS ) , and mortality at 3 months . Results Of 479 patients treated with MT , 52 ( 11 % ) had BAO . The onset to reperfusion time lapse was longer in patients with BAO ( median ( IQR ) 385 min ( 320–540 ) vs 315 min ( 240–415 ) , p<0.001 ) , as was the duration of the procedures ( 100 min ( 40–130 ) vs 60 min ( 39–90 ) , p=0.006 ) . Moreover , the recanalization rate was lower ( 75 % vs 84 % , p=0.01 ) . A trend toward more procedural complications was observed in patients with BAO ( 32 % vs 21 % , p=0.075 ) . The frequency of SICH was 2 % vs 5 % ( p=0.25 ) . At 3 months , patients with BAO had a lower rate of independence ( mRS 0–2 ) ( 40 % vs 58 % , p=0.016 ) and higher mortality ( 33 % vs 12 % , p<0.001 ) . The rate of futile recanalization was 50 % in BAO versus 35 % in anterior circulation occlusions ( p=0.05 ) . Age and duration of the procedure were significant predictors of futile recanalization in BAO . Conclusions MT is more laborious and shows more procedural complications in BAO than in anterior circulation strokes . The likelihood of futile recanalization is higher in BAO and is associated with greater age and longer procedure duration . A refinement of endovascular procedures for BAO might help optimize the results Background Despite recent advances in acute stroke treatment , basilar artery occlusion ( BAO ) is associated with a death or disability rate of close to 70 % . R and omised trials have shown the safety and efficacy of intravenous thrombolysis ( IVT ) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke , but these results do not directly apply to patients with an acute BAO because only few , if any , of these patients were included in r and omised acute stroke trials . Recently the results of the Basilar Artery International Cooperation Study ( BASICS ) , a prospect i ve registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment ( IAT ) is superior to IVT . Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely . Design BASICS is a r and omised controlled , multicentre , open label , phase III intervention trial with blinded outcome assessment , investigating the efficacy and safety of additional IAT after IVT in patients with BAO . The trial targets to include 750 patients , aged 18 to 85 years , with CT angiography or MR angiography confirmed BAO treated with IVT . Patients will be r and omised between additional IAT followed by optimal medical care versus optimal medical care alone . IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0–3 . Discussion The BASICS registry was observational and has all the limitations of a non-r and omised study . As the IAT approach becomes increasingly available and frequently utilised an adequately powered r and omised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed ( clinical trials.gov : NCT01717755 ) Basilar artery occlusion ( BAO ) remains one of the most devastating subtypes of ischemic stroke , and prognosis is poor if early recanalization is not achieved . The purpose of this study was to evaluate the safety and technical feasibility of mechanical thrombectomy with the Solitaire AB stent ( Covidien , Irvine , CA , USA ) for the treatment of acute BAO through a single-center experience . Twenty-one patients with acute BAO were treated with mechanical thrombectomy with the Solitaire AB stent device between 1st September 2011 and 1st December 2014 . Recanalization was assessed using the Thrombolysis in Cerebral Infa rct ion ( TICI ) scale system . Clinical outcome was established at discharge by The National Institute of Health Stroke Scale ( NIHSS ) , and the mean time from symptom onset to recanalization determined . Authors had access to identifying information during or after data collection . The clinical status of patients on admission was severe , with a mean NIHSS score of 25.57±5.20 ( range : 16 - 38 ) , and the number of patients with TICI 2b or 3 was 0 . The mean time from symptom onset to recanalization was 579.00±188.78min ( range : 360 - 960min ) . At 3-month follow-up , eight ( 38.1 % ) patients had a good clinical outcome . At follow-up , the trial of ORG 10172 in acute stroke treatment ( TOAST ) classification was large-vessel atherosclerosis in 13 patients ( 61.9 % ) , cardioembolic in seven patients ( 33.3 % ) , and undetermined in one patient ( 4.8 % ) . In our series , application of the Solitaire AB stent retriever in acute BAO result ed in a high recanalization rate without procedural complications , and with good clinical outcome . Further prospect i ve trials are needed to confirm the potential clinical benefit of this treatment approach Tissue plasminogen activator ( tPA ) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset . The costs associated with this new treatment will be a factor in determining the extent of its utilization . Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients . A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients . One-way and multiway sensitivity analyses ( using Monte Carlo simulation ) were performed to estimate the overall uncertainty of the model results . In the NINDS rt-PA Stroke Trial , the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients ( 10.9 versus 12.4 days ; p = 0.02 ) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home ( 48 % versus 36%;p = 0.002 ) . The Markov model estimated an increase in hospitalization costs of $ 1.7 million and a decrease in rehabilitation costs of $ 1.4 million and nursing home cost of $ 4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities . Multiway sensitivity analysis revealed a greater than 90 % probability of cost savings . The estimated impact on long-term health outcomes was 564 ( 3 to 850 ) quality -adjusted life-years saved over 30 years of the model per 1,000 patients . Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect size and funding source ) , face validity with eight experts , and completion time for the RoBANS approach . RESULTS RoBANS contains six domains : the selection of participants , confounding variables , the measurement of exposure , the blinding of the outcome assessment s , incomplete outcome data , and selective outcome reporting . The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial . There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS . The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies . The mean time required to complete RoBANS was approximately 10 min . The external experts who were interviewed evaluated RoBANS as a " fair " assessment tool . CONCLUSIONS RoBANS shows moderate reliability , promising feasibility , and validity . The further refinement of this tool and larger validation studies are required Background and Purpose — Diffusion-perfusion MRI in patients with anterior circulation occlusions has demonstrated salvage of threatened tissue after thrombolytic therapy . Similar studies have not been reported with posterior circulation occlusions . Methods — Patients with acute basilar artery occlusion treated with intra-arterial thrombolytics were studied with multimodal MRI before treatment , several hours after treatment , and at day 7 . Results — Ten patients were studied ( 9 men , 1 woman ) . Mean age was 70 years , and median pretreatment National Institutes of Health Stroke Scale ( NIHSS ) score was 14 . In 6 patients imaged before treatment and at day 7 , mean pretreatment diffusion-weighted imaging ( DWI ) lesion volume was 11 cm3 , and day 7 , lesion volume was 2.6 cm3 . Significant mismatch was visualized in all 5 patients with pretreatment perfusion-diffusion imaging ( mean , 73 % ; range , 49 % to 99 % ) . Late imaging obtained in 4 of these 5 patients demonstrated that mean posttreatment DWI lesion volume ( 21 cm3 ) was less than the mean initial perfusion lesion volume ( 62 cm3 ) . Although there was no direct correlation between pretreatment DWI volume and initial NIHSS ( r = −0.113 ) , there was good correlation between pretreatment perfusion-weighted imaging volume and initial NIHSS ( r = 0.72 ) . Conclusions — In this first report of diffusion-perfusion MRI in patients with acute basilar artery occlusions treated with intra-arterial thrombolysis , significant mismatch was visualized on pretreatment studies , suggesting that large volumes of salvageable tissue were present . Final infa rct volumes were smaller than pretreatment perfusion volumes , suggesting that substantial volumes of tissue were salvaged by thrombolytic reperfusion Background and purpose Physicians treating patients with posterior circulation strokes ( PCS ) tended to debate more on whether or not to introduce anticoagulation rather than performing investigations to identify stroke aetiology , as in patients with anterior circulation strokes ( ACS ) . Recent findings suggest that stroke aetiologies of PCS and ACS are more alike than dissimilar , suggesting that PCS deserve the same investigations as ACS . The characteristics and current diagnostic evaluation between patients with PCS and ACS were compared . Methods 312 consecutive patients with first ever ACS and 93 patients with first ever PCS were prospect ively analysed . Results Patients with ACS and PCS did not differ in terms of demographic characteristics , prevalence of vascular risk factors , diagnostic evaluation or stroke aetiology . The median National Institutes of Health Stroke Scale score was 8 in ACS and 4 in PCS ( p=0.004 ) . Brain imaging revealed more often pathological findings in ACS than PCS . The proportion of non-thrombolysed patients with a favourable clinical outcome ( modified Rankin score 0–2 ) was similar in ACS and PCS ( 67.0 % vs 78.4 % ; p=0.08 ) . In non-thrombolysed patients , stroke severity was an independent predictor of clinical outcome both in ACS ( OR 1.60 , 95 % CI 1.2 to 2.1 ; p<0.0001 ) and in PCS ( OR 1.22 , 95 % CI 1.03 to 1.44 ; p=0.02 ) while age predicted poor outcome only in ACS ( OR 1.11 , 95 % CI 1.01 to 1.22 ; p=0.007 ) . In thrombolysed patients , stroke severity was the only outcome predictor in ACS ( OR 1.14 , 95 % CI 1.04 to 1.25 ; p=0.004 ) while we identified no statistically relevant predictor of PCS outcome . Conclusions In PCS and ACS , baseline variables , aetiology and outcome are more alike than different Rationale Endovascular treatment plus st and ard medical therapy is superior to st and ard medical therapy alone for acute anterior proximal intracranial large artery occlusion strokes . The benefit of endovascular treatment in acute ischemic stroke caused by basilar artery occlusion remains unproven . Aim This study compares the safety and efficacy of endovascular treatment plus st and ard medical therapy versus st and ard medical therapy alone in acute ischemic stroke due to basilar artery occlusion . Design The study is a multicenter r and omized control trial with blinded outcome assessment . A projected total 344 subjects with acute basilar arterial occlusion within 8 h of estimated occlusion time will be enrolled over three years in China . Patients will be assigned to endovascular treatment plus st and ard medical therapy and st and ard medical therapy alone group in 1:1 ratio for study centers . Study outcomes The primary outcome measure is a favorable functional outcome , defined as a modified Rankin Score of 0–3 at 90 days . The primary safety measure is mortality at 90 days . Trial registration Clinical Trials.gov ( NCT 02441556 ) . Summary The BEST trial will provide valuable insights into the safety and efficacy of endovascular treatment for acute ischemic stroke patients with basilar artery occlusion BACKGROUND The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain . Patients with a clinical deficit that is disproportionately severe relative to the infa rct volume may benefit from late thrombectomy . METHODS We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infa rct volume , with mismatch criteria defined according to age ( < 80 years or ≥80 years ) . Patients were r and omly assigned to thrombectomy plus st and ard care ( the thrombectomy group ) or to st and ard care alone ( the control group ) . The co primary end points were the mean score for disability on the utility‐weighted modified Rankin scale ( which ranges from 0 [ death ] to 10 [ no symptoms or disability ] ) and the rate of functional independence ( a score of 0 , 1 , or 2 on the modified Rankin scale , which ranges from 0 to 6 , with higher scores indicating more severe disability ) at 90 days . RESULTS A total of 206 patients were enrolled ; 107 were assigned to the thrombectomy group and 99 to the control group . At 31 months , enrollment in the trial was stopped because of the results of a prespecified interim analysis . The mean score on the utility‐weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group ( adjusted difference [ Bayesian analysis ] , 2.0 points ; 95 % credible interval , 1.1 to 3.0 ; posterior probability of superiority , > 0.999 ) , and the rate of functional independence at 90 days was 49 % in the thrombectomy group as compared with 13 % in the control group ( adjusted difference , 33 percentage points ; 95 % credible interval , 24 to 44 ; posterior probability of superiority , > 0.999 ) . The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups ( 6 % in the thrombectomy group and 3 % in the control group , P=0.50 ) , nor did 90‐day mortality ( 19 % and 18 % , respectively ; P=1.00 ) . CONCLUSIONS Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infa rct , outcomes for disability at 90 days were better with thrombectomy plus st and ard care than with st and ard care alone . ( Funded by Stryker Neurovascular ; DAWN Clinical Trials.gov number , NCT02142283 . BACKGROUND S The circle of Willis ( CoW ) is a primary collateral pathway that compensates quickly for a drop in cerebral blood flow . Using the complete CoW as a surrogate marker for good collateral circulation , its prognostic value after intravenous thrombolysis was examined . METHODS We prospect ively studied 64 consecutive patients with acute ischemic stroke treated with tissue plasminogen activator within 3 hours of stroke onset between October 2005 and June 2012 in our hospital . The study protocol was based on st and ard guidelines for intravenous thrombolysis . On computed tomographic angiography 24 hours after thrombolysis , the CoW was complete in 21 ( 32.8 % ) cases and incomplete in 43 ( 67.2 % ) . RESULTS Patients with complete CoW were more likely to have early improvement in National Institute of Health Stroke Scale ( NIHSS ) score ( median improvement 2 vs 0 at 2 hours ; 4 vs 1 at 24 hours ) , be independent at 3 months ( 42 % vs 19 % ) . In the incomplete CoW group , the rate of symptomatic intracerebral haemorrhage ( SICH ) according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study ( SITS-MOST ) definition was almost 3 times higher . Complete CoW was one of the strongest predictors of good functional outcome at 3 months ( odds ratio 2.32 ; P = .01 ) . CONCLUSIONS Complete CoW independently predicted functional independence and survival |
11,937 | 25,313,793 | Participation of demographic subgroups differed by intervention type and study location .
Rates of participation of demographic groups of interest did not vary with time .
Limited data suggest efficacy , particularly of early therapy initiation followed by treatment interruption , may vary by demographic variables , in this case sex . | This systematic review was undertaken to determine the extent to which adult subjects representing sex ( female ) , race ( nonwhite ) , and age ( > 50 years ) categories are included in clinical studies of HIV curative interventions and thus , by extension , the potential for data to be analyzed that may shed light on the influence of such demographic variables on safety and /or efficacy . | Background : The contribution of immune activation to accelerated HIV-disease progression in older individuals has not been delineated . Methods : Prospect i ve multicenter cohort of older ( ≥45 years ) and younger ( 18–30 years ) HIV-infected adults initiating 192 weeks of antiretroviral therapy ( ART ) . Longitudinal models of CD4 cell restoration examined associations with age-group , thymic volume , immune activation , and viral load . Results : Forty-five older and 45 younger adults ( median age 50 and 26 years , respectively ) were studied . Older patients had fewer naive CD4 cells ( P < 0.001 ) and higher HLA-DR/CD38 expression on CD4 ( P = 0.05 ) and CD8 cells ( P = 0.07 ) than younger patients at any time on ART . The rate of naive and total CD4 cell increase was similar between age groups , but older patients had a faster mean rate of B-cell increase ( by + 0.7 cells/week ; P = 0.01 ) , to higher counts than healthy controls after 192 weeks ( P = 0.003 ) . Naive CD4 increases from baseline were associated with immune activation reductions ( as declines from baseline of % CD8 cells expressing HLA-DR/CD38 ; P < 0.0001 ) , but these increases were attenuated in older patients , or in those with small thymuses . A 15 % reduction in activation was associated with naive gains of 29.9 and 6.2 cells/&mgr;l in younger , versus older patients , or with gains of 25.7 , 23.4 , and 2.1 cells/&mgr;l in patients with the largest , intermediate , and smallest thymuses , respectively ( P < 0.01 for interactions between activation reduction and age-group or thymic volume ) . Conclusion : Older patients had significant B-cell expansion , higher levels of immune activation markers , and significantly attenuated naive CD4 cell gains associated with activation reduction Objective : To prospect ively examine differences in baseline characteristics and study outcomes between HIV‐infected women and men during a clinical trial of nucleoside analogue therapy . Methods : ACTG 175 r and omized HIV‐infected patients with CD4 + counts between 200 and 500 cells/mm3 to one of four nucleoside analogue regimens : zidovudine ( ZDV ) , didanosine ( ddl ) , ZDV + ddI , or ZDV + zalcitabine ( ddC ) . Differences in time to first dose modification , voluntary withdrawal , development of toxicity and symptomatology , and AIDS progression were compared by gender . Results : The study included 438 women and 2029 men . Baseline values of HIV RNA plasma concentrations were significantly lower for women ( 0.3 log10 ) than men in a subset of patients in whom assays were taken and this difference persisted after adjustment for CD4 + count . Women reported reducing dosage and discontinue ddI‐containing regimens more frequently than men did ; adjustment for weight did not completely explain this difference . Women were at lower risk than men for progression to a study endpoint ( 19 % of women versus 24 % of men ; p < .0001 ) . Among those antiretroviral‐naive study subjects receiving ZDV , men were four times more likely to progress to a study endpoint than women . Conclusions : Differences in pretreatment characteristics and on study experiences were demonstrated between women and men enrolled in this clinical trial . The suggestion of a gender difference in response to ZDV monotherapy by antiretroviral‐naive study subjects and the lower baseline values for HIV RNA in women compared with those in men provides evidence for gender differences in the relationship between virus replication , CD4 + decline , and responses to nucleoside analogue therapy Objective : To determine the impact of age and initial HAART regimen class on virologic and immunologic response within 24 months after initiation . Design : Pooled analysis of data from 19 prospect i ve cohort studies in the North American AIDS Cohort Collaboration on Research and Design ( NA-ACCORD ) . Methods : Twelve thous and , one hundred and ninety-six antiretroviral-naive adults who initiated HAART between 1998 and 2008 using a boosted protease inhibitor-based regimen or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen were included in our study . Discrete time-to-event models estimated adjusted hazard odds ratios ( aHOR ) and 95 % confidence intervals ( CIs ) for suppressed viral load ( ≤500 copies/ml ) and , separately , at least 100 cells/μl increase in CD4 cell count . Truncated , stabilized inverse probability weights accounted for selection biases from discontinuation of initial regimen class . Results : Among 12 196 eligible participants ( mean age = 42 years ) , 50 % changed regimen classes after initiation ( 57 and 48 % of whom initiated protease inhibitor and NNRTI-based regimens , respectively ) . Mean CD4 cell count at initiation was similar by age . Virologic response to treatment was less likely in those initiating using a boosted protease inhibitor [ aHOR = 0.77 ( 0.73 , 0.82 ) ] , regardless of age . Immunologic response decreased with increasing age [ 18–<30 : ref ; 30–<40 : aHOR = 0.92 ( 0.85 , 1.00 ) ; 40–<50 : aHOR = 0.85 ( 0.78 , 0.92 ) ; 50–<60 : aHOR = 0.82 ( 0.74 , 0.90 ) ; ≥60 : aHOR = 0.74 ( 0.65 , 0.85 ) ] , regardless of initial regimen . Conclusion : We found no evidence of an interaction between age and initial antiretroviral regimen on virologic or immunologic response to HAART ; however , decreased immunologic response with increasing age may have implication s for age-specific when-to-start guidelines BACKGROUND Individuals infected with human immunodeficiency virus ( HIV ) have higher risk than HIV-negative individuals for diseases associated with aging . T-cell senescence , characterized by expansion of cells lacking the costimulatory molecule CD28 , has been hypothesized to mediate these risks . METHODS We measured the percentage of CD28(-)CD4(+ ) and CD8(+ ) T cells from HIV-infected treatment-naive adults from 5 Adult Clinical Trials Group ( ACTG ) antiretroviral therapy ( ART ) studies and the ALLRT ( ACTG Longitudinal Linked R and omized Trials ) cohort , and from 48 HIV-negative adults . Pretreatment and 96-week posttreatment % CD28(- ) cells were assessed using linear regression for associations with age , sex , race/ethnicity , CD4 count , HIV RNA , ART regimen , and hepatitis C virus ( HCV ) infection . RESULTS In total , 1291 chronically HIV-infected adults were studied . Pretreatment , lower CD4 count was associated with higher % CD28(-)CD4(+ ) and % CD28(-)CD8(+ ) cells . For CD8(+ ) cells , younger age and HCV infection were associated with a lower % CD28(- ) . ART reduced % CD28(- ) levels at week 96 among virally suppressed individuals . Older age was strongly predictive of higher % CD28(-)CD8(+ ) . Compared to HIV-uninfected individuals , HIV-infected individuals maintained significantly higher % CD28(- ) . CONCLUSIONS Effective ART reduced the proportion of CD28(- ) T cells . However , levels remained abnormally high and closer to levels in older HIV-uninfected individuals . This finding may inform future research of increased rates of age-associated disease in HIV-infected adults Background Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals . The factors associated with D-dimer levels during HIV infection , however , remain poorly understood . Methods In this cross-sectional study , participants in three r and omized controlled trials with measured D-dimer levels were included ( N = 9,848 ) . Factors associated with D-dimer were identified by linear regression . Covariates investigated were : age , gender , race , body mass index , nadir and baseline CD4 + count , plasma HIV RNA levels , markers of inflammation ( C-reactive protein [ CRP ] , interleukin-6 [ IL-6 ] ) , antiretroviral therapy ( ART ) use , ART regimens , co-morbidities ( hepatitis B/C , diabetes mellitus , prior cardiovascular disease ) , smoking , renal function ( estimated glomerular filtration rate [ eGFR ] and cystatin C ) and cholesterol . Results Women from all age groups had higher D-dimer levels than men , though a steeper increase of D-dimer with age occurred in men . Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels . In this subgroup , the degree of hepatic fibrosis , as demonstrated by higher hyaluronic acid levels , but not viral load of hepatitis viruses , was positively correlated with D-dimer . Other factors independently associated with higher D-dimer levels were black race , higher plasma HIV RNA levels , being off ART at baseline , and increased levels of CRP , IL-6 and cystatin C. In contrast , higher baseline CD4 + counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels . Conclusions D-dimer levels increase with age in HIV+ men , but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases . In hepatitis B/C co-infected individuals , hepatic fibrosis , but not hepatitis viral load , was associated with higher D-dimer levels There is intense interest in developing curative interventions for HIV . How such a cure will be quantified and defined is not known . We applied a series of measurements of HIV persistence to the study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor . Sample s from blood , spinal fluid , lymph node , and gut were analyzed in multiple laboratories using different approaches . No HIV DNA or RNA was detected in peripheral blood mononuclear cells ( P BMC ) , spinal fluid , lymph node , or terminal ileum , and no replication-competent virus could be cultured from P BMC s. However , HIV RNA was detected in plasma ( 2 laboratories ) and HIV DNA was detected in the rectum ( 1 laboratory ) at levels considerably lower than those expected in ART-suppressed patients . It was not possible to obtain sequence data from plasma or gut , while an X4 sequence from P BMC did not match the pre-transplant sequence . HIV antibody levels were readily detectable but declined over time ; T cell responses were largely absent . The occasional , low-level PCR signals raise the possibility that some HIV nucleic acid might persist , although they could also be false positives . Since HIV levels in well-treated individuals are near the limits of detection of current assays , more sensitive assays need to be developed and vali date d. The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure BACKGROUND Short-course antiretroviral therapy ( ART ) in primary human immunodeficiency virus ( HIV ) infection may delay disease progression but has not been adequately evaluated . METHODS We r and omly assigned adults with primary HIV infection to ART for 48 weeks , ART for 12 weeks , or no ART ( st and ard of care ) , with treatment initiated within 6 months after seroconversion . The primary end point was a CD4 + count of less than 350 cells per cubic millimeter or long-term ART initiation . RESULTS A total of 366 participants ( 60 % men ) underwent r and omization to 48-week ART ( 123 participants ) , 12-week ART ( 120 ) , or st and ard care ( 123 ) , with an average follow-up of 4.2 years . The primary end point was reached in 50 % of the 48-week ART group , as compared with 61 % in each of the 12-week ART and st and ard-care groups . The average hazard ratio was 0.63 ( 95 % confidence interval [ CI ] , 0.45 to 0.90 ; P=0.01 ) for 48-week ART as compared with st and ard care and was 0.93 ( 95 % CI , 0.67 to 1.29 ; P=0.67 ) for 12-week ART as compared with st and ard care . The proportion of participants who had a CD4 + count of less than 350 cells per cubic millimeter was 28 % in the 48-week ART group , 40 % in the 12-week group , and 40 % in the st and ard-care group . Corresponding values for long-term ART initiation were 22 % , 21 % , and 22 % . The median time to the primary end point was 65 weeks ( 95 % CI , 17 to 114 ) longer with 48-week ART than with st and ard care . Post hoc analysis identified a trend toward a greater interval between ART initiation and the primary end point the closer that ART was initiated to estimated seroconversion ( P=0.09 ) , and 48-week ART conferred a reduction in the HIV RNA level of 0.44 log(10 ) copies per milliliter ( 95 % CI , 0.25 to 0.64 ) 36 weeks after the completion of short-course therapy . There were no significant between-group differences in the incidence of the acquired immunodeficiency syndrome , death , or serious adverse events . CONCLUSIONS A 48-week course of ART in patients with primary HIV infection delayed disease progression , although not significantly longer than the duration of the treatment . There was no evidence of adverse effects of ART interruption on the clinical outcome . ( Funded by the Wellcome Trust ; SPARTAC Controlled-Trials.com number , IS RCT N76742797 , and EudraCT number , 2004 - 000446 - 20 . ) Objective : To assess the association of race with clinical outcomes in HIV-positive women on continuous HAART . Design : Prospect i ve study that enrolled women from 1994 to 1995 and 2001 to 2002 . Setting : Women 's Interagency HIV Study , a community-based cohort in five US cities . Participants : One thous and , four hundred and seventy-one HIV-positive continuous HAART users . Main outcome measures : Times to AIDS and non-AIDS death and incident AIDS-defining illness ( ADI ) after HAART initiation . Results : In adjusted analyses , black vs. white women had higher rates of AIDS death [ adjusted hazard ratio ( aHR ) 2.14 , 95 % confidence interval ( CI ) 1.30 , 3.50 ; P = 0.003 ] and incident ADI ( aHR 1.58 , 95 % CI 1.08 , 2.32 ; P = 0.02 ) , but not non-AIDS death ( aHR 0.91 , 95 % CI 0.59 , 1.39 ; P = 0.65 ) . Cumulative AIDS death incidence at 10 years was 17.3 and 8.3 % for black and white women , respectively . Other significant independent pre-HAART predictors of AIDS death included peak viral load ( aHR 1.70 per log10 , 95 % CI 1.34 , 2.16 ; P < 0.001 ) , nadir CD4 + cell count ( aHR 0.65 per 100 cells/&mgr;l , 95 % CI 0.56 , 0.76 ; P < 0.001 ) , depressive symptoms by Center for Epidemiology Studies Depression score at least 16 ( aHR 2.10 , 95 % CI 1.51 , 2.92 ; P < 0.001 ) , hepatitis C virus infection ( aHR 1.57 , 95 % CI 1.02 , 2.40 ; P = 0.04 ) , and HIV acquisition via transfusion ( aHR 2.33 , 95 % CI 1.21 , 4.49 ; P = 0.01 ) . In models with time-up date d HAART adherence , association of race with AIDS death remained statistically significant ( aHR 3.09 , 95 % CI 1.38 , 6.93 ; P = 0.006 ) . Conclusion : In continuous HAART-using women , black women more rapidly died from AIDS or experienced incident ADI than their white counterparts after adjusting for confounders . Future studies examining behavioral and biologic factors in these women may further the underst and ing of HAART prognosis ABSTRACT The RV144 HIV-1 vaccine trial demonstrated partial efficacy of 31 % against HIV-1 infection . Studies into possible correlates of protection found that antibodies specific to the V1 and V2 ( V1/V2 ) region of envelope correlated inversely with infection risk and that viruses isolated from trial participants contained genetic signatures of vaccine-induced pressure in the V1/V2 region . We explored the hypothesis that the genetic signatures in V1 and V2 could be partly attributed to selection by vaccine-primed T cells . We performed a T-cell-based sieve analysis of breakthrough viruses in the RV144 trial and found evidence of predicted HLA binding escape that was greater in vaccine versus placebo recipients . The predicted escape depended on class I HLA A*02- and A*11-restricted epitopes in the MN strain rgp120 vaccine immunogen . Though we hypothesized that this was indicative of postacquisition selection pressure , we also found that vaccine efficacy ( VE ) was greater in A*02-positive ( A*02 + ) participants than in A*02− participants ( VE = 54 % versus 3 % , P = 0.05 ) . Vaccine efficacy against viruses with a lysine residue at site 169 , important to antibody binding and implicated in vaccine-induced immune pressure , was also greater in A*02 + participants ( VE = 74 % versus 15 % , P = 0.02 ) . Additionally , a re analysis of vaccine-induced immune responses that focused on those that were shown to correlate with infection risk suggested that the humoral responses may have differed in A*02 + participants . These exploratory and hypothesis-generating analyses indicate there may be an association between a class I HLA allele and vaccine efficacy , highlighting the importance of considering HLA alleles and host immune genetics in HIV vaccine trials . IMPORTANCE The RV144 trial was the first to show efficacy against HIV-1 infection . Subsequently , much effort has been directed toward underst and ing the mechanisms of protection . Here , we conducted a T-cell-based sieve analysis , which compared the genetic sequences of viruses isolated from infected vaccine and placebo recipients . Though we hypothesized that the observed sieve effect indicated postacquisition T-cell selection , we also found that vaccine efficacy was greater for participants who expressed HLA A*02 , an allele implicated in the sieve analysis . Though HLA alleles have been associated with disease progression and viral load in HIV-1 infection , these data are the first to suggest the association of a class I HLA allele and vaccine efficacy . While these statistical analyses do not provide mechanistic evidence of protection in RV144 , they generate testable hypotheses for the HIV vaccine community and they highlight the importance of assessing the impact of host immune genetics in vaccine-induced immunity and protection . ( This study has been registered at Clinical Trials.gov under registration no. NCT00223080 . BACKGROUND It is unclear whether there are differences between men and women with human immunodeficiency virus type 1 ( HIV-1 ) infection in the plasma level of viral RNA ( the viral load ) . In men , the initial viral load after seroconversion predicts the likelihood of progression to the acquired immunodeficiency syndrome ( AIDS ) , but the relation between the two has not been assessed in women . Currently , the guidelines for initiating antiretroviral therapy are applied uniformly to women and men . METHODS From 1988 through 1998 , the viral load and the CD4 + lymphocyte count were measured approximately every six months in 156 male and 46 female injection-drug users who were followed prospect ively after HIV-1 seroconversion . RESULTS The median initial viral load was 50,766 copies of HIV-1 RNA per milliliter in the men but only 15,103 copies per milliliter in the women ( P<0.001 ) . The median initial CD4 + count did not differ significantly according to sex ( 659 and 672 cells per cubic millimeter , respectively ) . HIV-1 infection progressed to AIDS in 29 men and 15 women , and the risk of progression did not differ significantly according to sex . For each increase of 1 log in the viral load ( on a base 10 scale ) , the hazard ratio for progression to AIDS was 1.55 ( 95 percent confidence interval , 0.97 to 2.47 ) among the men and 1.43 ( 95 percent confidence interval , 0.76 to 2.69 ) among the women . The median initial viral load was 77,822 HIV-1 RNA copies per milliliter in the men in whom AIDS developed and 40,634 copies per milliliter in the men in whom it did not ; the corresponding values in the women were 17,149 and 12,043 copies per milliliter . Given the recommendation that treatment should be initiated when the viral load reaches 20,000 copies per milliliter , 74 percent of the men but only 37 percent of the women in our study would have been eligible for therapy at the first visit after seroconversion ( P<0.001 ) . CONCLUSIONS Although the initial level of HIV-1 RNA was lower in women than in men , the rates of progression to AIDS were similar . Treatment guidelines that are based on the viral load , rather than the CD4 + lymphocyte count , will lead to differences in eligibility for antiretroviral treatment according to sex In 1998 a collaboration between Duke University and the University of North Carolina , Chapel Hill ( UNC ) was founded to enhance identification of persons with acute HIV-1 infection ( AHI ) . The Duke-UNC AHI Research Consortium Cohort consists of patients ≥18 years old with a positive nucleic acid amplification test ( NAAT ) and either a negative enzyme immunoassay ( EIA ) test or a positive EIA with a negative/indeterminate Western blot . Patients were referred to the cohort from acute care setting s and state-funded HIV testing sites that use NAAT testing on pooled HIV-1 antibody-negative sample s. Between 1998 and 2010 , 155 patients with AHI were enrolled : 81 ( 52 % ) African-Americans , 63 ( 41 % ) white , non-Hispanics , 137 ( 88 % ) males , 108 ( 70 % ) men who have sex with men ( MSM ) , and 18 ( 12 % ) females . The median age was 27 years ( IQR 22 - 38 ) . Most ( n=138/155 ) reported symptoms with a median duration of 17.5 days . The median nadir CD4 count was 408 cells/mm(3 ) ( IQR 289 - 563 ) ; the median observed peak HIV-1 level was 726,859 copies/ml ( IQR 167,585 - 3,565,728 ) . The emergency department was the most frequent site of initial presentation ( n=55/152 ; 3 missing data ) . AHI diagnosis was made at time of first contact in 62/137 ( 45 % ; 18 missing data ) patients . This prospect ively enrolled cohort is the largest group of patients with AHI reported from the Southeastern United States . The demographics reflect the epidemic of this geographic area with a high proportion of African-Americans , including young black MSM . Highlighting the challenges of diagnosing AHI , less than half of the patients were diagnosed at the first healthcare visit . Women made up a small proportion despite increasing numbers in our clinics Objective : To establish whether a gender difference in virologic response to highly active antiretroviral treatment ( HAART ) exists . Methods : A cohort of HIV‐positive individuals was examined . Outcomes : Achievement of viral load < 500 copies/ml and “ failure ” ( failure to suppress viral load < 500 copies/ml after 24 weeks or two consecutive measurements above this level after having suppressed below it ) . Hazard ratios ( HRs ) comparing the rate in women to that in men were derived using the Cox model . Results : Of 366 male subjects , 79 % were white and 82 % were homosexual . Sixtythree percent of the 91 female subjects were African and 87 % were heterosexual . The median follow‐up after HAART was 94 weeks . The baseline CD4 count was higher in men ( 228 × 106 per liter ) than in women ( 171 × 106 per liter ) ( p = .01 ) , but the viral load was similar ( p = .88 ) . The median time to < 500 copies/ml was 16 weeks . Women achieved a viral load of < 500 copies/ml at a faster rate than men , with an adjusted HR of 1.46 ( 95 % confidence interval [ CI ] : 0.99‐2.16 ; p = .06 ) . Some 261 patients failed treatment ( 58 % of men and 53 % of women ) with an HR of 0.78 ( 95 % CI : 0.51‐1.21 ; p = .27 ) . Conclusions : Women may achieve virologic suppression at a faster rate than men and have a more durable response . Further research should examine these responses in conjunction with clinical outcomes , because gender differences in virologic response may ultimately be of little relevance if clinical outcomes are similar A week 48 efficacy and safety analysis with respect to gender and race was conducted using pooled data from the phase III , double‐blind , double‐dummy efficacy comparison in treatment‐naïve , HIV‐infected subjects of TMC278 and efavirenz ( ECHO ) and TMC278 against HIV , in a once‐daily regimen versus efavirenz ( THRIVE ) trials Background : Whether structured treatment interruptions ( STIs ) can induce anti-HIV immune response and control HIV replication following discontinuation of highly active antiretroviral therapy ( HAART ) in patients with primary HIV infection is controversial . Methods : In this multicenter , prospect i ve trial , patients with early symptomatic primary HIV infection were given HAART continuously for 34 weeks . Afterward , patients with plasma viral load ( PVL ) < 50 copies/mL entered the STI phase , which consisted of 3 consecutive periods of 2 , 4 , and 8 weeks off HAART , each separated by 12 weeks on HAART . HAART was permanently stopped at week 84 and patients were followed up for 24 weeks . The primary endpoint for definition of virologic success was a PVL < 50 copies/mL during the 6 months following HAART discontinuation . Results : Of the 29 patients enrolled , 26 completed the trial . Six months after HAART discontinuation , only 1 patient ( 3.8 % , 95 % CI : 0.1 % to 19.6 % ) had PVL < 50 copies/mL , whereas 6 of 26 ( 23.1 % , 95 % CI : 9.0 % to 43.7 % ) had PVL < 1000 copies/mL. Female gender was the only parameter significantly associated with a PVL < 1000 copies/mL. No other parameter , either at baseline or before HAART discontinuation , predicted virologic success at week 108 . A major protease inhibitor resistance mutation ( L90 M ) developed in 3 patients . Conclusions : This trial failed to confirm that a significant proportion of patients with primary HIV infection can maintain suppression of viremia after a sequence of HAART/STIs followed by HAART discontinuation Objective : To determine whether racial differences exist in the rate of CD4 lymphocyte decline in HIV‐1‐infected homosexual men . Design : Prospect i ve cohort study . Study population : Non‐Hispanic white ( n = 321 ) and black ( n = 102 ) HIV‐1‐seropositive homosexual and bisexual men were recruited from the Baltimore/Washington , DC metropolitan areas between 1984–1985 and 1987–1990 , and evaluated semiannually . Main measurements : Changes in CD4 lymphocyte count and CD4 percentage over time were analysed using linear regression methods for the 271 white and 69 black participants who had at least four semiannual CD4 lymphocyte measurements . Results : Rate of decline in CD4 lymphocyte count over 6 months was much slower among black than white seroprevalent men at all levels of baseline CD4 count ( baseline 201–400 × 106/l : + 0.24 versus ‐17.7 × 106/l ; 401–600 × 106/l : ‐11.3 versus ‐23.9 × 106/l : 601–800 × 106/l : ‐15.1 versus ‐35.2 × 106/l ; > 800 × 106/l : ‐4.3 versus ‐42.7 × 106/l for black versus white , respectively ) , although this was only statistically significant for the lowest and highest strata of baseline CD4 count . These racial differences persisted after adjustment for recruitment period ( 1984–1985 or 1987–1990 ) , follow‐up duration , age and zidovudine therapy or Pneumocystis carinii pneumonia prophylaxis . Similar findings were observed among the 70 white and 11 black seroconverters . Black participants were also less likely than a subgroup of white participants matched on baseline CD4 lymphocyte count to be HIV‐1 p24 antigen‐positive . However , after acid dissociation of sample s initially p24 antigen‐negative , there were no significant differences in the prevalence of p24 antigenemia at enrollment or after 1 year of follow‐up . Conclusions : This analysis suggests a more gradual decline in CD4 lymphocyte count among black than white Americans . The clinical significance of and reasons for this are unclear , but the lower prevalence of p24 antigenemia due to immune complexing among black Americans suggests that racial differences in the immune response to HIV may exist . Additional studies are needed to vali date these findings in a larger cohort of non‐whites , and to assess their relationship with other measures of cellmediated immune function BACKGROUND In phase 2 trials , the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus ( HCV ) genotype 1 , 2 , or 3 infection . METHODS We conducted two phase 3 studies in previously untreated patients with HCV infection . In a single-group , open-label study , we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1 , 4 , 5 , or 6 ( of whom 98 % had genotype 1 or 4 ) . In a noninferiority trial , 499 patients with HCV genotype 2 or 3 infection were r and omly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks . In the two studies , the primary end point was a sustained virologic response at 12 weeks after the end of therapy . RESULTS In the single-group study , a sustained virologic response was reported in 90 % of patients ( 95 % confidence interval , 87 to 93 ) . In the noninferiority trial , a sustained response was reported in 67 % of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group . Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection ( 56 % vs. 97 % ) . Adverse events ( including fatigue , headache , nausea , and neutropenia ) were less common with sofosbuvir than with peginterferon . CONCLUSIONS In a single-group study of sofosbuvir combined with peginterferon-ribavirin , patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90 % at 12 weeks . In a noninferiority trial , patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response ( 67 % ) . Adverse events were less frequent with sofosbuvir than with peginterferon . ( Funded by Gilead Sciences ; FISSION and NEUTRINO Clinical Trials.gov numbers , NCT01497366 and NCT01641640 , respectively . ) CONTEXT A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation ( HCT ) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions . OBJECTIVE To describe outcomes of patients 60 years or older after receiving minimally toxic nonmyeloablative allogeneic HCT . DESIGN , SETTING , AND PARTICIPANTS From 1998 to 2008 , 372 patients aged 60 to 75 years were enrolled in prospect i ve clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine , 90 mg/m(2 ) , before related ( n = 184 ) or unrelated ( n = 188 ) donor transplants . Postgrafting immunosuppression included mycophenolate mofetil and a calcineurin inhibitor . MAIN OUTCOME MEASURES Overall and progression-free survival were estimated by Kaplan-Meier method . Cumulative incidence estimates were calculated for acute and chronic graft-vs-host disease , toxicities , achievement of full donor chimerism , complete remission , relapse , and nonrelapse mortality . Hazard ratios ( HRs ) were estimated from Cox regression models . RESULTS Overall , 5-year cumulative incidences of nonrelapse mortality and relapse were 27 % ( 95 % CI , 22%-32 % ) and 41 % ( 95 % CI , 36%-46 % ) , respectively , leading to 5-year overall and progression-free survival of 35 % ( 95 % CI , 30%-40 % ) and 32 % ( 95 % CI , 27%-37 % ) , respectively . These outcomes were not statistically significantly different when stratified by age groups . Furthermore , increasing age was not associated with increases in acute or chronic graft-vs-host disease or organ toxicities . In multivariate models , HCT-specific comorbidity index scores of 1 to 2 ( HR , 1.58 [ 95 % CI , 1.08 - 2.31 ] ) and 3 or greater ( HR , 1.97 [ 95 % CI , 1.38 - 2.80 ] ) were associated with worse survival compared with an HCT-specific comorbidity index score of 0 ( P = .003 overall ) . Similarly , st and ard relapse risk ( HR , 1.67 [ 95 % CI , 1.10 - 2.54 ] ) and high relapse risk ( HR , 2.22 [ 95 % CI , 1.43 - 3.43 ] ) were associated with worse survival compared with low relapse risk ( P < .001 overall ) . CONCLUSION Among patients aged 60 to 75 years treated with nonmyeloablative allogeneic HCT , 5-year overall and progression-free survivals were 35 % and 32 % , respectively |
11,938 | 15,867,409 | Exercise therapy decreased pain and improved physical function by modest amounts in adults with chronic low back pain .
In adults with acute low back pain , exercise therapy , conservative management , and no treatment had similar effects on pain .
They synthesized the evidence by using a levels-of- evidence approach because of the heterogeneity and insufficiency of the literature and concluded that the evidence did not support effectiveness of exercises for acute low back pain but that exercises may be helpful for chronic low back pain .
We considered studies to provide evidence that the exercise therapy was ineffective if the comparison group statistically significantly improved and the exercise group did not statistically significantly improve . | Context Many experts recommend exercise therapy for nonspecific low back pain .
The Editors Low back pain is one of the leading causes of disability .
Exercise therapy is a management strategy that is widely used in low back pain .
It encompasses a heterogeneous group of interventions ranging from general physical fitness or aerobic exercise to muscle-strengthening and various types of flexibility and stretching exercises .
Recent review s on related topics have been restricted by population ( 2 - 4 ) or type of exercise therapy ( 5 ) and have used only qualitative methods of synthesis ( 2 , 3 , 5 , 6 ) .
We aim ed to assess the effectiveness of exercise therapy for reducing pain and disability in adults with nonspecific acute , subacute , and chronic low back pain compared with no treatment ( including placebo and sham treatment ) and other conservative treatments . | Study Design . A prospect i ve r and omized controlled trial . Objectives . To examine the effectiveness of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain . Summary of Background Data . Strong evidence exists that manual therapy provides more effective short-term pain relief than does placebo treatment in the management of chronic low back pain . The evidence for long-term effect is lacking . Methods . Two hundred four chronic low back pain patients , whose Oswestry disability index was at least 16 % , were r and omly assigned to either a manipulative-treatment group or a consultation group . All were clinical ly examined , informed about their back pain , provided with an educational booklet , and were given specific instructions based on the clinical evaluation . The treatment included four sessions of manipulation and stabilizing exercises aim ing to correct the lumbopelvic rhythm . Question naires inquired about pain intensity , self-rated disability , mental depression , health-related quality of life , health care costs , and production costs . Results . At the baseline , the groups were comparable , except for the percentage of employees ( P = 0.01 ) . At the 5- and 12-month follow-ups , the manipulative-treatment group showed more significant reductions in pain intensity ( P < 0.001 ) and in self-rated disability ( P = 0.002 ) than the consultation group . However , we detected no significant difference between the groups in health-related quality of life or in costs . Conclusions . The manipulative treatment with stabilizing exercises was more effective in reducing pain intensity and disability than the physician consultation alone . The present study showed that short , specific treatment programs with proper patient information may alter the course of chronic low back pain STUDY DESIGN A r and omized controlled comparative trial with an 8-month follow-up period was conducted . OBJECTIVE To compare the effect of the McKenzie treatment method with that of intensive dynamic strengthening training in patients with subacute or chronic low back pain . SUMMARY OF BACKGROUND DATA R and omized studies indicate that the efficacy of the McKenzie method in the treatment of patients with acute or subacute low back pain is debatable . Currently , no r and omized studies examining the effects of this method for patients with chronic low back pain have been published . METHODS For this study , 260 consecutive patients with low back pain and at least 8 weeks duration of symptoms ( 85 % of the patients had more than 3 months duration of symptoms ) were r and omized into two groups : Group A was treated with the McKenzie method ( n = 132 ) , and Group B was treated with intensive dynamic strengthening training ( n = 128 ) . The treatment period for both groups was 8 weeks at an outpatient clinic , followed by 2 months of self-training at home . Treatment results were recorded at the end of the treatment period at the clinic , then 2 and 8 months after . In both groups , 30 % of the patients were lost to follow-up evaluation . An intention-to-treat analysis of the main effect variables , disability , and pain was performed for all the patients included in the study . A supplementary analysis of the 180 patients who completed the full treatment program also was undertaken . RESULTS Intention-to-treat analysis showed a tendency toward a difference in reduction of disability in favor of the McKenzie group at the 2-month follow-up assessment ( P = 0.04 ) , but no differences at the end of treatment and at the 8-month follow-up evaluation . No differences in reduction of pain were observed at any time between the groups . The supplementary analysis of the patients who had completed the full intervention showed a tendency toward a difference in favor of the McKenzie method in reduction of pain at the end of treatment ( P = 0.02 ) . This difference reached statistical significance at the 2-month follow-up assessment ( P = 0.01 ) , but no difference was found after 8 months . The supplementary analysis showed no differences between the groups with regard to reduction of disability . CONCLUSION The McKenzie method and intensive dynamic strengthening training seem to be equally effective in the treatment of patients with subacute or chronic low back pain Study Design . A r and omized controlled trial with a 6-month follow-up period was conducted . Objective . To compare lumbar extension exercise and whole-body vibration exercise for chronic lower back pain . Summary of Background Data . Chronic lower back pain involves muscular as well as connective and neural systems . Different types of physiotherapy are applied for its treatment . Industrial vibration is regarded as a risk factor . Recently , vibration exercise has been developed as a new type of physiotherapy . It is thought to activate muscles via reflexes . Methods . In this study , 60 patients with chronic lower back pain devoid of “ specific ” spine diseases , who had a mean age of 51.7 years and a pain history of 13.1 years , practice d either isodynamic lumbar extension or vibration exercise for 3 months . Outcome measures were lumbar extension torque , pain sensation ( visual analog scale ) , and pain-related disability ( pain disability index ) . Results . A significant and comparable reduction in pain sensation and pain-related disability was observed in both groups . Lumbar extension torque increased significantly in the vibration exercise group ( 30.1 Nm/kg ) , but significantly more in the lumbar extension group ( + 59.2 Nm/kg ; SEM 10.2;P < 0.05 ) . No correlation was found between gain in lumbar torque and pain relief or pain-related disability ( P > 0.2 ) . Conclusions . The current data indicate that poor lumbar muscle force probably is not the exclusive cause of chronic lower back pain . Different types of exercise therapy tend to yield comparable results . Interestingly , well-controlled vibration may be the cure rather than the cause of lower back pain BACKGROUND AND PURPOSE The prescriptive validity of a treatment-oriented extension-mobilization category for patients with low back syndrome ( LBS ) was examined . SUBJECTS Of a total of 39 patients with LBS referred for physical therapy , 24 patients ( 14 male , 10 female ) , aged 14 to 50 years ( means = 31.3 , SD = 11.6 ) , were classified as having signs and symptoms indicating treatment with an extension-mobilization approach . The remaining subjects were dismissed from the study . Patients in the extension-mobilization category were r and omly assigned to either an experimental ( treatment ) group ( n = 14 ) or a comparison group ( n = 10 ) . METHODS The experimental and comparison group subjects were treated with either mobilization and extension ( a treatment matched to the category ) or a flexion exercise regimen ( an unmatched treatment ) . Outcome was assessed with a modified Oswestry Low Back Pain Question naire administered initially and at 3 and 5 days after initiation of treatment . Data were analyzed with a 2 x 3 ( treatment group x treatment period ) analysis of variance . RESULTS The subjects ' rate of improvement , as indicated by the Oswestry question naire scores , was dependent on the treatment group to which they were assigned . Subjects treated with extension and mobilization positively responded at a faster rate than did those treated with a flexion-oriented program . CONCLUSION AND DISCUSSION This study illustrates that a priori classification of selected patients with LBS into a treatment category of extension and mobilization and subsequently treating the patients accordingly with specified interventions can be an effective approach to conservative management of selected patients BACKGROUND Chiropractic manipulation and strenuous exercise therapy have been shown effective in the treatment of nonspecific back pain . Bone- setting , the predecessor of modern manual therapies , still survives in some parts of Finl and and was compared with a light exercise therapy and non-manipulative , pragmatic physiotherapy in a year-long r and omized controlled trial on patients with long-term back pain . METHODS One hundred fourteen ambulatory patients of working age with back pain for 7 weeks or more were r and omly assigned to the therapies , which were offered in up to 10 sessions during a 6-week treatment period . The outcome was measured by the Oswestry Disability Question naire . Sick-leaves and visits to health centers were recorded for 1 year before and after the therapy . RESULTS The Oswestry disability scores improved most in the bone- setting group ( P = .02 , Kruskall-Wallis test ) . Visits to health centers for back pain were reduced only in the physiotherapy group ( P = .01 , Wilcoxon test ) . Sick-leaves were not significantly different between groups . A secondary analysis based on the use of additional therapies after the intervention showed a possible subgroup with an enhanced effect from bone- setting . CONCLUSIONS Traditional bone- setting seemed more effective than exercise or physiotherapy on back pain and disability , even 1 year after therapy Abstract Objective : To evaluate effectiveness of an exercise programme in a community setting for patients with low back pain to encourage a return to normal activities . Design : R and omised controlled trial of progressive exercise programme compared with usual primary care management . Patients ' preferences for type of management were elicited independently of r and omisation . Participants : 187 patients aged 18 - 60 years with mechanical low back pain of 4 weeks to 6 months ' duration . Interventions : Exercise classes led by a physiotherapist that included strengthening exercises for all main muscle groups , stretching exercises , relaxation session , and brief education on back care . A cognitive-behavioural approach was used . Main outcome measures : Assessment s of debilitating effects of back pain before and after intervention and at 6 months and 1 year later . Measures included Rol and disability question naire , Aberdeen back pain scale , pain diaries , and use of healthcare services . Results : At 6 weeks after r and omisation , the intervention group improved marginally more than the control group on the disability question naire and reported less distressing pain . At 6 months and 1 year , the intervention group showed significantly greater improvement in the disability question naire score ( mean difference in changes 1.35 , 95 % confidence interval 0.13 to 2.57 ) . At 1 year , the intervention group also showed significantly greater improvement in the Aberdeen back pain scale ( 4.44 , 1.01 to 7.87 ) and reported only 378 days off work compared with 607 in the control group . The intervention group used fewer healthcare re sources . Outcome was not influenced by patients ' preferences . Conclusions : The exercise class was more clinical ly effective than traditional general practitioner management , regardless of patient preference , and was cost effective . Key messages Patients with back pain need to return to normal activities as soon as possible but are often afraid that movement or activity may be harmful An exercise programme led by a physiotherapist in the community and based on cognitive-behavioural principles helped patients to cope better with their pain and function better even one year later Patients ' preferences for type of management did not affect outcome Patients in the intervention group tended to use fewer healthcare re sources and took fewer days off work This type of exercise programme should be more widely BACKGROUND The effectiveness of massage therapy for low-back pain has not been documented . This r and omized controlled trial compared comprehensive massage therapy ( soft-tissue manipulation , remedial exercise and posture education ) , 2 components of massage therapy and placebo in the treatment of subacute ( between 1 week and 8 months ) low-back pain . METHODS Subjects with subacute low-back pain were r and omly assigned to 1 of 4 groups : comprehensive massage therapy ( n = 25 ) , soft-tissue manipulation only ( n = 25 ) , remedial exercise with posture education only ( n = 22 ) or a placebo of sham laser therapy ( n = 26 ) . Each subject received 6 treatments within approximately 1 month . Outcome measures obtained at baseline , after treatment and at 1-month follow-up consisted of the Rol and Disability Question naire ( RDQ ) , the McGill Pain Question naire ( PPI and PRI ) , the State Anxiety Index and the Modified Schober test ( lumbar range of motion ) . RESULTS Of the 107 subjects who passed screening , 98 ( 92 % ) completed post-treatment tests and 91 ( 85 % ) completed follow-up tests . Statistically significant differences were noted after treatment and at follow-up . The comprehensive massage therapy group had improved function ( mean RDQ score 1.54 v. 2.86 - 6.5 , p < 0.001 ) , less intense pain ( mean PPI score 0.42 v. 1.18 - 1.75 , p < 0.001 ) and a decrease in the quality of pain ( mean PRI score 2.29 v. 4.55 - 7.71 , p = 0.006 ) compared with the other 3 groups . Clinical significance was evident for the comprehensive massage therapy group and the soft-tissue manipulation group on the measure of function . At 1-month follow-up 63 % of subjects in the comprehensive massage therapy group reported no pain as compared with 27 % of the soft-tissue manipulation group , 14 % of the remedial exercise group and 0 % of the sham laser therapy group . INTERPRETATION Patients with subacute low-back pain were shown to benefit from massage therapy , as regulated by the College of Massage Therapists of Ontario and delivered by experienced massage therapists OBJECTIVE To determine if the use of an isokinetic device for trunk exercise is more effective than st and ard physiotherapy in promoting motor disinhibition for patients with chronic low back pain . POPULATION chronic low back pain out patients who are treated in a Rheumatology or PM & R unit within an academic hospital . METHODOLOGY This is a prospect i ve , controlled , r and omized study , with two groups of treatment : one treated with isokinetic techniques and the other with st and ard physiotherapy , six sessions for each treatment during 2 weeks . Outcome measures include pain ( VSA ) , trunk mobility ( Schöber index , distance from fingers to floor ) , muscle extensibility and muscle strength ( Biering-Sorensen and Shirado-Ito test ) , and functional capacity ( Quebec scale ) . RESULTS Seventeen subjects were enrolled . The results suggest that both isokinetic exercise and physiotherapy result in improved range of motion , extensibility , muscle strength , and pain , without any significant superiority of one technique over the other . However , each technique has specific advantage . DISCUSSION Despite method ologic limitations , this study shows that isokinetic exercise is not better than physiotherapy in reversing motor inhibition in chronic low back pain . Our results are consistent with those of other studies in the literature , with regard to the absence of established overall superiority of one exercise technique or program over the other in this population , and with regard to partial benefits of specific exercise techniques . CONCLUSION The non-specific benefit of one technique indicates that further studies are needed to evaluate the benefit of combining exercise techniques in chronic low back pain , in order to address the multiple factors involved in this pathology Abstract Objective To measure the effectiveness of routine physiotherapy compared with an assessment session and advice from a physiotherapist for patients with low back pain . Design Pragmatic , multicentre , r and omised controlled trial . Setting Seven British NHS physiotherapy departments . Participants 286 patients with low back pain of more than six weeks ' duration . Intervention Routine physiotherapy or advice on remaining active from a physiotherapist . Both groups received an advice book . Main outcome measures Primary outcome was scores on the Oswestry disability index at 12 months . Secondary outcomes were scores on the Oswestry disability index ( two and six months ) , scores on the Rol and and Morris disability question naire and SF-36 ( 2 , 6 and 12 months ) , and patient perceived benefit from treatment ( 2 , 6 , and 12 months ) . Results 200 of 286 patients ( 70 % ) provided follow up information at 12 months . Patients in the therapy group reported enhanced perceptions of benefit , but there was no evidence of a long term effect of physiotherapy in either disease specific or generic outcome measures ( mean difference in change in Oswestry disability index scores at 12 months −1.0 % , 95 % confidence interval −3.7 % to 1.6 % ) . The most common treatments were low velocity spinal joint mobilisation techniques ( 72 % , 104 of 144 patients ) and lumbar spine mobility and abdominal strengthening exercises ( 94 % , 136 patients ) . Conclusions Routine physiotherapy seemed to be no more effective than one session of assessment and advice from a physiotherapist STUDY DESIGN A r and omized clinical trial . OBJECTIVES To examine the relative efficacy of three active therapies for chronic low back pain . SUMMARY OF BACKGROUND DATA There is much evidence documenting the efficacy of exercise in the conservative management of chronic low back pain , but many questions remain regarding its exact prescription and method of application . The most successful method must be identified to enable refinement of future rehabilitation programs to target the specific needs of the patient with chronic low back pain and the budget of the healthcare provider . METHODS One hundred forty-eight patients with chronic low back pain were r and omized to one of the following treatments , which they attended twice a week for 3 months : 1 ) modern active physiotherapy , 2 ) muscle reconditioning on training devices , or 3 ) low-impact aerobics . Pretherapy and posttherapy , objective measurements of lumbar mobility were performed , and question naires were administered inquiring about self-rated pain and disability , and psychosocial factors . Similar question naires were administered 6 months after therapy . The data were analyzed using the intention-to-treat principle . RESULTS Of the 148 patients , 16 ( 10.8 % ) dropped out of the therapy . One hundred thirty-seven question naires ( 93 % ) were available for analysis at all three time points . After therapy , significant reductions were observed in pain intensity , frequency , and disability ; Fear-Avoidance Beliefs about physical activity ( FABQactivity ) ; and " praying/hoping , " " catastrophizing , " and " pain behavior " coping strategies -- each with no group differences in the extent of the response . These effects were maintained over the subsequent 6 months , with the exception of disability and FABQactivity for the physiotherapy group . There were small but significant posttherapy increases in lumbar mobility , with aerobics and devices showing a greater response than physiotherapy . CONCLUSION The general lack of treatment specificity suggests that the main effects of the therapies were educed not through the reversal of physical weaknesses targeted by the corresponding exercise modality , but rather through some " central " effect , perhaps involving an adjustment of perception in relation to pain and disability . The direct costs associated with administering physiotherapy were three times as great , and devices four times as great , as those for aerobics . Administration of aerobics as an efficacious therapy for chronic low back pain has the potential to relieve some of the huge financial burden associated with the condition Study Design . The study was carried out as an open , r and omized , multicenter , parallel‐group study with an observation period of 12 months . Four Norwegian physiotherapy institutes took part . Patients were subsequently followed for 12 months of home exercise on their own , without the supervision of a physiotherapist . Objectives . 1 ) To investigate and compare the effects of two different exercise programs on low back problems in patients after a 1‐year training program under the supervision of a physiotherapist . 2 ) To investigate the effect supervision by , and motivation from , physiotherapists has on training compliance and efficacy . Summary of Background Data . After ordinary physiotherapy treatment for low back problems , patients were r and omly allocated either to a conventional training program design ed by physiotherapists or to a training program using a new Norwegian‐developed training apparatus called the TerapiMaster . The study included 153 patients with low back problems , all of whom had been referred to physiotherapy by their general practitioners . One hundred twenty‐six patients were followed for an additional 12 months when performing home exercise programs on their own . Methods . Monitoring patient satisfaction with the training program , compliance with the program , and absenteeism from work during the training period . Results . Patient satisfaction with both training programs was high , with about 83 % of participating patients completing the study in accordance with the protocol . Mean absenteeism ( SD ) during the preceding year totaled 82.5 days ( 19.8 ) in the conventional training group and 61.6 days ( 14.7 ) in the TerapiMaster group . Significant reductions to 17.2 days ( 6.0 ) and 15.4 days ( 5.3 ) in the two groups , respectively , were recorded during the training period , corresponding to a 75 % to 80 % reduction compared with the preceding 1‐year period . Mean absenteeism showed a further significant decline during the 12‐month period without supervised training . The average values were 9.9 days ( 3.2 ) for conventional training and 9.3 days ( 3.1 ) for the TerapiMaster , respectively . Conclusions . Both exercise programs reduced absenteeism significantly ( 75‐80 % ) . No difference in the effects of the two different programs was discernible . Regular follow‐up through encouragement and variation in the training programs appear to be important factors for motivating patients to adhere to regular exercise programs for low back problems . This thesis was corroborated by the 12‐month study of unsupervised exercise OBJECTIVE To determine whether traditional bone- setting or continuous light exercise therapy could case back pain and improve function better than ordinary physiotherapy . DESIGN Observer-blinded , r and omized clinical trial with a 6-month follow-up . SETTING An outpatient institution for folk medicine research . PATIENTS Of 147 back pain patients recruited from local health centers and by newspaper announcements , 132 were found eligible ( non-retired-no contraindications to manipulation ) and entered . A final 114 ( one dropout ) with back pain for longer than 7 weeks were included in this intent to treat analysis . INTERVENTIONS Bone- setting , guidance for continuous light back movements or physiotherapy for up to ten 1-hour sessions during 6 weeks . MAIN OUTCOME MEASURES Spinal mobility and muscular performance . Back pain assessed by visual analog scales ( VAS ) . RESULTS The physical measures changed only modestly , from one tenth to half of st and ard deviation , while the VAS was halved . The thoracolumbar side-bending , the modified Schober , and the VAS were significantly better improved by bone- setting than by exercise but not better than by physiotherapy . CONCLUSION Neither bone- setting nor exercise differed significantly from physiotherapy , but bone- setting improved lateral and forward bending of the spine and back pain more than did exercise Study Design . A r and omized clinical trial with 1-year and 3-year telephone question naire follow-ups . Objective . To report a specific exercise intervention ’s long-term effects on recurrence rates in acute , first-episode low back pain patients . Summary of Background Data . The pain and disability associated with an initial episode of acute low back pain ( LBP ) is known to resolve spontaneously in the short-term in the majority of cases . However , the recurrence rate is high , and recurrent disabling episodes remain one of the most costly problems in LBP . A deficit in the multifidus muscle has been identified in acute LBP patients , and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity . Any relation between this deficit and recurrence rate was investigated in the long-term . Methods . Thirty-nine patients with acute , first-episode LBP were medically managed and r and omly allocated to either a control group or specific exercise group . Medical management included advice and use of medications . Intervention consisted of exercises aim ed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle . One year and three years after treatment , telephone question naires were conducted with patients . Results . Question naire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group . One year after treatment , specific exercise group recurrence was 30 % , and control group recurrence was 84 % ( P < 0.001 ) . Two to three years after treatment , specific exercise group recurrence was 35 % , and control group recurrence was 75 % ( P < 0.01 ) . Conclusion . Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone 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 Objectives : To describe postural sway and its associations to background factors , low back pain and functional capacity . To evaluate the changes in postural sway after three months of therapeutic exercise in the gym or at home . Design : A one-year r and omized experimental trial evaluated postural sway in three study groups : intensive training , home exercise and control group . Setting : Subjects were recruited from seven local occupational health care centres in Central Finl and and were examined at Central Finl and Hospital by medical doctors . Measurements and therapeutic exercise programmes were carried out in the Research Laboratory of Sport and Health Sciences at Jyväskylä University . Subjects : Initially , 49 male and 41 female subjects ( aged 20–55 years ) with nonspecific and subacute low back pain were examined . Main outcome measures : Postural sway using a force platform , the Oswestry Index , as well as a measure of low back pain intensity were measured at the initial stage of the study , directly after interventions , as well as at three and nine months after the interventions . Results : The background variables were not strongly correlated with postural sway . No changes occurred in the amplitude of sway during the study , but the sway velocity of the home exercise group increased . Conclusions : Postural sway measurements with a force platform may be suitable for detecting impairments of balance performance among subjects with pronounced functional or activity limitations and severe low back pain problems . In order to enhance balance performance , specific and customized exercise programmes are required BACKGROUND The prescription of exercise as a conservative treatment for lumbar pain is frequent and seems effective for the chronic cases of nonspecific low back pain . However , there is no evidence favoring one type of exercise over another . Often , exercise programs are prescribed without adequate evaluation of the individual characteristics like posture , muscular force , and extensibility . Patients with totally different causes of low back pain will often be given the same type of exercises . OBJECTIVE Our objective was to compare the effectiveness of 2 home exercise programs in decreasing disability and pain related to subacute and chronic nonspecific low back pain . To do so we compared a specific ( individualized ) exercise program with a program of commonly prescribed exercises for low back pain . METHOD In a control group study , 20 patients with chronic or subacute nonspecific low back pain participated after giving their informed consent . All subjects were evaluated ( physical evaluation of lumbar and pelvic muscles [ 1 ] force and [ 2 ] extensibility , [ 3 ] trunk range of motion ) and then divided in 2 groups : 10 patients received specific exercises ( experimental group ) based on their evaluation , and 10 patients received a commonly prescribed exercise program for low back pain ( control group ) . Six weeks later a second physical evaluation was conducted . Pain ( visual analog pain scale ) and disability ( modified Oswestry ) question naires were also completed by each subject at both evaluations . DESIGN This was a r and omized experimental study . RESULTS Both groups had similar age , weight , and sex characteristics . The experimental group showed significant improvements for some components targeted by the program . The control group significantly had improvement of some physical characteristics not related to their initial deficits . Even if both groups showed some improvements in muscular force and extensibility , only the members of the group who received specific exercises significantly reduced their level of pain and disability . Both groups showed a similar rate of participation in the program . CONCLUSION The results of this study suggest that applying a specific physical evaluation and exercise prescription is an appropriate treatment for people having subacute or chronic nonspecific pain . Thus clinicians should prescribe exercise programs based on individual muscular deficits rather than most commonly prescribed exercise programs Study Design . R and omized parallel-group comparative trial with a 6-month follow-up period . Objective . To compare , in chronic low back pain patients , the effectiveness of a functional restoration program , including intensive physical training , occupational therapy , and psychological support to an active individual therapy consisting of 3 hours physical therapy per week during 5 weeks . Summary of Background Data . Controlled studies conducted in the United States showed a benefit of functional restoration in patients with low back pain , especially on return to work . R and omized Canadian and European trials had less favorable results . In France , there has been up to now no r and omized study . Controlled studies suggested a positive effect of functional restoration programs . Methods . Eighty-six patients with low back pain were r and omized to either the functional restoration ( 44 patients ) or the active individual therapy ( 42 patients ) program . One person in each group never started the program . Two patients did not complete the functional restoration program , and one was lost to follow-up at 6 months . The mean number of sick-leave days in the 2 previous years was 6 months . Results . After adjustment on the variable ≪ workplace enrolled in an ergonomic program ≫ , the mean number of sick-leave days was significantly lower in the functional restoration group . Physical criteria and treatment appreciation were also better . There was no significant difference in the intensity of pain , the quality of life and functional indexes , the psychological characteristics , the number of contacts with the medical system , and the drug intake . Conclusions . This study demonstrates the effectiveness of a functional restoration program on important outcome measures , such as sick leave , in a country that has a social system that protects people facing difficultiesat work OBJECTIVE To evaluate the effectiveness of a program design ed to reduce back pain in nursing aides . METHODS Female nursing aides from a university hospital who had suffered episodes of back pain for at least six months were included in the study . Participants were r and omly divided into a control group and an intervention group . The intervention program involved a set of exercises and an educational component stressing the ergonomic aspect , administered twice a week during working hours for four months . All subjects answered a structured question naire and the intensity of pain was assessed before and after the program using a visual analogue scale ( VAS ) . Student 's t-test or the Wilcoxon Rank Sum Test for independent sample s , and Chi-square test or the Exact Fisher test for categorical analysis , were used . The McNemar test and the Wilcoxon matched pairs test were used to compare the periods before and after the program . RESULTS There was a statistically significant decrease in the frequency of cervical pain in the last two months and in the last seven days in the intervention group . There was also a reduction in cervical pain intensity in the two periods ( 2 months , 7 days ) and lumbar pain intensity in the last 7 days . CONCLUSIONS The results suggest that a program of regular exercise with an emphasis on ergonomics can reduce musculoskeletal symptoms in nursing personnel The aim of this study was to determine whether grade d activity restored occupational function in industrial blue-collar workers who were sick-listed for 8 weeks because of subacute , nonspecific , mechanical low back pain ( LBP ) . Patients with LBP , who had been examined by an orthopedic surgeon and a social worker , were r and omly assigned to either an activity group ( n = 51 ) or a control group ( n = 52 ) . Patients with defined orthopedic , medical , or psychiatric diagnoses were excluded before r and omization . The grade d activity program consisted of four parts : ( 1 ) measurements of functional capacity ; ( 2 ) a work-place visit ; ( 3 ) back school education ; and ( 4 ) an individual , submaximal , gradually increased exercise program , with an operant-conditioning behavioral approach , based on the results of the tests and the dem and s of the patient 's work . Records of the amount of sick leave taken over a 3-year period ( ie , the 1-year periods before , during , and after intervention ) were obtained from each patient 's Social Insurance Office . The patients in the activity group returned to work significantly earlier than did the patients in the control group . The median number of physical therapist appointments before return to work was 5 , and the average number of appointments was 10.7 ( SD = 12.3 ) . The average duration of sick leave attributable to LBP during the second follow-up year was 12.1 weeks ( SD = 18.4 ) in the activity group and 19.6 weeks ( SD = 20.7 ) in the control group . Four patients in the control group and 1 patient in the activity group received permanent disability pensions . The grade d activity program made the patients occupationally functional again , as measured by return to work and significantly reduced long-term sick leave The effects of exercise for isolated lumbar extensor muscles were examined in 54 chronic low-back pain patients . Subjects were r and omly assigned to a 10-week exercise program ( N = 31 ) or a wait-list control group ( N = 23 ) . Results indicated a significant increase in isometric lumbar extension strength for the treatment group and a significant reduction in reported pain compared with the control group ( P 0.05 ) . Treated subjects reported less physical and psychosocial dysfunction whereas the control group increased in pain , and physical and psychosocial dysfunction . There were no concomitant changes in reported daily activity levels . These results show that lumbar extension exercise is beneficial for strengthening the lumbar extensors and results in decreased pain and improved perceptions of physical and psychosocial functioning in chronic back pain patients . However , these improvements were not related to changes in activities or psychological distress Context Low back pain causes frequent disability and lost productive time . Contribution This r and omized trial compared a behavioral-oriented grade d activity program with usual care in 134 Dutch airline company workers who had missed work because of persistent low back pain . Grade d activity consisted of biweekly 1-hour exercise sessions with physiotherapists who emphasized operant-conditioning principles . Over 6 months of follow-up , participants in the grade d activity program missed 58 days of work , while participants receiving usual care missed 87 days . Implication s A behavioral-oriented grade d activity program returned participants with low back pain to work more often than did usual care . The Editors Nonspecific low back pain is an uncomfortable medical condition that causes frequent disability and absence from work . Most episodes of low back pain resolve fairly quickly and cause only short periods of absence from work . However , some workers with low back pain miss work for several days to weeks and are at risk for more permanent disability ( 1 ) . To reduce the individual and socioeconomic burden related to this absenteeism , we need effective intervention strategies in occupational health care setting s that promote safe and rapid return to work . One promising and often-advocated intervention strategy for workers with prolonged nonspecific low back pain is active rehabilitation that is directed toward return to normal activity and work ( 2 ) . Examples are grade d activity interventions that include physical exercise , application of operant-conditioning behavioral principals , and promotion of improved functioning and safe return to work even if pain persists ( 3 - 6 ) . In a r and omized , controlled trial , Lindstrm and colleagues ( 3 , 4 ) found that a grade d activity intervention reduced absence from work more than did traditional care in Swedish workers employed in the automobile industry . We investigate , in a second r and omized , controlled trial , whether absence from work because of low back pain is reduced more with grade d activity intervention than with traditional care in an occupational health care setting in the Netherl and s. Methods Study Design and Sample The study was a single-blind , r and omized , controlled trial in an occupational health services center ( KLM Health , Safety and Environment ) at Schiphol Airport , Amsterdam , the Netherl and s. The center provides occupational health services for all employees of a major Dutch airline ( KLM Royal Dutch Airlines ) . The source sample ( n = 20 000 ) consisted of workers who were employed in the following organizational units of the airline : baggage and aircraft turnaround services , passenger services , engineering and maintenance , cargo , and cabin and cockpit . Workers who were listed as absent from work because of low back pain were invited for a consultation with the occupational physician . Those who were thought to be eligible for inclusion were referred to the research assistant , who judged whether they met the inclusion criteria : full or partial absence from work because of nonspecific low back pain and low back pain symptoms with a minimum duration of 4 weeks in succession . The exclusion criteria were low back pain with radiation below the knee with signs of nerve-root compression ( 7 ) ; cardiovascular contraindications for physical activity , as checked according to the Physical Activities Readiness Question naire ( 8 , 9 ) ; any conflict between worker and employer with legal involvement ; or pregnancy . Workers who met the inclusion criteria were informed of the purpose and procedures of the study and were enrolled after giving informed consent . The Medical Ethical Committee of the VU University Medical Center , Amsterdam , the Netherl and s , approved the study . Treatment Allocation The participants were assigned to grade d activity or usual care on the basis of block r and omization , after prestratification for the organizational unit in the workplace from which they were recruited ( the 5 organizational units listed earlier ) and for the severity of pain symptoms ( scored on a scale of 0 to 10 ; severity scores were < 6 or 6 points ) . This result ed in a total of 10 strata . R and omized , permuted blocks of 4 allocations were generated for each stratum through a computer-generated r and om-sequence table . Opaque , sequentially numbered , sealed envelopes were prepared for each stratum by a research er who was not involved in enrolling the participants or assigning them to their groups . The envelopes contained a sheet of paper that indicated 1 of the 2 interventions . Participants learned their group assignments after a research assistant completed the baseline measurements and delivered the sealed envelopes . Blinding The research assistants who collected the data were blinded to the treatment allocation . All participants were repeatedly asked not to reveal any information about their treatment allocation . The participants and treatment providers were not blinded to treatment allocation . Interventions In the Dutch occupational health care system , occupational physicians guide disabled workers who are absent from work through their disability period . These occupational physicians are employed by occupational health services that are paid for by the companies . The occupational physicians adhere to back pain management strategies that consist of advising workers on ergonomics , prevention , and return-to-work schedules and advising and communicating with other stakeholders ( such as health care providers and representatives of the workplace ) . Disabled workers who participated in the present study were assigned to either grade d activity or usual care within the context of the Dutch occupational health care setting . Grade d Activity The intervention group received the usual guidance from the occupational physician about work-related problems and barriers to return to work as well as the grade d activity intervention supervised by a physiotherapist . Three physiotherapists who worked in a private practice at Schiphol Airport provided the treatment according to the grade d activity protocol . Two of those physiotherapists were also trained as manual therapists , and 1 was also a human movement scientist . Before the study , the physiotherapists had been specifically trained to treat patients with low back pain according to behavioral principles . A research physiotherapist who was experienced in treating patients with chronic pain in rehabilitation centers instructed the physiotherapists in three 2-hour sessions and practice d patienttherapist interactions with them through role-play . Before the study , the physiotherapists treated several patients according to the grade d activity protocol to gain more experience . The physiotherapists made audiotapes of the intervention sessions before and during the study period . The contents of these audiotapes were assessed and discussed with the research physiotherapist in 3 additional meetings . Furthermore , the physiotherapists summarized the treatment after each session , and research ers used these summaries to review the sessions . The same physiotherapist treated participants each time , except for temporary st and -in sessions that were supervised by colleagues because of holidays or other reasons . Specific therapists were not systematic ally selected to treat specific participants ; selection was based on pragmatic reasons , such as the time available in the work schedules of the physiotherapists or the days of treatment preferred by the participants . Table 1 presents the concept and content of the grade d activity intervention . The intervention consisted of 1-hour exercise sessions that participants attended twice per week until they returned completely to regular work or until the maximum therapy duration of 3 months was reached . At the start of the intervention , the physiotherapist inquired about the participant 's medical history and completed a brief physical examination consisting of flexion , extension , and lateroflexion of the lumbar spine and a brief screening for nerve-root pain ( 10 ) . The purpose of the physical examination was to confirm the diagnosis of benign , nonspecific low back pain and to reduce participants ' fears about any presumed underlying disease . The participants were reassured that despite the annoying pain , nothing was seriously wrong with their backs . Subsequently , the physiotherapist and participant decided on a set of general exercises and individually tailored exercises . Both types of exercises had to be performed during each session . The general exercises were aerobic exercises , such as cycling or rowing , and strengthening exercises for large muscle groups , and most were carried out in a gym while using exercise equipment . The strengthening exercises were a floor abdominal sit-up exercise , a dynamic back extension exercise , a leg-press exercise , a latissimus pull-down exercise , and st and ing up from a low chair . Participants in the grade d activity group had to perform not only these general exercises but also individually tailored exercises , which imitated physical tasks at work or difficult and painful activities of daily living . For example , a participant who reported back problems while lifting and moving suitcases from a luggage wagon into an airplane might be given an exercise to practice lifting and moving a suitcase with a certain number of repetitions . During the first 3 sessions , the maximal performance ( for example , the maximum number of repetitions ) was assessed for each exercise separately , and the average score for each exercise over the 3 sessions was used as a baseline value for specifying a gradually progressive exercise scheme . Subsequently , the participant was asked to propose a date for full return to regular work , which would consequently be the end point of the physical exercise program . Before returning to full regular work , participants could return to work with modified hours and duties . Advised by the physiotherapist , the participant Study Design . A r and omized parallel-group comparative trial with a 1-year follow-up period was performed . Objective . To compare the effect of a comprehensive functional restoration program involving intensive physical training , ergonomic training , and behavioral support ( 39 hours per week for 3 weeks ) with the effect of outpatient intensive physical training ( 1.5 hours three times per week for 8 weeks ) . Summary of Background Data . Nonr and omized studies conducted in the United States favor functional restoration for patients with chronic low back pain . Two previously reported r and omized studies from the authors ’ Back Center in Copenhagen concur with this recommendation , although the positive effects in one of the studies had faded out after 2 years . R and omized functional restoration studies in Canada and Finl and have failed to demonstrate any substantive effect . Methods . Initially , 138 patients with chronic low back pain were included in the current study . They then were r and omized to either functional restoration ( n = 64 ) or outpatient intensive physical training ( n = 74 ) . Of the initial 138 patients , 11 never started ( 5 and 6 , respectively ) ; 21 dropped out during treatment ( 8 and 13 ) ; and 7 of the graduates did not take part in the 1-year follow-up evaluation ( 3 and 4 ) . The conclusions were drawn from the 99 patients ( 48 and 51 , respectively ) who graduated and participated in a 1-year follow-up evaluation . The median age of the patients was 42 years ( range , 21–55 years ) The female-to-male ratio was 68 to 31 , and the median sick leave days during the preceding 3 years was 180 ( range , 0–1080 days ) . The average back pain was rated 5.5 on a scale of 0 ( no pain ) to 10 ( maximal pain ) . For these variables , there were no important differences between the groups . However , the functional restoration group tended to be more capable of work at baseline ( 58%vs 42%;P = 0.09 ) . Results . At the 1-year follow-up evaluation , overall assessment favored functional restoration . Otherwise , no significant differences were observed regarding work capability , sick leave for those at work , health care contacts , back pain , leg pain , or self-reported activities of daily living . Conclusions . Only in terms of overall assessment , the functional restoration program was superior to a comparatively short time-consuming outpatient physical training program . Discussion . It may be that lower economic benefits during sick leave in the United States lead to favorable results from functional restoration programs , whereas greater benefits in Canada , Finl and , and Denmark result in different conclusions . Finally , it may be that the difference in results across studies points simply to whether the studies were r and omized Different training models are effective for the treatment of chronic low back pain , but no consensus has been found . Earlier studies have emphasized training of spinal mobility and back strength . To evaluate if other physiological parameters , such as coordination , are of equal importance , we performed a r and omized trial on 40 consecutive patients with chronic low back pain . Two training models were compared : 1 ) intensive training of muscle endurance and 2 ) muscle training , including coordination . In both groups , training was performed 1 hour twice a week for 3 months . Pain score , disability score , and spinal mobility improved in both training groups without differences between the two groups . Only intensive training of muscle endurance improved isokinetic back muscle strength . At study entry , we found a significant correlation between spinal mobility and dysfunction , but after the training , no correlation was found between improvement of spinal mobility or isokinetic back extension strength and improvement of function or pain level . We conclude that coordination training for patients with chronic low back pain is as equally effective as endurance training The results of a multicentered r and omised clinical trial are reported of bed rest and of a physiotherapy and education programme for patients who presented in family practice with an acute episode of low back pain . No beneficial effect of either treatment was observed on several clinical outcome measures , including straight leg raising , lumbar flexion , activities of daily living , and pain . In fact the results favoured early mobilisation over bed rest and suggested that the physiotherapy and education programme was doing more harm than good . Moreover , additional analyses , which focused on clinical ly interesting patient subgroups , discovered no subset of patients who benefited from either of the treatments under study . Having failed to identify any clinical ly important benefits , or other explanations for these negative results , we can only conclude that family doctors have little reason to prescribe either bed rest or isometric exercises to patients who suffer from low back pain BACKGROUND AND PURPOSE Clinicians treating patients with low back pain often use exercise to reduce pain and improve function . The aim of this study was to evaluate the effectiveness of trunk extensor endurance training in reducing pain and decreasing disability in subjects with subacute low back pain ( ie , onset of back pain within 7 days to 7 weeks ) . SUBJECTS AND METHODS Patients were r and omly assigned to either an experimental group or a control group . A visual analog scale and the pain rating index ( PRI ) of the McGill Pain Question naire ( MPQ ) were used to obtain baseline measurements of pain . The Rol and Morris Disability Question naire ( RMDQ ) was used to measure disability , and the Sorensen Test was used to measure trunk extensor endurance . Subjects in the experimental group attended exercise sessions 3 times a week for 6 weeks . Subjects in the control group did not do exercises . Both groups were given back care advice and hot packs for 15 minutes , 3 to 5 times per week . Re assessment s were carried out at 3 and 6 weeks . RESULTS There were differences between the 2 groups at 3 weeks in regard to pain intensity during the evaluation session and pain experienced over the preceding 24 hours , the total MPQ PRI , the sensory component of the MPQ PRI , and the RMDQ . At 6 weeks , no differences were found for pain measurements , disability scores , and holding time on the Sorensen Test . CONCLUSION AND DISCUSSION Trunk extensor endurance training reduced pain and improved function at 3 weeks but result ed in no improvement at 6 weeks when compared with the control group . Endurance exercise is considered to expedite the recovery process for patients with an acute episode of low back pain STUDY DESIGN A prospect i ve , r and omized , controlled trial with a stratification block design in which a Mensendieck exercise program was compared with the experience of a control group . OBJECTIVE To evaluate the effect of a Mensendieck program on the incidence of recurrent episodes of low back pain in patients with a history of the condition who currently are working . SUMMARY OF BACKGROUND DATA One episode of low back pain increases the risk of further episodes of the condition . The Mensendieck approach combines education and exercise . This approach has been used for many years in Sc and inavia and the Netherl and s. However , the effects on low back pain have not been evaluated previously in a r and omized , controlled trial . METHODS A total of 77 men and women , mean age 39.6 years ( range , 21.2 - 49.8 years ) , who had finished treatment for a low back pain episode , were stratified according to incidence of low back pain episodes and symptoms of sciatica over the preceding 3 years . The patients were assigned at r and om to either the Mensendieck program or a control group . The Mensendieck group received 20 group sessions of exercises and ergonomic education in 13 weeks . At 5- and 12-month follow-up examinations , the patients were assessed for recurrence of low back pain , days of sick leave , low back pain , and functional scores . RESULTS After 12 months , there was a significant reduction in recurrent low back pain episodes in the Mensendieck group compared with the control group ( P < 0.05 ) . There was a trend toward fewer days of sick leave because of low back pain in the Mensendieck group , but no significant differences between the groups . There was reduction in pain and improvement in function in both groups , with no significant differences between the groups . CONCLUSIONS A secondary prophylaxis Mensendieck exercise program of 20 group sessions significantly reduced the incidence of low back pain recurrences in a population with history of the condition . However , there were no differences between the groups with regard to days of sick leave , low back pain , and function OBJECTIVES To study the relative efficacy of three different treatment for chronic low back pain ( CLBP ) . Two preplanned comparisons were made : ( a ) Spinal manipulative therapy ( SMT ) combined with trunk strengthening exercises ( TSE ) vs. SMT combined with trunk stretching exercises , and ( b ) SMT combined with TSE vs. nonsteroidal anti-inflammatory drug ( NSAID ) therapy combined with TSE . STUDY DESIGN Interdisciplinary , prospect i ve , observer-blinded , r and omized clinical trial with a 1-yr follow-up period . The trial evaluated therapies in combination only and was not design ed to test the individual treatment components . SETTING Primary contact , college out-patient clinic . PATIENTS In total , 174 patients aged 20 - 60 yr were admitted to the study . MAIN OUTCOME MEASURES Patient-rated low back pain , disability , and functional health status at 5 and 11 wk . INTERVENTIONS Five weeks of SMT or NSAID therapy in combination with supervised trunk exercise , followed by and additional 6 wk of supervised exercise alone . RESULTS Individual group comparisons after 5 and 11 wk of intervention on all three main outcome measures did not reveal any clear clinical ly important or statistically significant differences . There seemed to be a sustained reduction in medication use at the 1-yr follow-up . in the SMT/TSE group . Continuance of exercise during the follow-up year , regardless of type , was associated with a better outcome . CONCLUSION Each of the three therapeutic regimens was associated with similar and clinical ly important improvement over time that was considered superior to the expected natural history of long-st and ing CLBP . For the management of CLBP , trunk exercise in combination with SMT or NSAID therapy seemed to be beneficial and worthwhile . The magnitude of nonspecific therapeutic ( placebo ) effects , cost-effectiveness and relative risks of side effects associated with these types of therapy need to be addressed in future studies A number of treatments are widely prescribed for chronic back pain , but few have been rigorously evaluated . We examined the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) , a program of stretching exercises , or a combination of both for low back pain . Patients with chronic low back pain ( median duration , 4.1 years ) were r and omly assigned to receive daily treatment with TENS ( n = 36 ) , sham TENS ( n = 36 ) , TENS plus a program of exercises ( n = 37 ) , or sham TENS plus exercises ( n = 36 ) . After one month no clinical ly or statistically significant treatment effect of TENS was found on any of 11 indicators of outcome measuring pain , function , and back flexion ; there was no interactive effect of TENS with exercise . Overall improvement in pain indicators was 47 percent with TENS and 42 percent with sham TENS ( P not significant ) . The 95 percent confidence intervals for group differences excluded a major clinical benefit of TENS for most outcomes . By contrast , after one month patients in the exercise groups had significant improvement in self-rated pain scores , reduction in the frequency of pain , and greater levels of activity as compared with patients in the groups that did not exercise . The mean reported improvement in pain scores was 52 percent in the exercise groups and 37 percent in the nonexercise groups ( P = 0.02 ) . Two months after the active intervention , however , most patients had discontinued the exercises , and the initial improvements were gone . We conclude that for patients with chronic low back pain , treatment with TENS is no more effective than treatment with a placebo , and TENS adds no apparent benefit to that of exercise alone In a r and omized , observer-blind trial , 150 men and women , aged 21 - 64 years , with chronic/subchronic low-back pain , followed one of these three treatment regimens : 1 ) intensive , dynamic back-muscle exercises ; 2 ) conventional physiotherapy , including isometric exercises for the trunk and leg muscles ; and 3 ) placebo-control treatment involving semihot packs and light traction . Eight treatment sessions were given during the course of 4 weeks , each session lasting 1 hour . The short-term effect was evaluated at the end of the treatment period and 1 month later , and the long-term effect at 6 and 12 months . The evaluations included recording of changes in pain level and assessment of overall treatment effect , which were indicated on visual interval scales . Subgroups of patients could be identified according to their treatment responses : physiotherapy was the superior treatment for the male participants , whereas the intensive back exercises appeared to be most efficient for the female participants . Patients with moderate or hard physical occupations tended toward a better response with physiotherapy , whereas intensive back exercises seemed most effective for those with sedentary/light job functions PURPOSE The purpose of this r and omized pilot study was to evaluate a possible design for a 6-week modified hatha yoga protocol to study the effects on participants with chronic low back pain . PARTICIPANTS Twenty-two participants ( M = 4 ; F = 17 ) , between the ages of 30 and 65 , with chronic low back pain ( CLBP ) were r and omized to either an immediate yoga based intervention , or to a control group with no treatment during the observation period but received later yoga training . METHODS A specific CLBP yoga protocol design ed and modified for this population by a certified yoga instructor was administered for one hour , twice a week for 6 weeks . Primary functional outcome measures included the forward reach ( FR ) and sit and reach ( SR ) tests . All participants completed Oswestry Disability Index ( ODI ) and Beck Depression Inventory ( BDI ) question naires . Guiding questions were used for qualitative data analysis to ascertain how yoga participants perceived the instructor , group dynamics , and the impact of yoga on their life . ANALYSIS To account for drop outs , the data were divided into better or not categories , and analyzed using chi-square to examine differences between the groups . Qualitative data were analyzed through frequency of positive responses . RESULTS Potentially important trends in the functional measurement scores showed improved balance and flexibility and decreased disability and depression for the yoga group but this pilot was not powered to reach statistical significance . Significant limitations included a high dropout rate in the control group and large baseline differences in the secondary measures . In addition , analysis of the qualitative data revealed the following frequency of responses ( 1 ) group intervention motivated the participants and ( 2 ) yoga fostered relaxation and new awareness/learning . CONCLUSION A modified yoga-based intervention may benefit individuals with CLB , but a larger study is necessary to provide definitive evidence . Also , the impact on depression and disability could be considered as important outcomes for further study . Additional functional outcome measures should be explored . This pilot study supports the need for more research investigating the effect of yoga for this population Study Design . Prospect i ve , r and omized trial . Objectives . To compare the McKenzie method of treatment of acute low back pain with patient education in “ mini back school ” after 5 years ; the 1-year results have already been published . Summary of Background Data . The 5-year results after the initial treatment are presented in this study of 89 subjects . Included in the study were 22 women and 67 men with an average age of 39.6 ± 10.5 years ( range 22–66 years ) . Methods . Sixty-two subjects ( 70 % ) were interviewed by telephone , while the remaining 27 subjects ( 30 % ) were examined and interviewed personally . Information of sick leave was obtained from the Swedish National Health Insurance Office . Results . The results showed that subjects who received treatment according to the McKenzie principle 5 years earlier had significantly less recurrences of pain and fewer were on sick leave compared with the subjects who received education in mini back school . The other variables did not show any statistically significant differences . Conclusions . The difference between the two treatments was much less after 5 years compared with the 1-year results 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 Degenerative disc disease may affect younger and middle-aged people with a kind of premature disc degeneration . The majority of these low back pain patients are not c and i date s for a spinal fusion and are in need of a structured conservative treatment . In a controlled clinical trial , 27 low back pain patients ( mean age 40 years , range 25 - 48 ) with a mean duration of symptoms of 7.4 years , were r and omized to mobilizing ( n = 12 ) or stabilizing ( n = 15 ) daily half hour exercise for an eight weeks period . A clinical overall score ( COS ) based on pain intensity ( VAS ) , physical signs , functional status ( Oswestry ) and analgetics was used as outcome criterion . The treatment results were best for the group undergoing stabilizing treatment . They achieved a 17 % reduction in COS , compared to a 10 % increase in the group undergoing mobilizing treatment ( p = 0.02 ) . These types of exercises are discussed in relation to the instability theory in disc degeneration OBJECTIVE To evaluate the short-term effect of physical exercise and a cognitive intervention in low back pain . DESIGN R and omized controlled trial . SUBJECTS Ninety-three patients sick-listed for 8 - 12 weeks for sub-acute low back pain were r and omized to an exercise regime ( n = 30 ) , a cognitive intervention ( n = 34 ) or a control group ( n = 29 ) . METHODS Primary outcome measures were pain , disability , sick-listing and satisfaction with care . Secondary outcome measures were self-efficacy for pain and for function , fear-avoidance beliefs , emotional distress , generic health status and life satisfaction . RESULTS Eighteen percent of subjects dropped out . Drop-out was most frequent in the exercise group . At 18 weeks after inclusion fear-avoidance beliefs were reduced in both intervention groups . The cognitive group demonstrated significant improvement in disability , self-efficacy for pain , emotional distress , general health and life satisfaction . Patients in the exercise group were significantly more satisfied with the treatment , and patients following the exercise protocol reduced pain significantly . No effect on sick-listing was seen . CONCLUSION Cognitive intervention improved disability and may be feasible for most patients sick-listed in the sub-acute phase . Physical exercise reduced patients ' symptoms , but requires high motivation by patients . Despite positive effects in intervention groups on variables considered as negative prognostic factors for long-term disability and sickness absence , interventions had no effect on sick-listing BACKGROUND Back extension exercises are commonly recommended to treat acute low back pain . Evidence of their beneficial effect is , however , weak . OBJECTIVES We aim ed to demonstrate a benefit of teaching back extension exercises in addition to usual GP care for acute low back pain . METHODS Patients with acute simple low back pain of less than 28 days duration , presenting to a GP , were r and omized either to attend a back class or to receive conventional management . Outcome was measured using changes in the Oswestry disability score and visual analogue pain scale ( VAS ) on six occasions during 1 year and also a VAS and patient assessment of degree of disability during the previous 6 months at 1 year . RESULTS Seventy-five patients were recruited . The principal outcome measures showed no difference between the two groups . The treatment group reported less chronic disability at 1 year ( 50 % versus 14 % , P < 0.007 ) . CONCLUSIONS A treatment effect has not been demonstrated , but some patients who would otherwise have reported mild pain were pain free after 1 year . This approach to treating back pain has not been shown to be effective . More much larger studies , with more intensive treatment , are required in order to decide whether physical therapy in primary care is beneficial as treatment for acute back pain Study Design . Two r and omized , prospect i ve clinical trials involving 238 chronic low back disability patients were carried out . Results at 2‐year follow‐up are presented . Objectives . To compare the clinical outcomes of a multidisciplinary functional restoration program with a nontreated control group ( Project A ) and with two less intensive but different training programs ( Project B ) . Summary of Background Data . The effectiveness of functional restoration programs has not been firmly established . Results from trials carried out in the United States differ from those in trials conducted in other countries . Only a few of these studies have been carried out as prospect i ve and r and omized clinical studies . Methods . Two hundred thirty‐eight patients with chronic low back disability of at least 6 months ' duration were included . There were 106 patients in project A and 132 patients in project B. Two years after completion of treatment , patients were mailed a question naire that included questions regarding their work status , pain and disability levels , number of sick leave days , number of medical care contacts , medication use , physical activity levels , and subjective overall assessment of their " back life situation . " Results . Patients in both studies were comparable at inclusion , except that patients in Project A were recruited from all of Denmark , whereas those in Project B were from the greater Copenhagen area . Thirteen patients did not report for treatment after r and omization . Of the remaining 225 patients , 20 ( 9 % ) did not complete treatment . The question naire response rate was 94 % . In Project A , those patients receiving treatment ( functional restoration ) reported significantly less contact with the health care system , fewer sick leave days , and a less disabled life style during the follow‐up period , compared with reports of patients in the control group . Other effect parameters did not demonstrate a significant difference between the two groups . In Project B , all effect parameters reported , except leg pain and medication usage , were significantly in favor of functional restoration , compared with reports from the less intensively treated groups . Conclusions . The functional restoration program seems effective in various parameters compared with the less intensive programs , but the differences in outcome in the two parallel studies indicate the necessity of testing a treatment program in different setting s , in that the statistical variation may be a major factor in results of different studies OBJECTIVE To determine the effectiveness of a special form of exercise therapy ( ' Cesar therapy ' ) on self reported recovery and improvement of posture amongst patients with chronic aspecific lower back pain . DESIGN Prospect i ve r and omized controlled and blinded investigation . METHOD After informed consent had been obtained , patients with chronic aspecific lower back pain were given , on a r and omized basis , either an exercise therapy ( experimental group , n = 112 ) or a st and ard treatment by their general practitioner ( control group , n = 110 ) . Outcome measures were self reported recovery of back pain and improvement of posture ( thoracic and lumbar spine , pelvis ) . Self reported recovery was determined by means of a dichotomized 7-point scale ( question naire ) . Posture was measured qualitatively by a panel of 11 Cesar therapists ( blinded ) and quantitatively by an optical-electronic posture recording system ( Vicon ) . Measurements were taken at baseline ( pre-r and omization ) and at 3 , 6 and 12 months after r and omization . RESULTS Three months after r and omization , patients who were treated according to Cesar therapy , reported an improvement in their back symptoms ( 80 % ) significantly more often than the control group ( 47 % ) . In both groups , however , only small improvements in posture were found . The judgement of the Cesar panel exhibited a significant difference between the two groups , with respect to the spine , in favour of Cesar therapy . Differences between the groups were still present 6 months after r and omization , but could no longer be detected at 12 months after r and omization . CONCLUSION Cesar therapy was significantly more effective than st and ard treatment among patients with chronic lower back pain for a period of 6 months after r and omization The purpose of this study was to compare the effect of the McKenzie method of treatment with patient education in “ mini back school ” in patients with acute low-back pain . The study included 100 patients , 23 women and 77 men with the average age 34.4 ± 9.7 ( range 18 - 61 ) years . The study included only those who were employed . The patients were r and omly allocated to two groups , one group receiving treatment according to the McKenzie technique and the other group receiving education in a “ mini back school . ” Assessment s were made after 3 weeks by an independent observer and after 52 weeks they were seen by one of the authors . Patients were assessed on seven variables : return to work , sick-leave during the initial episode , sick-leave during recurrences , recurrences of pain during the year of observation , patients ' ability to self-help , pain and movement . Although the effect of attention placebo can not be ruled out , the results demonstrated that the McKenzie method of treatment for patients with acute low-back pain was superior for five out of seven variables studied . The only variables that did not show any statistically significant differences were sick-leave during recurring episodes of pain and patients ' ability to self-help & NA ; The effect of intensive dynamic back extensor exercises for patients with chronic low back pain was investigated in a controlled clinical trial in which chronic low back pain patients underwent a 3‐month intensive training program with a total of 30 sessions . The 105 patients were divided into 3 groups : a treatment group , an alternative group which underwent 1/5 of the treatment group 's exercise program per session , and an alternative group in which treatment consisted of thermotherapy , massage and mild exercise . Regardless of whether the treatment outcome is assessed qualitatively or quantitatively , a statistically significant , favorable difference was found between the results for the treatment group and for the alternative groups at conclusion and at the 3‐month follow‐up . It appeared from the quantitative assessment that patients in the treatment group who completed the training program at least once a week for the entire 1‐year follow‐up period were the only patients with a significantly better back status after 1 year compared to the time of inclusion . Irrespective of sex , age , duration and degree of severity of back trouble , or of pre‐existing sciatica or pathological findings upon X‐ray of the spine , patients obtained a favorable result from the training program . The therapy was found to be without risk , but patients with clinical signs of current lumbar nerve root compression or radiological signs of spondylolysis or halisteresis of the spine were excluded from the study BACKGROUND AND PURPOSE Exercise and education is a common physiotherapy approach in the prevention of low back pain . A Mensendieck exercise programme consisting of exercises and ergonomical education has , in a previous study , been shown to be effective in preventing recurrent low back pain during one-year follow-up . The purpose of the present study was to evaluate the long-term effect of the Mensendieck exercise programme on people with recurrent episodes of low back pain who , when entering the study , had finished treatment for their last episode of low back pain . METHOD A r and omized controlled clinical trial in which 41 women and 36 men were allocated to either a Mensendieck or control group . The Mensendieck subjects received 20 group sessions of exercises and ergonomical education over 13 weeks . The control subjects were not offered any prophylactic therapy , but were free to receive treatment or exercises . Outcome measures were the number of recurrences of low back pain , sick leave , low back function and general functional status . RESULTS At three-year follow-up , 11 subjects had been lost to the study . Survival analysis showed a significant reduction ( p = 0.02 ) in subjects experiencing recurrent low back pain in the Mensendieck group compared to the control group . Significant improvements in pain and function scores were reported in both groups . There was no significant difference between the groups in pain , function or sick leave . CONCLUSION A Mensendieck exercise programme seems efficient in reducing recurrent episodes of low back pain at three-year follow-up , but it did not influence sick leave , pain or function scores Abstract We evaluated three different conservative treatment methods for acute low-back pain patients in groups following a manual therapy programme , an intensive training programme , or a general practitioner programme , the latter serving as the control group . Patients aged 19–64 years on sick leave for low-back pain with or without sciatica were included in a prospect i ve r and omised study evaluating outcomes such as impairment , pain , functional disability , socio-economic disability and satisfaction with the treatment or explanations . Evaluation by unbiased observers was performed at 1 , 3 and 12 months . The three treatment groups were comparable at baseline . With regard to satisfaction , the patients in the manual therapy programme and those in the intensive training programme were more satisfied with the treatment than those in the general practitioner programme at all follow-ups . With regard to the explanations of current low-back pain episodes , the patients in the manual therapy programme were more satisfied than those in the general practitioner programme at all follow-ups . The manual therapy programme group were also more satisfied with the explanations than those in the intensive training programme at the 1-month follow-up . However , no differences were revealed between the groups with respect to outcomes on measures of impairment , pain , functional disability or socio-economic disability . All three study groups showed rapid improvement . After 1 month a significant improvement was noted in all outcome values compared with the values on entry to the study . Within the limitations discussed in our study , it is concluded that ( 1 ) patients sick listed with acute low-back pain , with or without sciatica , will be significantly improved after 1 month regardless of conservative treatment programme ; ( 2 ) they will be more satisfied with the treatment if they are referred to a manual treatment programme or a training treatment programme ; ( 3 ) they will be more satisfied with the explanations of the acute low-back problem if they are referred to one of the above groups , especially the manual treatment group ; ( 4 ) they will not show any other differences with respect to subjective and objective variables , either at short-term or at long-term follow-ups Patients with nonspecific mechanical low back pain ( n = 103 ) , examined by an orthopaedic surgeon and a social worker , were r and omized to an activity group ( n = 51 ) and a control group ( n = 52 ) . Patients with defined orthopaedic , medical , or psychiatirc diagnoses were excluded before r and omization . No patients were excluded due to place of birth or difficulties in speaking or underst and ing the Swedish language . The purpose of the study was to compare mobility , strength and fitness after traditional care and after traditional care plus a grade d activity program with a behavioral therapy approach . A grade d activity program , with a behavioral therapy approach was given under the guidance of a physical therapist . The endpoint of the grade d activity program was return to work . This program significantly increased mobility , strength , and fitness more than could be explained by only a time recovery effect , especially in males . The patients in the activity group returned to work earlier than did the patients in the control group . Spinal rotation , abdominal muscle endurance time and lifting capacity were significantly correlated to rate of return to work . Traditional care plus a grade d activity program were superior to only traditional care , evaluated in terms of mobility , strength and fitness . The grade d activity program proved to be a successful method of restoring occupational function and facilitating return to work in subacute low back pain patients . The patients in the grade d activity program learned that it is safe to move , while regaining function STUDY DESIGN A r and omized study comparing the results of active rehabilitation and passive control treatment in patients with chronic low back pain with follow-up at 6 months and 1 year . OBJECTIVES To study the efficacy of active rehabilitation on pain , self-experienced disability , and lumbar fatigability . SUMMARY OF BACKGROUND DATA Exercises in an outpatient setting are widely used for the treatment of chronic low back pain . The efficacy of the active rehabilitation approach has been documented in r and omized control studies , but these studies have seldom been focused on lumbar fatigability , which is now recognized as a frequent problem among patients with chronic low back pain . METHODS Fifty-nine middle-aged patients ( 37 men and 22 women ) with nonspecific chronic low back pain were r and omly assigned to 12 weeks ' active rehabilitation or to a passive control treatment ( massage , thermal therapy ) . Pain and disability index , low back pain intensity ( visual analog scale , 100 mm ) , and the objective ly assessed lumbar muscle fatigability ( spectral electromyogram , mean power frequency slope [ MPFSLOPE ] ) in a new 90-second submaximal isoinertial back endurance test were recorded before and after the interventions and at 6-month and 1-year follow-up visits . RESULTS Results of repeated measures multivariate analysis of variance indicated that back pain intensity ( visual analog scale ) and functional disability ( pain and disability index score ) decreased , and lumbar endurance ( MPFSLOPE ) improved significantly more ( P < 0.05 ) in the active rehabilitation group than in the passive control treatment group , when measured at a 1-year follow-up examination . The group difference in visual analog scale and pain and disability index changes became even more significant at the end of 1 year . The change in lumbar endurance was significantly greater in the active rehabilitation group than in the passive control treatment group at the 6-month follow-up , but not at the 1-year follow-up . CONCLUSIONS The active progressive treatment program was more successful in reducing pain and self-experienced disability and also in improving lumbar endurance than was the passive control treatment . However , the group difference in lumbar endurance tended to diminish at the 1-year follow-up Study Design . A multicenter , r and omized , single‐blinded controlled trial with 1‐year follow‐up . Objectives . To evaluate the efficiency of progressively grade d medical exercise therapy , conventional physiotherapy , and self‐exercise by walking in patients with chronic low back pain . Summary and Background Data . Varieties of medical exercise therapy and conventional physiotherapy are considered to reduce symptoms , improve function , and decrease sickness absence , but this opinion is controversial . Methods . Patients with chronic low back pain or radicular pain sick‐listed for more than 8 weeks and less than 52 weeks ( Sickness Certificate II ) were included . The treatment lasted 3 months ( 36 treatments ) . Pain intensity , functional ability , patient satisfaction , return to work , number of days on sick leave , and costs were recorded . Results . Of the 208 patients included in this study , 71 were r and omly assigned to medical exercise therapy , 67 to conventional physiotherapy , and 70 to self‐exercise . Thirty‐three ( 15.8 % ) patients dropped out during the treatment period . No difference was observed between the medical exercise therapy and conventional physiotherapy groups , but both were significantly better than self‐exercise group . Patient satisfaction was highest for medical exercise therapy . Return to work rates were equal for all 3 intervention groups at assessment 15 months after therapy was started , with 123 patients were back to work . In terms of costs for days on sick leave , the medical exercise therapy group saved 906,732 Norwegian Kroner ( NOK ) ( $ 122,531.00 ) , and the conventional physiotherapy group saved NOK 1,882,560 ( $ 254,200.00 ) , compared with the self‐exercise group . Conclusions . The efficiency of medical exercise therapy and conventional physiotherapy is shown . Leaving patients with chronic low back pain untampered poses a risk of worsening the disability , result ing in longer periods of sick leave One hundred and twelve patients with acute mechanical low back pain were r and omly divided into three treatment groups . All patients received ergonomic advice and then either a non-steroidal anti-inflammatory drug or conservative or manipulative types of physiotherapy . Serial assessment s of pain and spinal mobility showed similar response rates in all three treatment groups and no significant difference between therapies . The overall improvement ratings , time off work , and economic cost favoured the group treated with the nonsteroidal anti-inflammatory drug , but this group had a better range of spinal flexion at the onset so firm conclusions regarding the preferred management of these patients in general practice can not be drawn . Treatment failures occurred in all groups highlighting the need for a variety of therapeutic approaches in managing the patient with low back pain Summary Several new studies have indicated that an active approach to patients with chronic disabling low back pain ( LBP ) seems effective . Some of these studies emphasize the importance of dealing with the patient 's total situation in comprehensive multidisciplinary programs — the bio-psycho-social model . However , these programs are expensive . The aim of this study was to evaluate the rehabilitation outcome from three different active programs in terms of : ( 1 ) return-to-work rate , ( 2 ) days of sick leave , ( 3 ) health-care contacts , ( 4 ) pain and disability scores , and ( 5 ) staying physically active . The subjects included 132 patients r and omized to the study , of whom 123 started one of the treatment programs . They had all had at least 6 months of chronic LBP . The patients were r and omized into one of three programs : group 1 — a full-time , intensive 3-week multidisciplinary program , including active physical and ergonomic training and psychological pain management , followed by 1 day weekly for the subsequent 3 weeks ; group 2 — active physical training , twice a week for 6 weeks , for a total of 24h ; group 3 — psychological pain management combined with active physical training , twice a week for 6 weeks , also for a total of 24h . The results presented here are based on data collected 4 months following treatment , which shows an 86 % response rate . The initial examination and the follow-up evaluation were performed by a blinded observer . The results show that 4 months after treatment , the intensive multidisciplinary program is superior to the less intensive programs in terms of return-to-work rate , health-care contacts , pain and disability scores , and staying physically active . In conclusion , it seems that although the multidisciplinary program is initially expensive compared to the less intensive programs , the savings in sick pay , early retirement pensions , and health care contacts make it economically worthwhile . Long-term follow-up will show whether this effect continues OBJECTIVES To examine the relative efficacy of three active therapies for patients with chronic low back pain . METHODS One hundred and forty-eight subjects with chronic low back pain were r and omized to receive , twice weekly for 3 months , ( i ) active physiotherapy , ( ii ) muscle reconditioning on training devices , or ( ii ) low-impact aerobics . Question naires were administered to assess pain intensity , pain frequency and disability before and after therapy and at 6 and 12 months of follow-up . RESULTS One hundred and thirty-two of the 148 patients ( 89 % ) completed the therapy programmes and 127 of the 148 ( 86 % ) returned a question naire at all four time-points . The three treatments were equally efficacious in significantly reducing pain intensity and frequency for up to 1 yr after therapy . However , the groups differed with respect to the temporal changes in self-rated disability over the study period ( P=0.03 ) : all groups showed a similar reduction after therapy , but for the physiotherapy group disability increased again during the first 6 months of follow-up whilst the other two groups showed a further decline . In all groups the values then remained stable up to the 12-month follow-up . The larger group size and minimal infrastructure required for low-impact aerobics rendered it considerably less expensive to administer than the other two programmes . CONCLUSIONS The introduction of low-impact aerobic exercise programmes for patients with chronic low back pain may reduce the enormous costs associated with its treatment The purpose of the present study was to investigate the long-term effect of the Active Back School programme on minimizing recurrences of episodes of low back pain . Forty-three subjects were r and omly allocated to the Active Back School group and 38 to the control group . There were no significant differences between the groups with regard to baseline characteristics . The Active Back School programme comprised 20 lessons each divided into a 20-min theoretical and a 40-min exercise part during a 13-week period . Nine participants ( 11 % ) dropped out during the study period . Recurrence of new low back pain episodes was significantly less ( p = 0.04 ) , and the time from inclusion to the first new low back pain episode was significantly on the side of the Active Back School group ( p < 0.01 ) . The duration of sick leave was found to be significantly shorter ( p < 0.01 ) in the Active Back School group compared to the control group . The Active Back School reduced the recurrence and severity of new low back pain episodes at 36 months ' follow-up BACKGROUND AND OBJECTIVES The aim of this study was to determine whether low power laser therapy ( Gallium-Arsenide ) is useful or not for the therapy of chronic low back pain ( LBP ) . STUDY DESIGN / MATERIAL S AND METHODS This study included 75 patients ( laser + exercise-25 , laser alone-25 , and exercise alone-25 ) with LBP . Visual analogue scale ( VAS ) , Schober test , flexion and lateral flexion measures , Rol and Disability Question naire ( RDQ ) and Modified Oswestry Disability Question naire ( MODQ ) were used in the clinical and functional evaluations pre and post therapeutically . A physician , who was not aware of the therapy undertaken , evaluated the patients . RESULTS Significant improvements were noted in all groups with respect to all outcome parameters , except lateral flexion ( P < 0.05 ) . CONCLUSIONS Low power laser therapy seemed to be an effective method in reducing pain and functional disability in the therapy of chronic LBP OBJECTIVES To determine the effect of a series of electro-acupuncture ( EA ) treatment in conjunction with exercise on the pain , disability , and functional improvement scores of patients with chronic low-back pain ( LBP ) . DESIGN A blinded prospect i ve r and omized controlled study . SUBJECTS AND INTERVENTIONS A total of 52 patients were r and omly allocated to an exercise group ( n = 26 ) or an exercise plus EA group ( n = 26 ) and treated for 12 sessions . OUTCOME MEASURES Numerical Rating Scale ( NRS ) , Aberdeen LBP scale , lumbar spinal active range of movement ( AROM ) , and the isokinetic strength were assessed by a blinded observer . Repeated measures analysis of variance ( R-ANOVA ) with factors of group and time was used to compare the outcomes between the two groups at baseline ( before treatment ) , immediately after treatment , 1-month follow-up , and 3-month follow-up . The level of significance was set at p = 0.05 . RESULTS Significantly better scores in the NRS and Aberdeen LBP scale were found in the exercise plus EA group immediately after treatment and at 1-month follow-up . Higher scores were also seen at 3-month follow-up . No significant differences were observed in spinal AROM and isokinetic trunk concentric strength between the two groups at any stage of follow-up . CONCLUSIONS This study provides additional data on the potential role of EA in the treatment of LBP , and indicates that the combination of EA and back exercise might be an effective option in the treatment of pain and disability associated with chronic LBP BACKGROUND Bed rest and back-extension exercises are often prescribed for patients with acute low back pain , but the effectiveness of these two competing treatments remains controversial . METHODS We conducted a controlled trial among employees of the city of Helsinki , Finl and , who presented to an occupational health care center with acute , nonspecific low back pain . The patients were r and omly assigned to one of three treatments : bed rest for two days ( 67 patients ) , back-mobilizing exercises ( 52 patients ) , or the continuation of ordinary activities as tolerated ( the control group ; 67 patients ) . Outcomes and costs were assessed after 3 and 12 weeks . RESULTS After 3 and 12 weeks , the patients in the control group had better recovery than those prescribed either bed rest or exercises . There were statistically significant differences favoring the control group in the duration of pain , pain intensity , lumbar flexion , ability to work as measured subjectively , the Oswestry back-disability index , and number of days absent from work . Recovery was slowest among the patients assigned to bed rest . The overall costs of care did not differ significantly among the three groups . CONCLUSIONS Among patients with acute low back pain , continuing ordinary activities within the limits permitted by the pain leads to more rapid recovery than either bed rest or back-mobilizing exercises Study Design A clinical study was conducted on 39 patients with acute , first‐episode , unilateral low back pain and unilateral , segmental inhibition of the multifidus muscle . Patients were allocated r and omly to a control or treatment group . Objectives To document the natural course of lumbar multifidus recovery and to evaluate the effectiveness of specific , localized , exercise therapy on muscle recovery . Summary of Background Data Acute low back pain usually resolves spontaneously , but the recurrence rate is high . Inhibition of multifidus occurs with acute , first‐episode , low back pain , and pathologic changes in this muscle have been linked with poor outcome and recurrence of symptoms . Methods Patients in group 1 received medical treatment only . Patients in group 2 received medical treatment and specific , localized , exercise therapy . Outcome measures for both groups included 4 weekly assessment s of pain , disability , range of motion , and size of the multifidus cross‐sectional area . Independent examiners were blinded to group allocation . Patients were reassessed at a 10‐week follow‐up examination . Results Multifidus muscle recovery was not spontaneous on remission of painful symptoms in patients in group 1 . Muscle recovery was more rapid and more complete in patients in group 2 who received exercise therapy ( P = 0.0001 ) . Other outcome measurements were similar for the two groups at the 4‐week examination . Although they resumed normal levels of activity , patients in group 1 still had decreased multifidus muscle size at the 10‐week follow‐up examination . Conclusions Multifidus muscle recovery is not spontaneous on remission of painful symptoms . Lack of localized , muscle support may be one reason for the high recurrence rate of low back pain following the initial episode Objectives . To assess the efficacy of a prolotherapy injection and exercise protocol in the treatment of chronic nonspecific low back pain . Design . R and omized controlled trial with two-by-two factorial design , triple-blinded for injection status , and single-blinded for exercise status . Setting . General practice . Participants . One hundred ten participants with nonspecific low-back pain of average 14 years duration were r and omized to have repeated prolotherapy ( 20 % glucose/0.2 % lignocaine ) or normal saline injections into tender lumbo-pelvic ligaments and r and omized to perform either flexion/extension exercises or normal activity over 6 months . Main outcome measures Pain intensity ( VAS ) and disability scores ( Rol and -Morris ) at 2.5 , 4 , 6 , 12 , and 24 months . Results . Follow-up was achieved in 96 % at 12 months and 80 % at 2 years . Ligament injections , with exercises and with normal activity , result ed in significant and sustained reductions in pain and disability throughout the trial , but no attributable effect was found for prolotherapy injections over saline injections or for exercises over normal activity . At 12 months , the proportions achieving more than 50 % reduction in pain from baseline by injection group were glucose-lignocaine : 0.46 versus saline : 0.36 . By activity group these proportions were exercise : 0.41 versus normal activity : 0.39 . Corresponding proportions for > 50 % reduction in disability were glucose-lignocaine : 0.42 versus saline 0.36 and exercise : 0.36 versus normal activity : 0.38 . There were no between group differences in any of the above measures . Conclusions . In chronic nonspecific low-back pain , significant and sustained reductions in pain and disability occur with ligament injections , irrespective of the solution injected or the concurrent use of exercises Design . Cross-sectional analysis of the factors influencing self-rated disability associated with chronic low back pain and prospect i ve study of the relationship between changes in each of these factors and in disability following active therapy . Objectives . To examine the relative influences of pain , psychological factors , and physiological factors on self-rated disability . Summary of Background Data . In chronic LBP , the interrelationship between physical impairment , pain , and disability is particularly complicated , due to the influence of various psychological factors and the lack of unequivocal methods for assessing impairment . Investigations using new “ belief ” question naires and “ sophisticated ” performance tests , which have shown promise as discriminating measures of impairment , may assist in clarifying the situation . Previous studies have rarely investigated all these factors simultaneously . Methods . One hundred forty-eight patients with cLBP completed question naires and underwent tests of mobility , strength , muscle activation , and fatigability , and ( in a subgroup ) erector spinae size and fiber size/type distribution . All measures were repeated after 3 months active therapy . Relationships between each factor and self-rated disability ( Rol and and Morris question naire ) at baseline , and between the changes in each factor and changes in disability following therapy , were examined . Results . Stepwise linear regression showed that the most significant predictors of disability at baseline were , in decreasing order of importance : pain ; psychological distress ; fear-avoidance beliefs ; muscle activation levels ; lumbar range of motion ; gender . Only changes in pain , psychological distress , and fear-avoidance beliefs significantly accounted for the changes in disability following therapy . Conclusion . A combination of pain , psychological and physiological factors was best able to predict baseline disability , although its decrease following therapy was determined only by reductions in pain and psychological variables . The active therapy programm — in addition to improving physical function — appeared capable of modifying important psychological factors , possibly as a result of the positive experience of completing the prescribed exercises without undue harm It has been estimated that one fourth to one half of all patients treated in physical therapy clinics suffer from low-back pain . The purpose of this study was to compare the effects of spinal flexion ( Group I ) and extension ( Group II ) exercises on low-back pain severity and thoracolumbar spinal mobility in chronic mechanical low-back pain patients . Both groups had significantly less low-back pain after treatment ( P < .10 ) . There was no significant difference , however , between the spinal flexion and extension exercises in reduction of low-back pain severity . The results indicated a significant difference between the groups in increasing the sagittal mobility ( P < .10 ) . The results did not indicate any significant difference between and within groups in increasing the coronal and transverse mobility of the thoracolumbar spine . Either the spinal flexion or extension exercises could be used to reduce chronic mechanical low-back pain severity , but the flexion exercises had an advantage in increasing the sagittal mobility within a short period of time OBJECTIVE To perform a cost-minimization analysis of three conservative treatment regimes for acute low-back pain ( LBP ) . DESIGN A prospect i ve r and omized clinical trial . Patients were assigned at r and om to one of three treatment programmes : General Practitioner Programme ( GPP- ) controls , Manual Therapy Programme ( MTP ) or Intensive Training Programme ( ITP ) . SETTING Primary care and physiotherapists in Stockholm , Sweden . PATIENTS 180 patients sick-listed for acute LBP . MAIN OUTCOME MEASURES Direct , indirect and total costs for three treatment programmes . RESULTS The direct costs for treatment were lowest in the GPP group -- 2744 Swedish crowns ( SEK ) per patient . More patients in the MTP and ITP underwent operations for disk hernia and radiological investigations than in the GPP . Indirect costs , defined as sick-leave for LBP represent about 90 % of the total cost . CONCLUSIONS With respect to total costs , the findings were similar between the three treatment programmes . The GPP had the lowest direct costs . It is not possible to conclude which treatment programme is to be recommended as a least cost alternative . The strong effect of indirect costs on the total cost stresses that further studies should focus on methods of shortening sick-leave Study design . A prospect i ve , r and omized investigation . Objectives . To compare the effect of dynamic strength back muscle training with that of a home training program and to evaluate the long-term effect of the home training program in patients with chronic low back pain . Summary of Background Data . In a health survey of 57-year-old women , those with chronic low back pain were selected using the Nordic Question naire . Of 172 women with low back pain , 74 participated in the study . Methods . The participants were r and omly assigned to either dynamic strength back exercises at a fitness center and a home training program or to the home training program for the first 3 months , after which both groups continued to pursue the home training program . Follow-up observation was by examination at 3 and 12 months and by mailed question naire after 3 years . The primary effect variables were disability , sickleave , and use of health care services . Results . Both training groups manifested significant improvement at the 3- and 12-month follow-up examinations , yet the adherence rate was much better in the group assigned to the fitness center . Those who adhered to the training program for the first year manifested significant improvement according to the 3-year follow-up question naire . There was a significant reduction in the number of women on sick-leave and in use of health care services after 1 year , but not after 3 years . Conclusions . The home training program was as effective as the supervised dynamic strength muscle training program and yielded lasting improvement after at least 1 year of adherence . The adherence rate was much better , however , when the training was supervised at the start The present aim was to compare the effects of stabilizing training with those of manual treatment in patients with sub-acute or chronic low-back pain ( LBP ) . Forty-seven patients were r and omized to a stabilizing training group ( ST group ) or a manual treatment group ( MT group ) . The patients underwent a 6-week treatment programme on a weekly basis . Pain , health and functional disability level at the start of treatment , after treatment , and at 3- and 12-month follow-ups were assessed . In the ST group all assessed variables improved significantly ( P<0.05 ) after the treatment period and were maintained long term . After the treatment period there was a significant difference between the groups in assessed function ( P<0.05 ) . More individuals in the ST group had improved than in the MT group . At the 3-month follow-up significantly more improved individuals were evident in the ST group regarding pain , general health and functional disability levels . In the long term , significantly more ( P<0.05 ) patients in the MT group reported recurrent treatment periods . The study did not indicate any clear short-term differences between the groups in the accessed outcome measures . In the long term , however , stabilizing training seemed to be more effective than manual treatment in terms of improvement of individuals and the reduced need for recurrent treatment periods 105 patients who had chronic low back pain without clinical signs of lumbar nerve root compression or radiological evidence of spondylolysis or osteomalacia were r and omised to three treatments : 30 sessions of intensive dynamic back extensor exercises over three months ; a similar programme at one-fifth the exercise intensity ; or one month of thermotherapy , massage , and mild exercises . The results consistently favoured intensive exercise , which had no adverse effects . Since these exercises can be conducted in groups , the intensive programme is no more costly than conventional strategies that require individual attention & 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 STUDY DESIGN A r and omized , controlled , single-center trial with a stratified group design . OBJECTIVE To investigate the secondary prophylactic effect of the Active Back School program on minimizing recurrences of low back pain episodes . SUMMARY OF BACKGROUND DATA The results of back school interventions are controversial . Previous work often used short intervention periods and low doses of practical training . However , studies with the highest method ologic scores have shown the best results , especially when conducted in occupational setting s and coupled with a comprehensive rehabilitation program . METHODS By block r and omization , 19 men and 24 women were allocated to Active Back School , with 18 men and 20 women as control subjects . The Slumps test and number of low back pain episodes during the previous 36 months were used as stratification factors . There were no significant differences between the groups with regard to demographic factors and initially observed variables . Active Back School consisted of 20 lessons over a 13-week period . Each lesson was divided into a 20-minute theoretical part and a 40-minute exercise part . All participants were examined on enrollment , then 5 and 12 months after initiation of the program . Outcome measures were recurrence of low back pain episodes and number of days of sick leave . RESULTS The recurrence of new low back pain episodes was significantly lower ( P < 0.05 ) and the time from inclusion to the first new episode significantly longer ( P < 0.01 ) in the Active Back School group than in the control group . In the Active Back School group , seven participants took sick leave because of low back pain episodes during the first 12 months of follow-up compared with 11 among the control subjects . The number of sick leave days was significantly lower ( P < 0.05 ) in the Active Back School group than in the control group . CONCLUSION Active Back School reduced the recurrence and severity of new low back pain episodes according to results of follow-up examinations performed 5 and 12 months after enrollment Low back pain is one of the most common and important musculoskeletal disorders . In addition , chronic low back pain can deteriorate the patient 's physical , psychosocial and socioeconomic status . The objective of this quasi-experimental research was to assess the efficacy of an aerobic exercise and health education program in the treatment of chronic low back pain . Seventy-two patients whose ages ranged from 30 to 50 years who had chronic low back pain were enrolled and r and omly assigned into two groups . Eight men and 28 women in the experimental group participated in a series of 3 health education sessions and an aerobic exercise training program . Nine men and 27 women in the control group received regular health education and a lumbar flexion exercise program . After a 3-month period of treatment , the results revealed the experimental group had statistically significant improvement of pain score and resting pulse rates when compared to the values of the control group ( p-value < 0.001 and < 0.01 , respectively ) . The average serum High Density Lipoprotein-Cholesterol ( HDL-C ) in the experimental group was also significantly higher ( p-value < 0.05 ) than that of the control group . This health education program is useful and may be applicable to patients with chronic low back pain as an alternative treatment QUESTION Aim of the study was to evaluate the influence of elastic lumbar belts on the effect of muscle training for patients with low back pain . METHODS 97 male subjects aged from 23 to 42 years with and without low back pain participated in the investigation . The low back pain patients ( n = 63 ) were r and omized into a training group without and a training group with elastic lumbar belts and a control group . The subjects with healthy backs ( n = 34 ) were divided age-matched into a training group with elastic lumbar belts and a control group . The three training groups took part in a muscle strenghtening program over 8 weeks . The control groups did not receive any alternative physiotherapeutic treatment . All groups were tested at the beginning , after 8 weeks and further 6 months later . RESULTS The data obtained for the control groups remained virtually unchanged over the period of investigation . However , a significant increase of the muscle flexibility of the lower limbs could be proved for the training groups . Furthermore the coordination between the lumbar spine and pelvis when flexing the trunk deeply forward was more leveled out for the training groups with patients suffered low back pain . The results confirmed a reduction for pain severity and for limitations in activities of daily living as well . The modifications for the criteria investigated were significant stronger for the training group with patients using the elastic lumbar belt . CONCLUSIONS The effectiveness of the muscle strengthening program for patients with low back pain could be improved significantly by means of the elastic lumbar belt as an applicable therapy instrument in the functional rehabilitation of spinal injuries Study Design . A multicenter , r and omized , controlled trial with 1-year follow-up . Objectives . To compare the effect of manual therapy to exercise therapy in sick-listed patients with chronic low back pain ( > 8 wks ) . Summary and Background Data . The effect of exercise therapy and manual therapy on chronic low back pain with respect to pain , function , and sick leave have been investigated in a number of studies . The results are , however , conflicting . Methods . Patients with chronic low back pain or radicular pain sick-listed for more than 8 weeks and less than 6 months were included . A total of 49 patients were r and omized to either manual therapy ( n = 27 ) or to exercise therapy ( n = 22 ) . Sixteen treatments were given over the course of 2 months . Pain intensity , functional disability ( Oswestry disability index ) , general health ( Dartmouth COOP function charts ) , and return to work were recorded before , immediately after , at 4 weeks , 6 months , and 12 months after the treatment period . Spinal range of motion ( Schober test ) was measured before and immediately after the treatment period only . Results . Although significant improvements were observed in both groups , the manual therapy group showed significantly larger improvements than the exercise therapy group on all outcome variables throughout the entire experimental period . Immediately after the 2-month treatment period , 67 % in the manual therapy and 27 % in the exercise therapy group had returned to work ( P < 0.01 ) , a relative difference that was maintained throughout the follow-up period . Conclusions . Improvements were found in both intervention groups , but manual therapy showed significantly greater improvement than exercise therapy in patients with chronic low back pain . The effects were reflected on all outcome measures , both on short and long-term follow-up BACKGROUND AND METHODS There are few data on the relative effectiveness and costs of treatments for low back pain . We r and omly assigned 321 adults with low back pain that persisted for seven days after a primary care visit to the McKenzie method of physical therapy , chiropractic manipulation , or a minimal intervention ( provision of an educational booklet ) . Patients with sciatica were excluded . Physical therapy or chiropractic manipulation was provided for one month ( the number of visits was determined by the practitioner but was limited to a maximum of nine ) ; patients were followed for a total of two years . The bothersomeness of symptoms was measured on an 11-point scale , and the level of dysfunction was measured on the 24-point Rol and Disability Scale . RESULTS After adjustment for base-line differences , the chiropractic group had less severe symptoms than the booklet group at four weeks ( P=0.02 ) , and there was a trend toward less severe symptoms in the physical therapy group ( P=0.06 ) . However , these differences were small and not significant after transformations of the data to adjust for their non-normal distribution . Differences in the extent of dysfunction among the groups were small and approached significance only at one year , with greater dysfunction in the booklet group than in the other two groups ( P=0.05 ) . For all outcomes , there were no significant differences between the physical-therapy and chiropractic groups and no significant differences among the groups in the numbers of days of reduced activity or missed work or in recurrences of back pain . About 75 percent of the subjects in the therapy groups rated their care as very good or excellent , as compared with about 30 percent of the subjects in the booklet group ( P<0.001 ) . Over a two-year period , the mean costs of care were $ 437 for the physical-therapy group , $ 429 for the chiropractic group , and $ 153 for the booklet group . CONCLUSIONS For patients with low back pain , the McKenzie method of physical therapy and chiropractic manipulation had similar effects and costs , and patients receiving these treatments had only marginally better outcomes than those receiving the minimal intervention of an educational booklet . Whether the limited benefits of these treatments are worth the additional costs is open to question |
11,939 | 29,039,967 | This systematic review highlights the potential for a Mediterranean diet intervention to reduce central obesity and in turn reduce obesity-related chronic disease risk and associated public health burden | ABSTRACT Central obesity is associated with chronic low- grade inflammation , and is a risk factor for cardiometabolic syndrome .
The Mediterranean diet pattern has a convincing evidence -base for improving cardiometabolic health .
This review investigated the impact of Mediterranean diet interventions on central obesity , specifically . | BACKGROUND The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus ( DM2 ) is unclear . Trials comparing the effectiveness of diets are frequently limited by short follow-up times and high dropout rates . AIM The effects of a low carbohydrate Mediterranean ( LCM ) , a traditional Mediterranean ( TM ) , and the 2003 American Diabetic Association ( ADA ) diet were compared , on health parameters during a 12-month period . METHODS In this 12-month trial , 259 overweight diabetic patients ( mean age 55 years , mean body mass index 31.4 kg/m(2 ) ) were r and omly assigned to one of the three diets . The primary end-points were reduction of fasting plasma glucose , HbA1c and triglyceride ( TG ) levels . RESULTS 194 patients out of 259 ( 74.9 % ) completed follow-up . After 12 months , the mean weight loss for all patients was 8.3 kg : 7.7 kg for ADA , 7.4 kg for TM and 10.1 kg for LCM diets . The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet ( -2.0 and -1.6 % , respectively , p < 0.022 ) . HDL cholesterol increased ( 0.1 mmol/l + /- 0.02 ) only on the LCM ( p < 0.002 ) . The reduction in serum TG was greater in the LCM ( -1.3 mmol/l ) and TM ( -1.5 mmol/l ) than in the ADA ( -0.7 mmol/l ) , p = 0.001 . CONCLUSIONS An intensive 12-month dietary intervention in a community-based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups . Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control The influence of the source of dietary fat on postpr and ial thermogenesis and substrate oxidation rates , was examined in twelve postmenopausal women aged 57 - 73 years , with BMI 21.9 - 38.3 kg/m(2 ) . A single blind , r and omised , paired comparison of two high-fat , isoenergetic , mixed test meals was conducted . The major source of fat was either cream ( CREAM ) or extra virgin olive oil ( EVOO ) . RMR , diet-induced thermogenesis ( DIT ) and substrate oxidation rates over 5 h were measured by indirect calorimetry . There were no differences in body weight , RMR , fasting carbohydrate or fat oxidation rates between the two occasions . DIT ( EVOO 97 ( SD 46 ) v. CREAM 76 ( SD 69 ) kJ/5 h and EVOO 5.2 ( SD 2.5 ) v. CREAM 4.1 ( SD 3.7)% energy ) did not differ between the two test meals . The postpr and ial increase in carbohydrate oxidation rates , relative to their respective fasting values ( DeltaCOX ) , was significantly lower following the EVOO meal ( EVOO 10.6 ( SD 8.3 ) v. CREAM 17.5 ( SD 10 ) g/5 h ; paired t test , P=0.023 ) , while postpr and ial fat oxidation rates ( DeltaFOX ) were significantly higher ( EVOO 0.0 ( SD 4.4 ) v. CREAM -3.6 ( sd 4.0 ) g/5 h ; P=0.028 ) . In the eight obese subjects , however , DIT was significantly higher following the EVOO meal ( EVOO 5.1 ( SD 2.0 ) v. CREAM 2.5 ( sd 2.9 ) % ; P=0.01 ) . This was accompanied by a significantly lower DeltaCOX ( EVOO 10.9 ( SD 9.9 ) v. CREAM 17.3 ( SD 10.5 ) g/5 h ; P=0.03 ) and significantly higher DeltaFOX ( EVOO 0.11 ( SD 4.4 ) v. CREAM -4.1 ( SD 4.5 ) g/5 h , P=0.034 ) . The present study showed that olive oil significantly promoted postpr and ial fat oxidation and stimulated DIT in abdominally obese postmenopausal women The aim of this dynamic prospect i ve follow-up study was to assess the association between olive oil consumption and the likelihood of weight gain or the incidence of overweight or obesity in a large Mediterranean cohort of 7,368 male and female Spanish university graduates ( the SUN Project ) who were followed for a median period of 28.5 mon . A vali date d Food Frequency Question naire was administered at baseline , and respondents also completed a follow-up question naire after 28.5 mon . Changes in participants ' consumption of olive oil and their weight were assessed during follow-up . A higher baseline consumption of olive oil was associated with a lower likelihood of weight gain , although the differences were not statistically significant . The adjusted difference in weight gain ( kg ) was −0.16 [ 95 % confidence interval ( C1 ) : −0.42 to + 0.11 ] for participants in the upper quintile of olive oil consumption ( median : 46 g/d ) compared with those in the lowest quintile ( median : 6 g/d ) . For participants with a high baseline consumption of olive oil whose olive oil consumption also increased during follow-up , we found a slightly increased but nonsignificant risk of incidence of over-weight or obesity ( adjusted odds ratio=1.19 , 95 % C1 : 0.73 to 1.95 ) . Our study , carried out in a sample of free-living people , shows that a high amount of olive oil consumption is not associated with higher weight gain or a significantly higher risk of developing overweight or obesity in the context of the Mediterranean food pattern Six healthy adult males were fed four different diets to determine the effects of the quantity of fat ( 30 % or 40 % of energy as fat ) and type of fat ( polyunsaturated or saturated ) on utilization of fatty acids . Each diet was fed for 15 d. The ratio of dietary polyunsaturated to saturated fat ( P : S ) was formulated at either 0.2 or 1.0 at both fat intakes . Subjects provided breath tests to measure background 13C and response to [1 - 13C]10:0 and [1 - 13C]16:0 fed with a test meal . Increasing the P : S increased whole-body oxidation of labeled 10:0 by 30 % after consumption of both low- and high-fat diets . When labeled 16:0 was fed , the amount of 13C excreted in breath increased by a factor of 2.4 after the low-fat diet with a high P : S compared with the diet with a low P : S. The results suggest that the amount and type of fat in the diet affect utilization of individual fatty acids in normal subjects A r and omised crossover study of eight overweight or obese men ( aged 24 - 49 years , BMI 25.5 - 31.3 kg/m(2 ) ) , who followed two diets for 4 weeks each , was performed to determine whether substitution of saturated fat with monounsaturated fat affects body weight and composition . Subjects were provided with all food and beverages as modules ( selected ad libitum ) of constant macronutrient composition , but differing energy content . The % total energy from saturated fat , monounsaturated fat and polyunsaturated fat was 24 , 13 and 3 % respectively on the saturated fatty acid (SFA)-rich diet and 11 , 22 and 7 % respectively on the monounsaturated fatty acid (MUFA)-rich diet . MUFA accounted for about 80 % of the unsaturated fats consumed on both diets . Body composition , blood pressure , energy expenditure ( resting and postpr and ial metabolic rates , substrate oxidation rate , physical activity ) , serum lipids , the fatty acid profile of serum cholesteryl esters and plasma glucose and insulin concentrations were measured before and after each diet period . Significant ( P < or = 0.05 ) differences in total cholesterol and the fatty acid composition of serum cholesteryl esters provided evidence of dietary adherence . The men had a lower weight ( -2.1 ( SE 0.4 ) kg , P=0.0015 ) and fat mass ( -2.6 ( SE 0.6 ) kg , P=0.0034 ) at the end of the MUFA-rich diet as compared with values at the end of the SFA-rich diet . No significant differences were detected in energy or fat intake , energy expenditure , substrate oxidation rates or self-reported physical activity . Substituting dietary saturated with unsaturated fat , predominantly MUFA , can induce a small but significant loss of body weight and fat mass without a significant change in total energy or fat intake OBJECTIVE We examined associations between two Mediterranean diet ( MD ) adherence indexes ( the MD index , MDI , and the MD score , MDS ) and several blood biomarkers of diet and disease . SUBJECTS We studied 328 individuals from Catalonia ( Northeastern Spain ) , ages 18 - 75 , who provided fasting blood sample s , a subset of the 2346 individuals as part of a larger representative and r and om sample from the 1992 - 1993 Catalan Nutritional Survey . DESIGN AND METHOD Diet was measured using 24-h recalls . Biomarkers studied were plasma levels of beta-carotene , alpha-tocopherol , retinol , vitamins B12 , C and folates as well as serum total cholesterol , HDL cholesterol , LDL cholesterol and triglycerides . Multivariate linear regression was used to analyse associations of the nutrient biomarkers with the dietary pattern indexes , adjusting for potential confounders . RESULTS AND CONCLUSIONS Subjects with higher MD adherence , as measured by the two dietary indexes , had significantly higher plasma concentrations of beta-carotene , folates , vitamin C , alpha-tocopherol and HDL cholesterol . The most highly significant relationship was that between folates and the adherence to the MD Pattern , as determined by both indexes . These research findings suggest the potential usefulness of biomarkers as complementary tools for assessing adherence to a dietary pattern . This type of data not only informs the development of robust dietary adherence indexes , but it also provides specific clues about the potential physiological mechanisms that explain the beneficial effects of the MD pattern on chronic disease risk BACKGROUND Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score ( MDS ) is associated with lower obesity risk . The newly proposed Nordic Diet could hold similar beneficial effects . Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity , studies should consider both diet and genetics . OBJECTIVE We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score ( NDS ) and changes in weight ( Δweight ) , waist circumference ( ΔWC ) , and waist circumference adjusted for body mass index ( BMI ) ( ΔWC BMI ) . DESIGN We conducted a case-cohort study with a median follow-up of 6.8 y that included 11,048 participants from 5 European countries ; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during follow-up . A r and omly selected subcohort included 6548 participants , including 5496 noncases . Cases and noncases were compared in analyses by using logistic regression . Continuous traits ( ie , Δweight , ΔWC , and ΔWC BMI ) were analyzed by using linear regression models in the r and om subcohort . Interactions were tested by including interaction terms in models . RESULTS A higher MDS was significantly inversely associated with case status ( OR : 0.98 ; 95 % CI : 0.96 , 1.00 ) , ΔWC ( β = -0.010 cm/y ; 95 % CI : -0.020 , -0.001 cm/y ) , and ΔWC BMI ( β = -0.008 ; 95 % CI:-0.015 , -0.001 ) per 1-point increment but not Δweight ( P = 0.53 ) . The NDS was not significantly associated with any outcome . There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain ( P = 0.05 ) , which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles . FTO did not modify observed associations . CONCLUSIONS A high MDS is associated with a lower ΔWC and ΔWC BMI , regardless of FTO and TCF7L2 risk alleles . For Δweight , findings were less clear , but the effect may depend on the TCF7L2 rs7903146 variant . The NDS was not associated with anthropometric changes during follow-up BACKGROUND AND AIMS Diets high in monounsaturated fatty acids ( MUFA ) such as a Mediterranean diet may reduce the risk of cardiovascular diseases by improving insulin sensitivity and serum lipids . Besides being high in MUFA , a Mediterranean diet also contains abundant plant foods , moderate wine and low amounts of meat and dairy products , which may also play a role . We compared the effects of a high MUFA-diet with a diet high in saturated fatty acids ( SFA ) and the additional effect of a Mediterranean diet on insulin sensitivity and serum lipids . METHODS AND RESULTS A r and omized parallel controlled-feeding trial was performed , in 60 non-diabetics ( 40 - 65 y ) with mild abdominal obesity . After a two week run-in diet high in SFA ( 19 energy-% ) , subjects were allocated to a high MUFA-diet ( 20 energy-% ) , a Mediterranean diet ( MUFA 21 energy-% ) , or the high SFA-diet , for eight weeks . The high MUFA and the Mediterranean diet did not affect fasting insulin concentrations . The high MUFA-diet reduced total cholesterol ( -0.41 mmol/L , 95 % CI -0.74 , -0.09 ) and LDL-cholesterol ( -0.38 mmol/L , 95 % CI -0.65 , -0.11 ) compared with the high SFA-diet , but not triglyceride concentrations . The Mediterranean diet increased HDL-cholesterol concentrations ( + 0.09 mmol/L , 95 % CI 0.0 , 0.18 ) and reduced the ratio of total cholesterol/HDL-cholesterol ( -0.39 , 95 % CI -0.62 , -0.16 ) compared with the high MUFA-diet . CONCLUSION Replacing a high SFA-diet with a high MUFA or a Mediterranean diet did not affect insulin sensitivity , but improved serum lipids . The Mediterranean diet was most effective , it reduced total and LDL-cholesterol , and also increased HDL-cholesterol and reduced total cholesterol/HDL-cholesterol ratio Abdominal obesity is a strong predictor of metabolic disorders . Prospect i ve data on the association between the Mediterranean diet and surrogate markers of abdominal adiposity are scarce . The present study evaluated the relationship between adherence to the Mediterranean diet and ( 1 ) changes in waist circumference ( WC ) and ( 2 ) 10-year incidence of abdominal obesity . We conducted a prospect i ve , population -based study in 3058 male and female Spaniards aged 25 - 74 years , followed from 2000 to 2009 . Dietary intake and leisure-time physical activity levels were recorded using vali date d question naires . Weight , height and WC were measured . Adherence to the Mediterranean diet , determined using the previously vali date d REGICOR-Mediterranean diet score ( R-MDS ) , based on the distribution of population food intake and on the dietary recommendations ( MDS-rec ) , was negatively associated with WC gain ( P = 0.007 and 0.024 , respectively ) in fully adjusted models . In the multivariate logistic analysis , the odds of abdominal obesity incidence decreased across the tertiles of the R-MDS , but the association was not significant . In conclusion , adherence to the Mediterranean diet was associated with lower abdominal fat gain , but not with 10-year incidence of abdominal obesity OBJECTIVES We studied the effect of the Mediterranean diet on plasma levels of C-reactive protein ( CRP ) , white blood cell counts , interleukin (IL)-6 , tumor necrosis factor (TNF)-alpha , amyloid A , fibrinogen , and homocysteine . BACKGROUND To the best of our knowledge , the mechanism(s ) by which the Mediterranean diet reduces cardiovascular risk are not well understood . METHODS During the 2001 to 2002 period , we r and omly enrolled 1,514 men ( 18 to 87 years old ) and 1,528 women ( 18 to 89 years old ) from the Attica area of Greece ( of these , 5 % of men and 3 % of women were excluded because of a history of cardiovascular disease ) . Among several factors , adherence to the Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet . Higher values of the score meant closer adherence to the Mediterranean diet . RESULTS Participants who were in the highest tertile of the diet score had , on average , 20 % lower CRP levels ( p = 0.015 ) , 17 % lower IL-6 levels ( p = 0.025 ) , 15 % lower homocysteine levels ( p = 0.031 ) , 14 % lower white blood cell counts ( p = 0.001 ) , and 6 % lower fibrinogen levels ( p = 0.025 ) , as compared with those in the lowest tertile . The findings remained significant even after various adjustments were made . Borderline associations were found regarding TNF-alpha ( p = 0.076 ) , amyloid A levels ( p = 0.19 ) , and diet score . CONCLUSIONS Adherence to the traditional Mediterranean diet was associated with a reduction in the concentrations of inflammation and coagulation markers . This may partly explain the beneficial actions of this diet on the cardiovascular system BACKGROUND AND AIM The effect of the quality of dietary fat on body composition is unknown . Our objective was to determine whether body composition is modified by the isocaloric substitution of a diet rich in saturated fat by a diet high in monounsaturated fat ( Mediterranean diet ) or a carbohydrate-rich diet in overweight subjects with hypercholesterolemia . METHODS AND RESULTS The study involved 34 hypercholesterolemic males aged 18 - 63 years with a body mass index ( BMI ) of 28.2 ( 2.6 ) , all of whom consumed a diet rich in saturated fat ( SAT ) for 28 days . They were then r and omly divided into two groups of 17 subjects and underwent two dietary periods of 28 days each in a crossover design : a Mediterranean diet high in monounsaturated fat ( MONO ) and a carbohydrate-rich diet ( CHO ) . The order of the diets was different for the two group . The CHO diet contained 57 % CHO and 28 % total fat ( < 10 % saturated fat , 12 % monounsaturated fat and 6 % polyunsaturated fat ) ; the Mediterranean diet contained 47 % CHO and 38 % fat ( < 10 % saturated fat , 22 % monounsaturated fat--75 % of which was provided by olive oil- and 6 % polyunsaturated fat ) . The variables measured at the end of each dietary intervention period were : 1 ) body composition by means of bioelectrical impedance ; 2 ) plasma lipoproteins using enzymatic techniques ; and 3 ) fatty acids in cholesterol esters by means of gas chromatography . BMI and the waist/hip ratio remained the same during the three dietary periods . A decrease in fat was observed when changing from a saturated fat diet ( 23.3 ( 6.3 ) kg ) to a Mediterranean diet ( 20.8 ( 7.2 ) kg ) ( p < 0.05 ) , or a carbohydrate-rich diet ( 20.6 ( 6.7 ) kg ) ( p < 0.05 ) . Lean mass increased when changing from a SAT diet ( 58.4 ( 7.0 ) kg ) to a CHO diet ( 60.2 ( 7.0 ) kg ) ( p < 0.05 ) . CONCLUSION The isocaloric substitution of a saturated fat-rich diet by a Mediterranean or carbohydrate-rich diet decreases total body fat in hypercholesterolemic males CONTEXT : Long-term success in weight loss with dietary treatment has been elusive . OBJECTIVE : To evaluate a diet moderate in fat based on the Mediterranean diet compared to a st and ard low-fat diet for weight loss when both were controlled for energy . DESIGN : A r and omized , prospect i ve 18 month trial in a free-living population . PATIENTS : A total of 101 overweight men and women ( 26.5–46 kg/m2).INTERVENTION : ( 1 ) Moderate-fat diet ( 35 % of energy ) ; ( 2 ) low-fat diet ( 20 % of energy).MAIN OUTCOME MEASUREMENTS : Change in body weight . RESULTS : After 18 months , 31/50 subjects in the moderate-fat group , and 30/51 in the low fat group were available for measurements . In the moderate-fat group , there were mean decreases in body weight of 4.1 kg , body mass index of 1.6 kg/m2 , and waist circumference of 6.9 cm , compared to increases in the low-fat group of 2.9 kg , 1.4 kg/m2 and 2.6 cm , respectively ; P≤0.001 between the groups . The difference in weight change between the groups was 7.0 kg . ( 95 % CI 5.3 , 8.7 ) . Only 20 % ( 10/51 ) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54 % ( 27/50 ) in the moderate-fat group , ( P<0.002 ) . The moderate-fat diet group was continued for an additional year . The mean weight loss after 30 months compared to baseline was 3.5 kg ( n=19 , P=0.03 ) . CONCLUSIONS : A moderate-fat , Mediterranean-style diet , controlled in energy , offers an alternative to a low-fat diet with superior long-term participation and adherence , with consequent improvements in weight loss Aims /hypothesisMost studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat , carbohydrate , fibre , fruits and vegetables . Instead , we aim ed to compare diets that were available during human evolution with more recently introduced ones . Methods Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were r and omised to receive ( 1 ) a Palaeolithic ( ‘ Old Stone Age ’ ) diet ( n = 14 ) , based on lean meat , fish , fruits , vegetables , root vegetables , eggs and nuts ; or ( 2 ) a Consensus ( Mediterranean-like ) diet ( n = 15 ) , based on whole grains , low-fat dairy products , vegetables , fruits , fish , oils and margarines . Primary outcome variables were changes in weight , waist circumference and plasma glucose AUC ( AUC Glucose0–120 ) and plasma insulin AUC ( AUC Insulin0–120 ) in OGTTs . Results Over 12 weeks , there was a 26 % decrease of AUC Glucose0–120 ( p = 0.0001 ) in the Palaeolithic group and a 7 % decrease ( p = 0.08 ) in the Consensus group . The larger ( p = 0.001 ) improvement in the Palaeolithic group was independent ( p = 0.0008 ) of change in waist circumference ( −5.6 cm in the Palaeolithic group , −2.9 cm in the Consensus group ; p = 0.03 ) . In the study population as a whole , there was no relationship between change in AUC Glucose0–120 and changes in weight ( r = −0.06 , p = 0.9 ) or waist circumference ( r = 0.01 , p = 1.0 ) . There was a tendency for a larger decrease of AUC Insulin0–120 in the Palaeolithic group , but because of the strong association between change in AUC Insulin0–120 and change in waist circumference ( r = 0.64 , p = 0.0003 ) , this did not remain after multivariate analysis . Conclusions /interpretationA Palaeolithic diet may improve glucose tolerance independently of decreased waist circumference Purpose To determine the effect of Mediterranean-type diet and close dietetic supervision on dietary antioxidant intake and plasma total antioxidant capacity ( TAC ) in patients with abdominal obesity . Methods Ninety subjects with abdominal obesity , 46 in intervention group , 44 in control group , participated in a 2-month , r and omized , parallel dietary intervention . All participants were counseled on Greek Mediterranean diet . The intervention group was under close dietetic supervision , followed a specific relevant daily and weekly food plan consuming antioxidant-rich foods and food products . Total dietary antioxidant intake was calculated from the volunteers ’ food diaries , and plasma TAC using plasma ORAC assay and plasma ferric-reducing antioxidant power ( FRAP ) assay , both at baseline and at 2 months . Results Following the 2-month period , total dietary antioxidant intake was increased in the intervention group compared to the control group ( P = 0.000 ) . In addition , increased intake of total fat , due to higher consumption of monounsaturated fatty acids , as well as increased intakes of dietary fiber , vitamin C and alcohol was also observed in the intervention group compared to the control group ( P < 0.05 ) . Plasma TAC was increased in the intervention group compared to the control group ( P = 0.039 ) using the ORAC assay , while there was a trend toward a TAC increase ( P = 0.077 ) using the FRAP assay . Conclusion Adherence to a Mediterranean-type diet , with emphasis on an increase in foods rich in antioxidants and close dietetic supervision , can increase total dietary antioxidant intake and plasma TAC in patients with abdominal obesity OBJECTIVE The Mediterranean dietary pattern improves cardiovascular disease factors . More research is needed on the usefulness of a Mediterranean dietary pattern in terms of weight loss . The objective of this study was to assess the effectiveness of behavioral therapy based on the Mediterranean diet for the treatment of obesity and to determine the main obstacles to weight loss . METHODS A total of 1406 obese subjects ( body mass index , 31+/-5kg/m(2 ) ) , aged 20 - 65 y , from a Mediterranean area in southeast Spain were subjected to a weight-reduction program . To evaluate effectiveness , weight loss , body fat distribution , biochemical variables , blood pressure changes , mean duration of treatment , percentage of attrition , and the ability to fulfill a Mediterranean diet pattern were assessed . To determine the main barriers to losing weight , a " Barriers to Weight Loss " checklist was completed . RESULTS The behavioral therapy program was effective for the treatment of obesity . The average weight loss was 7.7 kg . The duration of treatment was 34 wk . Eighty-nine percent of subjects fulfilled the Mediterranean principles during the program , and all the variables studied were significantly improved . Attrition was 4 - 9 % , with the main reason being stress ( 37 % ) . Main obstacles to weight loss were " losing motivation , " being " prone to stress-related eating , " and being liable to eat when bored . Recording food intake and assisting group therapy were also important tools for losing weight ( P < or = 0.05 ) . CONCLUSIONS Dietary/behavioral treatment based on Mediterranean dietary principles is effective in clinical practice . Nutrition professionals should encourage their patients to record food intake and to attend group therapy Obesity is a cardiovascular risk factor associated with endothelial dysfunction , but the effect of different weight loss strategies on endothelial function is not known . The effect of diet on endothelial function in two hypocaloric diets , a very-low-carbohydrate diet ( A ) and a Mediterranean diet ( M ) , was measured by brachial artery flow-mediated dilation ( FMD ) . Design Using a longitudinal , r and omized , open study design , subjects were engaged in a 2-month weight loss diet . FMD , inflammatory cytokines [ interleukin-6 ( IL-6 ) and tumour necrosis factor-alpha ] and a marker of oxidative stress [ 8-iso-prostagl and in F2alpha ( 8-iso-PGF2alpha ) ] were measured in subjects on three occasions : before initiating the diet ( T0 ) , after 5 - 7 days of dieting ( T5 ) and after 2 months of dieting ( T60 ) . The very short- and medium-term time points were established to discriminate respectively the effect of the diet itself ( T5 ) from that of weight loss ( T60 ) . Twenty overweight/obese but otherwise healthy women ( BMI : 27 - 34.9 kg m(-2 ) ; age 30 - 50 years ) completed the study . Results Group A lost more weight ( mean + /- SEM ; -7.6 + /- 0.8 kg ) than group M ( -4.9 + /- 0.6 kg , P = 0.014 ) at T60 . The FMD was not significantly different between the two groups at T0 ( group A : 12.2 + /- 2.9 % vs. group B : 10.3 + /- 2.3 % , P = ns ) . In group A , FMD was significantly reduced at T5 and returned to baseline at T60 ; in group M , FMD increased at T5 and returned to baseline at T60 ( P = 0.007 for diet x time interaction ) . Serum concentrations of IL-6 and 8-iso-PGF2alpha were not significantly different between the two groups at T0 and increased significantly at T5 only in group A ( P < 0.001 and P < 0.005 respectively ) . Conclusion As endothelial dysfunction is known to be associated with acute cardiovascular events , this study suggests that the cardiovascular risk might be increased in the first days of a very-low-carbohydrate diet BACKGROUND & AIMS Non-alcoholic fatty liver disease ( NAFLD ) affects up to 30 % of the population and signifies increased risk of liver fibrosis and cirrhosis , type 2 diabetes , and cardiovascular disease . Therapies are limited . Weight loss is of benefit but is difficult to maintain . We aim ed at examining the effect of the Mediterranean diet ( MD ) , a diet high in monounsaturated fatty acids , on steatosis and insulin sensitivity , using gold st and ard techniques . METHODS Twelve non-diabetic subjects ( 6 Females/6 Males ) with biopsy-proven NAFLD were recruited for a r and omised , cross-over 6-week dietary intervention study . All subjects undertook both the MD and a control diet , a low fat-high carbohydrate diet ( LF/HCD ) , in r and om order with a 6-week wash-out period in- between . Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ( (1)H-MRS ) . RESULTS At baseline , subjects were abdominally obese with elevated fasting concentrations of glucose , insulin , triglycerides , ALT , and GGT . Insulin sensitivity at baseline was low ( M=2.7 ± 1.0 mg/kg/min(-1 ) ) . Mean weight loss was not different between the two diets ( p=0.22 ) . There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD : 39 ± 4 % versus 7 ± 3 % , as measured by (1)H-MRS ( p=0.012 ) . Insulin sensitivity improved with the MD , whereas after the LF/HCD there was no change ( p=0.03 between diets ) . CONCLUSIONS Even without weight loss , MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD , compared to current dietary advice . This diet should be further investigated in subjects with NAFLD |
11,940 | 29,689,054 | Evidence partially supported the use of CHWs in promoting psychosocial outcomes in PLWH . | BACKGROUND Community health worker ( CHW ) interventions are a successful strategy to promote health among HIV-negative and persons living with HIV ( PLWH ) .
Psychosocial factors are critical dimensions of HIV/AIDS care contributing to prognosis of the disease , yet it is unclear how CHW interventions improve psychosocial outcomes in PLWH .
The purpose of this study was to critically appraise the types , scope , and nature of CHW interventions design ed to address psychosocial outcomes in PLWH . | Purpose . The purpose of this study was to test the feasibility and assess outcomes of health care adherence based on whether participants engage in particular risky behaviors relevant to general health or living with human immunodeficiency virus ( HIV ) infection and the frequency of these adherent behaviors . Health adherent behaviors include both self-advocacy and decreased stigma as underlying key components . Design . A r and omized control trial comparing peer-led attention control support and intervention groups . Setting . Community-based women 's drop-in center in an urban , black neighborhood of Boston , Massachusetts . Subjects . Aging , low-income , black women living with HIV infection . Intervention . Peer-led , small-group , structured writing using film clips from Women 's Voices Women 's Lives as a writing prompt . Measures . Demographic and outcome data that included adherence , self-advocacy , and stigma ; collected at baseline , 6 weeks , and 6 months . Analysis . Repeated- measures analysis of variance scores were examined between groups and waves . Paired- sample t-tests were used to examine mean differences across time . Results . Sample included 110 women ( intervention , n = 56 ; comparison , n = 54 ) . Retention was 85.5 % . Repeated- measures analysis indicated intervention group condom use ( n = 69 , F = 8.02 , df = 1 , p < .01 ) and safe sex ( n = 71 , F = 13.02 , df = 1 , p < .01 ) was higher than that of comparison group . A time effect was also found in the Silencing the Self Scale ( n = 91 , Pillai 's trace = 7.21 , df = 2 , p < .01 ) . Conclusion . This study demonstrates the feasibility of a tailored , peer-led , and culturally relevant interventions and tentative efficacy in population s affected by health disparities . Key limitations include no comparison intervention format with women who ca n't write and the need to test generalizability Abstract Multimedia technologies offer powerful tools to increase capacity of health workers to deliver st and ardized , effective , and engaging antiretroviral medication adherence counseling . Masivukeni — is an innovative multimedia-based , computer-driven , lay counselor-delivered intervention design ed to help people living with HIV in re source -limited setting s achieve optimal adherence . This pilot study examined medication adherence and key psychosocial outcomes among 55 non-adherent South African HIV+ patients , on antiretroviral therapy ( ART ) for at least 6 months , who were r and omized to receive either Masivukeni or st and ard of care ( SOC ) counseling for ART non-adherence . At baseline , there were no significant differences between the SOC and Masivukeni groups on any outcome variables . At post-intervention ( approximately 5–6 weeks after baseline ) , -clinic-based pill count adherence data available for 20 participants ( 10 per intervention arm ) showed a 10 % improvement for— participants and a decrease of 8 % for SOC participants . Masivukeni participants reported significantly more positive attitudes towards disclosure and medication social support , less social rejection , and better clinic – patient relationships than did SOC participants . Masivukeni shows promise to promote optimal adherence and provides preliminary evidence that multimedia , computer-based technology can help lay counselors offer better adherence counseling than st and ard approaches 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 Hope is an essential dimension of successful coping in the context of illnesses such as HIV/AIDS , because positive expectations for the future alleviate emotional distress , enhance quality of life and have been linked to the capacity for behavioural change . The social environment ( e.g. family , peers ) is a regulator of hope for people living with HIV/AIDS ( PLWHA ) . In this regard , the dual aim of this article is ( 1 ) to analyze the influence of a peer adherence support ( PAS ) intervention and the family environment on the state of hope in PLWHA and ( 2 ) to investigate the interrelationship between the two determinants . Methods The Effective AIDS Treatment and Support in the Free State study is a prospect i ve r and omized controlled trial . Participants were recruited from 12 public antiretroviral treatment ( ART ) clinics across five districts in the Free State Province of South Africa . Each of these patients was assigned to one of the following groups : a control group receiving st and ard care , a group receiving additional biweekly PAS or a group receiving PAS and nutritional support . Latent cross-lagged modelling ( Mplus ) was used to analyse the impact of PAS and the family environment on the level of hope in PLWHA . Results The results of the study indicate that neither PAS nor the family environment has a direct effect on the level of hope in PLWHA . Subsequent analysis reveals a positive significant interaction between family functioning and PAS at the second follow-up , indicating that better family functioning increases the positive effect of PAS on the state of hope in PLWHA . Conclusions The interplay between well-functioning families and external PAS generates higher levels of hope , which is an essential dimension in the success of lifelong treatment . This study provides additional insight into the important role played by family dynamics in HIV/AIDS care , and it underscores the need for PAS interventions that are sensitive to the context s in which they are implemented Summary Background The treatment of perinatal depression is a public-health priority because of its high prevalence and association with disability and poor infant development . We integrated a cognitive behaviour therapy-based intervention into the routine work of community-based primary health workers in rural Pakistan and assessed the effect of this intervention on maternal depression and infant outcomes . Methods We r and omly assigned 40 Union Council clusters in rural Rawalpindi , Pakistan , in equal numbers to intervention or control . Married women ( aged 16–45 years ) in their third trimester of pregnancy with perinatal depression were eligible to participate . In the intervention group , primary health workers were trained to deliver the psychological intervention , whereas in the control group untrained health workers made an equal number of visits to the depressed mothers . The primary outcomes were infant weight and height at 6 months and 12 months , and secondary outcome was maternal depression . The interviewers were unaware of what group the participants were assigned to . Analysis was by intention to treat . The study is registered as IS RCT N65316374 . Findings The number of clusters per group was 20 , with 463 mothers in the intervention group and 440 in the control group . At 6 months , 97 ( 23 % ) of 418 and 211 ( 53 % ) of 400 mothers in the intervention and control groups , respectively , met the criteria for major depression ( adjusted odds ratio ( OR ) 0·22 , 95 % CI 0·14 to 0·36 , p<0·0001 ) . These effects were sustained at 12 months ( 111/412 [ 27 % ] vs 226/386 [ 59 % ] , adjusted OR 0·23 , 95 % CI 0·15 to 0·36 , p<0·0001 ) . The differences in weight-for-age and height-for-age Z scores for infants in the two groups were not significant at 6 months ( −0·83 vs −0·86 , p=0·7 and −2·03 vs −2·16 , p=0·3 , respectively ) or 12 months ( −0·64 vs −0·8 , p=0·3 and −1·10 vs −1·36 , p=0·07 , respectively ) . Interpretation This psychological intervention delivered by community-based primary health workers has the potential to be integrated into health systems in re source -poor setting s. Funding Wellcome Trust Background Among people living with HIV ( PLHIV ) on antiretroviral therapy ( ART ) , it is important to determine how quality of life ( QOL ) may be improved and HIV-related stigma can be lessened over time . This study assessed the effect of peer support on QOL and internal stigma during the first year after initiating ART among a cohort of PLHIV in north-eastern Vietnam . Methods A sub- sample study of a r and omised controlled trial was implemented between October 2008 and November 2010 in Quang Ninh , Vietnam . In the intervention group , participants ( n = 119 ) received adherence support from trained peer supporters who visited participants ’ houses biweekly during the first two months , thereafter weekly . In the control group , participants ( n = 109 ) were treated according to st and ard guidelines , including adherence counselling , monthly health check and drug refills . Basic demographics were measured at baseline . QOL and internal stigma were measured using a Vietnamese version of the WHOQOL-HIVBREF and Internal AIDS-related Stigma Scale instruments at baseline and 12 months . T-tests were used to detect the differences between mean values , multilevel linear regressions to determine factors influencing QOL . Results Overall , QOL improved significantly in the intervention group compared to the control group . Among participants initiating ART at clinical stages 3 and 4 , education at high school level or above and having experiences of a family member dying from HIV were also associated with higher reported QOL . Among participants at clinical stage 1 and 2 , there was no significant effect of peer support , whereas having children was associated with an increased QOL . Viral hepatitis was associated with a decreased QOL in both groups . Lower perceived stigma correlated significantly but weakly with improved QOL , however , there was no significant relation to peer support . Conclusion The peer support intervention improved QOL after 12 months among ART patients presenting at clinical stages 3 and 4 at baseline , but it had no impact on QOL among ART patients enrolled at clinical stages 1 and 2 . The intervention did not have an effect on Internal AIDS-related stigma . To improve QOL for PLHIV on ART , measures to support adherence should be context ualized in accordance with individual clinical and social needs OBJECTIVE To evaluate the effectiveness of a culturally adapted , primary care – based nurse – community health worker ( CHW ) team intervention to support diabetes self-management on diabetes control and other biologic measures . RESEARCH DESIGN AND METHODS Two hundred sixty-eight Samoan participants with type 2 diabetes were recruited from a community health center in American Samoa and were r and omly assigned by village clusters to the nurse-CHW team intervention or to a wait-list control group that received usual care . RESULTS Participants had a mean age of 55 years , 62 % were female , mean years of education were 12.5 years , 41 % were employed , and mean HbA1c was 9.8 % at baseline . At 12 months , mean HbA1c was significantly lower among CHW participants , compared with usual care , after adjusting for confounders ( b = −0.53 ; SE = 0.21 ; P = 0.03 ) . The odds of making a clinical ly significant improvement in HbA1c of at least 0.5 % in the CHW group was twice the odds in the usual care group after controlling for confounders ( P = 0.05 ) . There were no significant differences in blood pressure , weight , or waist circumference at 12 months between groups . CONCLUSIONS A culturally adapted nurse-CHW team intervention was able to significantly improve diabetes control in the U.S. Territory of American Samoa . This represents an important translation of an evidence -based model to a high-risk population and a re source -poor setting In the current context of human re source shortages in South Africa , various community support interventions are being implemented to provide long-term psychosocial care to persons living with HIV/AIDS ( PLWHA ) . However , it is important to analyze the unintended social side effects of such interventions in regards to the stigma felt by PLWHA , which might threaten the successful management of life-long treatment . Latent cross-lagged modeling was used to analyze longitudinal data on 294 PLWHA from a r and omized controlled trial ( 1 ) to determine whether peer adherence support ( PAS ) and treatment buddying influence the stigma experienced by PLWHA ; and ( 2 ) to analyze the interrelationships between each support form and stigma . Results indicate that having a treatment buddy decreases felt stigma scores , while receiving PAS increases levels of felt stigma at the second follow up . However , the PAS intervention was also found to have a positive influence on having a treatment buddy at this time . Furthermore , a treatment buddy mitigates the stigmatizing effect of PAS , result ing in a small negative indirect effect on stigma . The study indicates the importance of looking beyond the intended effects of an intervention , with the goal of minimizing any adverse consequences that might threaten the successful long-term management of HIV/AIDS and maximizing the opportunities created by such support OBJECTIVE To evaluate the acceptability , practicality , and short-term efficacy of a health education program to improve disease self-management in patients with symptomatic HIV/AIDS . DESIGN R and omized controlled trial , baseline and 3-month follow-up question naire assessment s. SETTING San Francisco Bay communities . PARTICIPANTS Seventy-one men with symptomatic HIV or AIDS were r and omly assigned to a seven-session group educational intervention ( N=34 ) or a usual-care control group ( N=37 ) . INTERVENTION Interactive health education groups were used to teach wide-ranging disease self-management skills and information : symptom assessment and management , medication use , physical exercise , relaxation , doctor-patient communication , and nutrition . Each group was led by two trained peer-leaders ( one of whom was HIV-positive ) recruited from the community . MAIN OUTCOME MEASURES The primary outcome of interest was symptom status . Secondary outcomes were self-efficacy and health behaviors . Analysis of covariance was used to compare experimental and control group mean outcomes , adjusting for baseline value differences . RESULTS The symptom severity index ( number of symptoms moderate or greater severity ) decreased in the experimental , and increased in the control group ( -0.9 versus + 0.5 ; p < .03 ) . Pain , fatigue , and psychological symptoms were not significantly different between groups . Self-efficacy for controlling symptoms improved in the experimental , and decreased in the control group ( + 4 versus -7 ; p < .02 ) . Changes in stress/relaxation exercises and HIV/AIDS knowledge were not different between groups . A trend was shown toward more frequent physical exercise in the experimental group compared with less in the control group ( + 1.3 versus -0.5 times/week ; p=.06 ) . CONCLUSIONS Health education emphasizing self-management skills for HIV/AIDS patients can be implemented and evaluated and was accepted by patients , peer-leaders , and health care providers . Whether this educational program can lead to prolonged improvement in HIV symptoms and behaviors can be adequately addressed only by a larger trial of longer duration Objective . The authors used data from a larger study to evaluate the long-term effects of a peer advocate intervention on condom and contraceptive use among HIV-infected women and women at high risk for HIV infection . Methods . HIV-infected women in one study and women at high risk for HIV infection in a second study were selected from the Women and Infants Demonstration Project and assigned to a st and ard or an enhanced HIV prevention treatment group . The enhanced intervention included support groups and one-on-one contacts with peer advocates tailored to clients ' needs . The authors interviewed women at baseline and at 6- , 12- and 18-months , and measured changes in consistency of condom and contraceptive use and in self-efficacy and perceived advantages and disadvantages of condom and contraceptive use . Results . Of HIV-infected women , the enhanced group had improved consistency in condom use , increased perceived advantages of condom use , and increased level of self-efficacy compared with the st and ard group . Of women at risk , the enhanced intervention group at six months maintained consistent condom use with a main partner and perceived more benefit of condom use compared with the st and ard group . These differences diminished at 12 months . Conclusions . The enhanced intervention was generally effective in the HIV+ study . In the at-risk study , however , intervention effects were minimal and short-lived . Factors related to the theory , intervention design , and sample characteristics help explain these differences Abstract This study tested an intervention program based on a chronic pain management model for pain . We conducted a trial of a 6-week , peer-led exercise and education intervention on pain in amaXhosa women living with HIV/AIDS . Participants were monitored over 15 months of routine care before r and omization . The control group was provided with educational workbooks , and the experimental group attended the intervention . Pain was reassessed monthly for 4 months . There was no significant reduction in pain during 15 months of routine care and no difference between groups at any of the time points ( d = 0.04 ) . Both groups experienced equivalent pain reduction during the intervention compared with the period of routine care with meaningful reductions in pain at months 3 ( Cohen ’s d = 0.41 ) and 4 ( Cohen ’s d = 0.59 ) . Provision of a workbook and participating in a 6-week peer-led exercise and education intervention are efficacious methods to treat pain in amaXhosa women living with HIV/AIDS OBJECTIVE To determine the efficacy of a peer-led social support intervention involving support groups and telephone contacts compared with st and ard clinical care to enhance antiretroviral medication adherence . DESIGN R and omized controlled trial with follow-up . Participants were 136 HIV-positive indigent mainly African American and Puerto Rican men and women recruited from an outpatient clinic in the Bronx , New York . The 3-month intervention was delivered by other HIV-positive clinic patients trained in addressing barriers to adherence and sensitively providing appraisal , spiritual , emotional , and informational adherence-related social support . MAIN OUTCOME MEASURES Medical chart- abstract ed HIV-1 RNA viral load , antiretroviral adherence according to electronic drug monitoring and participant self-report , and social support and depressive symptomatology . All assessment s conducted at baseline , 3 months , and 6 months . RESULTS Intent-to-treat and as-treated analyses indicated no between-conditions intervention effects on the primary outcome of HIV-1 RNA viral load or any of the secondary outcomes at immediate postintervention or follow-up . Post hoc analyses within the intervention condition indicated greater intervention exposure was associated with higher self-reported adherence , higher social support , and lower depressive symptomatology at follow-up , even after controlling for baseline adherence . CONCLUSION Null findings , consistent with the limited literature on efficacious highly active antiretroviral therapy ( HAART ) adherence interventions , may be due to insufficient exposure to the intervention , its low intensity , or the nature of the sample -a heterogeneous HAART-experienced group of patients with high levels of substance use and multiple other competing stressors . Overall , findings highlight the need for more comprehensive and intensive efforts to battle nonadherence Background : Non-adherence to antiretroviral ( ART ) treatment remains a prevalent problem even among the segment of the U.S. HIV population that is ‘ linked ’ to medical care . Methods : Controlled pilot feasibility study with ART experienced adult patients ( n = 20 ) linked to HIV medical care without suppressed viral load . Patients were r and omized to a peer-led HIV medication adherence intervention named ` Ready ' or a time equivalent ` healthy eating ' control arm . Lay individuals living with HIV were trained to facilitate ` Ready ' . Results : Patients had been prescribed a mean of three prior ART regimens . The group r and omized to ` Ready ' had significantly improved adherence . MEMS and pharmacy refill data correlated with viral load log drop . Higher readiness for healthful behavior change correlated with viral load drop and approached significance . Conclusion : A peer-led medication adherence intervention had a positive impact among adults who had experienced repeated non-adherence to HIV treatment . A larger study is needed to examine intervention dissemination and efficacy Forty-six Chinese patients with symptomatic human immunodeficiency virus ( HIV ) participated in a comparative study assessing the effectiveness of cognitive-behavioral group therapy ( CBT ) and peer support/counseling group therapy ( PSC ) in relation to improving mood and quality of life and decreasing uncertainty in illness as compared to a group receiving routine treatment with no formal psychosocial intervention . The CBT group consisted of 10 subjects , the PSC group of 10 subjects , and the comparison group of 26 subjects . There was a 24 % attrition rate . The intervention groups received 12 weekly sessions of therapy over 3 months . Assessment of mood states was carried out before r and omization ( baseline data ) , immediately postintervention ( 3-month time point ) and followed-up 3 months later ( 6-month time point ) . Assessment of quality of life and uncertainty in illness was carried out before r and omization and at the 6-month follow-up time point . Results indicated that the mood of the participants in the CBT group improved in terms of anger , tension-anxiety , depression , confusion , and overall mood . The quality of life in this group was significantly improved compared to the other two groups , as was uncertainty in illness . In the PSC group a worsening of psychologic functioning was observed immediately postintervention , but this picture dramatically improved at the follow-up assessment with improvements of up to 34 % . Quality of life also improved over time in this group by almost 5 % , but results did not reach statistical significance . This study demonstrated that psychologic interventions could decrease psychologic distress and improve quality of life in symptomatic HIV patients , indicating their use should be incorporated in the management of care of people living with HIV/AIDS Abstract Objective . To test the impact of participation in a peer-based intervention for symptom management for women living with HIV infection on selected outcome measures including , symptom intensity , medication adherence , viral control , and quality of life . Design . R and omized clinical trial . Methods . Participants were recruited using a convenient , consecutive sampling method . Those participants r and omized to the experimental condition attended seven , peer-led sessions over seven weeks . Participants r and omized to the control condition received a copy of HIV Symptom Management Strategies : A Manual for People Living with HIV/AIDS . Participants completed four surveys assessing change over time in the aforementioned outcome variables . Results . Eighty-nine HIV-infected women followed over 14 weeks and there were no differences between the two groups on baseline demographic variables . Mixed-effects regression indicated no significant difference between groups across time in total symptom intensity score and medication adherence . There was a significant difference between groups across time for two of the nine quality of life scales – HIV Mastery ( χ 2=25.08 ; p<0.005 ) and Disclosure Worries ( χ 2=24.67 ; p<0.005 ) . Conclusions . In urban-dwelling women living with HIV/AIDS , results suggest that a peer-based symptom management intervention may not decrease symptom intensity or increase medication adherence . There is positive evidence that suggests that the intervention may increase some important aspects of quality of life . However , further research is warranted to eluci date the effect of peer-based interventions in achieving positive self-management outcomes This r and omized clinical trial ( N = 253 ) evaluated the efficacy of a theory-based intervention design ed to reduce both alcohol use and incidence of unprotected sexual behaviors among HIV-positive men who have sex with men with alcohol use disorders . An integrated , manualized intervention , using both individual counseling and peer group education/support , was compared with a control condition in which participants received re source referrals . The intervention was based on the transtheoretical model 's stages and processes of change , and motivational interviewing was used to enhance client readiness for change . Major findings include treatment effects for reduction in number of drinks per 30-day period , number of heavy drinking days per 30-day period , and number of days on which both heavy drinking and unprotected sex occurred . Practitioners employing this intervention may achieve enhanced client outcomes in reduction of both alcohol use and risky sexual behavior There is a lack of theory-based r and omized controlled trials to examine the effect of antiretroviral adherence in sub-Saharan Africa . We assessed the effectiveness of a lay health worker lead structured group intervention to improve adherence to antiretroviral therapy ( ART ) in a cohort of HIV-infected adults . This two-arm r and omized controlled trial was undertaken at an HIV clinic in a district hospital in South Africa . A total of 152 adult patients on ART and with adherence problems were r and omized 1:1 to one of two conditions , a st and ard adherence intervention package plus a structured three session group intervention or to a st and ard adherence intervention package alone . Self-reported adherence was measured using the Adult AIDS Clinical Trials Group adherence instrument prior to , post intervention and at follow-up . Baseline characteristics were similar for both conditions . At post-intervention , adherence information knowledge increased significantly in the intervention condition in comparison to the st and ard of care , while adherence motivation and skills did not significantly change among the conditions over time . There was a significant improvement in ART adherence and CD4 count and a significant reduction of depression scores over time in both conditions , however , no significant intervention effect between conditions was found . Lay health workers may be a useful adjunct to treatment to enhance the adherence information component of the medication adherence intervention , but knowledge may be necessary but not sufficient to increase adherence in this sample . Psychosocial informational interventions may require more advanced skill training in lay health workers to achieve superior adherence outcomes in comparison st and ard care in this re source -constrained setting |
11,941 | 24,349,435 | Studies relied heavily on service utilisation as a measure of strategy success , which did not always correspond to improved quality . | OBJECTIVES Efforts to scale-up maternal and child health services in lower and middle income countries will fail if services delivered are not of good quality .
Although there is evidence of strategies to increase the quality of health services , less is known about the way these strategies affect health system goals and outcomes .
We conducted a systematic review of the literature to examine this relationship . | Background : The need to provide high quality prenatal care services , which take account of women ’s views and specifically address their need for information , support and communication , has been advocated and group prenatal care , had been suggested as one of the ways to achieve this objective . The purpose of this study was to examine the impact of group versus individual prenatal care on satisfaction and prenatal care use . Methods : This was a cluster-r and omized controlled trial with the health center as the r and omization unit that conducted in 2007 . Satisfaction was measured through a st and ardized question naire , and the Kotelchuck Adequacy of Prenatal Care Utilization Index was used to measure prenatal care utilization . Results : We recruited 678 women ( group prenatal care , ( N= 344 ) and individual prenatal care , ( N=334 ) in the study . Women in group prenatal care model were more satisfied than women in individual prenatal care model in all areas evaluated , including information , communication , co-ordination and quality of care . Group care women were significantly more likely to have adequate prenatal care than individual care women were ( OR=1.35 95 % CI=1.26–1.44 ) . Conclusions : Group prenatal care was associated with a significant improvement in client satisfaction and prenatal care utilization . This model of care has implication s for the planning and provision of prenatal services within public health system , which is moving toward a better quality health care , and increasing use of services OBJECTIVES To estimate the impact of the Integrated Management of Childhood Illness ( IMCI ) strategy on early-childhood mortality , we evaluated a malaria-control project in Benin that implemented IMCI and promoted insecticide-treated nets ( ITNs ) . METHODS We conducted a before- and -after intervention study that included a nonr and omized comparison group . We used the preceding birth technique to measure early-childhood mortality ( risk of dying before age 30 months ) , and we used health facility surveys and household surveys to measure process indicators . RESULTS Most process indicators improved in the area covered by the intervention . Notably , because ITNs were also promoted in the comparison area children 's ITN use increased by about 20 percentage points in both areas . Regarding early-childhood mortality , the trend from baseline ( 1999 - 2001 ) to follow-up ( 2002 - 2004 ) for the intervention area ( 13.0 % decrease ; P < .001 ) was 14.1 % ( P < .001 ) lower than was the trend for the comparison area ( 1.3 % increase ; P = .46 ) . CONCLUSIONS Mortality decreased in the intervention area after IMCI and ITN promotion . ITN use increased similarly in both study areas , so the mortality impact of ITNs in the 2 areas might have canceled each other out . Thus , the mortality reduction could have been primarily attributable to IMCI 's effect on health care quality and care-seeking BACKGROUND Evidence about the best methods with which to accelerate progress towards achieving the Millennium Development Goals is urgently needed . We assessed the effect of performance-based payment of health-care providers ( payment for performance ; P4P ) on use and quality of child and maternal care services in health-care facilities in Rw and a. METHODS 166 facilities were r and omly assigned at the district level either to begin P4P funding between June , 2006 , and October , 2006 ( intervention group ; n=80 ) , or to continue with the traditional input-based funding until 23 months after study baseline ( control group ; n=86 ) . R and omisation was done by coin toss . We surveyed facilities and 2158 households at baseline and after 23 months . The main outcome measures were prenatal care visits and institutional deliveries , quality of prenatal care , and child preventive care visits and immunisation . We isolated the incentive effect from the re source effect by increasing comparison facilities ' input-based budgets by the average P4P payments made to the treatment facilities . We estimated a multivariate regression specification of the difference-in-difference model in which an individual 's outcome is regressed against a dummy variable , indicating whether the facility received P4P that year , a facility-fixed effect , a year indicator , and a series of individual and household characteristics . FINDINGS Our model estimated that facilities in the intervention group had a 23 % increase in the number of institutional deliveries and increases in the number of preventive care visits by children aged 23 months or younger ( 56 % ) and aged between 24 months and 59 months ( 132 % ) . No improvements were seen in the number of women completing four prenatal care visits or of children receiving full immunisation schedules . We also estimate an increase of 0·157 st and ard deviations ( 95 % CI 0·026 - 0·289 ) in prenatal quality as measured by compliance with Rw and an prenatal care clinical practice guidelines . INTERPRETATION The P4P scheme in Rw and a had the greatest effect on those services that had the highest payment rates and needed the least effort from the service provider . P4P financial performance incentives can improve both the use and quality of maternal and child health services , and could be a useful intervention to accelerate progress towards Millennium Development Goals for maternal and child health . FUNDING World Bank 's Bank-Netherl and s Partnership Program and Spanish Impact Evaluation Fund , the British Economic and Social Research Council , Government of Rw and a , and Global Development Network OBJECTIVE To compare the maternal outcome , in terms of postpartum infection , of deliveries conducted by trained traditional birth attendants ( TBAs ) with those conducted by untrained birth attendants . METHODS The study took place in a rural area of Bangladesh where a local NGO ( BRAC ) had previously undertaken TBA training . Demographic surveillance in the study site allowed the systematic identification of pregnant women . Pregnant women were recruited continuously over a period of 18 months . Data on the delivery circumstances were collected shortly after delivery while data on postpartum morbidity were collected prospect ively at 2 and 6 weeks . All women with complete records who had delivered at home with a non-formal birth attendant ( 800 ) were included in the analysis . The intervention investigated was TBA training in hygienic delivery comprising the ' three cleans ' ( h and -washing with soap , clean cord care , clean surface ) . The key outcome measure was maternal postpartum genital tract infection diagnosed by a symptom complex of any two out of three symptoms : foul discharge , fever , lower abdominal pain . RESULTS Trained TBAs were significantly more likely to practice hygienic delivery than untrained TBAs ( 45.0 vs. 19.3 % , p < 0.0001 ) . However , no significant difference in levels of postpartum infection was found when deliveries by trained TBAs and untrained TBAs were compared . The practice of hygienic delivery itself also had no significant effect on postpartum infection . Logistic regression models confirmed that TBA training and hygienic delivery had no independent effect on postpartum outcome . Other factors , such as pre-existing infection , long labour and insertion of h and s into the vagina were found to be highly significant . CONCLUSIONS Trained TBAs are more likely to practice hygienic delivery than those that are untrained . However , hygienic delivery practice s do not prevent postpartum infection in this community . Training TBAs to wash their h and s is not an effective strategy to prevent maternal postpartum infection . More rigorous evaluation is needed , not only of TBA training programmes as a whole , but also of the effectiveness of the individual components of the training OBJECTIVE To determine the effects of hospital quality assurance interventions on compliance with clinical st and ards , availability of essential drugs , client satisfaction , and utilization . DESIGN Quasi-experimental , prospect i ve study with four intervention hospitals and four control hospitals . All eight facilities were purposively selected and of comparable complexity . SETTING Ministry of Health secondary care facilities in Ecuador . INTERVENTIONS Facility-based quality improvement teams , job clarification , st and ards communication , refresher training , strengthening hospital pharmacy committees , monthly monitoring of compliance indicators , and formation of users ' committees . MEASURES Compliance with input and process st and ards , utilization of services , and patient satisfaction were measured monthly in both groups through review of clinical and administrative records , exit interviews , and patient satisfaction surveys . RESULTS After 12 months , the quality assurance interventions produced rapid increases in compliance with clinical st and ards in the intervention hospitals as compared with the control group . These improvements appeared as early as 2 months after the onset of the interventions . No differences were found between intervention and control groups in terms of trends in utilization patterns or client satisfaction . CONCLUSION Quality assurance interventions made a difference in technical quality of care . Patient satisfaction and utilization do not appear to be directly associated with short-term improvements in compliance with clinical st and ards . Quality improvement interventions may require longer periods and a specific aim at clients ' needs to demonstrate effects on utilization and satisfaction outcome variables Prenatal and delivery care are critical both for maternal and newborn health . Using the Demographic and Health Surveys ( DHS ) data for thirty-two low-income countries across Asia , sub-Saharan Africa and Latin America , and employing a two-level r and om-intercept model , this paper empirically assesses the influence of prenatal attendance and a wide array of observed individual- , household- and community-level characteristics on a woman 's decision to give birth at a health facility or at home . The results show that prenatal attendance does appreciably influence the use of facility delivery in all three geographical regions , with women having four visits being 7.3 times more likely than those with no prenatal care to deliver at a health facility . These variations are more pronounced for Sub-Saharan Africa . The influence of the number of prenatal visits , maternal age and education , parity level , and economic status of the birthing women on the place of delivery is found to vary across the three geographical regions . The results also indicate that obstetrics care is geographically and economically more accessible to urban and rural women from the non-poor households than those from the poor households . The strong influence of number of visits , household wealth , education and regional poverty on the site of delivery setting suggests that policies aim ed at increasing the use of obstetric care programs should be linked with the objectives of social development programs such as poverty reduction , enhancing the status of women , and increasing primary and secondary school enrollment rate among girls BACKGROUND We report the preliminary findings from a continuing cluster r and omised evaluation of the Integrated Management of Childhood Illness ( IMCI ) strategy in Bangladesh . METHODS 20 first-level outpatient facilities in the Matlab sub-district and their catchment areas were r and omised to either IMCI or st and ard care . Surveys were done in households and in health facilities at baseline and were repeated about 2 years after implementation . Data on use of health facilities were recorded . IMCI implementation included health worker training , health systems support , and community level activities guided by formative research . FINDINGS 94 % of health workers in the intervention facilities were trained in IMCI . Health systems supports were generally available , but implementation of the community activities was slow . The mean index of correct treatment for sick children was 54 in IMCI facilities compared with 9 in comparison facilities ( range 0 - 100 ) . Use of the IMCI facilities increased from 0.6 visits per child per year at baseline to 1.9 visits per child per year about 21 months after IMCI introduction . 19 % of sick children in the IMCI area were taken to a health worker compared with 9 % in the non-IMCI area . INTERPRETATION 2 years into the assessment , the results show improvements in the quality of care in health facilities , increases in use of facilities , and gains in the proportion of sick children taken to an appropriate health care provider . These findings are being used to strengthen child health care nationwide . They suggest that low levels of use of health facilities could be improved by investing in quality of care and health systems support BACKGROUND WHO and UNICEF launched the Integrated Management of Childhood Illness ( IMCI ) strategy in the mid-1990s to reduce deaths from diarrhoea , pneumonia , malaria , measles , and malnutrition in children younger than 5 years . We assessed the effect of IMCI on health and nutrition of children younger than 5 years in Bangladesh . METHODS In this cluster r and omised trial , 20 first-level government health facilities in the Matlab subdistrict of Bangladesh and their catchment areas ( total population about 350 000 ) were paired and r and omly assigned to either IMCI ( intervention ; ten clusters ) or usual services ( comparison ; ten clusters ) . All three components of IMCI-health-worker training , health-systems improvements , and family and community activities-were implemented beginning in February , 2002 . Assessment included household and health facility surveys tracking intermediate outputs and outcomes , and nutrition and mortality changes in intervention and comparison areas . Primary endpoint was mortality in children aged between 7 days and 59 months . Analysis was by intention to treat . This study is registered , number IS RCT N52793850 . FINDINGS The yearly rate of mortality reduction in children younger than 5 years ( excluding deaths in first week of life ) was similar in IMCI and comparison areas ( 8.6%vs 7.8 % ) . In the last 2 years of the study , the mortality rate was 13.4 % lower in IMCI than in comparison areas ( 95 % CI -14.2 to 34.3 ) , corresponding to 4.2 fewer deaths per 1000 livebirths ( 95 % CI -4.1 to 12.4 ; p=0.30 ) . Implementation of IMCI led to improved health-worker skills , health-system support , and family and community practice s , translating into increased care-seeking for illnesses . In IMCI areas , more children younger than 6 months were exclusively breastfed ( 76%vs 65 % , difference of differences 10.1 % , 95 % CI 2.65 - 17.62 ) , and prevalence of stunting in children aged 24 - 59 months decreased more rapidly ( difference of differences -7.33 , 95 % CI -13.83 to -0.83 ) than in comparison areas . INTERPRETATION IMCI was associated with positive changes in all input , output , and outcome indicators , including increased exclusive breastfeeding and decreased stunting . However , IMCI implementation had no effect on mortality within the timeframe of the assessment . FUNDING Bill & Melinda Gates Foundation , WHO 's Department of Child and Adolescent Health and Development , and US Agency for International Development |
11,942 | 12,137,631 | The two most rigorous studies showed limited evidence of an effect on prevalence .
In the US COMMIT study there was no differential decline in prevalence between intervention and control communities , and there was no significant difference in the quit rates of heavier smokers who were the target intervention group .
In the Australian CART study there was a significantly greater quit rate for men but not women .
REVIEW ER 'S CONCLUSIONS The failure of the largest and best conducted studies to detect an effect on prevalence of smoking is disappointing . | BACKGROUND Since smoking behaviour is determined by social context , the best way to reduce the prevalence of smoking may be to use community-wide programmes which use multiple channels to provide reinforcement , support and norms for not smoking .
OBJECTIVES To assess the effectiveness of community interventions for reducing the prevalence of smoking . | OBJECTIVES This paper presents a prospect i ve examination of sociodemographic , psychosocial , and physiologic characteristics associated with positive change in cardiovascular disease risk factors during a 6-year multiple risk factor intervention study . METHODS Data are presented on 221 women and 190 men ( aged 25 through 74 years ) who participated in four cohort surveys ( 1979 through 1985 ) . A signal detection model was used to identify baseline variables that best divide the sample into subgroups on the basis of the probability of positive change in a composite risk factor score . RESULTS Sixty-nine percent of the respondents showed a positive change in risk factor score during the intervention . The subgroup with the highest proportion of positive changers ( 83 % ) was composed of older adults ( > 55 years ) with the highest perceived risk , highest health media use , and highest blood pressure and cholesterol levels . The subgroup with the lowest proportion of positive changers ( 42 % ) was the least educated , was the most likely to be Hispanic , and had the lowest health knowledge and self-efficacy scores . CONCLUSIONS The differing composition of subgroups who respond or do not respond to community cardiovascular disease interventions illustrates the need to develop specific interventions that target different age , socioeconomic , and cultural subgroups A comprehensive community based programme to control cardiovascular diseases was started in North Karelia , Finl and , in 1972 . Reductions in smoking , serum cholesterol concentrations , and blood pressure were among the central intermediate objectives . The effect of the programme during the 10 year period 1972 - 82 was evaluated by examining independent r and om population sample s at the outset ( 1972 ) and five ( 1977 ) and 10 ( 1982 ) years later both in the programme and in a matched reference area . Over 10 000 subjects were studied in 1972 and 1977 ( participation rate about 90 % ) and roughly 8000 subjects in 1982 ( participation rate about 80 % ) . Analyses were conducted of the estimated effect of the programme on the risk factor population means by comparing the baseline and five year and 10 year follow up results in the age range 30 - 59 years . The effect of the programme ( net reduction in North Karelia ) at 10 years among the middle aged male population was estimated to be a 28 % reduction in smoking ( p less than 0.001 ) , a 3 % reduction in mean serum cholesterol concentration ( p less than 0.001 ) , a 3 % fall in mean systolic blood pressure ( p less than 0.001 ) , and a 1 % fall in mean diastolic blood pressure ( p less than 0.05 ) . Among the female population the reductions were respectively , 14 % ( NS ) , 1 % ( NS ) , 5 % ( p less than 0.001 ) , and 2 % ( p less than 0.05 ) . During the first five years of the project ( 1972 - 7 ) the programme effectively reduced the population mean values of the major coronary risk factors . At 10 years the effects had persisted for serum cholesterol concentrations and blood pressure and were increased for smoking The National Research Program 1 A on " Primary Prevention of cardiovascular disease in Switzerl and ' was design ed to determine whether community health education can reduce cardiovascular risk factors in the population . Two communities ( 12,000 inhabitants each ) in the French speaking and two ( 16,000 inhabitants each ) in the German speaking part of the country were selected either for intervention or comparison . Following baseline screening in 1977 ( stratified r and om sample s ) and the community intervention program ( 1978 - 1980 ) , a final assessment on the initial participants was performed at the end of 1980 . Amongst the regular smokers , 26,2 % stopped during this period in the intervention communities whereas 18,1 % did so in the reference cities . 4,7 % of non-smokers began to smoke during the same period in the intervention communities whereas 7,8 % did so in the reference cities . Plasma thiocyanate measurement suggested reliable answers on smoking status . These results suggest that community health education may be effective in preventing harmful health consequence of smoking Abstract Objectives : To estimate the extent to which changes in the main coronary risk factors ( serum cholesterol concentration , blood pressure , and smoking ) explain the decline in mortality from ischaemic heart disease and to evaluate the relative importance of change in each of these risk factors . Design : Predicted changes in ischaemic heart disease mortality were calculated by a ligistic regression model using the risk factor levels assessed by cross sectional population surveys , in 1972 , 1977 , 1982 , 1987 , and 1992 . These predicted changes were compared with observed changes in mortality statistics . Setting : North Karelia and Kuopio provinces , Finl and . Subjects : 14 257 men and 14 786 women aged 30–59 r and omly selected from the national population register . Main outcome measures : Levels of the risk factors and predicted and observed changes in mortality from ischaemic heart disease . Results — The observed changes in the risk factors in the population from 1972 to 1992 predicted a decline in mortality from ischaemic heart disease of 44 % ( 95 % confidence interval 37 % to 50 % ) in men and 49 % ( 37 % to 59 % ) in women . The observed decline was 55 % ( 51 % to 58 % ) and 68 % ( 61 to 74 ) respectively . Conclusion : An assessment of the data on the risk factors for ischaemic heart disease and mortality suggests that most of the decline in mortality from ischaemic heart disease can be explained by changes in the three main coronary risk factors BACKGROUND This article provides a descriptive overview of the implementation process of the Heart , Body , and Soul program . The program objective was to test strategies to reduce the prevalence of cigarette smoking among urban African Americans in East Baltimore . METHOD This study constitutes a prospect i ve r and omized trial among inner-city African Americans design ed to improve quit rates among church attenders . A r and om-digit-dialing survey was conducted to establish baseline levels of self-reported cigarette smoking , examine attendant attitudes , and determine the presence of known cardiovascular risk factors among community residents of the catchment area . A similar survey was conducted among churchgoers to establish a baseline . Twenty-two churches were recruited and r and omly assigned to either intensive or minimal ( self-help ) intervention strategies . Baseline health screenings were held in all participating churches . Innovative culturally specific smoking cessation strategies mediated through lay volunteers from participating churches were implemented in the intensive intervention churches . RESULTS Pastors of all churches were directly involved in all aspects of the planning and implementation process . A total of 29 volunteer lay smoking-cessation specialists were trained and successfully implemented the intensive interventions in churches . An additional 272 church members were trained to conduct their church 's health screenings . CONCLUSION The essential component of this successful implementation process were building trust and acceptance and providing the technical support to encourage smoking-cessation strategies . This description of the project is presented to assist others involved in church-based trials in urban African American communities The Belgian Heart Disease Prevention Project is a controlled , multifactorial prevention trial involving 19,390 males aged 40–59 years employed by 30 Belgian industries . These industries were paired and r and omized into a control or intervention unit . In each intervention factory , the subjects from the two highest deciles of a coronary risk-score distribution curve were given individual advice twice a year . A health education campaign was also organized in each intervention factory . In the control group , 10 % of r and omly chosen subjects had the same baseline examination as the whole of the intervention group . After 2 years , high-risk subjects and r and om sample s of the control and intervention group were compared regarding the coronary risk profile by means of a multiple logistic function ( MLF ) . In the intervention high-risk group , the MLF showed a decrease of 20 % , and in the control group there was an increment of 12.5 % ( p < 0.001 ) . Comparing the r and om sample s an increment of 25 % was found in the control group vs a drop of 2.26 in the intervention group ( p < 0.001 ) . The coronary risk profile can be altered in a middle-aged male working population through mass media health education supplemented by face-to-face counseling in high-risk subjects Purpose . To present an evaluation of a 5-year , community-based , chronic disease prevention project managed by a state health department to determine whether the department could replicate similar previous projects that had received more funding and other re sources . Design . The evaluation used a matched comparison design and a review of archive and interview data . Setting . Florence , South Carolina ( population : 56,240 ) . Subjects . A r and om sample of 1642 persons in Florence ( and 1551 in the comparison ) who responded to a risk factor question naire and underwent a physical assessment ; 70 . 7 % of baseline subjects participated in the postintervention . Forty key persons were interviewed concerning project effectiveness . Interventions by Project . Walk-a-thons , a speakers ' bureau , media messages , restaurant food labeling , and cooking seminars . More than 31,000 participants were involved in 585 activities . Measures . Question naires focused on hypertension , obesity , high cholesterol , smoking , and exercise . Physical assessment s determined lipid , lipoprotein , apolipoprotein , and blood pressure levels . Analysis of covariance was used for baseline and postintervention comparisons . Content analysis was used on archive and interview data . Results . The project had a slightly favorable intervention effect on cholesterol and smoking , but failed to have an effect on other risk factors for cardiovascular disease . The project influenced community awareness , enlisted influential community members , and fostered linkages among local health services . Conclusions . Health departments can be instrumental in community risk reduction programming ; however , they may not replicate projects having greater re sources Few studies have prospect ively examined the characteristics associated with worksite adoption of tobacco-control initiatives . Data were collected as part of the Community Intervention Trial ( COMMIT ) for Smoking Cessation , which conducted interventions in 11 communities . This smoking cessation intervention was based on community organization principles and delivered through multiple community channels , including worksites , health care providers , the media , and cessation re sources . This article reports results from telephone interviews of intervention community worksites having 50 or more employees , conducted at baseline and the end of the intervention period . Among worksites that responded to both baseline and final surveys , 83 % had not adopted a smoke-free policy at baseline , and 61 % did not offer any cessation aid or quitting re sources at baseline . By the final survey , 34 % of those with no smoking ban at baseline had become smoke-free , and 36 % of those offering no cessation assistance at baseline were offering cessation re sources at the follow-up . The prevalence of policy adoption was higher among worksites employing more female employees and offering other health-promotion activities ; manufacturing businesses were significantly less likely than businesses other than service and wholesale/retail businesses to adopt policies . Adoption of cessation programs was significantly more likely among worksites employing 100 to 249 workers , compared with those employing 50 to 99 workers ; those predominantly employing men ; those offering other types of health-promotion activities ; and those with a higher rate of turnover . These results provide important information about the characteristics of worksites likely to engage in tobacco-control efforts . Health educators and others may choose to target those worksites most ready for adoption of tobacco control policies and programs , as indicated by these findings Since 1985 a small-scale community-based cardiovascular disease ( CVD ) preventive programme has been in operation in an inl and municipality , Norsjö , in Northern Sweden . The aim of this study was to assess the development of the relationship between social position and CVD risk factors in repeated cross-sectional surveys ( 1985 - 1990 ) among all men and women aged 30 , 40 , 50 and 60 years in the study area , using an age-stratified r and om sample from the Northern Sweden MONICA Study of 1986 and 1990 as reference population . These multiple cross-sectional surveys comprised a self-administered question naire and a health examination . Of the study population 95 % ( n = 1499 ) and 80 % of those in the reference area ( n = 3208 ) participated . Subjects were classified with regard to demographic , structural and social characteristics in relation to CVD risk factors and self-reported health status . Time trends in classical risk factor occurrence were assessed in terms of age- and sex- adjusted odds ratios using Mantel-Haenszel procedures . When simultaneously adjusting for several potential confounders we used a logistic regression analysis . Initially , more than half of the study population , both males and females , had and elevated ( > or = 6.5 mmol/l ) serum cholesterol level . After adjustments had been made for age and social factors it was found that the relative risk of hypercholesterolaemia dropped substantially and significantly among both sexes during the 6 years of CVD intervention in the study area . However , the probability of being a smoker was significantly reduced only in highly educated groups . Among other risk factors no single statistically significant change over time could be found . In the reference area there were no changes over time for the selected CVD risk factors . People in the study area had a less favourable perception of their health than those in the reference area . Social differences were found when perceived good health was measured , especially in variables indicating emotional and social support . When sex , age and social factors had been accounted for there was not clear change over the years in perceived good health INTRODUCTION Our objectives were ( 1 ) to examine the relationship between women 's intention of stopping smoking in the next month and a broad range of mediating variables and ( 2 ) to assess the implication s of these relationships for intervention components of a comprehensive community-wide health education program to help women quit smoking . METHODS In preparation for the community-wide program to help women quit smoking , baseline data were collected through a r and om digit dialing telephone survey of 6,324 adult women , 18 - 64 years of age . RESULTS At baseline , smoking prevalence , defined as smoking an average of one or more cigarettes per day , was 25.8 % and showed clear relationships with age and income , but most strikingly with education , indicating the need for programs for women of childbearing age with low incomes and fewer years of schooling . Among female smokers , knowledge of the health effects of smoking ; motivations toward quitting ; confidence in controlling weight , or h and ling stress , anger or boredom ; number of strategies named to cope when upset of angry ; number of community smoking cessation re sources named ; perceptions of support for quitting ; and perceptions of norms concerning women smoking varied significantly with level of intention to quit smoking in the next month . CONCLUSIONS These relationships provided support for the broad range of health behavior change strategies proposed for this community-based program to help women quit smoking OBJECTIVES Whether community-wide education changed cardiovascular risk factors and disease risk in Pawtucket , RI , relative to a comparison community was assessed . METHODS R and om- sample , cross-sectional surveys were done of people aged 18 through 64 years at baseline , during , and after education . Baseline cohorts were reexamined . Pawtucket citizens of all ages participated in multilevel education , screening , and counseling programs . RESULTS The downward trend in smoking was slightly greater in the comparison city . Small , insignificant differences favored Pawtucket in blood cholesterol and blood pressure . In the cross-sectional surveys , body mass index increased significantly in the comparison community ; a similar change was not seen in cohort surveys . Projected cardiovascular disease rates were significantly ( 16 % ) less in Pawtucket during the education program . This difference lessened to 8 % posteducation . CONCLUSIONS The hypothesis that projected cardiovascular disease risk can be altered by community-based education gains limited support from these data . Achieving cardiovascular risk reduction at the community level was feasible , but maintaining statistically significant differences between cities was not . Accelerating risk factor changes will likely require a sustained community effort with reinforcement from state , regional , and national policies and programs The study describes changes in cardiovascular risk factors during 10 years of a community intervention program conducted in a rural area in Central Italy . Two areas were involved , one for treatment and one for reference . In 1983 - 84 , 739 men and 859 women in the treatment area and 942 men and 1045 women in the control area , aged 20 - 69 years , were screened ; total and HDL cholesterol , systolic and diastolic blood pressure , fasting blood glucose , smoking habit , weight and height were measured . Between 1983 and 1993 several intervention activities based on community medicine were carried out in the treatment area . They were based on interaction with the local socio-sanitary institutions and school system in order to influence individual persons , small groups and entire community . Major effort was addressed to mass health education , nutrition education , antismoking-propag and a and detection and treatment of hypertension , diabetes and hyperlipidemia BACKGROUND AND PURPOSE Stroke has been the second leading cause of death in large cities in China since the 1980s . Meanwhile , the prevalences of hypertension and smoking have steadily increased over the last 2 decades . Therefore , a community-based intervention trial was initiated in 7 Chinese cities in 1987 . The overall goal of the study was to evaluate the effectiveness of an intervention aim ed at reducing multiple risk factors for stroke . The primary study objective was to reduce the incidence of stroke by 25 % over 3.5 years of intervention . METHODS In May 1987 in each of 7 the cities , 2 geographically separated communities with a registered population of about 10 000 each were selected as either intervention or control communities . In each community , a cohort containing about 2700 subjects ( > /=35 years old ) free of stroke was sample d , and a survey was administered to obtain baseline data and screen the eligible subjects for intervention . In each city , a program of treatment for hypertension , heart disease , and diabetes was instituted in the intervention cohort ( n approximately 2700 ) and health education was provided to the full intervention community ( n approximately 10 000 ) . A follow-up survey was conducted in 1990 . Comparisons of intervention and control cohorts in each city were pooled to yield a single summary . RESULTS A total of 18 786 subjects were recruited to the intervention cohort and 18 876 to the control cohort from 7 cities . After 3.5 years , 174 new stroke cases had occurred in the intervention cohort and 253 in the control cohort . The 3.5-year cumulative incidence of total stroke was significantly lower in the intervention cohort than the control cohort ( 0.93 % versus 1.34 % ; RR=0.69 ; 95 % CI , 0.57 to 0.84 ) . The incidence rates of nonfatal and fatal stroke , as well as ischemic and hemorrhagic stroke , were significantly lower in the intervention cohort than the control cohort . The prevalence of hypertension increased by 4.3 % in the intervention cohort and by 7.8 % in the control cohort . The average systolic and diastolic blood pressures increased more in the control cohort than in the intervention cohort . Among hypertensive individuals in the intervention cohort , awareness of hypertension increased by 6.7 % and the percentage of hypertensives who regularly took antihypertensive medication increased 13.2 % . All of these indices became worse in the control cohort . The prevalence of heart diseases and diabetes increased significantly in the both cohorts ( P<0.01 ) . The prevalence of consumption of alcohol increased slightly , and that of smoking remained constant in both cohorts . CONCLUSIONS A community-based intervention for stroke reduction is feasible and effective in the cities of China . The reduction , due to the intervention , in the incidence of stroke in the intervention cohort was statistically significant after 3.5 years of intervention . The sharp reduction in the incidence of stroke may be due to the interventions having blunted the expected increase in hypertension that accompanies aging as well as to better and earlier treatment of hypertension , particularly borderline hypertension . Applied health education to all the residents of the community may have prevented some normotensive individuals from developing hypertension and improved overall health awareness and knowledge The relationship between social class and seven important risk factors for coronary heart disease has been evaluated utilising data from the German Cardiovascular Prevention Study baseline survey . Of German residents aged 25 to 69 years , 16,430 were r and omly selected from both the six intervention regions and the Federal Republic of Germany to undergo the screening procedures between 1984 and 1986 . Among males the prevalence of cigarette smoking and lack of physical activity was associated with social class . For females , overweight and physical activity demonstrated a strong social gradient . No relationship existed between social class and hypercholesterolaemia . The prevalence of Type A behaviour was significantly higher for the upper social classes . The number of CHD risk factors per study subject increased with decreasing social class . Predicted cardiovascular mortality was clearly higher for the lower social class among males in general and for females younger than 60 years . These findings point to the need for risk factor intervention strategies focusing more on the lower social classes in order to achieve more adequate prevention of coronary heart disease BACKGROUND After 4 years a coronary heart disease risk factor intervention programme produced equally large and significantly reduced risk profiles in two intervention towns compared with a control town . Intervention effects through community participation were assessed after cessation of the active intervention programme . The impact of secular trends was assessed in the control town and in two previously unstudied towns . METHODS Cross-sectional surveys were done in a r and om sample of 1620 participants aged 15 - 64 years in the three original towns 12 years after the initial quasi-experimental study . Two years later 327 subjects , aged 35 - 44 years , were studied in the original control town and in two non-intervention towns . Risk factor knowledge , smoking and medical histories were determined by question naire . Blood pressure , anthropometry and blood lipids were recorded . Data were compared across towns , and with previous surveys . RESULTS At 12 years the low intensity intervention town maintained a significantly better risk factor profile than the control town , while the high intensity intervention town now matched the control town . No differences in risk factor profiles were found between the control town and the two new towns . Deaths from coronary heart disease and strokes showed a downward trend in the study area . CONCLUSIONS Outcome suggests large ongoing secular trends during the study could have overtaken the intervention effects in the high intensity town , but not in the low intensity intervention town , which showed an advantage over the control town . These results support the effectiveness of media-based , long term health promotion strategies to reduce cardiovascular disease risk profiles STUDY OBJECTIVE --This paper describes the objectives , design , and methods of evaluation of the impact of the coeur en santé St-Henri programme , as well as selected results from the evaluation to date . It discusses the possible effects of study design choices made to maintain the impact evaluation within budget . DESIGN --The impact of the programme is evaluated in a community trial which compares the prevalence of cardiovascular disease behavioural risk factors before and after programme implementation in the intervention and a matched comparison community , in both longitudinal cohort and independent sample surveys . In addition , repeated independent sample surveys are conducted in the intervention community to monitor awareness of and participation in the programme . PARTICIPANTS --The baseline sample for both the longitudinal cohort and independent sample surveys included 849 subjects from the intervention community ( 79.3 % of 1071 eligible subjects--8.0 % could not be contacted and 12.6 % refused ) and 825 subjects from the comparison community ( 77.8 % of 1066 eligible subjects--6.6 % could not be contacted and 15.6 % refused ) . The two surveys on awareness and participation conducted to date , included 461 ( 71.0 % of 649 eligible subjects ) and 387 ( 67.9 % of 570 eligible subjects ) subjects respectively from the intervention community . MEASUREMENTS --Baseline data for the longitudinal cohort and independent sample surveys on behavioural risk factor outcomes including use of tobacco , physical activity behaviour , high fat diet , and behaviours related to blood pressure and cholesterol control were collected in 35 minute telephone interviews in both the intervention and comparison communities . Data on awareness of and participation in the programme were collected in 10 minute interviews in the intervention community only in two independent sample surveys conducted seven and 22 months respectively after the baseline survey . RESULTS --With the exception of smoking , the intervention and comparison communities were similar at baseline with regard to the prevalence of behavioural risk factors studied . Awareness of the coeur en santé programme increased from 64.1 % in January 1993 to 72.9 % 15 months later . Participation in the programme increased from 21.3 % to 33.7 % . CONCLUSIONS --This paper presents background information on the evaluation of the impact of the coeur en santé programme , as a reference for future publications The Minnesota Heart Health Program ( MHHP ) is a research and demonstration project of population -wide primary prevention of cardiovascular disease . Study goals are to achieve reductions in cardiovascular disease risk factors and morbidity and mortality in three education communities compared with three reference communities . The program in the first of the three intervention communities , Mankato , has been operating for 3 of the planned 5 years . Early objectives of the program have been achieved based on data obtained from population -based r and om sample s surveyed in education and comparison communities . After 2 years of participation , Mankato was significantly more exposed to activities promoting cardiovascular disease prevention . In this town of 38,000 inhabitants , 190 community leaders were directly involved as program volunteers , 14,103 residents ( over 60 % of adults ) attended a screening education center , 2,094 attended MHHP health education classes , 42 of 65 physicians and 728 other health professionals participated in continuing education programs offered by MHHP , and distribution of printed media averaged 12.2 pieces per household . These combined educational strategies have result ed in widespread awareness of MHHP and participation by the majority of the Mankato adult population in its education activities A prospect i ve follow-up study was carried out to investigate the impact of a health education program and other factors related to patient 's social background and severity of heart attack on stopping smoking after heart attack . The study consisted of male patients below the age of 65 years , who had suffered a heart attack between April 1 and September 30 , 1977 , living in two provinces of eastern Finl and , North Karelia and Kuopio . Of the patients who smoked before the heart attack , 102 responded to both the 6- and the 12-month follow-up postal survey . Of these 102 patients , 25 stopped smoking within 12 months after the heart attack , while 77 continued to smoke . Continuing smoking was most strongly associated with working and unemployment before heart attack , maximum serum aspartate aminotransferase ( GOT ) concentration and subjective recovery after the heart attack . The quitting rate among men in the program area was 1.2-fold ( p=0.012 ) compared with the reference area men , after making allowance for the seven most confounding factors in the multivariate analysis . This observation indicates that either the community-based primary program or the secondary prevention program in North Karelia succeeded in dissuading patients from smoking after heart attack The objective of this study was to evaluate the effects of the ATS-Sardegna Campaign on lifestyle and cardiovascular disease ( CVD ) risk factors in the Sardinian population . The Campaign was a community-based public health action programme funded by the Sardinian Government with a view to prevent CVD and promote healthy behaviour . It was also part of the Targeted Project FAT.MA . of the Italian National Research Council ( CNR ) , with the main purpose of evaluating the effects of this public health initiative after a five- year intervention . The evaluation was effected with three parallel procedures : individual interviews with 1486 r and omly chosen people ; assessment of eating patterns through a food-frequency question naire ; measurement of the mean levels of the major CVD risk factors in 1729 r and omly chosen subjects ( 1044 in the calendar year 1992 , and 685 in 1995 , two and five years , respectively , after the beginning of the Campaign ) . Overall , we recorded a favourable trend in eating habits in both sexes ; a significant decrease in LDL-cholesterol in males , and in systolic and diastolic blood pressure in both sexes ; a non- significant decrease in prevalence of smokers among males and increase among females . The ATS-Sardegna Campaign was the first CVD prevention programme in Italy to have attained reduction in the risk profile of an entire region at the lowest ever borne cost BACKGROUND This study quantifies re sources used to conduct 26 community-wide quit-smoking contests , the percentage of smokers that participated in these contests , and the statistical associations between re source inputs and participation percentages . METHODS Data collected from the 11 COMMIT intervention communities ( adult population range 47,490 - 185,913 ) included number of contest participants , contest procedures , and re source inputs . Stepwise regression was used to find the most meaningful association(s ) of independent variables with contest participation percentage . RESULTS Contest participation percentages ranged from 0.27 to 3.11 % of smokers ( mean = 1.26 % ) . Total cost ( COMMIT and community-contributed re sources and dollar expenditures ) to conduct a contest averaged $ 24,857 ( range $ 5,751-$74,556 ) , or $ 78.57 per contest participant . Expenditures in various specific re source categories varied greatly . Total expenditures per smoker in the community ( excluding expenditures for prizes ) was the independent variable most highly correlated with contest participation percentage , accounting for 63 % of the total variability in participation percentages . CONCLUSIONS The percentage of smoker participation in community-wide stop-smoking contests appears primarily to be a function of total re source expenditures , regardless of the specific types of re sources funded . Stop-smoking contests are judged to be quite cost effective . Study strengths and weaknesses are discussed BACKGROUND The objective of this study was to evaluate the reach of mass mailings of heart health education print material s in a low-income , urban community . Material s included a monthly newsletter and a self-help behavior change kit , both distributed to all 12,789 households in the study community . METHODS Recall , use , and self-reported impact of the material s were measured in a cross-sectional survey of a r and om sample of 345 adults conducted 2 weeks after distribution of the kit and 18 months after delivery of the first newsletter . RESULTS Over one-third of the subjects ( 38.6 % ) recalled the newsletter and 27.9 % had read one or more newsletters ; 21.7 % recalled the kit and 10.8 % had read it . Few subjects had read both material s. Female gender and older age were independent correlates of having seen and read the newsletters . Older age , being widowed/separated/divorced , and infrequent physical activity were correlates of having seen and read the kit . CONCLUSIONS Although the newsletter and kit formats might appeal to different segments of the population , mass mailings of heart health education print material s in a low-income urban community can reach large numbers of individuals . The cost effectiveness of repeated mailings of short , simple newsletters might be higher than a single mailing of a more complex behavior change kit The success of the Community Intervention Trial for Smoking Cessation ( COMMIT ) in changing smoking attitudes is examined by testing two primary hypotheses : ( 1 ) the priority of smoking as a public health problem increased more in the intervention communities than in the comparison communities , and ( 2 ) norms and values that support non-smoking increased more in the intervention than in the comparison communities . One community within each of 11 matched pairs was r and omly assigned to receive a 4-year ( 1989 - 92 ) community-based smoking control intervention . Community attitudes towards smoking were measured primarily by cross-sectional surveys in 1989 ( n = 9875 ) and 1993 ( n = 14117 ) but a cohort ( n = 5450 ) also provided attitude information . The main trial effect was on heavy smokers in the intervention communities who showed significantly more change in their beliefs about smoking as a public health problem . Despite the absence of an intervention-comparison difference , the magnitude of change in community-wide norms and values was related to the level of smoking control activities . In the cohort , light-to-moderate smokers in the intervention communities came to have stronger beliefs about smoking as a serious public health problem . COMMIT 's impact on the beliefs of heavy smokers about the seriousness of smoking as a public health problem has important public health implication OBJECTIVES This study evaluated a community organization approach that emphasized involvement of audiences in program planning and implementation in promoting nonsmoking among African American residents of low-income neighborhoods . METHODS The quasi-experimental design involved a 24-month intervention in 3 low-income , predominantly African American neighborhoods in St. Louis . Intervention neighborhoods were compared with comparable , untreated neighborhoods in Kansas City . RESULTS The program was successful in engaging audience members in its governance and in instigating numerous and diverse neighborhood activities to promote nonsmoking . The prevalence of smoking declined from 34 % to 27 % in program neighborhoods but only from 34 % to 33 % in comparison neighborhoods . This difference was apparent within all demographically defined sub sample s , indicating that observed changes were consistent and not attributable to confounding by demographic characteristics . CONCLUSIONS A community organization approach emphasizing local authority for program decisions and involvement of informal networks may have an appreciable impact on smoking among residents of low-income , African American neighborhoods The Belgian Heart Disease Prevention Project was a controlled , r and omized multifactorial intervention trial in middle-aged men which lasted 6 years . Significant net differences between intervention and control groups were observed in change in risk profile , in total mortality and in CHD incidence . The net difference in risk profile change was greatest at two years , intermediate at four years and minimal at six years . Total and cause-specific mortality rates were systematic ally followed from the 6th to the 10th year . Follow-up at 10 years was 99.3 % complete . The differences between intervention and control groups in total , coronary and cardiovascular mortality reduced from the 6th to the 10th year . The results suggest that changes in risk profile are rapidly followed by changes in cardiovascular mortality , but this applies in both directions . Thus risk reduction should be maintained in order to achieve a long-lasting preventive effect Abstract Objective : To assess the net 5 year effects of intervention of a community based demonstration project , the Heartbeat Wales programme , on modifiable behavioural risks for prevention of cardiovascular disease . Design and setting : Quasi-experimental design comparing results from two independent cross sectional population surveys conducted in 1985 and 1990 in Wales and a matched reference area in north east Engl and . Subjects : R and om , stratified sample s of people aged 18 - 64 years ( 18 538 in 1985 and 13 045 in 1990 ) in Wales and in north east Engl and ( 1483 and 4534 , respectively ) . Intervention : A coordinated range of activities for heart health promotion in Wales entailing public education campaigns along with supportive policy and infrastructure change . In the reference area no additional community heart health promotion was planned , though considerable activity did take place , “ contaminating ” the reference area . Main outcome measures : Fifteen self reported behavioural indicators relating to dietary choice , smoking , frequency of exercise , and weight . Results : Positive changes ( for health ) in behavioural outcomes were observed among the population in Wales , including a reduction in reported smoking prevalence and improvements in dietary choice . There was no net intervention effect for the programme over and above observed change in the reference area . Conclusions : No definite conclusions can be drawn concerning the efficacy of the programme in terms of behavioural outcomes . With hindsight , the difficulties of evaluating such a complex multifaceted intervention were underestimated . Further debate on the most appropriate methods for assessing the effectiveness of community based health promotion programmes is called for . Key messages Heartbeat Wales was set up in 1985 as a community based programme to demonstrate risk reduction for cardiovascular disease Important changes were observed in modifiable risks for cardiovascular disease in Wales between 1985 and 1990 There was an unexpectedly rapid uptake of heart health promotion activity in the reference area No net intervention effects were found for the programme over and above changes in the reference area Improvements in methods of evaluation for community based health promotion programmes are OBJECTIVES COMMIT ( Community Intervention Trial for Smoking Cessation ) investigated whether a community-level multichannel intervention would decrease the prevalence of adult cigarette smoking and increase quitting , with heavy smokers ( > or = 25 cigarettes per day ) receiving the highest priority . METHODS One community within each of 11 matched community pairs ( 10 in the United States , 1 in Canada ) was r and omly assigned to intervention . Baseline ( 1988 ) and final ( 1993 ) telephone surveys sample d households to determine prevalence of smoking behavior . RESULTS Among the target population aged 25 to 64 years , there was no intervention effect on heavy smoking prevalence , which decreased by 2.9 percentage points in both intervention and comparison communities . Overall smoking prevalence decreased by 3.5 in intervention communities vs 3.2 in comparison communities , a difference not statistically significant , while the mean quit ratios were 0.198 versus 0.185 , respectively , a difference of 0.013 ( 90 % test-based confidence interval = -0.003 , 0.028 ) . CONCLUSIONS Results are consistent with the cohort analysis reported separately , although the more powerful cohort design showed a statistically significant intervention effect upon light-to-moderate smokers . This community-based intervention did not have a significant impact on smoking prevalence beyond the favorable secular trends . In future efforts , additional strategies should be incorporated and rigorously evaluated A community cardiovascular disease ( CVD ) prevention programme was undertaken in 1989 in a Danish County ( Vejle ) . A r and om sample of 5192 adults were asked to complete a mailed question naire on knowledge , attitudes , and behaviour in relation to CVD risk factors . The response rate was 56 % . The question naire produced baseline data for programme planning and measuring the success of on-going interventions . Smoking , overweight , and unhealthy food habits were the most prevalent CVD risk factors . A CVD risk score was calculated from the data on smoking , food habits , exercise , stress , overweight , self-reported presence of hypertension , diabetes , and gender . A high score was commoner in men , in the least educated , in groups who judged their own risk as high , and in groups with negative health beliefs . The level of knowledge about CVD risk factors was high in general . Low knowledge was commonest in the youngest age group , in the least educated , in unskilled workers , and in groups with negative health beliefs . As social position and personality factors seem to play an important role in actions people may take in prevention of CVD , they should be considered in the planning of the health promotion activities in Vejle BACKGROUND As an important aspect of the COMMIT trial , worksite smoking-control consultations and supports were provided to employers in 11 diverse , moderate-sized communities . After a 4-year intervention period ( 1989 - 1992 ) , impacts on worksite policies , support re sources for smokers , and employee perceptions were assessed in these communities and in 11 matched Comparison communities . METHODS Data from two surveys are reported here . In each of the 22 COMMIT communities , a sample of worksites within each of four size strata were surveyed to determine worksite policies , activities , and re sources regarding smoking . Data from employees were obtained from independent community-wide surveys of community residents . RESULTS Overall , 44 % of the worksites surveyed reported having smoke-free policies , with no differences between Intervention and Comparison communities . Thirty-seven percent of Intervention community work-sites reported offering smoking cessation re sources or assistance for employees during the period of the study , compared to 31 % of Comparison community worksites ( P = 0.04 ) . Employees in Intervention communities , relative to those in Comparison communities , reported greater awareness of stop-smoking re sources , but equivalent increases in worksite smoking bans . CONCLUSION Although the level of worksite smoking-cessation activities was higher in Intervention than in Comparison communities , there remains a substantial need to increase the level of such activities and to integrate such activities with restrictive smoking policies To determine recent changes in physicians ' practice s for cardiovascular disease risk reduction , a r and omly selected sample of practicing primary care physicians in the upper Midwest was interviewed by telephone in 1987 and again in 1989 ( response rates , greater than 90 % ; N = 241 ) . The reported mean cutoff levels for labeling a total serum cholesterol level as abnormal dropped from 5.84 to 5.43 mmol/L ( 226 to 210 mg/dL ) and for initiating medication , from 7.34 to 6.54 mmol/L ( 284 to 253 mg/dL ) . The proportion of physicians using diuretics as preferred step 1 antihypertensive agents dropped from 60 % to 32 % . Preferences became evenly divided among diuretics , angiotensin-converting enzyme inhibitors , and beta-blockers . Advice about physical exercise changed little , but consensus among practicing physicians was high . Substantial improvements were found in smoking cessation activities . Practicing physicians are proving to be responsive to new scientific evidence and education in the prevention of cardiovascular disease BACKGROUND Until 1990 , smoking cessation interventions in the Netherl and s were limited . The utility and effectiveness of community-based smoking cessation programs have not been examined . METHODS In a treatment city ( Den Bosch ) a multicomponent community-based smoking cessation intervention was implemented in which local mass media and general practitioners draw smokers ' attention to a local quit line . Telephone counselors advised applicants on their choice between self-help and group treatment and optional telephone counseling . Another Dutch city ( Apeldoorn ) served as a control . Population sample s of smokers ( n = 547 and n = 546 ) were interviewed three times at approximately 7-month intervals . Self-help manual requesters ( n = 84 ) and group participants ( n = 83 ) were interviewed before and 6 months after treatment . RESULTS Treatment modalities were successful ; 13 % of self-help manual requesters and 22 % of group participants were abstinent after 6 months . On a population level the intervention result ed in significantly higher recall of self-help manual and group program in the treatment city . A modest intervention effect on prevalence of abstinence was found at the community level . CONCLUSIONS Treatment modalities were effective within their participants , but the intervention effectiveness on a community level was limited . No significant difference was found between quit rates after 14 months ( 7 % in treatment city and 9 % in control city ) . Several system failures could be identified . However , probably the intervention effect was seriously confounded by two national governmental publicity campaigns introducing and reinforcing a m and atory smoking ban and a series of national campaigns initiated by the united Dutch tobacco producers opposing the ban OBJECTIVE : To compare tobacco control practice s of physicians and their staff in Intervention communities with those in Comparison communities of the Community Intervention Trial for Smoking Cessation ( COMMIT ) . DESIGN : COMMIT was a r and omised trial testing community-based intervention for smoking cessation carried out over four years . SETTING : Eleven matched pairs of communities assigned r and omly to Intervention and Comparison conditions . PARTICIPANTS AND INTERVENTIONS : Physicians in the Intervention communities participated in continuing medical education ( CME ) . Training for office staff focused on tobacco control and office intervention " systems " . OUTCOME MEASURES : Smoking control attitudes and practice s reported by primary -care physicians in the 22 communities , smoking policies , and practice s of 30 r and omly selected medical offices in each community , and patient reports of physician intervention activities . RESULTS : Response rates to the physicians ' mail survey were 45 % and 42 % in Intervention and Comparison communities , respectively . Telephone interviews of office staff had response rates of 84 % in both conditions . Physicians in Intervention communities were more likely to attend training than those in Comparison communities ( 53 % and 26 % , respectively ( P<0.0005 ) ) . In both conditions , training attendees perceived themselves as being better prepared to counsel smokers than non-attendees ( P < or = 0.01 ) and reported more activity in smoking intervention . Intervention communities carried out more office-based tobacco control activities ( P = 0.002 ) . Smokers in Intervention communities were more likely to report receiving reading material about smoking from their physicians ( P = 0.026 ) . No other differences in physician intervention activities were reported by smokers between the Intervention and Comparison communities . CONCLUSIONS : The COMMIT intervention had a significant effect on some reported physician behaviours , office practice s , and policies . However , most physicians still did not use state-of-the-art smoking intervention practice s with their patients and there was little , or no , difference between patient reports of intervention activities of physicians in the Intervention and Comparison communities . Better systems and incentives are needed to attract physicians and their staff to CME and to encourage them to follow through on what they learn . The recently released Agency for Health Care Policy and Research clinical practice guideline for smoking cessation and other st and ards and policies outline these systems and offer suggestions for incentives to facilitate adoption of these practice s by physicians OBJECTIVES The Minnesota Heart Health Program was a research and demonstration project design ed to reduce risk factors for heart disease in whole communities . This paper describes smoking-specific interventions and outcomes . METHODS Three pairs of matched communities were included in the study . After baseline surveys , one community in each pair received a 5-year education program , while both cross-sectional and cohort surveys continued in all sites . Adult education programs for smoking cessation included Quit and Win contests , classes , self-help material s , telephone support , and home correspondence programs . RESULTS Encouraging short-term results were obtained for several adult education programs . Overall long-term outcomes were mixed , with evidence of an intervention effect only for women in cross-sectional survey data . Unexpectedly strong secular declines in smoking prevalence were observed in comparison communities . CONCLUSIONS The findings suggest that community education may be unlikely to exceed dramatic secular reductions in smoking prevalence . The success of several key interventions and the incorporation of Minnesota Heart Health Program interventions by education communities are encouraging , however Objectives : To describe a rural , hospital-based public health intervention program and to evaluate its effectiveness in cardiovascular disease ( CVD ) risk reduction using cross-sectional studies and a panel study . Methods : A rural population of 158,000 located in New York state comprised the intervention population . A similar but separate population was used for reference . A multifaceted , multimedia 5-year program provided health promotion and education initiatives to increase physical activity , decrease smoking , improve nutrition , and identify hypercholesterolemia and hypertension . To evaluate the effectiveness of the intervention , surveys were conducted at baseline in 1989 ( cross-sectional ) and at follow-up in 1994- 95 ( cross-sectional and panel ) . For cross-sectional studies , a r and om sample of adults was obtained using a three-stage cluster design . Self-reported and objective risk factor measurements were obtained . Comparison of pre- to post- changes in intervention versus reference population s was done using 2 × 2r and omized block ANOVA , 2 × 2 mixed ANOVA , and extension of the McNemar test . Results : Smoking prevalence declined ( from 27.9 % to 17.6 % ) in the intervention population . Significant adverse trends were observed for high-density lipoprotein cholesterol and triglycerides . Systolic blood pressure was reduced while diastolic blood pressure remained stable . Body mass index increased significantly in both population s. Conclusions : This rural , 5-year CVD community intervention program decreased smoking . The risk reduction may be attributable to tailoring of a multifaceted approach ( multiple risk factors , multiple messages , and multiple population subgroups ) to a target rural population . The study period was too short to identify changes in CVD morbidity and mortality This exploratory study examined the acceptability and efficacy of a videotape modeling smoking cessation as an adjunct to smoking cessation advice delivered during prenatal care . In a r and omized controlled trial involving 60 women , we compared the delivery of brief smoking cessation advice and a tipsheet to the same advice and tipsheet plus provision of the videotape . Outcomes included opinions about content and acceptability of the videotape , and smoking behavior change during pregnancy . The most highly endorsed features of the videotape were seeing other women quitting smoking ( 77 % ) , dealing with stress and bad feelings ( 69 % ) , talking about what to do with urges to smoke ( 69 % ) , and discussing ways to get support from families and friends ( 54 % ) . The reported quit rate in the last month of pregnancy , vali date d by exhaled carbon monoxide levels , and including women lost to follow-up as smokers , was 19.2 % in the intervention group and 0 % in the comparison group ( p = .02 ) . This study suggests that the use of videotapes modeling smoking behavior change may increase the effectiveness of the assistance in quitting smoking that is generally available in obstetric and family practice s or public maternity clinics OBJECTIVES The primary hypothesis of COMMIT ( Community Intervention Trial for Smoking Cessation ) was that a community-level , multi-channel , 4-year intervention would increase quit rates among cigarette smokers , with heavy smokers ( > or = 25 cigarettes per day ) of priority . METHODS One community within each of 11 matched community pairs ( 10 in the United States , 1 in Canada ) was r and omly assigned to intervention . Endpoint cohorts totaling 10,019 heavy smokers and 10,328 light-to-moderate smokers were followed by telephone . RESULTS The mean heavy smoker quit rate ( i.e. , the fraction of cohort members who had achieved and maintained cessation at the end of the trial ) was 0.180 for intervention communities versus 0.187 for comparison communities , a nonsignificant difference ( one-sided P = .68 by permutation test ; 90 % test-based confidence interval ( CI ) for the difference = -0.031 , 0.019 ) . For light-to-moderate smokers , corresponding quit rates were 0.306 and 0.275 ; this difference was significant ( P = .004 ; 90 % CI = 0.014 , 0.047 ) . Smokers in intervention communities had greater perceived exposure to smoking control activities , which correlated with outcome only for light-to-moderate smokers . CONCLUSIONS The impact of this community-based intervention on light-to-moderate smokers , although modest , has public health importance . This intervention did not increase quit rates of heavy smokers ; reaching them may require new clinical programs and policy changes We examined changes in five indicators of blood cholesterol awareness in two comparable biracial communities in South Carolina . One community received three years of cholesterol education and intervention activities implemented by a state health department and the other served as a comparison . Cross-sectional , interviewer-administered , r and om digit-dialed telephone surveys of 11,070 adults 18 years and older were conducted in 1987 , 1988 , 1989 , and 1991 . Changes in community levels of knowledge , preventive behavior , risk awareness , and treatment were assessed and compared between the two communities with analysis of covariance techniques that adjusted for age , race , and sex . Significant increases in knowledge , behavior , and risk awareness were observed for most groups defined by race , sex , or age in both communities . Significant net intervention increases between 1987 and 1991 were seen for knowledge of good cholesterol level ( + 16.4 % , P < .001 ) ; behavioral action of ever having blood cholesterol checked ( + 18.6 % , P < .001 ) ; and knowledge of personal level of blood cholesterol ( + 16.0 % , P < .01 ) . These results suggest that a community-wide blood cholesterol screening and education program can be effective in increasing blood cholesterol knowledge , risk awareness , and preventive behavior , thus serving as part of a public health strategy to lower and treat high blood cholesterol levels in a community OBJECTIVE To obtain a baseline measure of tobacco control activities carried out by physicians and of tobacco control policies and practice s in physician offices . DESIGN All primary care physicians in 11 communities were asked through a mail survey about their tobacco control practice s. Thirty offices in each community were r and omly selected and interviewed by telephone to determine office policies and practice s. SETTING Both surveys assessed primary care setting s in the 11 intervention communities . RESULTS The physicians ' survey ( response rate , 48 % ) indicated that physicians report intervention with smokers more than 70 % of the time , but the interventions rarely include key behavioral elements necessary for smoking modification . Physicians who received formal training in smoking cessation reported that they believed themselves to be more prepared and that they spent more time counseling patients than physicians who were not trained . The office survey ( response rate , 83.2 % ) indicated that smoke-free policies are in place in most clinics and offices and that many offices provide printed material s on smoking cessation . However , few offices had staff to coordinate smoking cessation activities . These surveys will be repeated following the intervention phase of the Community Intervention Trial for Smoking Cessation to assess changes in counseling practice s and office policies . CONCLUSION There is a positive relationship between attending training and intervening with more cessation activities . Physicians perceive themselves as prepared to help smokers , but few are providing more than advice to stop smoking BACKGROUND This article describes one outcome of a r and omized controlled trial of community action for cancer prevention . The aims of this article were to ( a ) explore the effectiveness of a community action program in decreasing community smoking rates in rural Australian towns and ( b ) describe the relationship between adult smoking quit and uptake rates and demographic variables . METHODS In 1992 , 20 towns were selected for r and omization . Community action involved formation of community committees and utilization of access point networks to initiate and maintain intervention strategies . At post-test , outcomes were proportion of " quitters " from a cohort of self-described smokers , proportion of " uptakers " from a cohort of self-described nonsmokers , and " net effect . " RESULTS Differences in quit rate , uptake rate , and net effect for intervention compared to control condition favored the intervention in all cases , although mainly nonsignificant . Significantly more male smokers quit in intervention towns than in control towns [ 7.0 % ( 95 % CI : 0.6 , 13.5 ) ] . CONCLUSIONS Given that CART utilized and improved upon strategies argued as effective in the literature , the limited success of the project in reducing adult smoking , considered in combination with COMMIT findings , suggests the need for further innovation in the field The National Research Program 1A on Primary Prevention of Cardiovascular Disease in Switzerl and was design ed to determine whether community health education can reduce cardiovascular risk factors in whole population groups . Two towns ( 12,000 inhabitants each ) in the French-speaking and two ( 16,000 inhabitants each ) in the German-speaking part of the country were selected for either intervention or comparison . Following baseline screening in 1977 ( stratified r and om sample s ) and the community intervention program ( 1978 - 1980 ) , a final assessment on the initial participants was made at the end of 1980 . In intervention towns , 26.2 % of the regular smokers quit during this period compared with 18.1 % in the reference towns . In addition , a significant net increase in the proportion of hypertensive patients under effective control was observed . A reduction in cholesterol levels was noted in both the intervention and the reference towns , with no difference between them . However , cholesterol levels in a subgroup of women participating in program activities as compared with those not participating were significantly reduced . The program , with extensive involvement of a diversity of community groups , has enjoyed continued support , even after the end of the research experience , thus demonstrating the viability and acceptability of community-oriented preventive action OBJECTIVE To evaluate the effects of community intervention on risk factors of cerebrovascular disease . METHODS With cluster sampling , 2,586 and 2,723 women and men aged 35 to 74 were selected r and omly as intervention cohort and control cohort , respectively , from about 300 thous and community population in Beijing , Shanghai and Changsha , during 1997 to 2000 . Their blood pressure , levels of blood lipid , body mass index ( BMI ) were measured and status of smoking and alcohol consumption were surveyed as indices of evaluation . Health education for smoking quit , alcohol consumption restriction and reinforced treatment for diabetic and hypertensive patients were implemented in the intervention communities . And , 2,544 and 2,533 persons in the two cohorts responded three years after intervention , and then all the indices mentioned above were measure again for them . RESULTS Average reduction in systolic blood pressure by 3.21 mm Hg and serum level of total cholesterol by 0.58 mmol/L was achieved in intervention cohort after intervention , but with 0.48 mmol/L increase in triglyceride . Average blood levels of both high density lipoprotein-cholesterol ( HDL-C ) and glucose increased in the two cohorts after intervention , but with 0.30 mmol/L net increase of blood glucose in control cohort . There was no significant difference in average increase of HDL-C between the two cohorts . BMI increased by 0.56 in control cohort , and no significant change in intervention cohort . Proportion of smoking decreased by 5.4 % in men and 2.4 % in women of intervention cohort , and no change in control cohort . CONCLUSION Level of risk factors for cerebrovascular disease reduced significantly with community intervention The Belgian Heart Disease Prevention Project is a controlled multifactorial prevention trial involving 19,390 men aged 40–59 years , employed by 30 Belgian industries . These industries were paired and r and omized into a control or intervention unit . In each intervention factory , the subjects from the two highest deciles of a coronary risk score distribution curve were given semiannual individual advice . Furthermore , a health education campaign was organized in each intervention factory . In the control group , 10 % of r and omly chosen subjects had the same baseline examination as the whole of the intervention group . After 2 years , high-risk subjects as well as r and om sample s of the control and intervention group were compared regarding smoking behavior . Among the high-risk subjects of the intervention group , 18.7 % stopped smoking against 12.2 % in the control group ( P ⩽ 0.05 ) . The r and om sample s of both the intervention and control groups showed an almost identical quitting rate ( 12.5 and 12.6 % ) . The drop in the number of cigarettes smoked daily by smokers at 2 years was significantly different when comparing the high-risk subjects of the intervention and control groups : 18.8 and 9.1 % ( P ⩽ 0.01 ) . In a stepwise discriminant function analysis three baseline factors discriminated significantly between high-risk ex-smokers and smokers of the intervention group at 2 years : number of cigarettes smoked daily at entry , earlier attempts to stop smoking , and geographic location in Belgium . For the control group , two baseline factors discriminated between ex-smokers and smokers at 2 years : study level and earlier attempts to stop smoking Objective : To carry out a community-based research approach to determine the most effective educational interventions to reduce smoking among African-American smokers . The intervention included preparation of the community , planning and developing a model of change , and developing a community-based intervention . The study population consisted of 2,544 r and omly selected adult African-American smokers residing in four sites in the northeastern and southeastern parts of the United States . The research design provided a comparison of active intervention sites with passive control sites as well as low income and moderate income areas . Major Outcome Measures : Point prevalence of non-smoking at the time of interview ; Period prevalence of non-smoking at the time of interview ; Period prevalence of quit attempts in the prior six months ; Number of smoke-free days in the prior six months ; Number of cigarettes smoked daily at the time of interview . Results : Based upon a survey eighteen months after baseline data was collected , all four measures of cigarette smoking behavior showed a strong statistically significant reduction of personal smoking behavior among those receiving active interventions versus the passive group . On the basis of process variable analysis , direct contact with the project staff in the prior six months was significantly higher in the active intervention areas . There was only a small non-significant increase in personal smoking behavior in moderate income groups as opposed to low income groups . Conclusion : An analysis of process variables strongly suggests that , within this African-American Community , “ h and s on ” or “ face to face ” approaches along with mass media , mailings , and other less personal approaches were more effective in reducing personal smoking behavior than media , mailings , and other impersonal approaches alone addressed to large audiences OBJECTIVE Racial differences in secular changes in cardiovascular disease risk factor knowledge and behaviors were assessed among adults with low levels of education throughout a community-wide cardiovascular disease prevention program . METHODS Four independent cross-sectional telephone surveys were conducted with the r and om-digit-dialing technique in 1987 , 1988 , 1989 , and 1991 in a biracial South Carolina community . Community-wide cardiovascular disease intervention programs were initiated in 1988 and continued through 1990 . Changes in the prevalence of cardiovascular risk factor knowledge , dietary fat intake , leisure-time physical activity , smoking , and cholesterol screening behavior were compared between African-American and white respondents in a population subset with less than 12 years of education using analysis of covariance regression techniques . RESULTS Mean intake of high fat foods was lower in 1991 than in 1987 among both white and African-American respondents ; the trend for lower mean intake began in 1989 among African-American adults . Prevalence of the correct exercise knowledge was higher in 1988 than in 1987 for both groups , but this trend was maintained only among white respondents . However , prevalence of leisure-time physical activity did not change significantly between 1987 and 1991 . Prevalence of cholesterol level knowledge and screening behavior increased over time among both groups ; however , greater increasing trends between 1987 and 1991 were observed among white adults . CONCLUSIONS Favorable secular changes in fat intake , exercise knowledge , cholesterol level knowledge , and cholesterol screening behavior were observed among both race groups during a time period that coincided with community-wide intervention efforts and messages . Greater changes in most of these behaviors and knowledge were observed among white adults suggesting that health behavior messages may not have reached all segments of this community To determine whether community health education can reduce the risk of cardiovascular disease , a field experiment was conducted in three northern California towns . In two of these communities there were extensive mass-media campaigns over a 2-year period , and in one of these , face-to-face counselling was also provided for a small subset of high-risk people . The third community served as a control . People from each community were interviewed and examined before the campaigns began and one and two years afterwards to assess knowledge and behaviour related to cardiovascular disease ( e.g. , diet and smoking ) and also to measure physiological indicators of risk ( e.g. , blood-pressure , relative weight , and plasma-cholesterol ) . In the control community the risk of cardiovascular disease increased over the two years but in the treatment communities there was a substantial and sustained decrease in risk . In the community in which there was some face-to-face counselling the initial improvement was greater and health education was more successful in reducing cigarette smoking , but at the end of the second year the decrease in risk was similar in both treatment communities . These results strongly suggest that mass-media education campaigns directed at entire communities may be very effective in reducing the risk of cardiovascular disease Abstract The Stanford Three-Community Study was an experiment in which media programs were used in two California towns to reduce the principal risk factors of cardiovascular disease , while a third town was followed as a control . Cohorts were selected in each community and surveyed annually for 4 yr . A statistical analysis using ANOVA and ANOCOVA revealed that there was significant variation between the three communities in baseline risk factor patterns and suggested that the communities , not individuals , be used as the experimental units in testing for reductions . To this end we have employed a regression analysis which fits a linear trend to the mean values of the four annual surveys in each community . This approach is contrasted with st and ard methodology which ignores the nonr and om allocation of people to communities and , therefore , produces exaggerated significance levels The German Cardiovascular Prevention Study is a multicentre community-based intervention study with the primary goal of reducing cardiovascular mortality by primary prevention measures . The intervention strategy comprises improving people 's life styles as well as health promotion so as to modify cardiovascular risk factors ( hypercholesterolemia , cigarette smoking , arterial hypertension , physical inactivity and over-weight ) . Design elements of the German Cardiovascular Prevention Study , now in its fifth year , were adopted from well known community intervention studies , including monitoring of mortality and morbidity , health examination surveys to assess distribution of cardiovascular risk factors , health attitudes and health behaviour in the community and use of formative and process evaluation to monitor the effects of intervention policies in the community . To identify risk factor profiles a cluster analysis was carried out from survey data . Four clusters were identified : a ) people with none or few risk factors ; b ) those with high prevalence of smoking ; c ) those with high prevalence of hypercholesterolemia and hypertension ; d ) high risk factor exposure individuals . The clusters are different along social indicators like age , sex and social status . Process evaluation data show that special strategies like interventive blood pressure screenings reached a relatively high proportion of people from lower socioeconomic status . But they also indicate that there is a long way to go from publicity of intervention programs to lasting changes in behaviour OBJECTIVES This intervention was implemented to reduce the prevalence of cigarette smoking among women . METHODS We used community organization approaches to create coalitions and task forces to develop and implement a multicomponent intervention in 2 counties in Vermont and New Hampshire , with a special focus on providing support to help women quit smoking . Evaluation was by pre-intervention and post-intervention r and om-digit-dialed telephone surveys in the intervention counties and the 2 matched comparison counties . RESULTS In the intervention counties , compared with the comparison counties , the odds of a woman being a smoker after 4 years of program activities were 0.88 ( 95 % confidence interval = 0.78 , 1.00 ) ( P = .02 , 1-tailed ) ; women smokers ' perceptions of community norms about women smoking were significantly more negative ( P = .002 , 1-tailed ) ; and the quit rate in the past 5 years was significantly greater ( 25.4 % vs 21.4 % ; P = .02 , 1-tailed ) . Quit rates were significantly higher in the intervention counties among younger women ( aged 18 to 44 years ) ; among women with household annual incomes of $ 25,000 or less ; and among heavier smokers ( those who smoked 25 or more cigarettes daily ) . CONCLUSIONS In these rural counties , community participation in planning and implementing interventions was accompanied by favorable changes in women 's smoking behavior BACKGROUND Given the relatively low spontaneous quit rates and poor treatment outcomes among African American smokers , this study was design ed to evaluate the effects of a multimodal culturally relevant intervention for smoking behavior change compared with a self-help strategy among urban African Americans in Baltimore churches . METHOD This r and omized controlled trial in urban African American churches used the stages of change model to compare the effectiveness of two interventions in moving smokers along a continuum toward smoking cessation . Twenty-two churches were r and omly assigned to either an intensive culturally specific intervention or a minimal self-help intervention . Smokers were interviewed at baseline church health fairs and at a 1-year follow-up . Self-reported quitters at follow-up were evaluated using saliva cotinine and exhaled carbon monoxide levels ( CO ) . Stages of change were measured by applying a st and ardized stages of change instrument to individual interview response sequences . Analysis compared the two intervention groups at 1-year follow-up with baseline stages . Outcomes included quit rates and positive progress along the stages of change . RESULTS Multiple logistic regression results , controlling for intrachurch correlation and demographic and baseline smoking characteristics , showed that the multimodal cultural intervention group was more likely to make positive progress along the stages of change continuum , compared with self-help intervention group ( OR = 1.68 ; P = 0.04 ) . Church denomination and intervention status interacted in the multivariate model ; Baptists in the intensive intervention were three times ( OR = 3.23 ; P = 0.010 ) more likely to make progress than all the other denomination groups . CONCLUSION The multimodal culturally relevant intervention was more likely than a self-help intervention to positively influence smoking behavior . This is the first community-based intervention study to report progress along the stages of change as a process-oriented measure of success . It is notable that a spiritually based model focusing on environmental sanctions was more likely than a st and ard church disseminated self-help intervention to positively influence smoking behavior in an urban African American population Abstract Objective : To assess effects of price , income , and health publicity on cigarette smoking by age , sex , and socioeconomic group . Design : Econometric multiple regression analysis of data on cigarette smoking from the British general household survey . Subjects : R and om sample of adult population in Britain interviewed for biennial general household surveys 1972 - 90 . Main outcome measures - Changes in cigarette consumption and prevalence of smoking . Results : Price elasticities of dem and for cigarettes ( percentage change in cigarette consumption for a 1 % change in price ) were significant at -0.5 ( 95 % confidence interval -0.8 to -0.1 ) for men and -0.6 ( -0.9 to -0.3 ) for women , were highest in socioeconomic group V ( -1.0 for men and -0.9 for women ) , and lowest ( not significantly different from zero ) in socioeconomic groups I and II . The gradient in price elasticities by socioeconomic group was significant for men ( F=5.6 , P=0.02 ) and for women ( F=6.1 , P=0.02 ) . Price was a significant factor in cigarette consumption by age for women in every age group and for men aged 25 - 34 . Cigarette consumption by young men aged 16 - 34 increased with income . There was a significant decrease in smoking over time by women in socioeconomic groups I and II and by men in all age and social groups except socioeconomic group V attributable to health publicity . Price significantly affected smoking prevalence in socioeconomic group V ( -0.6 for men and -0.5 for women ) and for all women ( -0.2 ) . Conclusions : Men and women in lower socioeconomic groups are more responsive than are those in higher socioeconomic groups to changes in the price of cigarettes and less to health publicity . Women of all ages , including teenagers , appear to have been less responsive to health publicity than have men but more responsive to price . Response to health publicity decreased linearly with age . Real price increases in cigarettes could narrow differences between socioeconomic groups in smoking and the related inequalities in health , but specific measures would be necessary to ameliorate effects on the most deprived families that may include members who continue to smoke . The use of a policy to steadily increase cigarette tax is likely to help achieve the government 's targets for smoking and smoking related diseases OBJECTIVES To determine if R and omized Controlled Trial ( RCT ) methodology was used appropriately in community health , we : ( 1 ) determined the proportion of non-r and omized studies that should have been RCTs , and ( 2 ) assessed the quality of the RCTs . METHODS The 1992 issues of six community health journals were manually search ed . Intervention studies were analyzed . Studies that did not use r and omization were analyzed for feasibility and practicality of RCT methods ; RCTs were analyzed for quality using a checklist . RCTs were compared with community health RCTs from The New Engl and Journal of Medicine . The proportion of studies meeting each criterion was determined . RESULTS Fourteen percent of 603 studies were interventions and 4 % were RCTs . Of those not using r and omization , 42 % should have . Mean RCT scores were significantly lower for the community health journals than for The New Engl and Journal of Medicine . Many criteria important to quality scored poorly . CONCLUSIONS RCTs are underused and lack method ologic rigor in community health . Conclusions regarding the effectiveness of interventions are therefore suspect Community trials remain the only design appropriate for the evaluation of lifestyle interventions that can not be allocated to individuals . The Minnesota Heart Health Program , conducted in Minnesota and the Dakotas between 1980 and 1993 , is one of the largest community trials ever conducted in the United States . That study suggests several lessons that should guide future community trials . Planners should 1 ) carefully assess the secular trends for their outcomes and be confident that they can demonstrate an intervention effect against those trends ; 2 ) be confident that they have effective programs than can be delivered to a sufficiently large fraction of their target population ; 3 ) avoid differences between study conditions in levels and trends for their outcomes through r and om allocation of a sufficient number of communities to each condition ; 4 ) develop good estimates of community-level st and ard errors prior to launching future trials ; and 5 ) take steps to ensure that power will be sufficient to test the hypotheses of interest The Stanford Five-City Project was initiated in 1978 to evaluate the effects of a community-wide health education program on cardiovascular risk factors , including blood pressure . Two treatment cities received an education program , which used the mass media , various community-based programs , and health professionals , design ed to encourage individuals to learn their blood pressure levels , stay in the care of a physician if hypertensive , achieve ideal weight , exercise regularly , and reduce dietary sodium . Physicians were encouraged to follow national hypertension treatment guidelines and were provided with a range of patient education material s. To evaluate the effect of the intervention on cardiovascular risk factors , four independent cross-sectional surveys of r and omly selected households and four repeated surveys of a cohort were conducted in both treatment cities and in two of the three control cities . After 5 - 1/3 years of intervention , blood pressure in the treatment cities exhibited an overall decline of 7.4 and 5.5 mmHg systolic and 5.0 and 3.7 mmHg diastolic in the cohort and independent surveys , respectively . These declines produced net changes between the treatment and control cities ranging from -1.1 to -3.8 mmHg . While the magnitude of these changes is not large , the results are significant from a public health perspective because they reflect changes in the overall community Summary Irel and has one of the highest death rates in the world from coronary heart disease ( CHD ) and has not shared in the rapid decline in mortality which has occurred in other countries . The Kilkenny Health Project was established as a community-based research and demonstration programme for cardiovascular disease prevention in County Kilkenny and as a pilot project for future national initiatives . The first phase of the health promotion programme in Kilkenny is being carried out between 1985 and 1990 . Changes in behaviour and in factors associated with CHD will be estimated by the difference in changes over time between Kilkenny and the reference area , as measured by independent r and om sample surveys of men and women aged 35 to 64 years . CHD and stroke events , fatal and non-fatal , will be registered in both areas from 1987–1992.The Project has studied attitudes to CHD and its prevention . Health behaviours have been studied in adults and in post- primary school pupils . Risk factors for CHD have been measured in adults in accordance with the methods of the international MONICA Project . It has been demonstrated that health and education professionals can incorporate preventive activities and health education into everyday practice Abstract Objective : To determine whether a community based coronary heart disease health promotion project , undertaken over four years , was associated with changes in the prevalence in adults of lifestyle risk factors known to affect the development of coronary heart disease , and to estimate whether such an approach was cost effective . Design : Prospect i ve , comparative study of the effects of a health promotion intervention on coronary heart disease lifestyle risk factors , assessed by postal question naire sent to a r and omly chosen sample , both at baseline and after four years . Subjects : Intervention and control population s of adults aged 18 - 64 in Rotherham , both from areas with a high incidence of coronary heart disease and similar socioeconomic composition . Main outcome measures : Changes in prevalence of lifestyle risk factors between the control and intervention communities from 1991 to 1995 . The effect of the intervention on certain lifestyle behaviours was evaluated using multiple logistic regression to model the proportion with a particular behaviour in the study communities as a function of age ( 18 - 40 or 41 - 64 years ) , sex , the year of observation ( 1991 or 1995 ) , and area ( intervention or control ) . Results : 6.9 % fewer people smoked and 8.7 % more drank low fat milk in the intervention area , but no other statistically significant changes between the areas were detected . The estimated cost per life year gained was £ 31 . Conclusions : It is possible to have a cost effective impact on coronary heart disease lifestyle risk factors in a population of adults over four years using only modest re sources . Key messages Little is known about the cost effectiveness of focused , heart disease health promotion projects in reducing cardiovascular risk factors over a short period in small population s of adults Research was undertaken to estimate the impact of a heart disease health promotion project — Action Heart— and relate the cost to estimates of health gain Major differences were observed in changes in prevalence of active smoking and consumption of low fat milk between the intervention and control areas over four years The estimated cost per life year gained was £ 31 Further research is required to ascertain whether the changes in risk factors will be sustained after the end of Action BACKGROUND The Alliance of Black Churches Health Project was begun in an effort to address the health problems of the African-American residents of two rural Virginia counties . Smoking cessation was chosen as the principal target behavior in one county . Church coalitions were chosen as the principal organizations through which to implement the interventions . METHOD A smoking cessation program was design ed that combined one-on-one counseling with self-help material s and community-wide activities . To provide these services , up to two smoking cessation counselors were trained from participating churches . To evaluate the impact , population -based cohorts of smokers were assembled in each county using a door-to-door survey . Respondents were recontacted after 18 months . Smoking cessation ( 1-month continuous abstinence ) , stages of change , and exposure to the interventions were assessed . RESULTS The overall smoking prevalence at baseline was 25.8 % . At follow-up , the smoking cessation rate in the intervention county was 9.6 % and in the control county 5.4 % ( P = 0.18 ) . Among those attending church once a month or more , the respective quit rates were 10.5 % and 5.9 % ( P = 0.20 ) . There was significantly more progress along the stages of change in the intervention than in the control county . There was also higher awareness of and contact with smoking cessation programs in the former compared with the latter . CONCLUSION Smoking cessation interventions for African Americans can be successfully implemented through a church coalition . The interventions were associated with significant progress along the stages of cessation . Although the quit rate was higher in the intervention community , the difference was not significant OBJECTIVE To evaluate the effect of community intervention for COPD and chronic cor-pulmonale . METHODS The baseline survey of the study was carried out in 1992 . The total population was r and omly divided into intervention and control regions . From 1992 the comprehensive community intervention trial was conducted in the intervention region . The data of baseline study has been published elsewhere . The family inquiry was made in all baseline population , 50 percent of high risk population and 100 percent of COPD and cor pulmonale population were reexamined . RESULTS Of the 3,739 subjects who should be investigated 3,316 subjects were really investigated ( 88.7 % of responsive rate ) . Of 814 subjects r and omly abstract ed from 3,316 in intervention and control regions , the awareness rates of smoking harm to health were 95.0 % and 80.0 % , of how to prevent and treat COPD were 62.0 % and 35.7 % , of regular visit by doctors were 46.1 % and 27.0 % respectively . The rate of ex-smoker was 28.2 % in intervention region more than that of 23 % in control region ( P = 0.004 ) . Of 3,075 subjects undergone lung function test , FEV1 decrements per capita yearly were 32.0 ml and 37.9 ml ( P = 0.001 ) ; FVC decrement were 42.0 ml and 48.3 ml ( P = 0.012 ) in intervention and control regions . The prevalence increment in COPD were 5.6 % and 8.0 % ( P = 0.03 ) , cor-pulmonale were 3.5 % and 6.7 % ( P = 0.02 ) compared to baseline survey in both regions . The mortality of cor-pulmonale were 72.9 and 95 per 100,000 per year ( P = 0.0044 ) from 1995 to 1999 . CONCLUSION The rate of quiting smoke is significantly increased by intervention . The declination of lung function significantly decreases . The increment in prevalence of COPD and cor-pulmonale significantly decreases . The mortality of cor-pulmonale decreases significantly in intervention region . The results indicates that the comprehensive intervention in community is an important measurement for decreasing incidence of COPD and mortality of cor-pulmonale |
11,943 | 28,651,764 | Conclusions : Compliance with removable orthodontic appliances and adjuncts is suboptimal , and patients routinely overestimate duration of wear .
HighlightsSuboptimal compliance is typical with all types of orthodontic appliances .
Actual wear time is approximately 5 hours per day less than stipulated .
Overreporting of appliance wear was found with all types of appliances . | Introduction : The primary aims of this systematic review were to assess objective levels of wear of removable orthodontic appliances and components vs both stipulated and self‐reported levels .
We also aim ed to consider patient experiences and the effectiveness of interventions geared at enhancing compliance . | In the United Kingdom ( UK ) over the last 10 years , there has been a significant increase in the use of vacuum-formed retainers ( VFRs ) rather than conventional Hawley retainers . There are currently no data to compare the cost-effectiveness of this change in practice . The two aims of this study were to compare ( 1 ) the cost-effectiveness of VFRs and Hawley retainers over 6 months , from the perspective of the National Health Service , orthodontic practice , and the patient and ( 2 ) patient satisfaction in the two retainer groups . A r and omized controlled trial ( RCT ) was carried out in a specialist orthodontic practice . Three hundred and ninety-seven eligible patients were r and omized to one of two retainer groups , and followed up for 6 months . All subjects were invited to complete patient satisfaction question naires . Additional data were collected for the cost analysis from the patient records and national data bases . Descriptive and bivariate analyses were used to compare patient satisfaction between retainer groups . In all , 196 subjects were r and omized to the Hawley group ( mean age 14 years 8 months , 63 per cent female , 37 per cent male ) and 201 to the VFR group ( mean age 15 years , 59 per cent female , 41 per cent male ) . VFRs were more cost-effective than Hawley retainers from all perspectives . The majority of subjects showed a preference for VFRs compared with Hawley retainers . There were also fewer breakages than in the Hawley group Background Retention is an important component of orthodontic treatment ; however , poor compliance with retainer use is often encountered , especially in adolescents . The purpose of this study was to prove the hypothesis that verbal instructions combined with images showing the severe consequences of poor compliance can increase retainer use . Methods This study was a r and omized controlled trial . The sample was recruited from Wenzhou , People ’s Republic of China , between February 2013 and May 2014 , and 326 participants were r and omized into three groups . Patients and parents in Group A ( n=106 ) were given routine retainer wear instructions only ; in Group B ( n=111 ) , images illustrating the severe consequences of poor compliance with Hawley retainer use were shown to patients , combined with routine instructions ; and in Group C ( n=109 ) , images illustrating the severe consequences of poor compliance with Hawley retainer use were shown to patients and parents , combined with routine instructions . Three months after debonding , question naires were used to investigate daily wear time and the reasons for poor compliance . Differences in means between the groups were tested by one-way analysis of variance . Results The mean daily wear time in Group C ( 15.09±4.13 hours ) was significantly greater than in Group A ( 12.37±4.58 hours , P<0.01 ) or Group B ( 13.50±4.22 hours , P<0.05 ) ; the mean daily wear time in Group B was greater than in Group A , but was not significant ( P=0.67 ) . Reasons for nonusage were forgetting to wear the retainer ( 51 % ) and finding the retainer bothersome to frequently insert and remove ( 42 % ) . Conclusion Verbal instructions combined with images showing the severe consequences of poor compliance can increase retainer use . Parents play an important role in compliance with retainer use in adolescent patients INTRODUCTION Intraoral elastics are commonly used in orthodontics and require regular changing to be effective . Unfortunately , poor compliance with elastics is often encountered , especially in adolescents . Intention for an action and its implementation can be improved using " if-then " plans that spell out when , where , and how a set goal , such as elastic wear , can be put into action . Our aim was to determine the effect of if-then plans on compliance with elastics . METHODS To identify common barriers to compliance with recommendations concerning elastic wear , semistructured interviews were carried out with 14 adolescent orthodontic patients wearing intraoral elastics full time . Emerging themes were used to develop if-then plans to improve compliance with elastic wear . A prospect i ve pilot study assessed the effectiveness of if-then planning aim ed at overcoming the identified barriers on compliance with elastic wear . Twelve participants were r and omized equally into study and control groups ; the study group received information about if-then planning . The participants were asked to collect used elastics , and counts of these were used to assess compliance . RESULTS A wide range of motivational and volitional factors were described by the interviewed participants , including the perceived benefits of elastics , cues to remember , pain , eating , social situations , sports , loss of elastics , and breakages . Compliance with elastic wear was highly variable among patients . The study group returned more used elastics , suggesting increased compliance , but the difference was not significant . CONCLUSIONS The use of if-then plans might improve compliance with elastic wear when compared with routine clinical instructions Both r and omized and nonr and omized studies are integral to orthodontic research and practice because they permit evaluation of relationships between exposures and outcomes , allowing the efficacy , effectiveness , and safety of interventions to be assessed . These design s allow clinical decisions to be informed . Nonr and omized design s include nonr and omized clinical trials , cohort studies , case-control studies , cross-sectional studies , case series , and ecological studies . There is debate surrounding the optimal research design ; however , both r and omized and nonr and omized design s are important to build a broad , informative evidence base . The design s are therefore complementary , with unique advantages and limitations . The applicability of either approach hinges on the clinical question posed , the feasibility of study ing it , and ethical considerations Early treatment for Class II malocclusion is frequently undertaken with the objective of correcting skeletal disproportion by altering the growth pattern . Because the majority of previous studies of growth modification for Class II malocclusion have been based on retrospective record review s , the efficacy of such an approach has not been well established . In this controlled clinical trial , patients in the mixed dentition with overjet > or = 7 mm were r and omly assigned to either early treatment with headgear , or modified bionator , or to observation . All patients were observed for 15 months with no other appliances used during this phase of the trial . The three groups , who were equivalent initially , experienced statistically significant differences ( p < 0.01 ) in skeletal change . There was considerable variation in the pattern of change within all three groups , with about 80 % of the treated children responding favorably . Although patients in both early treatment groups had approximately the same reduction in Class II severity , as reflected by change in the ANB angle , the mechanism of this change was different . The headgear group showed restricted forward movement of the maxilla , and the functional appliance group showed a greater increase in m and ibular length . The permanence of these skeletal changes and their impact on the subsequent treatment remains to be evaluated 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 In the first phase of a r and omized clinical trial of early versus late Class II treatment , statistically significant differences were observed between the treatment and observation groups . However , there were wide variations in response . The change in jaw relationship ( categorized as the annualized reduction in ANB angle ) was favorable or highly favorable in 76 % of the headgear , 83 % of the functional appliance , and 31 % of control ( observation only ) groups . The patient 's initial skeletal severity , age/maturity at the outset of treatment , growth pattern , and cooperation with treatment were examined as possible influences on early growth modification treatment . Correlations between the annualized change in the ANB angle and any of the possible influences were close to zero and not statistically significant . We conclude that there is little to be gained from precisely timing early treatment to specific age/maturity markers and that a favorable reduction in Class II skeletal problems can occur for patients in a broad range of skeletal severity and growth patterns . Cooperation , measured as the number of hours of reported wear , or the clinical assessment of compliance , explained little of the variation in treatment response . The wide variation in growth seen in the untreated patients highlights the importance of well-controlled studies if clinicians are to improve their ability to select children with the greatest chances of a favorable treatment response INTRODUCTION The aim of this study was to compare the effectiveness of Twin-block and Dynamax appliances for the treatment of Class II Division 1 malocclusion . METHODS This was a r and omized controlled trial involving 32 boys and 32 girls aged 10 to 14 years with Class II Division 1 malocclusion . They were r and omly allocated to either the Dynamax appliance group or the Twin-block appliance group . Treatment was provided by 4 clinicians at 2 centers . Records were taken at the start and the end of the functional phase and after all treatment . In addition , incisal overjet , the number of appliance breakages , and adverse events or side effects of the treatment were recorded at each patient visit . RESULTS The data monitoring committee in an interim analysis at 18 months after the start of the trial found significantly greater overjet reduction in the Twin-block group than in the Dynamax group and more breakages and adverse events with the Dynamax appliance . As a result , treatment with the Dynamax appliance was terminated , and those patients completed treatment with the Twin-block or a fixed appliance . Regression analysis showed a statistically significant difference in the performance over time between the Twin-block and Dynamax appliances in terms of reduction in overjet , with the Twin-block appliance performing significantly better than the Dynamax . The incidence of adverse events was greater in the Dynamax group ( 82 % ) than in the Twin-block group ( 16 % ) , with a statistically significant difference ( P < 0.001 ) between the 2 groups . CONCLUSIONS The Twin-block appliance was more effective than the Dynamax appliance when overjet was evaluated and the Dynamax appliance patients reported greater incidence of adverse events with their appliance than those who were treated with the Twin-block appliance Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies The aim of this controlled trial was to identify and quantify skeletal , soft tissue and dental changes during treatment , and immediately post-treatment with Twin Block ( TB ) or Dynamax appliance using the techniques of three-dimensional (3D)optical surface laser scanning , cephalometric , and clinical measurements . Sixty-two Caucasian subjects , 36 males aged 11 - 14 years and 26 females aged 10 - 13 years were enrolled in the study . The patients were placed in two groups , matched for gender and age and subsequently allocated r and omly for treatment with either a TB or Dynamax appliance . Active treatment lasted 9 months followed by 3 months ' post-treatment observation . Laser scanning and clinical measurements were taken at 3-monthly intervals and final cephalometric records after 12 months . Statistical analysis was performed using Wilcoxon 's matched-pairs signed-rank tests . The non-compliance rates were the same for both groups ( 9 per cent ) , but a greater incidence of breakages was found in the Dynamax group . The TB was found to produce slightly more antero-posterior skeletal change , median ANB reduction , TB=2 degrees , Dynamax 1.1 degree ( P=0.006 ) , and similar forward movements of the chin and was associated with larger increases in the vertical facial dimension , median total anterior face height increase ; TB=3.2 mm , Dynamax = 2.8 mm ( P=0.03 ) . The soft tissue vertical cephalometric increases were 3.6 mm with the TB , 2.0 mm with the Dynamax ( P=0.036 ) , and with laser scanning 5.05 and 2.6 mm , respectively , a difference which is likely to be more clinical ly relevant . The median post-treatment changes in soft tissue pogonion were -0.65 mm in the TB and + 0.22 mm in the Dynamax group . The optical surface scanning mark and measure system is a valid method for quantifying soft tissue changes The aim of this study was to evaluate the effectiveness of Herbst and Twin-block appliances for established Class II Division I malocclusion . The study was a multicenter , r and omized clinical trial carried out in orthodontic departments in the United Kingdom . A total of 215 patients ( aged 11 - 14 years ) were r and omized to receive treatment with either the Herbst or the Twin-block appliance . Treatment with the Herbst appliance result ed in a lower failure-to-complete rate for the functional appliance phase of treatment ( 12.9 % ) than did treatment with Twin-block ( 33.6 % ) . There were no differences in treatment time between appliances , but significantly more appointments ( 3 ) were needed for repair of the Herbst appliance than for the Twin-block . There were no differences in skeletal and dental changes between the appliances ; however , the final occlusal result and skeletal discrepancy were better for girls than for boys . Because of the high cooperation rates of patients using it , the Herbst appliance could be the appliance of choice for treating adolescents with Class II Division 1 malocclusion . The trade-off for use of the Herbst is more appointments for appliance repair The aim of this study was to evaluate the effectiveness of a fixed Twin-block appliance by using a study with a prospect i ve cohort design . Thirty-two children were included in the study over a 2-year period . Cephalometric data were analyzed with the Pancherz cephalometric analysis . Study models were analyzed with the PAR index , and the treatment processes were recorded from the patients ' records . The results showed that this appliance was effective in correcting Class II malocclusion ; the noncompliance rate was only 6 % . It can be concluded that this method of treatment might have some advantages over other fixed and removable functional appliances , but this should be tested with r and omized trial methodology Objective The goal of the present work was to determine the influence of screw activation rates and electronically tracked wear times on transverse maxillary expansion with removable orthodontic appliances . Methods In all , 28 patients were included in an open prospect i ve observational study covering approximately 6 months of maxillary transverse expansion . In each of these patients , the maxillary plate appliance used for treatment was fitted with a wear-time sensor to document wear time for the duration of the study . Patients were instructed to activate the transverse expansion screw in their plate appliance by 0.2 mm/week . The result ant gap-width increases were monitored with a caliper over three follow-up appointments scheduled at 2-month intervals . Results Largely linear increases in gap width due to screw activation were only noted within the first 4 months of treatment . The mean increases in gap width fell short of the values that were anticipated after calculations . Longer daily wear times were , on average , associated with larger gap widths . Conclusion Treatment can be objective ly monitored by referring to wear-time tracking and by measuring increases in gap width , thus , ensuring that the appliance fits well . In this way , the process can be customized to serve individual needs and to better utilize the full potential of therapy . ZusammenfassungFragestellungWie wirken sich Aktivierungsintervall und elektronisch gemessene Tragezeit auf die transversale Erweiterung des Oberkiefers mit herausnehmbaren KFO-Apparaturen aus?Patienten und Method ikIn einer prospektiven offenen Beobachtungsstudie mit 28 Patienten wurde die Spaltverbreiterung der Transversaldehnschraube einer Oberkiefer-Plattenapparatur mit integriertem Tragezeitsensor gemessen und die Tragezeiten während des etwa 6-monatigen Therapieabschnitts dokumentiert . Der alle 7 Tage um 0,2 mm zu erweiternde Spalt der Schraube wurde an drei Kontrollterminen in Abständen von jeweils etwa 2 Monaten mit einer Schieblehre gemessen . ErgebnisseDie Aktivierung löste nur in den ersten 4 Therapiemonaten eine annähernd linear steigende Zunahme der Spaltbreite aus . Die mediane Spaltverbreiterung lag i m Verlauf unter den errechneten Werten . Längere tägliche Tragezeiten führten i m Mittel zu größeren Spaltbreiten . SchlussfolgerungAuf der Basis der Tragezeitdokumentation in Verbindung mit der gemessenen Zunahme der Spaltbreite und der Passung der Apparatur kann die Therapie objektiv nachvollzogen und den Gegebenheiten des Patienten individuell angepasst und so optimiert werden |
11,944 | 25,963,579 | RCTs , which are the primary study type for regulatory su bmi ssions , showed a lack of bias .
Studies aim ed at HTA were not as well performed .
As a group , cross-sectional studies scored poorly for bias , with a primary failure to identify a representative sample . | Background The challenges of comparative effectiveness to support health technology assessment ( HTA ) agencies are important considerations in the choices of antipsychotic medications for the treatment of schizophrenia .
Objectives Our aim was to assess the study methods used and outcomes reported in the published literature to address the question of comparative effectiveness of newer antipsychotic agents and the adequacy and availability of evidence to support HTA agencies . | OBJECTIVE To examine the effectiveness of switching patients to lurasidone using 3 different dosing strategies . METHOD Adults with DSM-IV-defined schizophrenia or schizoaffective disorder in a nonacute phase of illness were r and omized to 1 of 3 lurasidone dosing regimens for the initial 2 weeks of the study : ( 1 ) 40 mg/d for 2 weeks ; ( 2 ) 40 mg/d for 1 week , increased to 80 mg/d on day 8 for week 2 ( up-titration group ) ; and ( 3 ) 80 mg/d for 2 weeks . Lurasidone was then flexibly dosed ( 40 - 120 mg/d ) for the subsequent 4 weeks of the study . The preswitch antipsychotic agent was tapered by day 7 to 50 % of the original dose and discontinued by the end of week 2 . Subjects were stratified on the basis of whether the primary preswitch antipsychotic medication was classified as " sedating " ( olanzapine or quetiapine ) or " nonsedating " ( all other antipsychotics ) . The primary outcome measure was time to treatment failure , defined as any occurrence of insufficient clinical response , exacerbation of underlying disease , or discontinuation due to an adverse event . The study was conducted from June 2010 to May 2011 . RESULTS Of 240 subjects treated in this study , 86 ( 35.8 % ) were treated with an antecedent sedating antipsychotic , and 154 ( 64.2 % ) were treated with an antecedent nonsedating antipsychotic . Nineteen ( 7.9 % ) of the 240 patients experienced treatment failure . No clinical ly relevant differences were observed when the 3 r and omized switch groups were compared . Treatment failure rates were 10/86 ( 11.6 % ) versus 9/154 ( 5.8 % ) among subjects who had been receiving a preswitch sedating versus nonsedating antipsychotic medication , respectively . Consistent with prior studies of lurasidone , there was no signal for clinical ly relevant adverse changes in body weight , glucose , insulin , lipids , or prolactin ; mean improvements in weight and lipids were observed . Movement disorder rating scales did not demonstrate meaningful changes . The incidence of akathisia as an adverse event was 12.5 % ; only 1 subject ( 0.4 % ) discontinued due to akathisia . CONCLUSIONS Switching patients to lurasidone can be successfully accomplished by starting at 40 mg/d for 2 weeks , or 80 mg/d for 2 weeks , or 40 mg/d for 1 week followed by 80 mg/d the second week . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01143077 Aripiprazole is a D2 and D3 receptor partial agonist that is unlike other second generation antipsychotics . The effectiveness of aripiprazole with regard to neurocognitive function and its adverse effects is unclear . The present study evaluates the comparative efficacy , effects on neurocognitive function , and adverse effects of aripiprazole and risperidone in the treatment of hospitalized patients with schizophrenia . This double-blind , cross-over study included 23 patients with schizophrenia who were r and omly assigned to be treated first with either aripiprazole or risperidone . After eight weeks on one medication , the patients were switched to the other medication for eight weeks . The patient assessment included the Positive and Negative Syndrome Scale ( PANSS ) , neurocognitive assessment s , and adverse events including extrapyramidal symptoms , vital signs , electrocardiogram , and clinical laboratory tests . The study findings indicated that psychopathology assessed with the PANSS , extrapyramidal symptoms and other adverse effects did not differ between aripiprazole and risperidone for the subjects remaining in treatment . In the neurocognitive assessment s , the score for disinhibition with aripiprazole was significantly lower than with risperidone ( p < 0.05 ) . In addition , serum prolactin levels were significantly lower with aripiprazole ( p < 0.001 ) . The treatment drop-out rate was higher for patients receiving aripiprazole than risperidone . In comparing aripiprazole and risperidone , risperidone is better from the viewpoint of treatment continuation . On the other h and , some adverse effects , such as hyperprolactinemia and disinhibition , are less severe with aripiprazole . Thus , for certain applications , aripiprazole may be a beneficial new treatment option for schizophrenia Few pharmacological intervention studies have examined the impact of medication on social cognition , particularly emotion perception . The goal of this r and omized , double-blind study is to compare the effects of several second generation antipsychotics and a first generation antipsychotic , perphenazine , on emotion perception in individuals with schizophrenia . Patients were assigned to receive treatment with olanzapine , queitapine fumarate , risperidone , ziprasidone or perphenazine for up to 18 months . Eight hundred and seventy three patients completed an emotion perception test immediately prior to r and omization and after 2 months of treatment . We also examined baseline predictors of emotion perception change . Most treatments were associated with a small , non-statistically significant improvement in emotion perception at two months , although they did not differ from one another . Greater improvement in emotion perception at 2 months was significantly predicted by lower baseline emotion perception and higher baseline neurocognitive functioning , and marginally predicted by less time on an antipsychotic Rationale The relative effectiveness of the atypical antipsychotic drugs and conventional agents in patients with early-stage schizophrenia has not been comprehensively determined . Objectives The aim of our study was to evaluate the efficacy and safety of seven antipsychotic drugs for the maintenance treatment in patients with early-stage schizophrenia . Methods In a 12-month open-label , prospect i ve observational , multicenter study , 1,133 subjects with schizophrenia or schizophreniform disorder within 5 years of onset were monotherapy with chlorpromazine , sulpiride , clozapine , risperidone , olanzapine , quetiapine , or aripiprazole . The primary measure was the rate of treatment discontinuation for any reason . Secondary outcomes included measures for clinical and functional outcomes and tolerability . Results The percentage of patients discontinued treatment within 12 months was 41.4 % for chlorpromazine , 39.5 % for sulpiride , 36.7 % for clozapine , 40.2 % for risperidone , 39.6 % for olanzapine , 46.9 % for quetiapine , and 40.2 % for aripiprazole , a nonsignificant difference ( p = 0.717 ) ; there were no significant differences among these seven treatments on discontinuation due to relapse , intolerability , patient decision , or nonadherence ( all p values ≥ 0.260 ) . Extrapyramidal symptoms were more prominent in chlorpromazine and sulpiride treatment groups . Anticholinergic side effects were most common with clozapine and chlorpromazine . Weight gain was most common with olanzapine and clozapine . Conclusions The efficacy of seven antipsychotic medications for the maintenance treatment appeared similar in early-stage schizophrenia . With regard to the high dropout rate and side effects , special programs are needed to keep efficacy and safety of antipsychotics maintenance treatment for schizophrenia with early ABSTRACT Objective : The Health Outcomes of a Canadian Community Cohort ( HOCCC ) study is a 1-year prospect i ve observational study of out patients with schizophrenia or related psychotic disorders . The purpose of the study was to compare effectiveness of antipsychotic treatment as measured by 1-year treatment completion rates . Design and methods : Patients ( N = 929 ) were enrolled if in the course of usual clinical practice they switched to a second-generation antipsychotic ( SGA ) . Observational data were collected for up to 1 year . The primary analysis compared 1-year treatment-completion rates for the olanzapine cohort with the other SGA cohort ( quetiapine , risperidone , clozapine ) , using a chi-squared test . Results : Of 929 patients enrolled , 64.8 % ( 516/796 ) of evaluable patients completed 1 year of treatment . There was no statistically significant difference in the proportion of treatment completers between the olanzapine cohort ( 67.4 % , 256/380 ) and the other SGA cohort ( 62.5 % , 260/416 ) . Treatment-completion rates were risperidone 62.0 % ( 127/205 ) , quetiapine 63.7 % ( 123/193 ) and clozapine 55.6 % ( 10/18 ) . Antipsychotic polypharmacy was common . Patients treated with olanzapine or risperidone had significantly higher increases in BMI than quetiapine-treated patients . There were no major differences between olanzapine monotherapy and pooled other SGA monotherapy groups in status of extrapyramidal symptoms from baseline to endpoint . Conclusions : Olanzapine and other SGAs exhibited similar rates of 1-year treatment completion . Further study of medication combinations is needed , given their perceived clinical value , and the high frequency of antipsychotic polypharmacy in clinical practice . Limitations : As most patients received several psychotropics and power was reduced in monotherapy analyses , comparisons between cohorts must be interpreted cautiously . Comparisons between individual antipsychotics were post hoc and not powered a priori . Accuracy and completeness of adverse event information for drugs other than olanzapine is limited Thomas SHL , Drici MD , Hall GC , Crocq MA , Everitt B , Lader MH , Le Jeunne C , Naber D , Priori S , Sturkenboom M , Thibaut F , Peuskens J , Mittoux A , Tanghøj P , Toumi M , Moore ND , Mann RD . Safety of sertindole versus risperidone in schizophrenia : principal results of the sertindole cohort prospect i ve study ( SCoP Abstract Objective : Although the use of innovative drug delivery systems , like orally disintegrating antipsychotic tablets ( ODT ) , may facilitate medication adherence and help reduce the risk of relapse and hospitalization , no information is available about the comparative cost-effectiveness of st and ard oral tablets ( SOT ) vs ODT formulations in the treatment of schizophrenia . This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of out patients with schizophrenia from a US healthcare perspective . The study also compared olanzapine ODT with risperidone and aripiprazole , two other atypical antipsychotics available in both ODT and SOT formulations . Methods : Published medical literature and a clinical expert panel were used to populate a 1-year Monte Carlo Micro-simulation model . The model captures clinical and cost parameters including adherence levels , treatment discontinuation by reason , relapse with and without inpatient hospitalization , quality -adjusted life years ( QALYs ) , treatment-emergent adverse events , healthcare re source utilization , and associated costs . Key outcomes were total annual direct cost per treatment , QALY , and incremental cost-effectiveness ( ICER ) per 1 QALY gained . Results : Based on model projections , olanzapine ODT therapy was more costly ( $ 9808 vs $ 9533 ) , but more effective in terms of a lower hospitalization rate ( 15 % vs 16 % ) and better QALYs ( 0.747 vs 0.733 ) than olanzapine SOT therapy . Olanzapine ODT was more cost-effective than olanzapine SOT ( ICER : $ 19,643 ) , more cost-effective than risperidone SOT therapy ( ICER : $ 39,966 ) , and dominant ( meaning less costly and more effective ) than risperidone ODT and aripiprazole in ODT or SOT formulations . Limitations : Lack of head-to-head r and omized studies comparing the three studied atypical antipsychotics required making input assumptions that need further study . Conclusions : This micro-simulation found that the utilization of olanzapine ODT for the treatment of schizophrenia is predicted to be more cost-effective than any other ODT or SOT formulations of the studied atypical antipsychotic medications Abstract Differences among antipsychotics in effectiveness have turned out to be a topic of increasing research interest , although comparisons between the different second-generation antipsychotics are scarce . From October 2005 to March 2011 , a prospect i ve , r and omized , open-label study comparing the effectiveness of aripiprazole , ziprasidone , and quetiapine in the short-term treatment of first-episode schizophrenia-spectrum disorders was undertaken . Two hundred two patients were r and omly assigned to aripiprazole ( n = 78 ) , ziprasidone ( n = 62 ) , or quetiapine ( n = 62 ) and followed up for 6 weeks . The primary effectiveness measure was all-cause of treatment discontinuation . In addition , an analysis based on per protocol population s was conducted in the analysis for clinical efficacy . The overall dropout rate at 6 weeks was small ( 6.4 % ) . The treatment discontinuation rate differed significantly between treatment groups ( aripiprazole , 15 % ; ziprasidone , 19 % ; and quetiapine , 35 % ; & khgr;2 = 8.529 ; P = 0.014 ) . Insufficient efficacy in the group of quetiapine is the main reason for discontinuation rate differences ( & khgr;2 = 10.139 ; P = 0.006 ) . The mean time to all-cause discontinuation was significantly different between the groups ( log-rank , 12.783 ; P = 0.001 ) . Quetiapine was associated with a greater depressive symptoms improvement than ziprasidone ( P = 0.045 ) . The rate of responders at 6 weeks differed between the groups ( F = 6 , 116 ; P = 0.047 ) , with a higher rate of the responders with aripiprazole . The profile of adverse effects varies between the treatments . Patients on quetiapine were less likely to be prescribed concomitant medications . Treatment with quetiapine was associated with a higher risk of treatment discontinuation during treatment owing to insufficient efficacy . Differences in effectiveness between second-generation antipsychotics would determine their position in everyday clinical practice and could help physicians choose the more efficacious antipsychotics INTRODUCTION Safety and efficacy results , collected in schizophrenia and schizoaffective disorder patients treated for up to nearly 3 years , are presented for asenapine and olanzapine . RESULTS Patients completing a 52-week r and omized double-blind core study on flexible-dose asenapine ( 5 or 10 mg BID ) or olanzapine ( 10 or 20 mg QD ) could continue treatment until study blind was broken.290 patients on asenapine and 150 on olanzapine continued treatment for variable lengths of time [ mean ± SD ( range ) 311.0 ± 146.1 ( 10 - 653 ) d and 327.4 ± 139.6 ( 15 - 631 ) d , respectively ] . Adverse event ( AE ) incidence was lower during the extension ( asenapine , 62 % ; olanzapine , 55 % ) than during the core study ( 78 % , 80 % ) . In both groups , body weight increase and incidence of extrapyramidal AEs were negligible during the extension . Mean PANSS total score changes during first year of treatment were - 37.0 for asenapine and - 35.3 for olanzapine , with further changes of 1.6 for asenapine and - 0.8 for olanzapine at the extension study endpoint . CONCLUSIONS Clinical stability on asenapine as well as olanzapine was maintained , with few recurrent or newly emerging AEs beyond 1 year of treatment BACKGROUND Schizophrenia is a severe chronic psychiatric disorder for which treatment compliance is important in the prevention of relapse . Second generation antipsychotics ( SGA ) , such as Risperidone , have been found to be more effective in the treatment of such patients than the high potency first generation antipsychotics ( FGA ) . This is an open study where the same group of patients was first treated with FGA and then were switched to Risperidone , in controlled hospital conditions , after a wash- out period . The aim of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with FGA would further benefit from a switch to an atypical antipsychotic drug . SUBJECTS AND METHODS Eighty hospitalized patients suffering from Schizophrenia or Schizoaffective disorder ( male 54 , female 26 ) were first treated with Haloperidol ( N=60 ) or Fluphenazine ( N=20 ) , and then were switched to Risperidone . Their clinical state was monitored using the PANSS scale for Schizophrenia , measuring the Total PANSS score . The KLAWANS scale for assessment of extrapyramidal syndrome ( EPS ) was also used . Administration and dosage of Trihexiphenidil ( THF ) was recorded . The study lasted for 8 weeks , with 4 screenings ( Visit 0-baseline- FGA , Visits 1 - 3 Risperidone on Day 14 , 28 and 56 , respectively ) . RESULTS The average age was 38 . Patients usually suffered the paranoid form of Schizophrenia ( 55 % ) . The duration of illness was more than 5 years ( 38.8 % ) . During the eight- week trial on Risperidone , using the PANSS total scores , we observed clinical improvement where the therapy switch had caused an initial worsening ( p<0.05 ) . Also , the compared baseline ( FGA ) and last visit showed a low , but statistically significant benefit in favor of Risperidone ( t=5.45 , df=79 , p<0.005 ) . Intensity of EPS measured by KLAWANS scores significantly decreased during time ( F=4.115 ; p=0.016 ; Partial Eta Square=0.058 ) . Average Trihexiphenidil doses followed Risperidone in a dose dependent manner ( r=0.748 , r=0.661 , respectively , p<0.01 ) with the consequent decrease of patients needing THF corrective therapy ( 68.8 % at the baseline toward 22.5 % on last visit ) . CONCLUSION Switch to Risperidone medication provided significant additional improvement in symptom severity , extrapyramidal side effects and need for anticholinergic medication . This suggests that one might expect better compliance in future treatment in this population of chronic schizophrenic patients BACKGROUND Because long-acting injectable ( LAI ) antipsychotics are largely reserved for persistently ill patients , little is known about the use of LAIs early in the course of illness for first-episode out patients . METHOD A prospect i ve , open-label , r and omized controlled trial was conducted in which out patients with first-episode DSM-IV schizophreniform disorder , schizophrenia , or schizoaffective disorder were enrolled from December 2004 to March 2007 . Participants were r and omly assigned at a 2:1 ratio to a recommendation of changing to LAI risperidone microspheres ( RLAI ) ( n = 26 ) or continuing oral antipsychotic treatment ( n = 11 ) for up to 104 weeks . Primary outcomes were time until initial nonadherence ( medication gap of ≥ 14 days ) and medication attitudes as assessed with the Rating of Medication Influences scale . Patients r and omly assigned to an RLAI recommendation could decline the recommendation , so analysis defined treatment groups by intent-to-treat and as-actually-treated . RESULTS Eighty-one percent of patients ( 30/37 ) stopped medication within 104 weeks . There was a trend toward an initial adherence benefit favoring RLAI acceptors at 12 weeks ( P = .058 ) , but no significant difference between RLAI and oral antipsychotic treatment in time to initial nonadherence during the overall study ( P = .188 ) . Medication attitudes did not differ between groups . CONCLUSIONS Acceptance of RLAI was associated with an initial adherence benefit that was not sustained over time . Early introduction of LAI therapy did not adversely affect adherence attitudes . The small size of the study and low power limit interpretation , but the few patients who remained adherent into a second year were all receiving RLAI . Nonadherence was almost universal in our first-episode cohort , but nonadherence was more easily detected among first-episode patients treated with LAI therapy than it was with oral antipsychotics . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00220714 BACKGROUND Naturalistic studies offer advantages over r and omized clinical trials by including patients seen in routine practice . Aripiprazole and quetiapine are the most recent second-generation antipsychotics available in the United Kingdom . We aim ed to study all patients who were prescribed these medications in a defined geographic area in order to identify and compare those who had a good clinical response . METHOD We conducted an electronic chart review of a sample of all people attending secondary mental health care in the county of Lanarkshire , Scotl and , who were treated with aripiprazole or quetiapine for schizophrenia and related psychoses ( ICD-10 criteria ) between 2002 and 2007 . To measure effectiveness , we retrospectively assigned Clinical Global Impressions ( CGI ) scores and examined medication discontinuation rates . RESULTS Eighty-nine patients were started on treatment with aripiprazole and 132 patients with quetiapine over the 5-year period . Those treated with quetiapine had a higher initial illness severity ( CGI-Severity of Illness scale ) ( p = .0003 ) , were more likely to be starting rather than switching antipsychotics ( p = .0003 ) , were more likely to have a mood disorder ( p = .03 ) , were less likely to be treatment resistant ( p = .005 ) , and had lower rates of prescription of additional antipsychotics ( p = .009 ) . After adjusting for these variables , the proportions who improved according to CGI were 74 % with aripiprazole and 67 % with quetiapine . Overall medication discontinuation rates were also similar , 42 % for aripiprazole and 45 % for quetiapine , with early discontinuation of aripiprazole being noticeable , often due to agitation ( 13 % of all patients treated with the drug ) . CONCLUSIONS Despite their different pharmacologic properties , aripiprazole and quetiapine were similarly effective in the majority of patients . Early discontinuation of aripiprazole due to agitation was an important finding Abstract Objective . The aim of the study was to compare efficacy and tolerability of aripiprazole with olanzapine in the short-term treatment of schizophrenia in an Indian population . Method . This was a r and omized double-blind controlled study comparing aripiprazole and olanzapine in the treatment of individuals with schizophrenia in an inpatient clinical setting . Sixty subjects between 18 and 65 years of age , who fulfilled the ICD-10 criteria for schizophrenia , were enrolled . Patients ’ detailed demographic and clinical evaluation was conducted and they were administered efficacy assessment scales ( BPRS , PANSS ) and safety assessment s scale ( Simpson Angus Scale , UKU side effect rating scale ) at regular intervals of 1 week each throughout the study . The laboratory tests ( complete haemogram , electrocardiogram ( ECG ) , lipid profile , liver and renal function tests ) were conducted at baseline and after 1-week intervals until 6 weeks of treatment . The patients were r and omly allocated to receive either aripiprazole or olanzapine . Results . Both aripiprazole and olanzapine led to significant reductions on BPRS and PANSS total score over a period of 6 weeks . Weight gain was observed more frequently in the olanzapine-treated group ( 22.20 % ) as compared to aripiprazole ( 7.70 % ) . More patients in the aripiprazole treatment group required comedications ( trihexiphenidyl and lorazepam ) than olanzapine recipients . Conclusion . This study demonstrates that aripiprazole is equally efficacious as olanzapine in the treatment of schizophrenia . Aripiprazole has a more benign side effect profile ( weight gain , blood sugar level , lipid profile ) as compared to olanzapine in the short-term treatment of schizophrenia . This study is the first in an Indian population to have compared aripiprazole and olanzapine Background When treating schizophrenia , improving patients ' productivity level is a major goal considering schizophrenia is a leading cause of functional disability . Productivity level has been identified as the most preferred treatment outcome by patients with schizophrenia . However , little has been done to systematic ally investigate productivity levels in schizophrenia . We set out to better underst and the change in productivity level among chronically ill patients with schizophrenia treated with olanzapine compared with other antipsychotic medications . We also assessed the links between productivity level and other clinical outcomes . Methods This post hoc analysis used data from 6 r and omized , double-blind clinical trials of patients with schizophrenia or schizoaffective disorder , with each trial being of approximately 6 months duration . Change in productivity level was compared between olanzapine-treated patients ( HGBG , n = 172 ; HGHJ , n = 277 ; HGJB , n = 171 ; HGLB , n = 281 ; HGGN , n = 159 ; HGDH , n = 131 ) and patients treated with other antipsychotic medications ( separately vs. haloperidol [ HGGN , n = 97 ; HGDH , n = 132 ] , risperidone [ HGBG , n = 167 ; HGGN , n = 158 ] , quetiapine [ HGJB , n = 175 ] , ziprasidone [ HGHJ , n = 271 ] and aripiprazole [ HGLB , n = 285 ] ) . Productivity was defined as functional activities/work including working for pay , study ing , housekeeping and volunteer work . Productivity level in the prior 3 months was assessed on a 5-point scale ranging from no useful functioning to functional activity/work 75 % to 100 % of the time . Results Chronically ill patients treated with olanzapine ( OLZ ) experienced significantly greater improvement in productivity when compared to patients treated with risperidone ( RISP ) ( OLZ = 0.22 ± 1.19 , RISP = -0.03 ± 1.17 , p = 0.033 ) or ziprasidone ( ZIP ) ( OLZ = 0.50 ± 1.38 , ZIP = 0.25 ± 1.27 , p = 0.026 ) , but did not significantly differ from the quetiapine , aripiprazole or haloperidol treatment groups . Among first episode patients , OLZ therapy was associated with greater improvements in productivity levels compared to haloperidol ( HAL ) , during the acute phase ( OLZ = -0.31 ± 1.59 , HAL = -0.69 ± 1.56 , p = 0.011 ) and over the long-term ( OLZ = 0.10 ± 1.50 , HAL = -0.32 ± 1.91 , p = 0.008 ) . Significantly more chronically ill and first episode patients treated with olanzapine showed moderately high ( > 50%-75 % of the time ) and high levels of productivity ( > 75%-100 % of the time ) at endpoint , when compared to risperidone or haloperidol-treated patients ( p < .05 ) , respectively . Higher productivity level was associated with significantly higher study completion rates and better scores on the positive , negative , disorganized thoughts , hostility and depression subscales of the Positive and Negative Symptom Scale ( PANSS ) . Conclusions Some antipsychotic medications significantly differed in beneficial impact on productivity level in the long-term treatment of patients with schizophrenia . Findings further highlight the link between clinical and functional outcomes , showing significant associations between higher productivity , lower symptom severity and better persistence on therapy . Trial Registration clinical trials.gov identifier NCT00088049 ; Abstract Background : The Schizophrenia Trial of Aripiprazole ( STAR ) showed superior efficacy for aripiprazole compared with atypical antipsychotic st and ard-of-care ( SOC ) for the community treatment of schizophrenia1 based on the Investigator Assessment Question naire total score . Objective : To determine the cost-effectiveness of aripiprazole compared with SOC medications from a health and social care system perspective . Methods : Information on health and social care service use was collected using the Client Socio-demographic and Service Receipt Inventory ( CSSRI ) . Unit costs attached to each service were used to calculate patients ’ healthcare and other costs . The primary outcome measure was Investigator ’s Assessment Question naire ( IAQ ) score ; secondary measures included the Clinical Global Impression (CGI)-Improvement response and Quality of Life Scale ( QLS ) . Incremental cost-effectiveness was measured over 26 weeks as the ratio of the difference in mean costs between aripiprazole and SOC ( olanzapine , quetiapine and risperidone ) to the difference in mean outcomes . Net benefit was used to plot the cost-effectiveness acceptability curve . Results : The analysis sample ( all r and omised subjects who met the study inclusion criteria ) included 282 individuals r and omised to aripiprazole and 266 to SOC ( olanzapine , n = 75 ; quetiapine , n = 110 and risperidone , n = 81 ) . The additional mean cost of achieving a clinical ly significant difference on the IAQ was £ 3896 , where a clinical ly significant difference was taken to be an 8-point improvement . The cost-effectiveness acceptability curve for the IAQ indicated that aripiprazole has a relatively high probability of being viewed as cost-effective for a range of plausible values attached to the incremental outcome difference . Additional costs of a clinical ly significant improvement on the CGI-Improvement and QLS were £ 575 and £ 835 , respectively . These measures therefore support the view that aripiprazole is more cost-effective than SOC from a health and social care perspective for people with schizophrenia treated in the community . Conclusion : In the STAR study , use of aripiprazole in the management of patients with schizophrenia was cost-effective 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 The relative effects of the atypical antipsychotic drugs and conventional agent on quality of life and psychosocial functioning in patients with early-stage schizophrenia is still uncertain because of an insufficient number of studies examining this issue . METHODS In a 12 months open-label , prospect i ve observational , multicenter study , 1029 subjects with schizophrenia or schizophreniform disorder within 5 years of onset were monotherapy with chlorpromazine , sulpiride , clozapine , risperidone , olanzapine , quetiapine or aripiprazole . The health-related quality of life and psychosocial functioning were assessed using Medical Outcomes Study 36-Item Short Form Health Survey ( SF-36 ) , the Global Assessment Scale ( GAS ) and the Activities of Daily Living Scale ( ADL ) , respectively . RESULTS At 12 months , treatment result ed in significant improvements in all 8 domain scores of SF-36 , GAS and ADL score ( all P-values < .001 ) . However , only olanzapine and quetiapine groups demonstrated greater improvement in the role-psychical score of SF-36 and GAS score than did the chlorpromazine group ( all P-values ≤ .002 ) . CONCLUSIONS All antipsychotics may improve quality of life and social function in patients with early-stage schizophrenia , but further studies are needed to determine whether atypical antipsychotics are superior to conventional agents OBJECTIVE To compare the efficacy of risperidone and olanzapine in schizophrenic patients with tardive dyskinesia on treatment with first-generation antipsychotics . METHOD We conducted a 24-week , rater-blinded , flexible-dose study . Sixty patients with DSM-IV schizophrenia ( n = 58 ) or schizoaffective disorder ( n = 2 ) met the DSM-IV research criteria for neuroleptic-induced tardive dyskinesia and were r and omly assigned to a risperidone or olanzapine group . The primary outcome was a comparison of the change in the total scores on the Abnormal Involuntary Movement Scale ( AIMS ) from baseline to study end point between the groups . The study was conducted from July 2000 to June 2004 . RESULTS The mean ± SD doses of risperidone and olanzapine from baseline to study end point were 1.9 ± 0.7 to 4.1 ± 1.4 mg/d and 8.1 ± 2.0 to 12.6 ± 5.4 mg/d , respectively . There were no statistically significant differences in demographic data , severity of tardive dyskinesia , or psychotic symptoms between risperidone and olanzapine groups at baseline assessment . Both groups showed significant improvement in mean ± SD AIMS total scores ( risperidone : −7.4 ± 6.9 , P < .0001 ; olanzapine : −6.2 ± 8.0 , P = .0002 ) . However , there was a more statistically significant change in the slope of AIMS total scores in the risperidone group than in the olanzapine group ( P = .0001 ) . CONCLUSIONS Our findings demonstrated that olanzapine may not have better potential for tardive dyskinesia improvement than risperidone did . Double-blinded , fixed dose studies with a larger sample size on schizophrenic patients with tardive dyskinesia from different ethnic groups are needed to confirm the results of our study . TRIAL REGISTRATION clinical trials.gov Identifier Objective : Atypical antipsychotics are increasingly drugs of first choice in schizophrenia . Amisulpride , a new atypical antipsychotic , is reported to be effective for both positive and negative symptoms of schizophrenia in Western countries but Indian experience is limited . The aim of the present study was therefore to conduct a trial of amisulpride versus olanzapine in Indian schizophrenia patients . Methods : Eighty adult patients of either sex were r and omized to receive st and ard doses of the two drugs orally , in a single blind manner , for 12 weeks , with follow up at 4 and 8 weeks . Effectiveness was assessed by changes in scores on the Brief Psychiatric Rating Scale ( BPRS ) , Scale for Assessment of Positive Symptoms ( SAPS ) , Scale for Assessment of Negative Symptoms ( SANS ) , and physician-administered Clinical Global Impression ( CGI ) scale . Tolerability was assessed by treatment-emergent adverse drug reactions ( ADRs ) . Results : Evaluable were 39 patients on amisulpride and 38 on olanzapine . The groups were comparable at baseline with respect to demographics , illness duration and rating scores . Final BPRS score was lower for olanzapine ( 33.2 ± 9.44 ) than for amisulpride ( 37.7 ± 9.67 ) . SAPS and SANS scores and CGI rating improved individually in both arms but remained comparable between groups throughout the study period , but olanzapine reduced SAPS score to a greater extent . ADRs were encountered in 67.5 % and 47.5 % of patients ( p = 0.113 ) on amisulpride and olanzapine , respectively . Tremor and insomnia were more frequent with amisulpride , while olanzapine caused more weight gain and sedation . No serious ADRs occurred . Conclusions : Amisulpride , although comparable to olanzapine on some measures , did not match the improvement seen with the latter drug in BPRS and SAPS scores . Despite differences in ADR profiles , overall tolerability was satisfactory for both drugs . In Indian patients , amisulpride should therefore be an alternative to olanzapine to a limited extent , such as when weight gain and sedation are undesirable Background How long an antipsychotic is effective in maintaining response is important in choosing the correct treatment for people with schizophrenia . This post-hoc analysis describes maintenance of response over 24 or 28 weeks in people treated for schizophrenia with olanzapine , risperidone , quetiapine , ziprasidone , or aripiprazole . Methods This was a post-hoc analysis using data from 5 double-blind , r and omized , comparative trials of 24 or 28 weeks duration in which olanzapine was compared to risperidone ( 1 study ; N = 339 ) , quetiapine ( 1 study ; N = 346 ) , ziprasidone ( 2 studies ; N = 548 and 394 ) or aripiprazole ( 1 study ; N = 566 ) for treatment of schizophrenia . For each study , time to loss of response in patients who met criteria for response at Week 8 and the proportion of patients who lost response following Week 8 were compared by treatment group . The number needed to treat ( NNT ) with olanzapine rather than comparator to avoid loss of one additional responder over 24 or 28 weeks of treatment was calculated for each study . Results Time maintained in response was significantly longer ( p < .05 ) for olanzapine compared to risperidone , quetiapine , and ziprasidone . Olanzapine did not significantly differ from aripiprazole . The proportion of patients who lost response was significantly lower for olanzapine versus risperidone , quetiapine , and ziprasidone ( p < .05 ) . NNTs to avoid one additional patient with loss of response with olanzapine versus risperidone , quetiapine and ziprasidone were favourable , ranging from 5 to 9 . Conclusion During 24 and 28 weeks of treatment , the antipsychotics studied differed in the time that treated patients with schizophrenia remained in response and the proportion of patients who lost response . Olanzapine treatment result ed in a consistent and statistically significant advantage in maintenance of response compared to treatment with risperidone , quetiapine and ziprasidone ; but not compared to treatment with aripiprazole Objectives : Aripiprazole and ziprasidone are 2 antipsychotic medications that are relatively devoid of the metabolic adverse effects associated with the second-generation antipsychotics . This study aim ed to evaluate the effectiveness of switching to ziprasidone in patients who had insufficient response or intolerance to aripiprazole for the treatment of schizophrenia . Methods : Nineteen patients receiving aripiprazole treatment for schizophrenia participated in this open-label 12-week study . Outcome measures included the Positive and Negative Syndrome Scale , Social and Occupational Functioning Assessment Scale , Calgary Depression Scale for Schizophrenia , Beck Depression Inventory , and Subjective Well-being under Neuroleptics Scale . Safety measures included metabolic parameters and scales to evaluate extrapyramidal adverse effects . Results : After switching to ziprasidone from aripiprazole , significant improvement of scores on the negative symptom subscale of the Positive and Negative Syndrome Scale , the Social and Occupational Functioning Assessment Scale , the Calgary Depression Scale for Schizophrenia , and the Beck Depression Inventory were observed at the study end point evaluation . Metabolic parameters including body weight , waist and hip circumferences , fasting blood glucose , and alanine aminotransferase showed statistically significant decreases . However , serum prolactin levels were significantly increased , and sedation was the most common adverse event . Conclusions : Switching to ziprasidone in patients with schizophrenia who showed insufficient response or intolerance to aripiprazole improved depression , negative symptoms , and metabolic disturbances . However , sedation and hyperprolactinemia were commonly associated with the switch to ziprasidone The objective of this study , the effect of aripiprazole on clinical symptoms and cognitive function in patients with chronic schizophrenia was compared to that of perospirone and olanzapine . The subjects were 31 patients , they were diagnosed with schizophrenia on the basis of the criteria of the DSM-IV . Clinical symptoms were assessed using Brief Psychiatric Rating Scale ( BPRS ) , and cognitive function was assessed using the Wisconsin Card Sorting Test ( Keio Version : KWCST ) and the St. Marianna University School of Medicine 's Computerized Memory Test ( STM-COMET ) as executive function and memory/attention function tests at baseline and 8 weeks after switching . As a result , comparison of the BPRS mean total score revealed no significant difference between aripiprazole and the other medications . Aripiprazole result ed in significant changes in the number of categories achieved ( CA ) and difficulty maintaining set ( DMS ) compared to olanzapine at the second level of the KWCST . Comparison thus revealed no difference in clinical effect between aripiprazole and the other medications , but might suggest possible differences between aripiprazole and olanzapine in the profiles of the improvement effects on executive function , memory , and attention function Second-generation antipsychotics ( SGA ) , especially clozapine and olanzapine , are associated with an increased metabolic risk . Recent research showed that plasma adiponectin levels , an adipocyte-derived hormone that increases insulin sensitivity , vary in the same way in schizophrenic patients as in the general population according to gender , adiposity and metabolic syndrome ( MetS ) . The aim of the present study was to investigate whether different SGAs differentially affect plasma adiponectin levels independent of body mass index ( BMI ) and MetS status . 113 patients with schizophrenia ( 65.5 % males , 32.3years old ) who were free of antipsychotic medication were enrolled in this open-label prospect i ve single-center study and received either risperidone ( n=54 ) or olanzapine ( n=59 ) . They were followed prospect ively for 12weeks . Average daily dose was 4.4mg/day for risperidone and 17.4mg/day for olanzapine . Plasma adiponectin levels as well as fasting metabolic parameters were measured at baseline , 6weeks and 12weeks . The two groups had similar baseline demographic and metabolic characteristics . A significant increase in body weight was observed over time . This increase was significantly larger in the olanzapine group than in the risperidone group ( + 7.0 kg versus + 3.1 kg , p<0.0002 ) . Changes in fasting glucose and insulin levels and in HOMA-IR , an index of insulin resistance , were not significantly different in both treatment groups . MetS prevalence increased significantly more in the olanzapine group as compared to the risperidone groups where the prevalence did not change over time . We observed a significant ( p=0.0015 ) treatment by time interaction showing an adiponectin increase in the risperidone-treated patients ( from 10,154 to 11,124ng/ml ) whereas adiponectin levels decreased in olanzapine treated patients ( from 11,280 to 8988ng/ml ) . This effect was independent of BMI and the presence/absence of MetS. The differential effect of antipsychotic treatment ( risperidone versus olanzapine ) on plasma adiponectin levels over time , independent of changes in waist circumference and antipsychotic dosing , suggests a specific effect on adipose tissues , similar to what has been observed in animal models . The observed olanzapine-associated reduction in plasma adiponectin levels may at least partially contribute to the increased metabolic risk of olanzapine compared to risperidone OBJECTIVE In both the United States and Europe there has been an increased interest in using comparative effectiveness research of interventions to inform health policy decisions . Prospect i ve observational studies will undoubtedly be conducted with increased frequency to assess the comparative effectiveness of different treatments , including as a tool for " coverage with evidence development , " " risk-sharing contracting , " or key element in a " learning health-care system . " The principle alternatives for comparative effectiveness research include retrospective observational studies , prospect i ve observational studies , r and omized clinical trials , and naturalistic ( " pragmatic " ) r and omized clinical trials . METHODS This report details the recommendations of a Good Research Practice Task Force on Prospect i ve Observational Studies for comparative effectiveness research . Key issues discussed include how to decide when to do a prospect i ve observational study in light of its advantages and disadvantages with respect to alternatives , and the report summarizes the challenges and approaches to the appropriate design , analysis , and execution of prospect i ve observational studies to make them most valuable and relevant to health-care decision makers . RECOMMENDATIONS The task force emphasizes the need for precision and clarity in specifying the key policy questions to be addressed and that studies should be design ed with a goal of drawing causal inferences whenever possible . If a study is being performed to support a policy decision , then it should be design ed as hypothesis testing-this requires drafting a protocol as if subjects were to be r and omized and that investigators clearly state the purpose or main hypotheses , define the treatment groups and outcomes , identify all measured and unmeasured confounders , and specify the primary analyses and required sample size . Separate from analytic and statistical approaches , study design choices may strengthen the ability to address potential biases and confounding in prospect i ve observational studies . The use of inception cohorts , new user design s , multiple comparator groups , matching design s , and assessment of outcomes thought not to be impacted by the therapies being compared are several strategies that should be given strong consideration recognizing that there may be feasibility constraints . The reasoning behind all study design and analytic choices should be transparent and explained in study protocol . Execution of prospect i ve observational studies is as important as their design and analysis in ensuring that results are valuable and relevant , especially capturing the target population of interest , having reasonably complete and nondifferential follow-up . Similar to the concept of the importance of declaring a prespecified hypothesis , we believe that the credibility of many prospect i ve observational studies would be enhanced by their registration on appropriate publicly accessible sites ( e.g. , clinical trials.gov and encepp.eu ) in advance of their execution INTRODUCTION Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions . The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia . METHODS The study was an 8-week , double-blind , parallel-group , r and omized , controlled multicenter trial ( NCT00145444 ) . Seventy-six patients with schizophreniform disorder , schizophrenia or schizoaffective disorder ( diagnosis < 5 y ) , and a maximum lifetime antipsychotic treatment < 16 weeks participated in the study . Efficacy of ziprasidone ( 80 - 160 mg/d ) and olanzapine 10 - 20 mg was measured using the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression ( CGI ) Scale , the Calgary Depression Scale for Schizophrenia ( CDSS ) , and the Heinrich Quality of Life Scale ( HQLS ) ; tolerability assessment s included laboratory assessment s , body weight , and electroencephalogram . RESULTS Olanzapine ( n = 34 ) and ziprasidone ( n = 39 ) showed equal efficacy as measured by the PANSS , CDSS , CGI , and HQLS . However , mean weight gain was significantly higher in the olanzapine group ( 6.8 vs 0.1 kg , P < .001 ) . Ziprasidone was associated with decreasing levels of triglycerides , cholesterol , and transaminases , while these parameters increased in the olanzapine group ( all P values < .05 ) . There were no significant differences in fasting glucose and prolactin levels or in cardiac or sexual side effects . Patients on ziprasidone used biperiden for extrapyramidal side effects more frequently ( P < .05 ) . DISCUSSION The results of this study indicate that ziprasidone and olanzapine have comparable therapeutic efficacy but differ in their side effect profile . However , there is a risk of a type II error with this sample size . Clinical ly significant weight gain and laboratory abnormalities appear early after initiating treatment and are more prominent with olanzapine , while more patients on ziprasidone received anticholinergic drugs to treat extrapyramidal symptoms OBJECTIVE This study was design ed to evaluate the short-term efficacy and safety of once-daily lurasidone ( 80 mg/day and 160 mg/day ) in the treatment of an acute exacerbation of schizophrenia . METHODS Participants , who were recently admitted in patients with schizophrenia with an acute exacerbation of psychotic symptoms , were r and omly assigned to 6 weeks of fixed-dose , double-blind treatment with lurasidone 80 mg ( n=125 ) , lurasidone 160 mg ( n=121 ) , quetiapine XR 600 mg ( QXR-600 mg ; n=119 ; active control included to test for assay sensitivity ) , or placebo ( n=121 ) , all dosed once daily in the evening . Efficacy was evaluated using a mixed-model repeated- measures analysis of the change from Baseline to Week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score ( the primary efficacy measure ) and Clinical Global Impressions severity ( CGI-S ) score ( the key secondary efficacy measure ) . RESULTS Treatment with both doses of lurasidone or with QXR-600 mg was associated with significantly greater improvement at Week 6 on PANSS total score , PANSS positive and negative subscale scores , and CGI-S score compared with placebo . The endpoint responder rate ( ≥ 20 % improvement in PANSS total score ) was higher in subjects treated with lurasidone 80 mg ( 65 % ; p<0.001 ) , lurasidone 160 mg ( 79 % ; p<0.001 ) , and QXR-600 mg ( 79 % ; p<0.001 ) compared with placebo ( 41 % ) . The proportion of patients experiencing ≥ 7 % weight gain was 4 % for each lurasidone group , 15 % for the QXR-600 mg group , and 3 % for the placebo group . Endpoint changes in levels of cholesterol , triglycerides , and low-density lipoprotein ( LDL ) cholesterol were comparable for both lurasidone groups and placebo , while the QXR-600 mg group showed a significant median increase compared with the placebo group in levels of cholesterol ( p<0.001 ) , LDL cholesterol ( p<0.01 ) , and triglycerides ( p<0.05 ) . CONCLUSIONS Lurasidone 80 mg and 160 mg doses administered once-daily in the evening , were safe and effective treatments for subjects with acute schizophrenia , with increased response rates observed at the higher dose . Dose-related adverse effects were limited , and both doses were generally well-tolerated Background To compare the efficacy and tolerability of paliperidone extended-release ( ER ) with risperidone immediate-release using propensity score methodology . Methods Six double-blind , r and omized , placebo-controlled , short-term clinical trials for acute schizophrenia with availability of individual patient-level data were identified ( 3 per compound ) . Propensity score pairwise matching was used to balance observed covariates between the paliperidone ER and risperidone patient population s. Scores were generated using logistic regression models , with age , body mass index , race , sex , baseline Positive and Negative Syndrome Scale ( PANSS ) total score and baseline Clinical Global Impressions – Severity ( CGI-S ) score as factors . The dosage range of paliperidone ER ( 6 - 12 mg/day ) was compared with 2 risperidone dosage ranges : 2 - 4 and 4 - 6 mg/day . The primary efficacy measure was change in PANSS total score at week 6 end point . Tolerability end points included adverse event ( AE ) reports and weight . AEs with rates ≥5 % and with a ≥2 % difference between paliperidone ER and risperidone were identified . Results Completion rates for placebo-treated subjects in paliperidone ER trials ( n = 95 ) and risperidone trials ( n = 122 ) groups were 36.8 % and 51.6 % , respectively ; end point changes on PANSS total scores were similar ( p = 0.768 ) . Completion rates for subjects receiving paliperidone ER 6 - 12 mg/day ( n = 179 ) , risperidone 2 - 4 mg/day ( n = 113 ) or risperidone 4 - 6 mg/day ( n = 129 ) were 64.8 % , 54.0 % and 66.7 % , respectively ( placebo-adjusted rates : paliperidone ER vs risperidone 2 - 4 mg/day , p = 0.005 ; paliperidone ER vs risperidone 4 - 6 mg/day , p = 0.159 ) . PANSS total score improvement with paliperidone ER was greater than with risperidone 2 - 4 mg/day ( difference in mean change score , -6.7 ; p < 0.05 ) and similar to risperidone 4 - 6 mg/day ( 0.2 ; p = 0.927 ) . Placebo-adjusted AEs more common with paliperidone ER were insomnia , sinus tachycardia and tachycardia ; more common with risperidone were somnolence , restlessness , nausea , anxiety , salivary hypersecretion , akathisia , dizziness and nasal congestion . Weight changes with paliperidone ER and risperidone were similar ( paliperidone ER vs risperidone 2 - 4 mg/day , p = 0.489 ; paliperidone ER vs risperidone 4 - 6 mg/day , p = 0.236 ) . Conclusions This indirect data base analysis suggested that paliperidone ER 6 - 12 mg/day may be more efficacious than risperidone 2 - 4 mg/day and as efficacious as risperidone 4 - 6 mg/day . The AE-adjusted incidence rates suggest differences between treatments that may be relevant for individual patients . Additional r and omized , direct , head-to-head clinical trials are needed to confirm these findings BACKGROUND Available data on atypical antipsychotic-induced weight gain are limited by a number of method ological factors . The objective of this report is to evaluate short-term ( N=1742 ) and long-term ( N=1649 ) weight effects in patients receiving st and ard doses of amisulpride , haloperidol , olanzapine , risperidone , ziprasidone , and placebo based on 21 r and omized , placebo-controlled , parallel-group studies from an integrated clinical trial data base . METHOD Analyses of the integrated ziprasidone schizophrenia trials data base were performed to estimate the weighted average of weight change and the percentage of subjects experiencing weight gain ( or weight loss ) across studies for each agent studied , based on fixed- and r and om-effects models . Duration s of treatment exposure in long-term trials were controlled by well-defined time windows ( 6 month : 150 to 210 days ; 1 year : 330 to 390 days ) . Weight gain or loss was defined using a 7 % change from baseline threshold . RESULTS During long-term therapy with 1-year treatment duration , incidence of weight gain for subjects treated with ziprasidone ( 17 % ) was not significantly different from the placebo ( 13 % ) or haloperidol ( 41 % ) groups based on 95 % confidence interval . In contrast , significantly greater weight gain incidence was observed for the olanzapine ( 57 % ) and risperidone ( 39 % ) groups compared to placebo . Median weight change of + 0.49 , -0.18 , + 1.50 and + 0.55 lb/month was observed for haloperidol , ziprasidone , olanzapine and risperidone subjects , respectively , indicating differential weight change patterns compared to placebo ( -0.32 ) . Similar results were observed for the short-term ( 4 - 12 weeks ) and 6-month treatment exposure cohorts . CONCLUSIONS Our results confirm significant differences in long-term weight effects among atypical antipsychotics , consistent with findings from prior meta- analysis of antipsychotic-induced weight gain [ Allison , D.B. , Mentore , J.L. , Heo , M. , Ch and ler , L.P. , Capelleri , J.C. , Infante , M.C. , Weiden , P.J. , 1999 . Antipsychotic induced weight gain : a comprehensive research synthesis . Am J Psychiatry 156 , 1686 - 1696 ] and the CATIE schizophrenia study [ Lieberman , J.A. , Stroup , T.S. , McEvoy , J.P. , et al. , 2005 . Effectiveness of antipsychotic drugs in patients with chronic schizophrenia . N Engl J Med 353 , 1209 - 1223 ] Schizophrenia is one of the most debilitating disorders with devastating effects on its victims and their families . Atypical antipsychotics ( AAPs ) because of their superior efficacy , reduced side effects , & better compliance , have rapidly become the mainstay of treatment . But , because of paucity of research & literature on the long-term metabolic side effect profile of these AAPs in Indian setup , this prospect i ve study has been carried out to compare the effects of olanzapine & risperidone on body weight , body mass index , & blood sugar level in schizophrenic patients . Among 60 newly diagnosed DSM-IV patients of schizophrenia enrolled , it was observed that mean body weight & BMI were significantly increased from baseline to 6 & 12 weeks in both olanzapine ( n = 30 ) & risperidone groups ( n = 30 ) ( P < 0.001 ) . Also , mean blood sugar was found to be significantly elevated after 6 & 12 weeks of treatment with olanzapine ( P < 0.001 ) but not in risperidone group . Thus , the present study underscores the need for baseline and six weekly monitoring of body weight and blood glucose in routine clinical practice with AAPs Objective The objectives of this study were to evaluate the effects of switching from quetiapine to ziprasidone on weight , safety , and effectiveness Methods In this study , 241 subjects with schizophrenia or schizo affective disorder who had been treated with quetiapine ( ≥300 mg/day ) for ≥3 months with either suboptimal efficacy or poor tolerability were enrolled in a 16-week , open-label , flexible-dose trial , with a 16-week follow-up ( total 32 weeks ) . Quetiapine was tapered and discontinued over the course of 2 weeks , while ziprasidone was titrated up and dosed at 40–80 mg b.i.d . The primary endpoint was weight change ( kg ) from baseline at 16 weeks . Secondary endpoints were change in waist/hip circumference , lipid profile , fasting glucose , and glycosylated hemoglobin ( HbA1c ) . Additional secondary endpoints included changes in scores on the Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impres sions Improvement and Severity Scales ( CGI-I and CGI-S ) , the Calgary Depression Scale for Schizophrenia ( CDSS ) , the Schizophrenia Cognition Rating Scale ( ScoRS ) , and the Global Assessment of Functioning ( GAF ) . Safety measures included adverse event ( AE ) reporting and administration of the Abnormal Involuntary Movement Scale ( AIMS ) . Results At week 16 , there was a small but statistically significant decrease in weight , with a mean change from baseline of −0.73 kg ( 1–sided 95 % upper confidence bound=−0.33 ) using the last observation carried forward [ LOCF ] approach . There were small mean decreases in levels of total cholesterol , low density lipoprotein ( LDL ) , and triglycerides at week 16 , but no change in fasting glucose or HbA1c . At week 16 , there were also significant changes indicating improvement in the secondary clinical assessment s , including the PANSS scores , CGI-S , CDSS , SCoRS and GAF . There was no change in the AIMS . AEs included insomnia ( 12.4 % ) , somnolence ( 13.7 % ) , and nausea ( 9.1 % ) . Conclusion Subjects switching from quetiapine to ziprasidone showed a small but significant decrease in weight as well as improved lipid profiles , regardless of their metabolic status and disease severity at baseline . Subjects also showed improvement in clinical symptoms and in cognitive functioning . Ziprasidone , with a comparatively neutral metabolic profile relative to other antipsychotics , may be an effective treatment alternative for patients experiencing weight gain or lack of tolerability with quetiapine . ( Journal of Psychiatric Practice 2011;17:100–109 ) OBJECTIVE This study compares the efficacy of risperidone and olanzapine to that of first-generation antipsychotics ( FGAs ) in patients with schizophrenia , who failed to show a response to initial trials of FGAs . METHOD This study was an 8-week treatment , r and omized , rater-blind , active-control study with 3 treatment arms . 48 patients , who showed inadequate response to 1 FGA , were enrolled and r and omized into risperidone , olanzapine , or FGA ( haloperidol or trifluoperazine ) groups . They were blindly assessed with the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression Scale-Severity , and the Extrapyramidal Symptom Rating Scale ( ESRS ) at baseline and biweekly . RESULTS All 3 groups demonstrated a significant decrease in the PANSS total , positive , and general scores from baseline to endpoint ( p-values range from 0.003 to 0.021 ) . There were no significant differences among the 3 groups in score changes . The olanzapine group had significant score reductions than the risperidone and FGAs groups in terms of the ESRS subjective total score and did not experience a significant increase in the dose of anticholinergics . The FGA group demonstrated that extrapyramidal syndrome ( EPS ) worsened under an increased dosage of anti-EPS drugs . Olanzapine was associated with significant body weight gain ( 2.69 ± 4.0 kg , p=0.026 ) , but there were no significant group differences on weight gain . CONCLUSIONS Haloperidol or trifluoperazine demonstrated similar efficacy as risperidone or olanzapine for patients with schizophrenia who had failed their first trial with a FGA . Related double-blind , fixed dose studies with a larger sample size are needed to confirm the results of our study OBJECTIVE The purpose of the present study was to evaluate the efficacy and tolerability of olanzapine long-acting injection for maintenance treatment of schizophrenia . METHOD Out patients with schizophrenia who had maintained stability on an oral regimen of olanzapine ( 10 , 15 , or 20 mg/day ) for 4 to 8 weeks were r and omly assigned to 24 weeks of double-blind treatment with " low " ( 150 mg every 2 weeks ; N=140 ) , " medium " ( 405 mg every 4 weeks ; N=318 ) , or " high " ( 300 mg every 2 weeks ; N=141 ) doses of olanzapine long-acting injection ; a very low reference dose of olanzapine long-acting injection ( 45 mg every 4 weeks ; N=144 ) ; or their stabilized dose of oral olanzapine ( N=322 ) . Rates of and time to psychotic exacerbation were estimated using Kaplan-Meier methodology . RESULTS At 24 weeks , the majority of oral olanzapine-treated patients ( 93 % ) , as well as most olanzapine long-acting injection-treated patients receiving high ( 95 % ) , medium ( 90 % ) , low ( 84 % ) , and very low doses ( 69 % ) , remained exacerbation free , with the therapeutic 4-week regimen ( medium dose ) and pooled 2-week regimen ( low and high doses ) demonstrating efficacy similar to that of oral olanzapine as well as to each other . The three st and ard long-acting doses were superior to the very low reference dose based on time to exacerbation . Incidence of weight gain > or = 7 % of baseline was 21 % for oral olanza-pine compared with 21 % , 15 % , 16 % , and 8 % for the high , medium , low , and very low olanzapine long-acting treatment groups , respectively . No clinical ly significant differences were observed between the long-acting injection and oral olanzapine groups in general safety parameters . Few injection-site reactions occurred ( 3 % ) . Two patients experienced sedation and delirium consistent with olanzapine overdose following possible accidental intravascular injection . CONCLUSIONS Olanzapine long-acting injection was efficacious in maintenance treatment of schizophrenia for up to 24 weeks , with a safety profile similar to oral olanzapine except for injection-related adverse events INTRODUCTION Negative symptoms of schizophrenia often predict an unfavorable clinical outcome . Disturbed dopamine transmission in different brain parts may underlie different aspects of negative symptoms , and the effect of antipsychotics on them may also differ . This pilot study investigated the potentially therapeutic effects of the partial dopamine agonist aripiprazole on different negative symptoms . METHODS This pilot study r and omly assigned patients with schizophrenia ( N=40 ) to either aripiprazole or risperidone . After 6 weeks of treatment , the severity of negative symptoms was determined by the PANSS . Subscales of self-report question naires were used to assess differences in initiative , anhedonia , social functioning and subjective well-being . RESULTS Patients treated with aripiprazole showed a significant improvement on measures for anhedonia and subjective wellbeing . Negative symptoms in general , lack of initiative and social inhibition were also lower in the aripiprazole treated group , but without reaching statistical significance . DISCUSSION According to this pilot study , aripiprazole appears to specifically improve anhedonia and subjective wellbeing compared to risperidone . This may be caused by a specific effect of aripiprazole on the limbic branch of the dopamine system . Future studies should replicate this finding with a larger sample size A recent r and omized , open-label , relapse prevention trial ( ConstaTRE ) compared outcomes with risperidone long-acting injectable ( RLAI ) versus the oral atypical antipsychotic quetiapine . This study also included a small descriptive arm in which patients could also be r and omized to aripiprazole . Results of this exploratory analysis are described here . Clinical ly stable adults with schizophrenia or schizoaffective disorder previously treated with oral risperidone , olanzapine , or an oral conventional antipsychotic were r and omized to RLAI or aripiprazole . Efficacy and tolerability were monitored for up to 24 months . A total of 45 patients were treated with aripiprazole ( 10–30 mg/day ) and 329 patients with RLAI ( 25–50 mg i.m . every 2 weeks ) . Relapse occurred in 27.3 % ( 95 % CI : 15.0–42.8 % ) of aripiprazole-treated and 16.5 % ( 95 % CI : 12.7–21.0 % ) of RLAI-treated patients . Kaplan – Meier estimates of mean ( st and ard error ) relapse-free period were 313.7 ( 20.4 ) days for aripiprazole and 607.1 ( 11.4 ) days for RLAI patients . Remission was achieved by 34.1 % ( 95 % CI : 20.5–49.9 % ) of aripiprazole and 51.1 % ( 95 % CI : 45.5–56.6 % ) of RLAI patients . Clinical global impression – change was improved ( “ minimally improved ” to “ very much improved ” ) in 26.4 % with RLAI and 15.9 % with aripiprazole patients . Tolerability was generally good for both treatment groups . Weight gain ( 7.0 % with RLAI vs. 4.4 % with aripiprazole ) , extrapyramidal adverse events ( AEs ) ( 10.3 % vs. 4.4 % ) , and potentially prolactin-related AEs ( 4.6 % vs. 0 % ) were more common with RLAI treatment , and gastrointestinal disorders were more common in aripiprazole-treated patients ( 22.2 % vs. 6.1 % ) . Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was numerically longer in RLAI-treated patients than in aripiprazole-treated patients although not statistically significant . Both treatments were generally well tolerated INTRODUCTION Aripiprazole , a dopamine D2 receptor partial agonist , has also partial agonist activity at serotonin (5-HT)1A receptors and antagonist activity at 5-HT2A receptors . METHODS In this 8-week , multicenter , r and omized , parallel-group , open-label , flexible-dose study , patients diagnosed with schizophrenia or schizoaffective disorder were r and omized to aripiprazole 15 - 30 mg/day or haloperidol 10 - 15 mg/day . RESULTS Patients treated with both aripiprazole and haloperidol improved from baseline in Positive and Negative Syndrome Scale total , positive , and negative scores as well as in Clinical Global Impressions scores ( all P<.001 ) . At the end of the study , the percentage of patients classified as responders -- according to > or=40 % reduction in the Positive and Negative Syndrome Scale negative subscale score -- was significantly higher in the aripiprazole group ( 20 % ) than in the haloperidol group ( 0 % ) ( P<.05 ) . Additionally , a higher number of patients receiving haloperidol required more anticholinergic medications ( P<.001 ) than aripiprazole-treated patients , whereas more aripiprazole ( 45.5 % ) than haloperidol-treated patients ( 12.9 % ) required benzodiazepines ( P=.002 ) . At endpoint , rates of preference of medication were higher in the aripiprazole group ( 63.2 % ) than in the haloperidol group ( 21.7 % ) , as expressed by patients and caregivers ( P=.001 ) . CONCLUSION Aripiprazole and haloperidol had similar efficacy in terms of reduction of overall psychopathology . Although aripiprazole has been demonstrated to be superior concerning negative symptoms and in terms of tolerability ( extrapyramidal symptoms ) and preferred by patients and caregivers than haloperidol , significantly more aripiprazole-treated patients required benzodiazepines The efficacy , safety and tolerability of ziprasidone versus the comparators olanzapine , risperidone or quetiapine were investigated in adult patients with chronic schizophrenia , schizoaffective and schizophreniform disorders , with lack of efficacy or intolerance to their previous antipsychotic treatment based on clinical judgement of the investigator . A total of 293 patients were r and omized to 12 weeks treatment with either ziprasidone 80–160 mg/day ( n=147 ) or with one of the comparator drugs ( n=146 ) . In the latter group the investigator could choose between olanzapine 10–20 mg/day ( n=24 ) , risperidone 4–8 mg/day ( n=22 ) or quetiapine 300–750 mg/day ( n=97 ) . The study comprised four visits including a baseline examination prior to r and omization and further examinations at the end of weeks 1 , 4 and 12 . Ziprasidone was non-inferior ( defined as a difference of = 7 units or less on the PANSS scale to the disadvantage of ziprasidone . ) to the composite group ( olanzapine , risperidone or quetiapine ) on the total PANSS score as well as on all subscores ( P<0.0001 ) ; there were no significant between-group differences in the CGI-S and I and UKU scores . Ziprasidone-treated patients lost an average of 2.1 kg in the 12 weeks of the study , the mean weight for risperidone and quetiapine remained unchanged , and patients receiving olanzapine gained 3.1 kg on average SOHO is a 3-year , prospect i ve , observational study of schizophrenia patients who started a new antipsychotic in 10 European countries . Cohorts of patients were defined according to the antipsychotic started at baseline : olanzapine , risperidone , quetiapine , amisulpride , clozapine , oral typical and depot typical antipsychotics . Tolerability in terms of rates of extrapyramidal symptoms ( EPS ) , tardive dyskinesia ( TD ) , anticholinergic use , loss of libido/impotence , amenorrhoea/galactorrhoea/gynaecomastia , and weight change was assessed in 4939 patients who started monotherapy . Logistic regression models related medication initiated at study entry to adverse events over follow-up , adjusting by baseline differences among treatment cohorts . Patients taking typical antipsychotics or risperidone were more likely to experience EPS and TD during follow-up than patients taking olanzapine . Patients taking olanzapine were less likely to have loss of libido/impotence during follow-up than patients in the risperidone , amisulpride , clozapine , oral typical and depot typical cohorts . Weight gain occurred in all groups , but was greater with olanzapine . In conclusion , antipsychotics have different tolerability profiles in terms of the adverse events we monitored . Results should be interpreted conservatively due to the observational study design OBJECTIVE To compare the effects of haloperidol , amisulpride , olanzapine , quetiapine , and ziprasidone on hostility in first-episode schizophrenia , schizoaffective disorder , or schizophreniform disorder . METHOD We used the data acquired in the European First-Episode Schizophrenia Trial , an open , r and omized trial ( conducted in 14 countries ) comparing 5 antipsychotic drugs in 498 patients aged 18 - 40 years with first-episode schizophrenia , schizoaffective disorder , or schizophreniform disorder . DSM-IV diagnostic criteria were used . Patients were assessed between December 23 , 2002 and January 14 , 2006 . Most subjects joined the study as in patients and then continued with follow-ups in outpatient clinic visits . The Positive and Negative Syndrome Scale ( PANSS ) was administered at baseline and at 1 , 3 , 6 , 9 , and 12 months after r and omization . We analyzed the scores on the PANSS hostility item in a subset of 302 patients showing at least minimal hostility ( a score > 1 ) at baseline . We hypothesized ( 1 ) that the treatments would differ in their efficacy for hostility and ( 2 ) that olanzapine would be superior to haloperidol . Our primary statistical analysis tested the null hypothesis of no difference among the treatment groups in change in hostility over time . Secondary analysis addressed the question of whether the effects on hostility found in the primary analysis were specific to this item . All our analyses were post hoc . RESULTS The primary analysis of hostility indicated an effect of differences between treatments ( F(4,889 ) = 4.02 , P = .0031 ) . Post hoc treatment-group contrasts for hostility change showed that , at months 1 and 3 , olanzapine was significantly superior ( P < .05 ) to haloperidol , quetiapine , and amisulpride in reducing hostility . Secondary analyses demonstrated that these results were at least partly specific to hostility . CONCLUSIONS Both hypotheses were supported . Olanzapine appears to be a superior treatment for hostility in early phases of therapy for first-episode schizophrenia , schizoaffective disorder , and schizophreniform disorder . This efficacy advantage of olanzapine must be weighed against its adverse metabolic effects and propensity to cause weight gain . TRIAL REGISTRATION IS RCT N Register Identifier : IS RCT N68736636 Data from the 3-year , prospect i ve , observational SOHO study were used to compare the effectiveness ( in terms of treatment discontinuation ) and the tolerability of olanzapine , risperidone , other atypicals and typical antipsychotics in 1009 previously untreated out patients with schizophrenia who started monotherapy at baseline . Kaplan-Meier survival analysis estimated the time to treatment discontinuation by the treatment group , Cox proportional hazards regression models identified the variables associated with treatment discontinuation ( adjusted for baseline differences between treatment groups ) , and logistic regression models compared the tolerability profiles of the different treatment groups . Of the 931 patients analyzed , 31.9 % discontinued the medication initiated at baseline during the 3-year follow-up . Olanzapine had the lowest rate of discontinuation ( 28.9 % ) , followed by other atypical ( 34.0 % ) , risperidone ( 36.2 % ) and typical antipsychotics ( 44.5 % ) . Compared to olanzapine , risk of treatment discontinuation was higher with typical antipsychotics ( hazard ratio [ HR ] 1.75 ; 95 % confidence interval [ CI ] 1.11 , 2.78 ) or risperidone ( HR 1.36 ; 95 % CI 1.02 , 1.82 ) . A higher baseline Clinical Global Impression ( CGI ) positive score was associated with a higher risk of treatment discontinuation ( HR 1.18 ; 95 % CI 1.06 , 1.30 ) . Olanzapine was associated with a lower frequency of extrapyramidal symptoms than other antipsychotics , fewer prolactin-related adverse events than risperidone and other atypical antipsychotics , but greater weight gain than typicals and risperidone . For all analyses , comparison with the other atypical group is limited due to its small sample size ( n=50 ) . In conclusion , treatment effectiveness and tolerability varied among antipsychotic medications in previously untreated patients with schizophrenia . The results should be interpreted conservatively given the observational study design OBJECTIVE The Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) study examined the comparative effectiveness of antipsychotic treatments for individuals with chronic schizophrenia . Patients who had discontinued antipsychotic treatment in phases 1 and 2 were eligible for phase 3 , in which they selected one of nine antipsychotic regimens with the help of their study doctor . We describe the characteristics of the patients who selected each treatment option and their outcomes . METHOD Two hundred and seventy patients entered phase 3 . The open-label treatment options were monotherapy with oral aripiprazole , clozapine , olanzapine , perphenazine , quetiapine , risperidone , ziprasidone , long-acting injectable fluphenazine decanoate , or a combination of any two of these treatments . RESULTS Few patients selected fluphenazine decanoate ( n=9 ) or perphenazine ( n=4 ) . Similar numbers selected each of the other options ( range 33 - 41 ) . Of the seven common choices , those who selected clozapine and combination antipsychotic treatment were the most symptomatic , and those who selected aripiprazole and ziprasidone had the highest body mass index . Symptoms improved for all groups , although the improvements were modest for the groups starting with relatively mild levels of symptoms . Side effect profiles of the medications varied considerably but medication discontinuations due to intolerability were rare ( 7 % overall ) . CONCLUSIONS Patients and their doctors made treatment selection s based on clinical factors , including severity of symptoms , response to prior treatments , and physical health status . Fluphenazine decanoate was rarely used among those with evidence of treatment non-adherence and clozapine was underutilized for those with poor previous response . Combination antipsychotic treatment warrants further study INTRODUCTION Although some previous studies have compared the 2 medicines , ziprasidone and olanzapine most selected chronic patients as subjects . Therefore , the present study was design ed to compare the efficacy and safety of ziprasidone vs. olanzapine in naive first-episode schizophrenia . METHODS 80 patients were r and omly assigned to a 6-week treatment either with 80 - 160 mg/day of ziprasidone or 10 - 20 mg/day of olanzapine . The primary efficacy measurements were the Positive and Negative Syndrome Scale and Clinical Global Impression-severity scale scores . The second efficacy measurement was the response rate of treatment . Tolerability assessment s were also performed . RESULTS 79 patients completed the trial . The average dose was 127.5 mg/day with ziprasidone and 19.1 mg/day with olanzapine . No significant differences were found between the 2 groups in primary or secondary efficacy measurements at each visit point ( all p>0.05 ) . Body weight significantly increased with olanzapine , and more extrapyramidal symptoms were observed with ziprasidone ( all p<0.05 ) . Both medicines were well tolerated , and no serious adverse events were observed . CONCLUSION Ziprasidone was as effective as olanzapine in short-term treatment for first-episode schizophrenia , and both medicines were well tolerated BACKGROUND Lurasidone is a new atypical antipsychotic agent with high affinity for D(2 ) , 5-HT(2A ) and 5-HT(7 ) receptors . The current study evaluated the safety and efficacy of lurasidone and ziprasidone in stable out patients diagnosed with schizophrenia or schizoaffective disorder . METHODS Adult out patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder that was chronic ( ≥6 months duration ) and stable were r and omized to 21 days of double-blind treatment with a fixed dose of lurasidone 120 mg once daily ( N=150 ) or ziprasidone 80 mg BID ( N=151 ) . Changes from baseline in efficacy measures were evaluated using mixed model for repeated measures ( MMRM ) analyses . RESULTS The proportion of patients who discontinued from the study was similar for lurasidone and ziprasidone ( 32.5 % vs. 30.7 % ) ; the proportion who discontinued due to adverse events was similar ( 10.4 % vs. 11.1 % ) . Treatment with lurasidone and ziprasidone was associated with a small endpoint reduction in median weight ( -0.65 kg vs. -0.35 kg ) and median total cholesterol ( -6.4 vs. -4.4 mg/dL ) ; no endpoint change was observed in median triglycerides ( 0.0 vs. 0.0 mg/dL ) . There were no clinical ly significant changes in other laboratory or ECG parameters . Improvement was observed on an MMRM analysis of the PANSS total score for lurasidone and ziprasidone at Week 1 ( -4.1 vs. -1.6 ; P=0.020 ) , Week 2 , ( -6.1 vs. -3.6 ; P=0.074 ) , and Week 3 ( -6.3 vs. -4.5 ; P=0.229 ) . CONCLUSION In this double-blind , fixed-dose comparison of lurasidone 120 mg and ziprasidone 160 mg , treatment with lurasidone was well-tolerated and safe , and was not associated with clinical ly significant changes from baseline in weight , metabolic parameters , or QTc interval . Study limitations include the relatively short trial duration and lack of placebo control Abstract Objective : Information about the cost-effectiveness of aripiprazole relative to other atypical antipsychotics in the treatment of patients with schizophrenia is limited . This information is needed to better inform drug formulary managers and population -based health care decision makers . The objective of this study was to compare the cost-effectiveness of olanzapine to aripiprazole in the treatment of schizophrenia from the perspective of public payers in the United States . Methods : Data for this post-hoc analysis came from a 28-week double-blind , r and omized trial of individuals with schizophrenia who were treated with olanzapine or aripiprazole ( clinical trial.gov identifier NCT00088049 ) . Two-thirds ( 67.7 % ) of the patients were male and the patients ’ mean age was 37.6 years . Utilities were calculated based on previously published methods using the Positive and Negative Syndrome Scale ( PANSS ) and treatment-emergent adverse events . Treatment costs were calculated based on previously published methods and were inflated to 2008 US dollars . A mixed model was used to compare outcomes on utilities . Propensity score-adjusted analysis of covariance was used for the cost analysis . Results : Olanzapine treatment was associated with statistically significantly greater total utility scores relative to aripiprazole ( 0.78 vs. 0.76 ; p = 0.024 ) and lower total treatment costs ( $ 22,831 vs. $ 24,749 ; p = 0.013 ) , although medication acquisition cost was significantly higher for olanzapine than aripiprazole ( $ 3524 vs. $ 2637 ; p < 0.001 ) . An incremental cost-effectiveness ratio was not calculated because olanzapine was found to be the dominant choice ( i.e. , greater effectiveness and lower total costs ) . Conclusions : This cost-effectiveness analysis is the first to use patient-level data from a r and omized , double-blind study comparing olanzapine and aripiprazole in the treatment of patients with schizophrenia . Olanzapine was found to be a dominant cost-effective choice , as it was associated with greater effectiveness at lower total costs relative to aripiprazole OBJECTIVE The study was design ed to evaluate the short-term efficacy and safety of lurasidone in the treatment of acute schizophrenia . METHOD Participants , who were recently admitted in patients with schizophrenia with an acute exacerbation of psychotic symptoms , were r and omly assigned to 6 weeks of double-blind treatment with 40 mg of lurasidone , 120 mg of lurasidone , 15 mg of olanzapine ( included to test for assay sensitivity ) , or placebo , dosed once daily . Efficacy was evaluated using a mixed-model repeated- measures analysis of the change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score ( as the primary efficacy measure ) and Clinical Global Impressions severity ( CGI-S ) score ( as the key secondary efficacy measure ) . RESULTS Treatment with both doses of lurasidone or with olanzapine was associated with significantly greater improvement at week 6 on PANSS total score , PANSS positive and negative subscale scores , and CGI-S score compared with placebo . There was no statistically significant difference in mean PANSS total or CGI-S change scores for the lurasidone groups compared with the olanzapine group . With responders defined as those with an improvement of at least 20 % on the PANSS , endpoint responder rates were significant compared with placebo for olanzapine only . The incidence of akathisia was higher with 120 mg of lurasidone ( 22.9 % ) than with 40 mg of lurasidone ( 11.8 % ) , olanzapine ( 7.4 % ) , or placebo ( 0.9 % ) . The proportion of patients experiencing ≥ 7 % weight gain was 5.9 % for the lurasidone groups combined , 34.4 % for the olanzapine group , and 7.0 % for the placebo group . CONCLUSIONS Lurasidone was an effective treatment for patients with acute schizophrenia . Safety assessment s indicated a higher frequency of adverse events associated with 120 mg/day of lurasidone compared with 40 mg/day INTRODUCTION This study aim ed to compare the effects of the two most commonly prescribed atypical antipsychotics , olanzapine and risperidone , on fasting blood sugar and serum lipid profile of the recipients . METHODS A r and omised , comparative , open clinical study was conducted on 60 schizophrenic patients . The patients were divided into two groups , one receiving olanzapine and the other receiving risperidone . The patients were assessed for changes in fasting blood sugar and serum lipid profile ( triglycerides [ TG ] , high-density lipoprotein [ HDL ] , low-density lipoprotein [ LDL ] , very-low-density lipoprotein [ VLDL ] and total cholesterol ) eight weeks after starting treatment . The number of patients positive for fasting blood sugar and lipid profile criteria of metabolic syndrome was calculated by applying the modified National Cholesterol Education Programme Adult Treatment Panel III guidelines ( NCEP ATP III ) criteria at eight weeks . RESULTS Patients treated with olanzapine showed a highly significant increase in the observed parameters , whereas those treated with risperidone showed a significant increase in fasting blood sugar , HDL and LDL levels , and a highly significant increase in other parameters . Intergroup comparison was insignificant except for TG , VLDL and total cholesterol levels . More men as compared to women fulfilled the NCEP ATP III criteria for metabolic syndrome in both groups . CONCLUSION Olanzapine has a higher propensity to cause derangement of some parameters of lipid profile than risperidone . These parameters include TG , VLDL and total cholesterol levels BACKGROUND Weight change data from r and omized clinical trials are often of limited duration and trials do not always report a full range of clinical ly relevant categorical end points . METHOD We conducted a post hoc analysis of data from the observational Worldwide Schizophrenia Outpatient Health Outcomes data base ( 2000 - 2005 ) on weight change in 4,626 patients completing 3 years of antipsychotic monotherapy with amisulpride , clozapine , olanzapine , quetiapine , risperidone , and oral and depot first-generation antipsychotics ( FGAs ) . Reported outcomes included mean and categorical weight changes and the trajectories of different measures of weight change . RESULTS Mean weight gain was lowest with amisulpride ( 1.8 kg ; 95 % CI , 0.2 - 3.3 ) and highest with olanzapine ( 4.2 kg ; 95 % CI , 3.9 - 4.5 ) . Weight change for all antipsychotics was most rapid during the first 6 months ; subsequent weight change was slower but did not plateau . All drugs showed considerable individual variation in weight change . The proportion losing ≥7 % of their baseline bodyweight was highest with quetiapine ( 10 % ; 95 % CI , 7%-16 % ) and lowest with depot FGAs ( 5 % ; 95 % CI , 3%-10 % ) . Between 7 % and 15 % of patients moved into an overweight or obese body mass index (kg/m2)category ( ≥25 ) . CONCLUSIONS The degree of weight gain varied between antipsychotics . All antipsychotics were associated with significant ( ≥7 % ) weight loss and gain from baseline . The mean rate of weight gain was maximal during the first 6 months but continued over 3 years without a plateau in this specific cohort . Patients should receive regular monitoring of weight throughout treatment OBJECTIVE To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders . METHOD Patients ( 8 to 19 years old ) who had improved during an 8-week , r and omized , double-blind acute trial of olanzapine , risperidone , or molindone ( plus benztropine ) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions . Adjunctive medications were allowed according to defined algorithms . St and ardized symptom , safety , and functional assessment s were conducted every 4 weeks . RESULTS Of the 116 youths r and omized in the acute trial , 54 entered maintenance treatment ( molindone , n = 20 ; olanzapine , n = 13 ; risperidone , n = 21 ) . Fourteen ( 26 % ) completed 44 weeks of treatment . Adverse effects ( n = 15 ) , inadequate efficacy ( n = 14 ) , or study nonadherence ( n = 8) were the most common reasons for discontinuation . The three treatment arms did not significantly differ in symptom decrease or time to discontinuation . Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone . Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial , no significant between-drug differences emerged in most of these parameters during maintenance treatment . CONCLUSIONS Only 12 % of youths with early-onset schizophrenia spectrum disorders continued on their originally r and omized treatment at 52 weeks . No agent demonstrated superior efficacy , and all were associated with side effects , including weight gain . Improved treatments are needed for early-onset schizophrenia spectrum disorders . Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents ; URL : http://www . clinical trials.gov , unique identifier : NCT00053703 OBJECTIVE This multisite r and omized trial addressed risks and benefits of staying on long-acting injectable haloperidol or fluphenazine versus switching to long-acting injectable risperidone microspheres . METHOD From December 2004 through March 2008 , adult out patients with a Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition diagnosis of schizophrenia or schizoaffective disorder who were taking haloperidol decanoate ( n = 40 ) or fluphenazine decanoate ( n = 22 ) were r and omly assigned to stay on current long-acting injectable medication or switch to risperidone microspheres and followed for 6 months under study protocol and an additional 6 months naturalistic follow-up . Kaplan-Meier and Cox regression analyses were used to examine the primary outcome ( time to treatment discontinuation ) , and r and om regression models were used to examine secondary outcomes . RESULTS Groups did not differ significantly in time to treatment discontinuation through 6 months of protocol -driven treatment . When the 6-month naturalistic follow-up period was included , time to treatment discontinuation was significantly shorter for individuals assigned to switch than for individuals assigned to stay ( 10 % of stayers discontinued versus 31 % of switchers ; P = .01 ) . Groups did not differ with respect to psychopathology , hospitalizations , sexual side effects , new-onset tardive dyskinesia , or new-onset extrapyramidal symptoms . However , those r and omized to switch to long-acting injectable risperidone microspheres had greater increases in body mass ( increase of 1.0 body mass index [ BMI ] versus decrease of -0.3 BMI ; P = .00 ) and prolactin ( maximum increase to 23.4 ng/mL versus decrease to 15.2 ng/mL , P = .01 ) compared to those r and omized to stay . CONCLUSION Switching from haloperidol decanoate or fluphenazine decanoate to risperidone microspheres result ed in more frequent treatment discontinuation as well as significant weight gain and increases in prolactin . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00044655 Objective : This r and omized , double-blind , multicentre extension study compared the efficacy , tolerability , and safety of ziprasidone and risperidone for schizophrenia or schizoaffective disorder . Methods : Patients who had responded to treatment for an acute exacerbation of illness in an 8–week study received ziprasidone , 80 to 160 mg/day ( n = 62 ) , or risperidone , 6 to 10 mg/day ( n = 77 ) , for up to 44 additional weeks . Primary efficacy variables included changes in Positive and Negative Syndrome Scale ( PANSS ) total score and Clinical Global Impression Severity ( CGI-S ) score . Tolerability and safety assessment s included movement disorders , adverse events , study discontinuation rates , and weight and metabolic parameters . Results : Both the ziprasidone and risperidone groups showed statistical improvement from baseline in PANSS and CGI-S scores at study end point with no significant differences between treatment groups . More risperidone-treated patients completed the study ( 41.6 % ) than ziprasidone-treated patients ( 33.9 % ) , but the difference was not statistically significant . Ziprasidone-treated patients who completed the study showed greater improvement in depressive symptoms assessed by Montgomery and Asberg Depression Rating Scale than risperidone-treated patients ( P < 0.05 ) . Ziprasidone was associated with a more favourable effect on extrapyramidal symptom ( EPS ) measures and prolactin as well as less weight gain than risperidone . Median dosages were ziprasidone 120 mg/day and risperidone 8 mg/day . Conclusions : Ziprasidone and risperidone demonstrated similar efficacy during long-term treatment of patients with schizophrenia or schizoaffective disorder . While more subjects on risperidone completed the extension study , ziprasidone was associated with fewer adverse effects on weight , EPS measures , and prolactin than risperidone PURPOSE Although olanzapine may have advantages over other second-generation antipsychotics ( SGAs ) regarding longer time to treatment discontinuation among chronically ill patients , little evidence has been provided for the comparative effectiveness of SGAs in the acute phase . We aim ed to determine if any of four SGAs were more effective in treating newly admitted acute schizophrenic patients . We performed a rater-blinded , r and omized controlled trial of four SGAs in 15 psychiatric emergency sites . Eligible patients were 18 - 64 years old and met diagnostic criteria for schizophrenia , acute schizophrenia-like psychotic disorder , or schizoaffective disorder . A final total of 78 patients were r and omly assigned by means of sealed envelopes to receive risperidone ( 3 - 12 mg/day ; n=20 ) , olanzapine ( 10 - 20 mg/day ; n=17 ) , quetiapine ( 300 - 750 mg/day ; n=20 ) , or aripiprazole ( 12 - 30 mg/day ; n=21 ) , with follow-up at 8 weeks . The primary outcome measure was all-cause treatment discontinuation . RESULTS Overall , 37 % ( 29/78 ) of patients discontinued the study medication before 8 weeks : 25 % for risperidone ; 12 % for olanzapine ; 55 % for quetiapine ; and 52 % for aripiprazole . Time to treatment discontinuation for any cause was significantly longer in the olanzapine group than in the quetiapine ( p=0.006 ) or aripiprazole ( p=0.008 ) groups , but not compared to the risperidone group ( p=0.32 ) . Time to treatment discontinuation was significantly longer in the risperidone group than in the quetiapine group ( p=0.048 ) , but not compared to the aripiprazole group ( p=0.062 ) . However , the rate of p.r.n . intramuscular haloperidol use was significantly higher in the aripiprazole group than in other groups ( p=0.029 ) . CONCLUSION Olanzapine and risperidone are superior to quetiapine and aripiprazole for the acute treatment of psychosis in hospitalized patients Abstract Two r and omized , double-blind , 26-week core studies ( Eastern [ EH ] and Western Hemisphere [ WH ] ) tested the hypothesis that asenapine is superior to olanzapine for persistent negative symptoms of schizophrenia ; 26-week extension studies assessed the comparative long-term efficacy and safety of these agents . In the core studies , 949 people were r and omized to asenapine ( n = 241 and 244 ) or olanzapine ( n = 240 and 224 ) ; 26-week completion rates with asenapine were 64.7 % and 49.6 % ( olanzapine , 80.4 % and 63.8 % ) in the EH and WH , respectively . In the EH and WH extensions , respectively ( asenapine , n = 134 and 86 ; olanzapine , n = 172 and 110 ) , 52-week completion rates were 84.3 % and 66.3 % with asenapine ( olanzapine , 89.0 % and 80.9 % ) . Asenapine was not superior to olanzapine in change in the 16-item Negative Symptom Assessment Scale total score in either core study , but asenapine was superior to olanzapine at week 52 in the WH extension study . Olanzapine was associated with modest , but significantly greater , changes in PANSS positive subscale score at various assessment times in both core studies and the WH extension study . Incidence of treatment-emergent adverse events was comparable between treatments across studies . Weight gain was consistently lower with asenapine . Extrapyramidal symptom – related adverse event incidence was higher with asenapine ( EH : 8.3 % ; 95 % confidence interval [ CI ] , 5.1%–12.5 % ; WH : 16.4 % ; 95 % CI , 11.9%–21.6 % ) than olanzapine ( EH : 3.3 % ; 95 % CI , 1.4%–6.4 % ; WH : 12.1 % ; 95 % CI , 8.1%–17.0 % ) , but Extrapyramidal Symptom Rating Scale – Abbreviated total score changes did not significantly differ between treatments . In conclusion , asenapine superiority over olanzapine was not observed in the core studies . Both treatments improved persistent negative symptoms , but discontinuation rates were higher with asenapine PURPOSE We examined whether early response/non-response to risperidone according to the Clinical Global Impressions-improvement scale ( CGI-I ) at 2 weeks could predict subsequent response . This prediction was also applied to olanzapine . We then investigated whether early non-responders ( ENRs ) to risperidone or olanzapine who switched to the other showed significantly greater improvement , compared with those staying on the initial antipsychotic . We performed a rater-blinded , r and omized controlled trial in 18 psychiatric emergency sites . Eligible patients were newly admitted patients with acute schizophrenia . Early response was defined as CGI-I ≤ 3 following 2 weeks of treatment . The primary outcome measure was achievement of remission and ≥ 50 % improvement in the Positive and Negative Syndrome Scale at 4 weeks . RESULTS At 4 weeks , 53 % of risperidone early responders ( ERs ) went into remission , whereas only 9 % of ENRs staying on risperidone ( n=11 ) did ( P=0.016 ) . Similarly , at 4 weeks , 81 % of risperidone ERs achieved ≥ 50 % response , whereas only 9 % of ENRs staying on risperidone achieved ≥ 50 % response ( P < 0.0001 ) . In contrast , 58 % of olanzapine ERs ( n=33 ) went into remission , whereas 38 % of ENRs staying on olanzapine ( n=8 ) did at 4 weeks ( P=0.44 ) . Similarly , 61 % of olanzapine ERs achieved ≥ 50 % response , whereas 25 % of ENRs staying on olanzapine achieved ≥ 50 % response ( P=0.12 ) . The negative likelihood ratio for the prediction of ≥ 50 % response at 4 weeks by early response status to risperidone at 2 weeks was 0.057 . CONCLUSION In newly admitted patients with acute schizophrenia , non-response to risperidone using CGI-I at 2 weeks can predict subsequent response . It looks like there is significant response to olanzapine that does n't occur until 4 weeks . Thus , clinicians may want to switch to another drug earlier when risperidone is the first drug , and later when olanzapine is the first drug Objective Although weight gain is one of the most widely studied adverse effects of second-generation antipsychotics , only relatively few studies have specifically evaluated the long-term effect of switching antipsychotic medication on body weight . We aim ed to evaluate the impact of switching antipsychotics on body mass index ( BMI ) during a 6-month follow-up period in a large cohort of patients with schizophrenia . Method Data came from a 6-month prospect i ve naturalistic survey in 6007 patients with schizophrenia . Results We prospect ively studied the effect on BMI of initiating or switching antipsychotic medication after 6 months of treatment among 3801 patients with schizophrenia in a real-life setting . Patients who were being treated with clozapine or olanzapine at baseline were more likely to experience a decrease in BMI during the follow-up period than the patients who were being treated with a conventional antipsychotic ( odds ratio , 2.25 and 1.68 , respectively ) . Patients treated with aripiprazole and , to a lesser extent , those treated with risperidone were more likely to experience a decrease in BMI during follow-up than patients treated with conventional antipsychotics ( odds ratio , 2.96 and 2.06 , respectively ) . Conclusions Our findings suggest that switching antipsychotics could be an effective strategy for reducing or preventing weight gain The incidence of treatment-emergent extrapyramidal symptoms ( EPSs ) and tardive dyskinesia ( TD ) in schizophrenic patients , and the clinical characteristics associated with an increased risk of developing EPSs and TD were examined . Patients ( N = 7728 ) in the 3-year , prospect i ve , observational Schizophrenia Outpatient Health Outcomes study were examined according to baseline antipsychotic drug exposure . At baseline , 4893 patients ( 63.3 % ) had no EPS , and 6921 ( 89.6 % ) had no TD . Extrapyramidal symptoms and TD were assessed separately during follow-up : frequency and time to appearance from Kaplan-Meier survival curves and factors associated with time to appearance using Cox proportional hazard regression models . The cumulative incidence of EPS ranged from 7.7 % ( olanzapine ) to 32.8 % ( depot typical drugs ) . Compared with olanzapine , patients taking depot typical drugs , oral typical drugs , risperidone , and amisulpride had a significantly higher risk of developing EPS . Differences from clozapine were marginally significant . High baseline clinical severity was associated with a significantly higher risk of developing EPS . The incidence of TD ranged from 2.8 % ( olanzapine ) to 11.1 % ( depot typical agent ) . Compared with olanzapine , patients taking depot typical agents , oral typical agents , and risperidone had a significantly higher risk of developing TD . Baseline factors associated with a significantly higher risk of developing TD were age , EPS , a higher negative Clinical Global Impression score , and presence of gynecomastia . In summary , patients treated with typical antipsychotic agents ( oral and depot ) and risperidone had a higher risk of developing EPS and TD than patients treated with olanzapine . Higher baseline clinical severity was associated with EPS development , whereas age , presence of EPS , a higher negative Clinical Global Impression score , and presence of gynecomastia were associated with TD development We conducted a secondary analysis of a completed study of the differential efficacy and side effects of aripiprazole versus haloperidol in early-stage schizophrenia ( ESS ) , a sub population of patients which does not include first episode or chronic patients . A sub population of 360 individuals with ESS were identified from a r and omized , multi-center , double-blind study of 1294 individuals with schizophrenia at different stages of illness who were r and omized to treatment with aripiprazole ( ESS = 237 ) or haloperidol ( ESS = 123 ) for one year . The primary outcome measure was response rate based on a 50 % reduction of Positive and Negative Syndrome Scale ( PANSS ) total scores . Secondary outcomes included several efficacy and safety measures , as well as treatment discontinuation . More individuals in the aripiprazole group ( 48 % ) than in the haloperidol group ( 28 % ; p < 0.01 ) completed the study . Response rates were greater in the aripiprazole group ( 38 % [ N = 91 ] ) than in the haloperidol group ( 22 % [ N = 27 ] ; p < 0.01 ) . Aripiprazole was associated with fewer extrapyramidal side effects . ESS subjects in the haloperidol group were more likely than those in the aripiprazole group to discontinue the study drug due to an adverse event other than worsening illness ( 29 % and 11 % , respectively ; p < 0.01 ) , and efficacy differences were reduced by interventions to mitigate side effects ( decreasing antipsychotic dose with or without adding antiparkinsonian medication ) . Aripiprazole has a favorable efficacy/safety profile in ESS and appeared to be superior to haloperidol on a number of efficacy and safety outcomes . However , excessive dosing of the antipsychotic medications , in particular haloperidol , may have played an important role in accounting for the differences between aripiprazole and haloperidol in this study Background : Despite much being written on the topic , there are few surveys investigating the prevalence of anticholinergic adverse effects of antipsychotic drugs . One study , however , used trial-derived data to calculate estimates . Objectives : To investigate the prevalence/incidence rates of anticholinergic effects as viewed from within relevant r and omized trials . Methods : Data were extracted from each relevant study included in Cochrane review s. Data were checked , extracted , and simple frequencies , and 95 % confidence intervals ( CIs ) were calculated . Results : Many trials in relevant review s reported no data on anticholinergic effects ( estimate 40,000 participants ) . However , data were extracted from 177 studies within 54 review s ( N = 27,328 participants ) . Most data are short-term ( < 12 weeks ) . For blurred vision , the newer generations of drugs have rates of between 10 % and 20 % ( eg , risperidone , n = 1460 , 6 r and omized controlled trials [ RCTs ] , 11.9 % prevalence ; CI , 10 - 14 ; olanzapine , n = 1584 ; 4 RCTs , 12.2 % prevalence ; CI , 11 - 14 ) . These estimates are similar to those of sulpiride ( n = 186 ; 2 RCTs , 12.4 % ; CI , 8 - 18 ) and chlorpromazine ( n = 294 ; 10 RCTs , 11.2 % ; CI , 8 - 15 ) , less than trifluoperazine ( n = 167 ; 8 RCTs , 31.1 % ; CI , 25 - 39 ) , but considerably more than perphenazine ( n = 410 ; 8 RCTs , 3.7 % ; CI , 2 - 6 ) . Data are presented on a range of anticholinergic effects across different periods . Conclusions : Anticholinergic symptoms are common adverse effects associated with the use of all antipsychotic drugs , and newer-generation drugs are not clearly distinguishable from many older compounds . Adverse effect data should be more accessible INTRODUCTION This study evaluated the safety/tolerability and effectiveness of aripiprazole titrated-dose versus fixed-dose switching strategies from risperidone in patients with schizophrenia experiencing insufficient efficacy and /or safety/tolerability issues . METHODS Patients were r and omized to an aripiprazole titrated-dose ( starting dose 5 mg/day ) or fixed-dose ( dose 15 mg/day ) switching strategy with risperidone down-tapering . Primary endpoint was rate of discontinuation due to adverse events ( AEs ) during the 12-week study . Secondary endpoints included positive and negative syndrome scale ( PANSS ) , clinical global impressions - improvement of illness scale ( CGI-I ) , preference of medication ( POM ) , subjective well-being under neuroleptics ( SWN-K ) and GEOPTE ( Grupo Español para la Optimización del Tratamiento de la Esquizofrenia ) scales . RESULTS Rates of discontinuations due to AEs were similar between titrated-dose and fixed-dose strategies ( 3.5 % vs. 5.0 % ; p=0.448 ) . Improvements in mean PANSS total scores were similar between aripiprazole titrated-dose and fixed-dose strategies ( -14.8 vs. -17.2 ; LOCF ) , as were mean CGI-I scores ( 2.9 vs. 2.8 ; p=0.425 ; LOCF ) and SWN-K scores ( + 8.6 vs.+10.3 ; OC,+7.8 vs.+9.8 ; LOCF ) . CONCLUSION Switching can be effectively and safely achieved through a titrated-dose or fixed-dose switching strategy for aripiprazole , with down-titration of risperidone Depressive symptomatology is an important target of treatment in first episode schizophrenia . This re analysis of the European First Episode Schizophrenia Trial ( EUFEST ) describes the depressive symptomatology and the effect of antipsychotic treatment in patients suffering from first episode schizophrenia and schizophreniform disorder r and omized to treatment with low dose haloperidol ( n=103 ) , amisulpride ( n=104 ) , olanzapine ( n=105 ) , quetiapine ( n=104 ) or ziprasidone ( n=82 ) for one year . At baseline , the mean score on the Calgary Depression Scale for Schizophrenia ( CDSS ) was 5.1 ( ±4.9 ) with 38.3 % of patients having a CDSS score≥6 , i.e. clinical ly relevant depressive symptom severity . During treatment depression scores decreased , the mean CDSS score being 1.1 ( ±2.1 ) and 3.0 % of patients having a CDSS≥6 at 52 weeks . The proportion of patients using antidepressants during the complete trial was 18.5 % in the haloperidol group , 28.6 % in the olanzapine group compared to 5.8 % in the quetiapine group , 12.5 % in the amisulpride group , and 9.8 % in the ziprasidone group . There were no differences over time in the probability of being depressed ( CDSS≥6 ) between the 5 treatment groups after adjustment for antidepressant use , nor in a sub analysis of patients who did not take any antidepressant . Depression scores at baseline or during the trial had no effect on treatment discontinuation or on the reduction of positive symptoms . In summary , the results of EUFEST did not demonstrate a differential effect of the antipsychotics studied on depressive symptomatology in patients with first episode schizophrenia BACKGROUND Data on attaining and maintaining symptom remission associated with specific antipsychotic medications are rare and variant . AIMS To examine remission rates and their variation by antipsychotic medication in chronic schizophrenia in the National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) given it has an 18-month duration and representative antipsychotic medications . METHODS Symptom remission was examined using the Remission in Schizophrenia Working Group remission criteria of attaining and maintaining for 6 months with mild ratings on 8 specific Positive and Negative Syndrome Scale ( PANSS ) items . Remission rates were assessed ( a ) up to 18 months across CATIE 's switching phases ( n = 1332 ) ; and ( b ) in phase 1 ( that involved double-blind r and omization to one of five antipsychotic medications ) to compare antipsychotic medication differences in attaining and maintaining remission among patients not in remission at baseline ( n = 941 ) . RESULTS At baseline 16.2 % of patients were in symptomatic remission . Across the medication phases of CATIE only 11.7 % attained and then maintained at least 6 months of symptomatic remission , and 55.5 % ( n = 623 ) experienced no symptom remission at any visit . During the first medication r and omization phase , attaining and maintaining remission for 6 months was highest for the olanzapine ( 12.4 % ) medication group followed by the quetiapine ( 8.2 % ) , perphenazine ( 6.8 % ) , ziprasidone ( 6.5 % ) , and risperidone ( 6.3 % ) groups . CONCLUSIONS As currently defined , remission appears to be a very difficult therapeutic target to attain and maintain in chronic schizophrenia and may differ by antipsychotic medication . Pragmatically , remission gradients may be effectively studied by applying modified duration and symptom criteria OBJECTIVE The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization . METHOD In a 6-week double-blind study , in patients with a recent exacerbation of schizophrenia were r and omly assigned to treatment with paliperidone extended-release , quetiapine , or placebo . A 2-week monotherapy phase was followed by a 4-week additive-therapy phase . Target doses were at the upper end of recommended ranges : paliperidone extended-release , 9 or 12 mg/day , and quetiapine , 600 or 800 mg/day . The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale ( PANSS ) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint . RESULTS Six-week completion rates were 77.5 % ( 124/160 ) with paliperidone extended-release , 66.7 % ( 106/159 ) quetiapine , and 63.8 % ( 51/80 ) placebo . Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 ( -11.4 versus -8.2 ) through the monotherapy phase endpoint ( -23.4 versus -17.1 ) . Only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks . At the 6-week study endpoint , there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy ( predominantly other antipsychotics ) . Common adverse events with paliperidone extended-release , quetiapine , and placebo , respectively , were tremor ( 13.9 % , 5.0 % , 7.5 % ) , somnolence ( 8.9 % , 11.9 % , 1.3 % ) , insomnia ( 10.1 % , 9.4 % , 11.3 % ) , and headache ( 12.0 % , 7.5 % , 13.8 % ) . Six-week adverse event-related discontinuation rates were 6.3 % , 10.1 % , and 6.3 % , respectively , in the paliperidone extended-release , quetiapine , and placebo groups . CONCLUSIONS Compared with quetiapine , paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization , with no unexpected tolerability findings BACKGROUND AND AIM Improving social functioning is critically important in early-episode schizophrenia , if patients are to achieve functional recovery . This post-hoc , pooled analysis of two studies compared the effect of aripiprazole versus haloperidol on social functioning in early-episode schizophrenia . METHODS Data were pooled from two 52 week , r and omized ( 2:1 ) , double-blind , multicenter studies involving 1294 patients with chronic schizophrenia who were in an acute psychotic episode and had a history of positive antipsychotic response during previous episodes . The early-episode group was defined as patients who are < or=40 years of age with < or=5 years ' duration of illness . Social functioning was assessed by mean change from baseline on the PANSS Prosocial subscale ( ANCOVA and LOCF ) , comprising six PANSS items , and the Modified Prosocial subscale , comprising four PANSS items . Measurements were taken at approximately monthly intervals for up to 1 year . RESULTS Aripiprazole ( n=237 ) demonstrated significant improvement versus haloperidol ( n=123 ) as early as Week 18 on both the Prosocial subscale ( -4.75 versus -3.78 , p<0.05 ) and on the Modified Prosocial subscale ( -3.16 versus -2.28 , p<0.05 ) . Patients receiving aripiprazole continued to show similar significant improvement versus haloperidol at all remaining timepoints through Week 52 using the Modified Prosocial subscale , but less consistent improvement with the Prosocial subscale . Significant advantage for the aripiprazole-treated patients was observed at Weeks 46 and 52 ( endpoint ) with both subscales . CONCLUSION In patients with early-episode schizophrenia , aripiprazole demonstrates greater improvement than haloperidol on PANSS items related to social functioning . The cognitive and functional implication s of these findings remain to be clarified in future studies Objective : To compare the efficacy and adverse effect profiles of 2 widely used atypical antipsychotics in the short-term phase of first-episode schizophrenia in patients who were treatment-naive . A secondary objective was to establish the effective dose of these drugs in this context . Methods : A total of 72 patients with a first episode of schizophreniform psychosis ( schizophrenia spectrum disorder ) with less than 2 weeks of exposure to antipsychotic medication were r and omized to quetiapine or risperidone in a single-blind 12-week controlled trial . Psychopathologic diagnoses and adverse effects were assessed by blinded raters at 4 weekly intervals . Medication was administered by a specialized clinical team following dosing guidelines . Data were analyzed using an intention-to-treat paradigm . Results : Both quetiapine and risperidone were associated with a reduction in immediate symptoms and relatively few adverse effects other than weight gain . There was no statistically significant difference between the 2 compounds in adverse effects , relative efficacies , or adherence to treatment . The median ( SD ) time to cessation for patients r and omized to quetiapine was 65.3 ( 41.85 ) days and that for risperidone was 82.5 ( 44.88 ) days . There was no statistically significant difference between time to discontinuation for the 2 compounds . The mean daily doses prescribed were 375 mg of quetiapine and 2.72 mg of risperidone . Conclusions : Quetiapine and risperidone are both effective treatments in first-episode schizophrenia at doses lower than those used in patients with long-term schizophrenia and are similar in efficacy and the incidence of adverse effects This study aims to determine the effectiveness of paliperidone extended release ( ER ) on cognitive function in patients with schizophrenia in comparison with risperidone . This was a 12-week , r and omized , open-label study on schizophrenia patients who were receiving risperidone . The patients were r and omized to a risperidone-continuation group or a paliperidone-switch group . The primary outcome measure was neurocognitive function , which was measured using a computerized battery . Secondary efficacy measures included the Positive and Negative Syndrome Scale , Social and Occupational Functioning Scale , and Calgary Depression Scale for Schizophrenia . In total , 58 patients participated in this trial . Improvements in recall after an interference phase in the verbal learning test were significantly greater in the paliperidone-switch than in the risperidone-continuation group . No significant differences in changes were observed in the other six neurocognitive domains measured . Improvements in the Social and Occupational Functioning Scale were significantly greater in the paliperidone ER-switch group than in the risperidone-continuation group . In other efficacy outcome measures , no significant differences were observed between the two drugs . Paliperidone ER had a side-effect profile similar to that of risperidone , including metabolic problems and prolactin-related adverse events . In conclusion , switching from risperidone to paliperidone ER may lead to additional cognitive and social functional improvements To compare the effectiveness of a switch from haloperidol ( N=99 ) , olanzapine ( N=82 ) , or risperidone ( N=104 ) to 12 weeks of treatment with 80–160 mg/day ziprasidone in patients with stable schizophrenia or schizoaffective disorder . Stable out patients with persistent symptoms or troublesome side effects were switched using one of three 1-week taper/switch strategies as determined by the investigator . Efficacy was assessed using the Brief Psychiatric Rating Scale score , Clinical Global Impression , Positive and Negative Symptom Scale , Montgomery – Åsberg Depression Rating Scale , and the Global Assessment of Functioning Scale , and tolerability by using st and ard measures of weight change , extrapyramidal symptoms , and laboratory findings . Suboptimal efficacy was the primary reason for switching . The preferred switch strategy was immediate discontinuation , and the preferred dosing regimen was 120 mg/day . Completer rates were 68 , 60 , and 86 % in the haloperidol , risperidone , and olanzapine pre-switch groups , respectively . At week 12 , a switch to ziprasidone result ed in statistically significant improvement from baseline on the Brief Psychiatric Rating Scale score , Clinical Global Impression-Improvement , Positive and Negative Symptom Scale , and Global Assessment of Functioning scales , reduction in extrapyramidal symptoms and a neutral impact on metabolic parameters . Switch from olanzapine and risperidone result ed in weight reduction and from haloperidol in some weight increase . In conclusion , oral ziprasidone of 80–160 mg/day with food was a clinical ly valuable treatment option for stable patients with schizophrenia or schizoaffective disorder experiencing suboptimal efficacy or poor tolerability with haloperidol , olanzapine , or risperidone AIM To assess changes in insulin sensitivity in non-diabetic adults with schizophrenia or schizoaffective disorder treated with olanzapine or risperidone . METHODS One hundred and thirty patients were r and omly assigned to 12 weeks double-blind treatment with olanzapine or risperidone . Insulin sensitivity was measured using a two-step euglycaemic , hyperinsulinaemic clamp procedure . Whole-body adiposity was measured using dual-energy X-ray absorptiometry . The primary endpoint was the within-group change from baseline in insulin sensitivity normalized to fat-free mass ( M(ffm ) /I ) during the clamp procedure 's low-insulin phase , using an analysis of covariance model including the covariate weight change . RESULTS Forty-one olanzapine-treated and 33 risperidone-treated patients completed baseline and endpoint clamp measurements . Mean M(ffm ) /I during the low-insulin phase declined 9.0 % ( p = 0.226 ) in olanzapine-treated patients and 13.2 % ( p = 0.047 ) in risperidone-treated patients ( between-group difference p = 0.354 ) . During the high-insulin phase , M(ffm ) /I declined 10.4 % ( p = 0.036 ) in olanzapine-treated patients and 2.1 % ( p = 0.698 ) in risperidone-treated patients ( between-group difference p = 0.664 ) . Changes in M(ffm ) /I correlated inversely with changes in body weight and adiposity , which were generally higher in olanzapine-treated patients . Significant within-group increases in fasting glucose , but not haemoglobin A1c ( HbA1c ) , were observed during olanzapine treatment . The fasting glucose change was not correlated with M(ffm ) /I changes . CONCLUSIONS Small , but statistically significant , decrements in insulin sensitivity were observed in olanzapine- and risperidone-treated patients at 1 of 2 insulin doses tested . Significant increases in fasting glucose and insulin and total fat mass were observed only in olanzapine-treated patients . Changes in insulin sensitivity correlated significantly with changes in weight or adiposity , but not with changes in glucose BACKGROUND Few studies have directly compared the efficacy and tolerability of atypical agents . METHODS This multicenter , r and omized , double-blind study compared the efficacy and tolerability of aripiprazole ( n = 355 ) with olanzapine ( n = 348 ) in patients with schizophrenia experiencing acute relapse . After a 6-week acute treatment phase , patients with Clinical Global Impression-Improvement = 1 - 3 or > or = 20 % reduction in the Positive and Negative Symptom Scale ( PANSS ) Total score could progress to the 46-week outpatient extension phase . Co- primary study objectives were to compare efficacy at Week 6 and weight gain liability from baseline to Week 26 . RESULTS The mean olanzapine dose was 15.4 mg/day compared with a mean aripiprazole dose of 23.0 mg/day . More patients treated with olanzapine ( 47 % ) completed the 52-week study than those treated with aripiprazole ( 39 % ) ; time to discontinuation was significantly in favor of olanzapine ( p < .05 ) . At Week 6 , mean change in PANSS Total score ( olanzapine , -29.5 ; aripiprazole , -24.6 [ r and om regression model ] ) showed a treatment difference of 4.9 points . As the pre-specified non-inferiority margin ( 6 points ) was within the 95 % confidence interval ( 2.2 - 7.6 ) for treatment difference , olanzapine proved to be superior to aripiprazole on this measure . More patients experienced significant weight gain at Week 26 with olanzapine ( 40 % ) than with aripiprazole ( 21 % ; p < .05 [ weighted generalized estimating equation analysis ] ) , with significant differences observed from Week 3 . Mean weight gain at Week 26 was significantly greater with olanzapine than with aripiprazole ( + 4.30 kg vs. + .13 kg , respectively ) . CONCLUSIONS Olanzapine had a statistically significant efficacy advantage over aripiprazole , whereas aripiprazole was associated with significantly less weight gain BACKGROUND Predefined response and remission criteria may hold more clinical relevance than mean scores on rating scales . We compared the effectiveness of low doses of haloperidol and regular doses of second generation antipsychotics ( SGAs ) on > or=50 % response and remission . METHODS In an open r and omized clinical trial in 14 countries , 498 unselected first-episode patients with schizophrenia were assigned to haloperidol ( 1 - 4 mg/d ; n=103 ) , amisulpride ( 200 - 800 mg/d ; n=104 ) , olanzapine ( 5 - 20mg/d ; n=105 ) , quetiapine ( 200 - 750 mg/d ; n=104 ) , or ziprasidone ( 40 - 160 mg/d ; n=82 ) . Primary outcomes were > or=50 % response and remission within 12 months , as measured with the Positive and Negative Syndrome Scale . Analysis was by intention-to-treat . RESULTS Within 12 months , the proportions of patients with > or=50 % response were 37 % for haloperidol , 67 % for amisulpride , 67 % for olanzapine , 46 % for quetiapine , and 56 % for ziprasidone . Comparisons with haloperidol showed a higher likelihood for > or=50 % response with amisulpride ( hazard ratio [ HR ] 2.27 , [ 95 % CI 1.51 - 3.42 ] ) , olanzapine ( HR 2.07 [ 1.38 - 3.10 ] ) , and ziprasidone ( HR 1.62 [ 1.02 - 2.56 ] ) . Within 12 months , the proportions of patients in remission were 17 % for haloperidol , 40 % for amisulpride , 41 % for olanzapine , 24 % for quetiapine , and 28 % for ziprasidone . Comparisons with haloperidol showed a better chance for remission on amisulpride ( HR 2.49 , [ 95 % CI 1.43 - 4.35 ] ) , olanzapine ( HR 2.58 [ 1.48 - 4.48 ] ) , quetiapine ( HR 1.96 [ 1.06 - 3.64 ] ) , and ziprasidone ( HR 2.03 [ 1.07 - 3.87 ] ) . CONCLUSIONS Substantial proportions of first-episode patients with schizophrenia showed clinical ly meaningful response and remission rates within 12 months . The proportions of response and remission were higher for most SGAs as compared to haloperidol Abstract Objective : To evaluate the efficacy and safety of 750 mg/day quetiapine fumarate ( Seroquel ) in the treatment of Chinese Han patients with schizophrenia . Methods : In this 6-week , multicenter , r and omized , rater single-blind study , a total of 119 patients with schizophrenia were r and omly assigned to quetiapine ( n = 60 , 750 mg/day ) or risperidone ( n = 59 , 4 mg/day ) . The efficacy was assessed by the Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impression – Change ( CGI-C ) and the Calgary Depression Scale for Schizophrenia ( CDSS ) . Safety and tolerability assessment s included treatment-emergent adverse events , laboratory tests and electrocardiograms . Results : The primary analysis demonstrated no significant difference between treatment in the two groups ( quetiapine vs. risperidone : 31.9 ± 17.5 vs. 33.3 ± 17.3 ; P = 0.668 ) . Improvements with both treatments were comparable for total PANSS , positive and negative subscores , general psychopathology subscales , and excitement and attack symptoms . Improvements in CGI-S were similar between treatment groups ( P = 0.046 ) . A more favorable trend was detected for quetiapine than risperidone in the reduction of CDSS scores from baseline , especially at week 1 ( 1.1 ± 2.2 vs. 0.3 ± 2.1 , P < 0.050 ) . The rate of extrapyramidal symptom ( EPS ) and hyperprolactinemia-related adverse events was significantly lower in the quetiapine group than the risperidone group ( 13.3 % vs. 43.3 % , P < 0.001 ) . Dizziness and somnolence were more common in the quetiapine group than the risperidone group . Conclusion : Quetiapine fumarate ( 750 mg/day ) has broad clinical efficacy comparable to 4 mg/day risperidone . Dizziness was common in the quetiapine group ( P = 0.029 ) , but the rate of somnolence was similar between the two groups ( P = 0.114 ) . EPS and hyperprolactinemia rates were significantly higher with risperidone ( P < 0.001 ) . Key limitations of this study include small sample size , short treatment periods , and no increase to 6 mg/day for risperidone because of its safety profile The aim of this study is to evaluate the long-term safety and tolerability of lurasidone in the treatment of schizophrenia . Clinical ly stable adult out patients with schizophrenia were r and omized in a 2 : 1 ratio to 12 months of double-blind treatment with once-daily , flexibly-dosed lurasidone ( 40–120 mg ) or risperidone ( 2–6 mg ) . Outcome measures included adverse events ( AEs ) , vital signs , ECG , and laboratory tests . Secondary assessment s included measures of psychopathology . A total of 427 patients were r and omized to treatment with lurasidone and 202 with risperidone . The three most frequent AEs in the lurasidone group ( vs. risperidone ) were nausea ( 16.7 vs. 10.9 % ) , insomnia ( 15.8 vs. 13.4 % ) , and sedation ( 14.6 vs. 13.9 % ) ; the three most frequent AEs in the risperidone group ( vs. lurasidone ) were increased weight ( 19.8 vs. 9.3 % ) , somnolence ( 17.8 vs. 13.6 % ) , and headache ( 14.9 vs. 10.0 % ) . A higher proportion of patients receiving risperidone had at least a 7 % endpoint increase in weight ( 14 vs. 7 % ) . The median endpoint change in prolactin was significantly higher for risperidone ( P<0.001 ) . A comparable improvement in efficacy measures was observed with both agents and the rates of relapse were similar . All-cause discontinuation rates were higher for lurasidone versus risperidone . Long-term treatment with lurasidone was generally well tolerated in this study , with minimal effects on weight and metabolic outcomes This open-label , rater-blinded , parallel-group study was design ed to evaluate noninferiority of paliperidone palmitate ( PP ) , a once-monthly injectable atypical antipsychotic , to once-biweekly risperidone long-acting injectable ( RIS-LAI ) in adult Chinese patients with acute schizophrenia . Eligible Chinese adults ( N=452 ) with schizophrenia were r and omized ( 1:1 ) to either PP ( N=229 ; deltoid injections on day 1 [ 150 mg eq. ] and day 8 [ 100 mg eq. ] ; then once-monthly deltoid or gluteal injections , flexibly dosed [ 50 , 100 , or 150 mg eq. ] ) , or RIS-LAI ( N=223 ; once-biweekly gluteal injections , flexibly dosed [ 25 , 37.5 or 50 mg ] ) . RIS-LAI-treated patients received oral risperidone supplementation ( 1 - 6 mg/day ) at initiation and with RIS-LAI dose increases . Mean ( SD ) Positive and Negative Syndrome Scale ( PANSS ) total score at baseline was 83.2 ( 12.44 ) . Mean ( SD ) change from baseline to endpoint in PANSS total scores ( primary efficacy measure ) was : -23.6 ( 16.28 ) for PP group and -26.9 ( 15.43 ) for RIS-LAI group . PP was noninferior to RIS-LAI ( least squares mean difference [ 95 % CI ] : -2.3 [ -5.20 ; 0.63 ] ; predetermined non-inferiority margin : -5.5 ) . Mean ( SD ) change from baseline to endpoint in Clinical Global Impression-Severity scale score was : -1.5 ( 1.24 ; PP group ) , -1.7 ( 1.16 ; RIS-LAI group ) and in Personal and Social Performance Scale scores was : 16.8 ( 14.76 ; PP group ) , 18.6 ( 13.92 ; RIS-LAI group ) . The incidence of treatment-emergent adverse events ( TEAEs ) was similar between the two groups ( 73 % [ PP ] ; 75 % [ RIS-LAI ] ) . The most common TEAEs were akathisia , tremor , and insomnia . The study demonstrated the noninferiority of PP ( 50 - 150 mg eq. , flexibly dosed , without oral paliperidone supplementation ) to risperidone-LAI ( 25 - 50 mg , flexibly dosed , with oral risperidone supplementation ) for the treatment of acute schizophrenia in adult Chinese patients . PP injections were generally tolerable , and no new safety signals were detected in this population The incidence of suicide attempts ( fatal and non-fatal ) was analysed in a prospect i ve cohort of patients with schizophrenia r and omly assigned to sertindole ( 4905 patients ) or risperidone ( 4904 patients ) in a parallel-group open-label study with blinded classification of outcomes ( the sertindole cohort prospect i ve study --SCoP ) . The total exposure was 6978 and 7975 patient-years in the sertindole and risperidone groups , respectively . Suicide mortality in the study was low ( 0.21 and 0.28 per 100 patients per year with sertindole and risperidone , respectively ) . The majority ( 84 % ) of suicide attempts occurred within the first year of treatment . Cox 's proportional hazards model analysis of the time to the first suicide attempt , reported by treating psychiatrists and blindly review ed by an independent expert group according to the Columbia Classification Algorithm of Suicide Assessment ( both defining suicide attempts by association of suicidal act and intent to die ) , showed a lower risk of suicide attempt for sertindole-treated patients than for risperidone-treated patients . The effect was statistically significant with both evaluation methods during the first year of r and omized treatment ( hazard ratios [ 95 % CI ] : 0.5 [ 0.31 - 0.82 ] , p=0.006 ; and 0.57 [ 0.35 - 0.92 ] , p=0.02 , respectively ) . With classification by an independent safety committee using a broader definition including all incidences of intentional self-harm , also those without clear suicidal intent , the results were not significant . A history of previous suicide attempts was significantly associated with attempted suicides in both treatment groups OBJECTIVE To evaluate the effectiveness of olanzapine versus aripiprazole in patients with schizophrenia . METHOD Patients aged 18 to 65 years with schizophrenia ( diagnosed according to DSM-IV-TR criteria ) were r and omly assigned to either olanzapine ( n = 281 ) or aripiprazole ( n = 285 ) for 28 weeks of double-blind treatment . The primary outcome was time to all-cause discontinuation . Efficacy was measured by Positive and Negative Syndrome Scale ( PANSS ) total change from baseline . Time-to-event data were analyzed via the Kaplan-Meier method . The study was conducted from October 2003 to July 2007 . RESULTS Treatment groups did not differ significantly in time to all-cause discontinuation ( p = .067 ) or all-cause discontinuation rate ( olanzapine , 42.7 % vs. aripiprazole , 50.2 % ; p = .053 ) . Olanzapine-treated patients had significantly longer time to efficacy-related discontinuation ( p < .001 ) and a significantly lower efficacy-related discontinuation rate ( olanzapine , 8.9 % vs. aripiprazole , 16.8 % ; p = .006 ) . Olanzapine-treated patients had a significantly greater mean decrease ( last observation carried forward ) in PANSS total score ( -30.2 ) than did aripiprazole-treated patients ( -25.9 , p = .014 ) . Olanzapine-treated patients had a mean weight change of + 3.4 kg ( vs. + 0.3 kg for aripiprazole-treated patients ; p < .001 ) and a significantly greater incidence of > or= 7 % body weight gain at any time ( 40.3 % vs. 16.4 % ; p < .001 ) . Fasting mean glucose change was + 4.87 mg/dL for olanzapine and + 0.90 mg/dL for aripiprazole ( p = .045 ) . Incidence of baseline glucose < 100 mg/dL and > or= 126 mg/dL at any time was 1.7 % for olanzapine and 0.6 % for aripiprazole ( p = .623 ) . Fasting mean total cholesterol change was + 4.09 mg/dL for olanzapine and -9.85 mg/dL for aripiprazole ( p < .001 ) . Incidence of baseline total cholesterol < 200 mg/dL and > or= 240 mg/dL at any time was 9.2 % for olanzapine and 1.5 % for aripiprazole ( p = .008 ) . Fasting mean triglycerides change was + 25.66 mg/dL for olanzapine and -17.52 mg/dL for aripiprazole ( p < .001 ) . Treatment groups did not significantly differ on measures of extrapyramidal symptoms . CONCLUSION Treatment groups did not differ significantly on the primary outcome . Olanzapine-treated patients had significantly greater improvement in symptom efficacy at 28 weeks as well as significantly greater mean increases in weight and glucose and significantly greater worsening on lipids parameters . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00088049 BACKGROUND The electronic Schizophrenia Treatment Adherence Registry ( e-STAR ) is a prospect i ve , observational study of patients with schizophrenia design ed to evaluate long-term treatment outcomes in routine clinical practice . METHODS Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection ( RLAI ) ( n=1345 ) or a new oral antipsychotic ( AP ) ( n=277 ; 35.7 % and 36.5 % on risperidone and olanzapine , respectively ) in Spain . Hospitalization prior to therapy was assessed by a retrospective chart review . RESULTS At 24 months , treatment retention ( 81.8 % for RLAI versus 63.4 % for oral APs , p<0.0001 ) and reduction in Clinical Global Impression Severity scores ( -1.14 for RLAI versus -0.94 for APs , p=0.0165 ) were significantly higher with RLAI . Compared to the pre-switch period , RLAI patients had greater reductions in the number ( reduction of 0.37 stays per patient versus 0.2 , p<0.05 ) and days ( 18.74 versus 13.02 , p<0.01 ) of hospitalizations at 24 months than oral AP patients . CONCLUSIONS This 2 year , prospect i ve , observational study showed that , compared to oral antipsychotics , RLAI was associated with better treatment retention , greater improvement in clinical symptoms and functioning , and greater reduction in hospital stays and days in hospital in patients with schizophrenia . Improved treatment adherence , increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia BACKGROUND Cognitive deficits are a core feature in schizophrenia . Cognitive deficits appear to be present at the onset of schizophrenia and persist after remission of psychotic symptoms . As cognitive deficits are associated with poor functional outcome , they form an important focus of treatment . There are relatively few head-to-head comparisons of the effects of second generation antipsychotics on cognition in recent onset schizophrenia . This is the first study to compare the effects of a short term treatment of olanzapine versus ziprasidone on cognitive functioning in recent onset schizophrenia . An earlier study conducted in chronic patients revealed an enhancement of cognition after treatment for both agents , but the extent of improvement was not significantly different between ziprasidone and olanzapine . METHOD Patients with recent onset schizophrenia with limited previous exposure to medical treatment underwent a double blind r and omized controlled treatment trial . Fifty-six patients completed the neuropsychological testing procedure prior to r and omization and after eight weeks of treatment and were included in the analysis . We tested cognitive functioning in general and verbal memory in particular . We calculated a single unweighted composite score based on nine cognitive tests to determine general cognitive functioning . RESULTS Cognition appeared enhanced after treatment , but was not significantly different between treatment groups , neither for the verbal memory measures , nor for the neurocognitive composite score . Furthermore , cognitive enhancement did not correlate to clinical improvement . CONCLUSION Cognitive deficits are not a reason for preferentially prescribing one of the two second generation antipsychotics tested over the other OBJECTIVE To compare longer-term safety and effectiveness of the 4 most commonly used atypical antipsychotics ( aripiprazole , olanzapine , quetiapine , and risperidone ) in 332 patients , aged > 40 years , having psychosis associated with schizophrenia , mood disorders , posttraumatic stress disorder , or dementia , diagnosed using DSM-IV-TR criteria . METHOD We used equipoise-stratified r and omization ( a hybrid of complete r and omization and clinician 's choice methods ) that allowed patients or their treating psychiatrists to exclude 1 or 2 of the study atypical antipsychotics due to past experience or anticipated risk . Patients were followed for up to 2 years , with assessment s at baseline , 6 weeks , 12 weeks , and every 12 weeks thereafter . Medications were administered employing open-label design and flexible dosages , but with blind raters . The study was conducted from October 2005 to October 2010 . OUTCOME MEASURES Primary metabolic markers ( body mass index , blood pressure , fasting blood glucose , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , and triglycerides ) , percentage of patients who stay on the r and omly assigned atypical antipsychotic for at least 6 months , psychopathology , percentage of patients who develop metabolic syndrome , and percentage of patients who develop serious and nonserious adverse events . RESULTS Because of a high incidence of serious adverse events , quetiapine was discontinued midway through the trial . There were significant differences among patients willing to be r and omized to different atypical antipsychotics ( P < .01 ) , suggesting that treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems . Yet , the atypical antipsychotic groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures . Overall results suggested a high discontinuation rate ( median duration 26 weeks prior to discontinuation ) , lack of significant improvement in psychopathology , and high cumulative incidence of metabolic syndrome ( 36.5 % in 1 year ) and of serious ( 23.7 % ) and nonserious ( 50.8 % ) adverse events for all atypical antipsychotics in the study . CONCLUSIONS Employing a study design that closely mimicked clinical practice , we found a lack of effectiveness and a high incidence of side effects with 4 commonly prescribed atypical antipsychotics across diagnostic groups in patients over age 40 , with relatively few differences among the drugs . Caution in the use of these drugs is warranted in middle-aged and older patients . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00245206 The objective of this study was to compare the effects of risperidone and olanzapine in schizophrenic patients with intolerant extrapyramidal side effects ( EPS ) on first generation antipsychotics . We conducted an 8-week , rater-blinded , flexible dose study . Seventy patients with schizophrenia , who met the DSM-IV research criteria of having neuroleptic-induced acute dystonia or parkinsonism , were r and omly assigned to risperidone or olanzapine group . The primary outcome was a comparison of the incidence of concomitant anticholinergic drugs usage between the groups to manage their acute dystonia and parkinsonism . The average doses of risperidone and olanzapine from baseline to study end point were 1.8—3.5 mg/day and 7.7—11.7 mg/day , respectively . There were no significant differences in demographic data , severity of EPS or psychotic symptoms between the groups at baseline assessment . Patients taking risperidone had significantly higher incidence of using anticholinergic drugs to manage acute dystonia or parkinsonism overall during the study ( OR = 5.17 , 95%CI = 1.49—17.88 , P = 0.013 ) . There was no significant between-group difference in the changing of rating scales of EPS and psychotic symptoms . The results of our study favour olanzapine as a better choice in schizophrenic patients with intolerant EPS . Double-blinded , fixed dose and different ethnical study for EPS-intolerant schizophrenic patients is needed to confirm the results of our study Diabetes mellitus occurs in schizophrenia patients at higher rates than in the general population . Reasons for this elevated risk are poorly understood and have not been examined prospect ively in antipsychotic-naïve , first-episode patients . This study aims to determine which antipsychotics are associated with diabetes development in antipsychotic-naïve schizophrenia patients . All antipsychotic-naïve patients diagnosed with schizophrenia in Denmark between 01 January 1997 and 31 December 2004 , followed until 31 December 2007 , allowing for ⩾3 years follow-up , unless death or diabetes onset occurred . Risk factors for the time to diabetes onset were assessed , including antipsychotics taken for at least 180 defined daily doses in the first year after first antipsychotic prescription ( ‘ initial treatment ’ ) . Risk factors for diabetes incidence were assessed , including antipsychotic use within 3 months before diabetes onset or study end ( ‘ current treatment ’ ) . Of 7139 patients , followed for 6.6 years ( 47 297 patient years ) , 307 developed diabetes ( annual incidence rate : 0.65 % ) . Time to diabetes onset was significantly shorter in patients with higher age ( hazard ratio ( HR ) : 1.03 , confidence interval ( CI ) : 1.02–1.03 ) and those with ‘ initial ’ treatment of olanzapine ( HR : 1.41 , CI : 1.09–1.83 ) , mid-potency first-generation antipsychotics ( FGAs ) ( HR : 1.60 , CI : 1.07–2.39 ) , antihypertensive ( HR : 1.87 , CI : 1.13–3.09 ) , or lipid-lowering drugs ( HR : 4.67 , CI : 2.19–10.00 ) . Significant factors associated with diabetes within 3 month of its development included treatment with low-potency FGAs ( odds ratio ( OR ) : 1.52 , CI : 1.14–2.02 ) , olanzapine ( OR : 1.44 , CI : 1.98–1.91 ) , and clozapine ( OR : 1.67 , CI : 1.14–2.46 ) , whereas aripiprazole was associated with lower diabetes risk ( OR : 0.51 , CI : 0.33–0.80 ) . In addition to general diabetes risk factors , such as age , hypertension , and dyslipidemia , diabetes is promoted in schizophrenia patients by initial and current treatment with olanzapine and mid-potency FGAs , as well as by current treatment with or low-potency first-generation antipsychotics and clozapine , whereas current aripiprazole treatment reduced diabetes risk . Patients discontinuing olanzapine or mid-potency FGA had no increased risk of diabetes compared with patient not treated with the drugs at anytime Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features . In a double-blind 6-week trial , 458 patients with acute schizophrenia were r and omly assigned to fixed-dose treatment with asenapine at 5 mg twice daily ( BID ) , asenapine at 10 mg BID , placebo , or haloperidol at 4 mg BID ( to verify assay sensitivity ) . With last observations carried forward ( LOCF ) , mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID ( −16.2 ) and haloperidol ( −15.4 ) than placebo ( −10.7 ; both P < 0.05 ) ; using mixed model for repeated measures ( MMRM ) , changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID ( −21.3 and −19.4 , respectively ) and haloperidol ( −20.0 ) than placebo ( −14.6 ; all P < 0.05 ) . On the Positive and Negative Syndrome Scale positive subscale , all treatments were superior to placebo with LOCF and MMRM ; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM . Treatment-related adverse events ( AEs ) occurred in 44 % and 52 % , 57 % , and 41 % of the asenapine at 5 and 10 mg BID , haloperidol , and placebo groups , respectively . Extrapyramidal symptoms reported as AEs occurred in 15 % and 18 % , 34 % , and 10 % of the asenapine at 5 and 10 mg BID , haloperidol , and placebo groups , respectively . Across all groups , no more than 5 % of patients had clinical ly significant weight change . Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol ; greater contrasts were seen in AEs , especially extrapyramidal symptoms OBJECTIVE This study was a comparative investigation of the effects on clinical symptoms and cognitive function of switching the treatment of schizophrenia patients from haloperidol decanoate depot to risperidone long-acting injection ( RLAI ) compared with a control group that continued receiving haloperidol decanoate depot . METHODS This study was a 24-week , non-r and omized , non-double blind , open-label trial . The subjects ' clinical symptoms were assessed using the Positive and Negative Syndrome Scale , and their cognitive function was assessed using the Wisconsin Card Sorting Test : Keio Version to assess executive function and the St. Marianna University School of Medicine 's Computerized Memory Test to assess memory and concentration at 0 and 24 weeks . RESULTS The mean change from baseline in the number of categories achieved at the second stage of the Wisconsin Card Sorting Test : Keio Version was significantly greater in the RLAI group than in the control group . The mean changes from baseline in the individual St. Marianna University School of Medicine 's Computerized Memory Tests were significantly greater in the RLAI group than in the control group . The RLAI group needed a lower dosage of biperiden compared with the control group , even though they had similar risperidone-equivalent daily dosages . CONCLUSION The results of this study suggest the possibility that switching from haloperidol decanoate depot to RLAI may improve cognitive function including memory , executive function , motor processing function , and attention INTRODUCTION Body mass index ( BMI ) increase is an undesired effect associated with antipsychotics , and crucial for patients ' global health and treatment compliance . We aim ed to investigate the relation between BMI during olanzapine or haloperidol treatments and leptin , neuropeptide Y ( NPY ) , adiponectin and lipid serum levels . METHODS In this 9-month , r and omized and naturalist study , 34 male patients , 18 on olanzapine and 16 on haloperidol group were enrolled , all were under monotherapy . Patient outcome was evaluated with positive and negative syndrome scale ( PANSS ) at every 3-month period . In each visit , BMI , leptin , NPY , lipid , olanzapine or haloperidol levels were also monitored . RESULTS AND DISCUSSION Leptin levels positively correlated with BMI in olanzapine ( r=0.64 , p<0.001 ) and haloperidol ( r=0.73 , p<0.001 ) groups ; only in olanzapine patients , the former also correlated with PANSS score ( r=0.54 , p<0.05 ) . NPY levels negatively correlated with olanzapine levels ( r=− 0.65 , p<0.01 ) . Adiponectin levels had not significantly varied . CONCLUSION Antipsychotics probably interfere on leptin and NPY signalling ways and disturb these hormones in eating behaviour control Abstract Background : Patients with schizophrenia or related disorders often switch antipsychotic therapy , most commonly due to lack of efficacy and side effects . The differences in anticipated efficacy and tolerability among atypical antipsychotics may drive switching behaviours . Switching to long-acting antipsychotics may improve adherence . Improving adherence is essential as relatively short medication gaps significantly increase the risk of schizophrenia hospitalizations . Long-term treatment with risperidone long-acting injectable ( RLAI ) , the first available long-acting atypical antipsychotic , versus oral atypical antipsychotics showed better adherence with RLAI . Stable patients with schizophrenia or related disorders treated with a stable dose of antipsychotic showed improved efficacy when switched to flexible doses of RLAI . The most common reason for patients to switch from olanzapine to another antipsychotic is excessive weight gain . Metabolic dysfunction also occurs more commonly with olanzapine than with risperidone . Patients switching from olanzapine to risperidone experienced significant decreases in body weight , body mass index and triglyceride levels , whereas patients switching from risperidone to olanzapine experienced significant increases in body weight and triglyceride levels . The efficacy , tolerability and safety of RLAI in non-acute patients with schizophrenia or schizoaffective disorder previously treated with oral olanzapine needs to be explored . Objective : The objective of this study was to evaluate the efficacy , tolerability and safety of switching from oral olanzapine to RLAI . Methods : This was a six-month , prospect i ve , multicentre , non-r and omized , single-arm , open-label trial . The trial evaluated non-acute adult patients with psychotic disorders treated with a stable olanzapine dose who required a treatment change . Three weeks after RLAI initiation , olanzapine was tapered off over 1 week or 3 weeks . Efficacy and safety measures included the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression-Severity ( CGI-S ) , Global Assessment of Functioning ( GAF ) and treatment-emergent adverse events ( TEAEs ) . Results : Among 96 patients analysed , significant endpoint efficacy changes versus baseline were observed for PANSS , CGI-S and GAF ( all p < 0.0001 ) . PANSS total score improvement was ≥20 % for 65.6 % of patients and ≥50 % for 31.3 % . TEAEs were similar in the 1- and 3-week taper groups ( 40.0 % and 46.5 % , respectively ) . TEAEs were generally mild ( 34.5 % ) or moderate ( 49.0 % ) in intensity . Conclusion : Switching non-acute patients with schizophrenia or schizoaffective disorder requiring a treatment change from a stable dose of oral olanzapine to RLAI improved psychiatric symptom control , functioning and patient treatment satisfaction . RLAI was generally well tolerated This 13-week double-blind study was design ed to assess noninferiority of the recently approved ( in the U.S. ) injectable atypical antipsychotic paliperidone palmitate ( PP ) versus risperidone long-acting injectable ( RIS-LAI ) in adult patients with schizophrenia . Patients ( N=1220 ) were r and omized ( 1:1 ) to either a ) PP : deltoid injections on day 1 ( 150 mg eq. ) , day 8 ( 100 mg eq. ) , and once-monthly flexible dosing as deltoid or gluteal injections on day 36 ( 50 mg eq. or 100 mg eq. ) and day 64 ( 50 mg eq. or 100 mg eq. or 150 mg eq. ) or b ) RIS-LAI : gluteal injections days 8 and 22 ( 25 mg ) , days 36 , 50 ( 25 or 37.5 mg ) and days 64 , 78 ( 25 , 37.5 or 50 mg ) . RIS-LAI-treated patients received oral supplementation with RIS 1 - 6 mg/day ( days 1 to 28 ) , and PP-treated patients received oral placebo . The safety analysis set ( n=1214 ) included 58 % men , 78 % white , with mean ( SD ) baseline PANSS total score : PP , 84.1 ( 12.09 ) ; and RIS-LAI , 83.6 ( 11.28 ) . Mean ( SD ) change from baseline to endpoint in PANSS total score decreased similarly in both groups ; PP ( -18.6 [ 15.45 ] ) and RIS-LAI ( -17.9 [ 14.24 ] ) . PP treatment was noninferior to RIS-LAI ( point estimate [ 95 % CI ] : 0.4 [ -1.62;2.38 ] , per- protocol analysis set [ primary analysis ] ) . The tolerability and safety of PP was generally similar to RIS-LAI with no new safety or tolerability findings The aim of this study was to compare the 12-month effectiveness of several second-generation antipsychotic drugs , with that of haloperidol in never-treated patients with first-episode psychosis . In total , 114 patients without life time exposure to any psychotropic medication were r and omized to haloperidol , olanzapine , risperidone , quetiapine or ziprasidone . Primary outcome was time to all-cause discontinuation . Secondary outcomes included discontinuation rates and symptom change as measured by the Positive and Negative Syndrome Scale ( PANSS ) . The overall discontinuation rate 64 % . At 12 months , the proportion of patients discontinuing treatment was 40.0 % for olanzapine , 56.5 % for quetiapine , 64.0 % for risperidone , 80.0 % for ziprasidone and 85.7 % for haloperidol . Mean time to antipsychotic discontinuation was higher in patients r and omized to second-generation antipsychotics than in those taking haloperidol . Significantly lower discontinuation was noted in patients on olanzapine than on haloperidol , or ziprasidone . Our results suggest that olanzapine might lead to longer treatment continuation in treatment naïve FEP patients than haloperidol and , possibly ziprasidone . Global psychopathology was significantly less reduced by haloperidol than with each individual SGA in this earliest phase of treatment |
11,945 | 28,461,756 | This analysis of the literature confirms the negative prognostic impact on survival of the MK in myeloid neoplasias . | In 2008 , the concept of the monosomal karyotype ( MK ) in adult acute myeloid leukemia ( AML ) patients was introduced , defined by the presence of a chromosomal aberration pattern characterized by the presence of at least two autosomal monosomies or of one monosomy plus one or more structural aberrations ( not including loss of a chromosome ) .
We present a systematic review of the literature about the influence of the MK on the outcome of patients affected by myeloid malignancies ( AML , myelodysplastic syndromes , and primary myelofibrosis ) . | BACKGROUND A complete remission is essential for prolonging survival in patients with acute myeloid leukemia ( AML ) . Daunorubicin is a cornerstone of the induction regimen , but the optimal dose is unknown . In older patients , it is usual to give daunorubicin at a dose of 45 to 50 mg per square meter of body-surface area . METHODS Patients in whom AML or high-risk refractory anemia had been newly diagnosed and who were 60 to 83 years of age ( median , 67 ) were r and omly assigned to receive cytarabine , at a dose of 200 mg per square meter by continuous infusion for 7 days , plus daunorubicin for 3 days , either at the conventional dose of 45 mg per square meter ( 411 patients ) or at an escalated dose of 90 mg per square meter ( 402 patients ) ; this treatment was followed by a second cycle of cytarabine at a dose of 1000 mg per square meter every 12 hours [ DOSAGE ERROR CORRECTED ] for 6 days . The primary end point was event-free survival . RESULTS The complete remission rates were 64 % in the group that received the escalated dose of daunorubicin and 54 % in the group that received the conventional dose ( P=0.002 ) ; the rates of remission after the first cycle of induction treatment were 52 % and 35 % , respectively ( P<0.001 ) . There was no significant difference between the two groups in the incidence of hematologic toxic effects , 30-day mortality ( 11 % and 12 % in the two groups , respectively ) , or the incidence of moderate , severe , or life-threatening adverse events ( P=0.08 ) . Survival end points in the two groups did not differ significantly overall , but patients in the escalated-treatment group who were 60 to 65 years of age , as compared with the patients in the same age group who received the conventional dose , had higher rates of complete remission ( 73 % vs. 51 % ) , event-free survival ( 29 % vs. 14 % ) , and overall survival ( 38 % vs. 23 % ) . CONCLUSIONS In patients with AML who are older than 60 years of age , escalation of the dose of daunorubicin to twice the conventional dose , with the entire dose administered in the first induction cycle , effects a more rapid response and a higher response rate than does the conventional dose , without additional toxic effects . ( Current Controlled Trials number , IS RCT N77039377 ; and Netherl and s National Trial Register number , NTR212 . Cytogenetics is considered one of the most valuable prognostic determinants in acute myeloid leukemia ( AML ) . However , many studies on which this assertion is based were limited by relatively small sample sizes or varying treatment approach , leading to conflicting data regarding the prognostic implication s of specific cytogenetic abnormalities . The Medical Research Council ( MRC ) AML 10 trial , which included children and adults up to 55 years of age , not only affords the opportunity to determine the independent prognostic significance of pretreatment cytogenetics in the context of large patient groups receiving comparable therapy , but also to address their impact on the outcome of subsequent transplantation procedures performed in first complete remission ( CR ) . On the basis of response to induction treatment , relapse risk , and overall survival , three prognostic groups could be defined by cytogenetic abnormalities detected at presentation in comparison with the outcome of patients with normal karyotype . AML associated with t(8;21 ) , t(15;17 ) or inv(16 ) predicted a relatively favorable outcome . Whereas in patients lacking these favorable changes , the presence of a complex karyotype , -5 , del(5q ) , -7 , or abnormalities of 3q defined a group with relatively poor prognosis . The remaining group of patients including those with 11q23 abnormalities , + 8 , + 21 , + 22 , del(9q ) , del(7q ) or other miscellaneous structural or numerical defects not encompassed by the favorable or adverse risk groups were found to have an intermediate prognosis . The presence of additional cytogenetic abnormalities did not modify the outcome of patients with favorable cytogenetics . Subgroup analysis demonstrated that the three cytogenetically defined prognostic groups retained their predictive value in the context of secondary as well as de novo AML , within the pediatric age group and furthermore were found to be a key determinant of outcome from autologous or allogeneic bone marrow transplantation ( BMT ) in first CR . This study highlights the importance of diagnostic cytogenetics as an independent prognostic factor in AML , providing the framework for a stratified treatment approach of this disease , which has been adopted in the current MRC AML 12 trial Cytogenetic classification by the revised international prognostic scoring system ( IPSS‐R ) and the prognostic value of monosomal karyotype ( MK ) were assessed in 783 patients with primary myelodysplastic syndromes ( MDS ) . At 22 months median follow‐up , 562 ( 72 % ) deaths were recorded . Percentages of patients with IPSS‐R “ very good , ” “ good , ” “ intermediate , ” “ poor , ” and “ very poor ” cytogenetic categories was 5 , 63 , 18 , 4 , and 10 % , respectively . The corresponding median survivals were 21 , 40 , 24 , 18 , and 6.5 months and the inter‐group differences ( good vs. very good/intermediate/poor vs. very poor ; P < 0.01 ) or similarities ( very good vs. intermediate vs. poor ; P = 0.79 ) were not significantly modified in multivariable analysis . Results were similar when analysis was restricted to 602 patients managed by supportive care . MK adversely affected survival in both poor and very poor karyotype groups ( P < 0.01 ) . In conclusion , we were unable to confirm the prognostic superiority of IPSS‐R‐very good karyotype or prognostically distinguish between very good , intermediate and poor karyotypes . Furthermore , we show additional prognostic information from MK in poor/very poor karyotype . Am . J. Hematol . 88:690–693 , 2013 . © 2013 Wiley Periodicals , BACKGROUND Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage . In this trial , we aim ed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens . METHODS In a phase III , international , multicentre , controlled , parallel-group , open-label trial , patients with higher-risk myelodysplastic syndromes were r and omly assigned one-to-one to receive azacitidine ( 75 mg/m(2 ) per day for 7 days every 28 days ) or conventional care ( best supportive care , low-dose cytarabine , or intensive chemotherapy as selected by investigators before r and omisation ) . Patients were stratified by French-American-British and international prognostic scoring system classifications ; r and omisation was done with a block size of four . The primary endpoint was overall survival . Efficacy analyses were by intention to treat for all patients assigned to receive treatment . This study is registered with Clinical Trials.gov , number NCT00071799 . FINDINGS Between Feb 13 , 2004 , and Aug 7 , 2006 , 358 patients were r and omly assigned to receive azacitidine ( n=179 ) or conventional care regimens ( n=179 ) . Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis . After a median follow-up of 21.1 months ( IQR 15.1 - 26.9 ) , median overall survival was 24.5 months ( 9.9-not reached ) for the azacitidine group versus 15.0 months ( 5.6 - 24.1 ) for the conventional care group ( hazard ratio 0.58 ; 95 % CI 0.43 - 0.77 ; stratified log-rank p=0.0001 ) . At last follow-up , 82 patients in the azacitidine group had died compared with 113 in the conventional care group . At 2 years , on the basis of Kaplan-Meier estimates , 50.8 % ( 95 % CI 42.1 - 58.8 ) of patients in the azacitidine group were alive compared with 26.2 % ( 18.7 - 34.3 ) in the conventional care group ( p<0.0001 ) . Peripheral cytopenias were the most common grade 3 - 4 adverse events for all treatments . INTERPRETATION Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care A monosomal karyotype ( MK ) , defined as ≥2 autosomal monosomies or a single monosomy in the presence of additional structural abnormalities , was recently identified as an independent prognostic factor conveying an extremely poor prognosis in patients with acute myeloid leukemia ( AML ) . In the present study , after excluding patients with t(15;17 ) , t(8;21 ) , inv(16 ) and normal karyotypes , 324 AML patients with cytogenetic abnormalities were the main subject of analysis . The incidences of MK were 13 % in patients aged 15 to 60 years and 18 % in those between 15 and 88 years old . MK was much more prevalent among elderly patients ( p<0.001 ) and was significantly associated with the presence of -7 , -5 , del(5q ) , abn12p , abn17p , -18 or 18q- , -20 or 20q- and CK ( for all p<0.001 except for abn12p p=0.009 ) , and + 8 or + 8q was less frequent in MK+ AML(p=0.007 ) . No correlation was noted between monosomal karyotype and FAB subtype ( p>0.05 ) ; MK remained significantly associated with worse overall survival among patients with complex karyotype ( p=0.032 ) ; A single autosomal monosomy contributed an additional negative effect in OS of patients with structural cytogenetic abnormalities ( P=0.008 ) . This report presents the prevalence , feature and prognostic impact of MK among a large series of Chinese AML patients from a single center for the first time Diagnostic karyotype provides the framework for risk-stratification schemes in acute myeloid leukemia ( AML ) ; however , the prognostic significance of many rare recurring cytogenetic abnormalities remains uncertain . We studied the outcomes of 5876 patients ( 16 - 59 years of age ) who were classified into 54 cytogenetic subgroups and treated in the Medical Research Council trials . In multivariable analysis , t(15;17)(q22;q21 ) , t(8;21)(q22;q22 ) , and inv(16)(p13q22)/t(16;16)(p13;q22 ) were the only abnormalities found to predict a relatively favorable prognosis ( P < .001 ) . In patients with t(15;17 ) treated with extended all-trans retinoic acid and anthracycline-based chemotherapy , additional cytogenetic changes did not have an impact on prognosis . Similarly , additional abnormalities did not have a significant adverse effect in t(8;21 ) AML ; whereas in patients with inv(16 ) , the presence of additional changes , particularly + 22 , predicted a better outcome ( P = .004 ) . In multivariable analyses , various abnormalities predicted a significantly poorer outcome , namely abn(3q ) ( excluding t(3;5)(q25;q34 ) ) , inv(3)(q21q26)/t(3;3)(q21;q26 ) , add(5q)/del(5q ) , -5 , -7 , add(7q)/del(7q ) , t(6;11)(q27;q23 ) , t(10;11)(p11 approximately 13;q23 ) , other t(11q23 ) ( excluding t(9;11)(p21 approximately 22;q23 ) and t(11;19)(q23;p13 ) ) , t(9;22)(q34;q11 ) , -17 , and abn(17p ) . Patients lacking the aforementioned favorable or adverse aberrations but with 4 or more unrelated abnormalities also exhibited a significantly poorer prognosis ( design ated " complex " karyotype group ) . These data allow more reliable prediction of outcome for patients with rarer abnormalities and may facilitate the development of consensus in reporting of karyotypic information in clinical trials involving younger adults with AML . This study is registered at http://www.is rct n.org as IS RCT N55678797 and IS RCT N17161961 Metaphase karyotyping is an established diagnostic st and ard in acute myeloid leukemia ( AML ) for risk stratification . One of the cytogenetic findings in AML is structurally highly abnormal marker chromosomes . In this study , we have assessed frequency , cytogenetic characteristics , prognostic impact , and underlying biological origin of marker chromosomes . Given their inherent gross structural chromosomal damage , we speculated that they may arise from chromothripsis , a recently described phenomenon of chromosome fragmentation in a single catastrophic event . In 2 large consecutive prospect i ve , r and omized , multicenter , intensive chemotherapy trials ( AML96 , AML2003 ) from the Study Alliance Leukemia , marker chromosomes were detectable in 165/1026 ( 16.1 % ) of aberrant non-core-binding-factor ( CBF ) karyotype patients . Adverse-risk karyotypes displayed a higher frequency of marker chromosomes ( 26.5 % in adverse-risk , 40.3 % in complex aberrant , and 41.2 % in abnormality(17p ) karyotypes , P < .0001 each ) . Marker chromosomes were associated with a poorer prognosis compared with other non-CBF aberrant karyotypes and led to lower remission rates ( complete remission + complete remission with incomplete recovery ) , inferior event-free survival as well as overall survival in both trials . In multivariate analysis , marker chromosomes independently predicted poor prognosis in the AML96 trial ≤60 years . As detected by array comparative genomic hybridization , about one-third of marker chromosomes ( 18/49 ) had arisen from chromothripsis , whereas this phenomenon was virtually undetectable in a control group of marker chromosome-negative complex aberrant karyotypes ( 1/34 ) . The chromothripsis-positive cases were characterized by a particularly high degree of karyotype complexity , TP53 mutations , and dismal prognosis . In conclusion , marker chromosomes are indicative of chromothripsis and associated with poor prognosis per se and not merely by association with other adverse cytogenetic features |
11,946 | 28,118,684 | The use of ultrasound was not demonstrated to improve students ' underst and ing of anatomy .
The benefit of ultrasound in teaching physical examination was inconsistent and rests on minimal evidence .
With POCUS , students ' diagnostic accuracy was improved for certain pathologies , but findings were inconsistent for others . | CONTEXT The use of point-of-care ultrasound ( POCUS ) in clinical care is growing rapidly and advocates have recently proposed the integration of ultrasound into undergraduate medical education ( UME ) .
The evidentiary basis for this integration has not been evaluated critically or systematic ally .
OBJECTIVES We conducted a critical and systematic review framed by the rationale s enumerated in academic publications by advocates of ultrasound in UME . | Background The exponential growth of image-based diagnostic and minimally invasive interventions requires a detailed three-dimensional anatomical knowledge and increases the dem and towards the undergraduate anatomical curriculum . This r and omized controlled trial investigates whether musculoskeletal ultrasound ( MSUS ) or arthroscopic methods can increase the anatomical knowledge uptake . Methods Second-year medical students were r and omly allocated to three groups . In addition to the compulsory dissection course , the ultrasound group ( MSUS ) was taught by eight , didactically and professionally trained , experienced student-teachers and the arthroscopy group ( ASK ) was taught by eight experienced physicians . The control group ( CON ) acquired the anatomical knowledge only via the dissection course . Exposure ( MSUS and ASK ) took place in two separate lessons ( 75 minutes each , shoulder and knee joint ) and introduced st and ard scan planes using a 10-MHz ultrasound system as well as arthroscopy tutorials at a simulator combined with video tutorials . The theoretical anatomic learning outcomes were tested using a multiple-choice question naire ( MCQ ) , and after cross-over an objective structured clinical examination ( OSCE ) . Differences in student ’s perceptions were evaluated using Likert scale-based items . Results The ASK-group ( n = 70 , age 23.4 ( 20–36 ) yrs . ) performed moderately better in the anatomical MC exam in comparison to the MSUS-group ( n = 84 , age 24.2 ( 20–53 ) yrs . ) and the CON-group ( n = 88 , 22.8 ( 20–33 ) yrs . ; p = 0.019 ) . After an additional arthroscopy teaching 1 % of students failed the MC exam , in contrast to 10 % in the MSUS- or CON-group , respectively . The benefit of the ASK module was limited to the shoulder area ( p < 0.001 ) . The final examination ( OSCE ) showed no significant differences between any of the groups with good overall performances . In the evaluation , the students certified the arthroscopic tutorial a greater advantage concerning anatomical skills with higher spatial imagination in comparison to the ultrasound tutorial ( p = 0.002 ; p < 0.001 ) . Conclusions The additional implementation of arthroscopy tutorials to the dissection course during the undergraduate anatomy training is profitable and attractive to students with respect to complex joint anatomy . Simultaneous teaching of basic-skills in musculoskeletal ultrasound should be performed by medical experts , but seems to be inferior to the arthroscopic 2D-3D-transformation , and is regarded by students as more difficult to learn . Although arthroscopy and ultrasound teaching do not have a major effect on learning joint anatomy , they have the potency to raise the interest in surgery The birth of the intermittent injectate-based conventional pulmonary artery catheter ( fondly nicknamed PAC ) was proudly announced in the New Engl and Journal of Medicine in 1970 by his parents HJ Swan and William Ganz . PAC grew rapidly , reaching manhood in 1986 where , in the US , he was shown to influence the management of over 40 % of all ICU patients . His reputation , however , was tarnished in 1996 when Connors and colleagues suggested that he harmed patients . This was followed by r and omized controlled trials demonstrating he was of little use . Furthermore , reports surfaced suggesting that he was unreliable and inaccurate . It also became clear that he was poorly understood and misinterpreted . Pretty soon after that , a posse of rivals ( bedside echocardiography , pulse contour technology ) moved into the neighborhood and cl aim ed they could assess cardiac output more easily , less invasively and no less reliably . To make matter worse , dynamic assessment of fluid responsiveness ( pulse pressure variation , stroke volume variation and leg raising ) made a mockery of his ‘ wedge ’ pressure . While a h and ful of die-hard followers continued to promote his mission , the last few years of his existence were spent as a castaway until his death in 2013 . His cousin ( the continuous cardiac output PAC ) continues to eke a living mostly in cardiac surgery patients who need central access anyway . This paper review s the rise and fall of the conventional PAC This study compared the efficacy of two cardiac anatomy teaching modalities , ultrasound imaging and cadaveric prosections , for learning cardiac gross anatomy . One hundred and eight first‐year medical students participated . Two weeks prior to the teaching intervention , students completed a pretest to assess their prior knowledge and to ensure that groups were equally r and omized . Students , divided into pre‐existing teaching groups , were assigned to one of two conditions ; “ cadaver ” or “ ultrasound . ” Those in the cadaver group received teaching on the heart using prosections , whereas the ultrasound group received teaching using live ultrasound images of the heart . Immediately after teaching , students sat a post‐test . Both teaching modalities increased students ' test scores by similar amounts but no significant difference was found between the two conditions , suggesting that both prosections and ultrasound are equally effective methods for teaching gross anatomy of the heart . Our data support the inclusion of either cadaveric teaching or living anatomy using ultrasound within the undergraduate anatomy curriculum , and further work is needed to compare the additive effect of the two modalities . Anat Sci Educ . © 2011 American Association of Anatomists Purpose We analyzed the efficacy of a point-of-care ultrasonographic protocol , based on a focused multiorgan examination , for the diagnostic process of symptomatic , non-traumatic hypotensive patients in the emergency department . Methods We prospect ively enrolled 108 adult patients complaining of non-traumatic symptomatic hypotension of uncertain etiology . Patients received immediate point-of-care ultrasonography to determine cardiac function and right/left ventricle diameter rate , inferior vena cava diameter and collapsibility , pulmonary congestion , consolidations and sliding , abdominal free fluid and aortic aneurysm , and leg vein thrombosis . The organ-oriented diagnoses were combined to formulate an ultrasonographic hypothesis of the cause of hemodynamic instability . The ultrasonographic diagnosis was then compared with a final clinical diagnosis obtained by agreement of three independent expert physicians who performed a retrospective hospital chart review of each case . Results Considering the whole population , concordance between the point-of-care ultrasonography diagnosis and the final clinical diagnosis was interpreted as good , with Cohen ’s k = 0.710 ( 95 % CI , 0.614–0.806 ) , p < 0.0001 and raw agreement ( Ra ) = 0.768 . By eliminating the 13 cases where the final clinical diagnosis was not agreed upon ( indefinite ) , the concordance increased to almost perfect , with k = 0.971 ( 95 % CI , 0.932–1.000 ) , p < 0.0001 and Ra = 0.978 . Conclusions Emergency diagnostic judgments guided by point-of-care multiorgan ultrasonography in patients presenting with undifferentiated hypotension significantly agreed with a final clinical diagnosis obtained by retrospective chart review . The integration of an ultrasonographic multiorgan protocol in the diagnostic process of undifferentiated hypotension has great potential in guiding the first-line therapeutic approach Ultrasound simulation allows students to virtually explore internal anatomy by producing accurate , moving , color , three‐dimensional rendered slices from any angle or approach leaving the organs and their relationships intact without requirement for consumables . The aim was to determine the feasibility and efficacy of self‐directed learning of cardiac anatomy with an ultrasound simulator compared to cadavers and plastic models . After a single cardiac anatomy lecture , fifty university anatomy students participated in a three‐hour supervised self‐directed learning exposure in groups of five , r and omized to an ultrasound simulator or human cadaveric specimens and plastic models . Pre‐ and post‐tests were conducted using pictorial and non‐pictorial multiple‐choice questions ( MCQs ) . Simulator students completed a survey on their experience . Four simulator and seven cadaver group students did not attend after r and omization . Simulator use in groups of five students was feasible and feedback from participants was very positive . Baseline test scores were similar ( P = 0.9 ) between groups . After the learning intervention , there was no difference between groups in change in total test score ( P = 0.37 ) , whether they were pictorial ( P = 0.6 ) or non‐pictorial ( P = 0.21 ) . In both groups there was an increase in total test scores ( simulator + 19.8 ±12.4%% and cadaver : + 16.4 % ± 10.2 , P < 0.0001 ) , pictorial question scores ( + 22.9 ±18.0 % , 19.7 ±19.3 % , P < 0.001 ) and non‐pictorial question scores ( + 16.7 ±18.2 % , + 13 ±15.4 % , P = 0.002 ) . The ultrasound simulator appears equivalent to human cadaveric prosections for learning cardiac anatomy . Anat Sci Educ 8 : 21–30 . © 2014 American Association of Anatomists Existing guidelines for the number of ultrasounds required before clinical competency are based not on scientific study but on consensus opinion . The objective of this study was to describe the learning curve of limited right upper quadrant ultrasound . This was a prospect i ve descriptive study . Ultrasounds collected over 1 year were review ed for interpretive and technical errors . Possible errors during bedside ultrasound of the gallbladder include incorrect interpretation , incomplete image acquisition , and improper or poor imaging techniques result ing in poor image quality . The ultrasound image quality was rated on a 4-point scale , with 1 = barely interpretable and 4 = excellent image quality . Required images were rated on an additional 4-point scale , with 4 = all required images were included and 1 = minimal images were recorded . There were 352 patients enrolled by 42 emergency physicians ( 35 residents and 7 attendings ) . Gallstones were identified in 13.9 % of the patients , and 4.3 % of the ultrasounds were indeterminate . Interpretive and technical error rates decreased as the clinician gained experience . The number of poor quality ultrasounds decreased after an average of seven ultrasounds . Inclusion of all required images increased after 25 ultrasounds . Sonographers who had performed over 25 ultrasounds showed excellent agreement with the expert over-read , with only two disagreements , both from a single individual . It was concluded that clinicians are clinical ly competent after performing 25 ultrasounds of the gallbladder OBJECTIVES We aim ed to investigate the potential benefit of adding goal -directed ultrasound examinations performed by on-call medical residents using a pocket-size imaging device in patients admitted to a medical department . METHODS A total of 992 emergency admissions to the medical department at a nonuniversity hospital in Norway were included . Patients admitted on date s with an on-call medical resident r and omized to use a pocket-size imaging device were eligible for pocket-size cardiac and abdominal ultrasound examinations or st and ard care . The cardiac examination included estimation of right and left ventricular sizes and global systolic function and regional left ventricular systolic function , evaluation for pleural and pericardial effusion , and valvular disease . The abdominal examination looked for signs of gross abnormalities of the liver , gallbladder , abdominal aorta , inferior vena cava , and urinary system . Six of 12 medical residents with limited ultrasound experience were r and omized to perform the examinations . Diagnostic corrections were made , and findings were confirmed by reference st and ard diagnostics . RESULTS A total of 199 patients were examined . Median times used were 5.7 minutes for the cardiac examination and 4.7 minutes for the abdominal examination . In 13 patients ( 6.5 % ) , the examination result ed in a major change in the primary diagnosis . In 21 patients ( 10.5 % ) , the diagnosis was verified , and in 48 ( 24.0 % ) , an additional important diagnosis was made . CONCLUSIONS By implementing pocket-size ultrasound examinations that took less than 11 minutes to the usual care , we corrected , verified , or added important diagnoses in more than 1 of 3 emergency medical admissions . Point-of-care examinations with a pocket-size imaging device increased medical residents ' diagnostic accuracy and capability Introduction : This study compared ultrasonography-guided ( USG ) placement with anatomic placement during internal jugular ( IJ ) central venous catheter ( CVC ) insertion by novice practitioners using a simulation model . Methods : A prospect i ve , r and omized , crossover study of 28 fourth year medical students was conducted with institutional review board approval . Participants viewed an instructional material before participation , and supervision was st and ardized . Participants were r and omly assigned to either USG or traditional l and mark method first , and each group served as its own crossover comparison . Paired t tests and & khgr;2 analysis were performed on matched-pair data . Results : Fifty-four percent of participants had at least one arterial stick without USG compared with 0 % when using USG . Significant differences were shown in the USG versus no-USG groups in number of needle advances until successful cannulation of the vein : mean with USG = 1.5 advances ( 95 % CI , 1.0–1.9 ) , mean without USG = 10.4 advances ( 95 % CI , 7.8–13 ) , P < 0.001 ; time to successful cannulation : mean with USG = 58 seconds ( 95 % CI , 48–72 seconds ) , mean without USG = 338 seconds ( 95 % CI , 286–390 seconds ) , P < 0.001 ; and success rates : 100 % with USG and 42.8 % without USG ( 95 % CI , 24.5%–61.1 % ) . The number needed to treat to avoid an arterial stick by using USG during IJ insertion by novice practitioners is ∼2 . Conclusions : The USG during IJ CVC placement by novice practitioners is essential to improve patient safety . If these data are extrapolated to impact on patient care , an arterial stick may be avoided in one of every two IJ CVCs placed by novice practitioners . The USG technology should be made available to novice practitioners needing to place CVCs CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women . All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD OBJECTIVES Learning to perform physical examination of the abdomen is a challenge for medical students . Medical educators need to find engaging , effective tools to help students acquire competence and confidence in abdominal examination techniques . This study evaluates the added value of ultrasound training when Year 1 medical students learn abdominal examination . METHODS The study used a r and omised trial with a wait-list control condition . Year 1 medical students were r and omised into 2 groups : those who were given immediate ultrasound training , and those for whom ultrasound training was delayed while they received st and ard instruction on abdominal examination . St and ardised patients ( SPs ) used a clinical skills assessment ( CSA ) checklist to assess student abdominal examination competence on 2 occasions - CSA-1 and CSA-2 - separated by 8 weeks . Students also estimated SP liver size for comparison with gold-st and ard ultrasound measurements . Students completed skills confidence surveys . RESULTS Proficiency in abdominal examination technique acquired from traditional instruction boosted with ultrasound training showed no advantage at CSA-1 . However , at CSA-2 the delayed ultrasound training group showed significant improvement . Students uniformly underestimated SP liver sizes and the estimates were not affected by ultrasound training . Student confidence in both groups improved from baseline to CSA-1 and CSA-2 . CONCLUSIONS Ultrasound training as an adjunct to traditional means of teaching abdominal examination improves students ' physical examination technique after students have acquired skills with basic examination manoeuvres Abstract Objective .—Physicians practicing in remote areas are typically limited in their choice of diagnostic tools . The goal of this study was to determine whether the use of a portable ultrasound ( US ) device on selected patients in a remote setting would alter physician diagnosis and management . Methods .—This was a prospect i ve observational study of the affects of US on physician decision making deep in the Amazon jungle . A battery-operated Sonosite 180 Plus with 2 interchangeable transducers ( 4–7-MHz broadb and intercavitary transducer and 2–5-MHz broadb and abdominal transducer ) was used . The patient population consisted of local tribal people . Two of the physicians on the team performed all US examinations . Team physicians requesting US examinations filled out a survey before and after the US examination . Before the US , the referring physician filled out a survey describing the patient 's initial complaint , pertinent past medical history and physical findings , and an initial ( pre-US ) differential diagnosis and planned treatment with expected disposition . After the results of the US were review ed with the referring physicians , the doctors were asked to fill out the remainder of the survey , allowing comparison of pre- and post-US differential diagnosis , treatment plan , and disposition . Results .—A total of 25 US studies were performed during this study ( 1 trauma US scan , 6 hepatobiliary studies , 5 transabdominal pelvic scans , 7 transvaginal pelvic studies , 3 renal studies , and 3 abdominal aortic scans ) . The monitor on the US unit experienced a rare failure shortly after being used at 17,000 ft and then 10 times at sea level , and no further US scans could be performed . US scan results dramatically altered the disposition of 7 patients , including 4 patients who avoided a potentially dangerous 2-day evacuation to more definitive medical care . Three patients were found to need rapid referral to the nearest clinic for surgical evaluation . Conclusions .—When used in a remote location , portable US provides a significant benefit that can dramatically alter disposition and treatment OBJECTIVES Increasing emphasis has been placed on point-of-care ultrasound in medical school . The overall effects of ultrasound curriculum implementation on the traditional physical examination skills of medical students are still unknown . We studied the effects on the Objective St and ardized Clinical Examination ( OSCE ) scores of year 1 medical students before and after ultrasound curriculum implementation . METHODS An ultrasound curriculum was incorporated into the physical diagnosis course for year 1 medical students in the 2012 - 2013 academic year . We performed a prospect i ve observational study comparing traditional OSCE scores of year 1 medical students exposed to the ultrasound curriculum ( post-ultrasound ) versus historic year 1 medical student controls ( pre-ultrasound ) with no ultrasound exposure . Question naire data were also obtained from year 1 medical students and physical diagnosis faculty to assess attitudes toward ultrasound implementation . RESULTS The final overall OSCE scores were grade d with a 5-point Likert-type scale from unsatisfactory to outst and ing . There was a significant increase in outst and ing scores in the post-ultrasound compared to the pre-ultrasound group ( 27.0 % versus 10.9 % ; P < .001 ) . The post-ultrasound group had significantly ( P < .05 ) increased first-time pass rates on blood pressure measurements , the abdominal examination , and professionalism . Student and physical diagnosis faculty question naire data showed an overall positive response , with most agreeing or strongly agreeing that ultrasound should be included in the future year 1 medical student curriculum . CONCLUSIONS Ultrasound implementation into a physical diagnosis curriculum for year 1 medical students is feasible and may improve their overall traditional physical examination skills BACKGROUND Physical examination is a crucial part in medical student curricula , but a decline in physical examination skills was noted in the last two decades . The benefic role of ultrasonography ( US ) as an adjuvant method for clinical examination was evaluated in many studies , but there are different approaches among countries and universities . The aim of this study was to evaluate the role of US in learning physical exam in 3rd year medical students . METHODS One hundred and four 3rd year medical students were r and omly enrolled . They were divided first in two equal groups ( I and II , with and without US , by rotation ) and then in smaller groups of 8 - 9 students . Pairs between smaller groups belonging to group I and II were r and omly established in order to be trained and evaluated by the same instructor . We verified the influence of US on the correctness of thyroid palpation , lung percussion ( inferior limit of the lung ) , and liver size estimation . They received no special training on US . After the learning sessions ( four sessions , one hour each ) a question naire was applied to each student . RESULTS For thyroid palpation , there were no significant differences regarding the gl and dimensions . For lung and liver palpation the results showed better results for some points in groups using US as adjuvant , but the most significant difference regarded the appreciation of self confidence ( in favor of US-groups ) . The majority of the students using US appreciated as very useful the informations provided by US . Also , we found a clear improvement in detecting the upper limit of the liver comparing with the inferior limit of the lung , as result of better clinical skills . DISCUSSION S AND CONCLUSION The results from this pilot study proved the utility of US in learning clinical examination . The students can better underst and the regional anatomy and can confirm immediately the physical findings . It is important for students to reach a certain level of knowledge regarding physical exam to better underst and the role of US . Overall , we can state that use of US in the daily clinical examination teaching greatly improved the students ' clinical examination abilities and that is a strong argument for integrating basic US into the medical school curriculum OBJECTIVES To determine whether the addition of ultrasound to traditional physical examination instruction improves junior medical students ' abilities to locate the femoral pulse . METHODS Initially , 150 second-year medical students were taught the femoral pulse examination using traditional bedside teaching on st and ardized patients and online didactic videos . Students were then r and omized into 2 groups : group 1 received ultrasound training first and then completed the st and ardized examination ; and group 2 performed the st and ardized examination first and then received ultrasound training . On the st and ardized patients , the femoral artery was marked with invisible ink before the sessions using ultrasound . Compared to these markers , students were then evaluated on the accuracy of femoral artery pulse palpation and the estimated location of the femoral vein . All students completed a self- assessment survey after the ultrasound sessions . RESULTS Ultrasound training improved the students ' ability to palpate the femoral pulse ( P= .02 ) . However , ultrasound did not facilitate correct estimation of the femoral vein 's anatomic location ( P = .09 ) . Confidence levels in localizing the femoral artery and vein were equal between groups at baseline , and both increased after the ultrasound sessions . CONCLUSIONS The addition of ultrasound teaching to traditional physical examination instruction enhanced medical student competency and confidence with the femoral vascular examination . However , underst and ing of anatomy may require emphasis on precourse didactic material , but further study is required OBJECTIVE This study was design ed to assess the clinical applicability of a small , h and held , portable transthoracic echocardiography device by noncardiologist intensivists . DESIGN Prospect i ve , observational study . After 10 one-hour tutorials , intensivists performed a limited transthoracic echocardiography ( TTE ) ( 2 - 4 views , without Doppler or M-mode ) examination with the 5.6-lb SonoHeart Echo System ( SonoSite , Bethell , WA ) on critically ill patients admitted to the surgical intensive care unit . After initial cardiac clinical assessment in 90 patients , a limited TTE was performed by an intensivist to assess left ventricular ( LV ) function and LV volume status . Each study was immediately review ed and repeated by an echocardiographer to determine the technical quality of the TTE and the accuracy of the intensivist 's interpretation . Data were analyzed and presented in proportions using descriptive statistics . SETTING Surgical intensive care unit of an academic medical center . PARTICIPANTS Ninety critically ill adult patients . INTERVENTIONS After initial cardiac clinical assessment , a limited TTE was performed by an intensivist to assess LV size and function , to rule out significant pericardial effusions , and to estimate circulatory volume . RESULTS Intensivists successfully performed a diagnostic limited TTE in 94 % of patients and interpreted their studies correctly in 84 % . Limited TTE provided new cardiac information and changed management in 37 % of patients . TTE added useful information in an additional 47 % of patients but did not alter immediate management . The mean " goal -directed TTE " acquisition time was 10.5 + /- 4.2 minutes . CONCLUSION After a brief formal training in using this h and held echocardiographic system in intensive care unit patients , surgical intensivists successfully performed and correctly interpreted a limited TTE in critically ill patients . Limited TTE provided new information and altered management in a significant number of patients . This study supports incorporating bedside goal -directed , limited TTE into intensivists ' training programs BACKGROUND H and held ultrasound is emerging as an important tool for point-of-care cardiac assessment . Although cardiac ultrasound skills are traditionally introduced during postgraduate training , the optimal time and methodology to initiate training in focused cardiac ultrasound ( FCU ) are unknown . The objective of this study was to develop and evaluate a novel curriculum for training medical students in the use of FCU . METHODS The study was conducted in two phases . In the first phase , 12 first-year medical students underwent FCU training over an 8-week period . In the second phase , 45 third-year medical students were r and omized to one of three educational programs . Program 1 consisted of a lecture-based approach with scan training by a sonographer . Program 2 coupled electronic education modules with sonographer scan training . Program 3 was fully self-directed , combining electronic modules with scan training on a high-fidelity ultrasound simulator . Image interpretation skills and scanning technique were evaluated after each program . RESULTS First-year medical students were able to modestly improve interpretation ability and acquire limited scanning skills . Third-year medical students exhibited similar improvement in mean examination score for image interpretation whether a lecture-based program or electronic modules was used . Students in the self-directed group using an ultrasound simulator had significantly lower mean quality scores than students taught by sonographers . CONCLUSIONS Third-year medical students were able to acquire FCU image acquisition and interpretation skills after a novel training program . Self-directed electronic modules are effective for teaching introductory FCU interpretation skills , while expert-guided training is important for developing scanning technique OBJECTIVES Bedside sonography is a growing field of medicine , but there is little evidence about how to teach it to medical students . A peer-mentoring system may help pre clinical medical students learn bedside sonography . METHODS In 2008 and 2009 , participating first-year medical students completed an image recognition test at 0 , 2 , and 4 months and were r and omized to an early or a late intervention group . In h and s-on sessions , senior medical students taught the early intervention group how to perform a Trinity hypotensive ultrasound protocol between months 0 and 2 and then taught the late intervention group the Trinity protocol between months 2 and 4 . Participants completed a practical examination at month 4 . We measured the improvement in knowledge after the intervention and retention of knowledge and skills in the early intervention group at month 4 . First-year medical students completed precourse and postcourse surveys about comfort and skills with sonography . RESULTS Eighty-six first-year medical students enrolled ; 79 completed the precourse survey ; 54 completed all knowledge tests ; 52 completed the practical examination ; and 49 completed the postcourse survey . Of the 125 non participants , 109 completed the precourse survey , and 25 completed the postcourse survey . Participants ' knowledge scores increased by 30 % after the intervention . The early intervention group retained 92 % of the knowledge gained . Thirty-six percent of participants were able to complete the Trinity protocol in 15 minutes during the practical examination , with no significant difference between the early and late intervention groups . Participants responded positively about the experience and indicated that h and s-on sessions were helpful . CONCLUSIONS Peer mentoring is a useful method for teaching sonography to pre clinical medical students BACKGROUND The exposure to ultrasound technology during medical school education is highly variable across institutions . OBJECTIVES The objectives of this study were to assess medical students ' perceptions of ultrasound use to teach Gross Anatomy along with traditional teaching methods , and determine their ability to identify sonographic anatomy after focused didactic sessions . METHODS Prospect i ve observational study . Phase I of the study included three focused ultrasound didactic sessions integrated into Gross Anatomy curriculum . During Phase II , first-year medical students completed a question naire . RESULTS One hundred nine subjects participated in this study ; 96 % ( 95 % confidence interval [ CI ] 92 - 99 % ) agreed that ultrasound-based teaching increased students ' knowledge of anatomy acquired through traditional teaching methods . Ninety-two percent ( 95 % CI 87 - 97 % ) indicated that ultrasound-based teaching increases confidence to perform invasive procedures in the future . Ninety-one percent ( 95 % CI 85 - 96 % ) believed that it is feasible to integrate ultrasound into the current Anatomy curriculum . Ninety-eight percent ( 95 % CI 95 - 100 % ) of medical students accurately identified vascular structures on ultrasound images of normal anatomy of the neck . On a scale of 1 to 10 , the average confidence level reported in interpreting the images was 7.4 ( 95 % CI 7.1 - 7.7 ) . Overall , 94 % ( 95 % CI 91 - 99 % ) accurately answered questions about ultrasound fundamentals and sonographic anatomy . CONCLUSIONS The majority of medical students believed that it is feasible and beneficial to use ultrasound in conjunction with traditional teaching methods to teach Gross Anatomy . Medical students were very accurate in identifying sonographic vascular anatomy of the neck after brief didactic sessions Background : The perioperative surgical home model highlights the need for trainees to include modalities that are focused on the entire perioperative experience . The focus of this study was to design , introduce , and evaluate the integration of a whole-body point-of-care ( POC ) ultrasound curriculum ( Focused periOperative Risk Evaluation Sonography Involving Gastroabdominal Hemodynamic and Transthoracic ultrasound ) into residency training . Methods : For 2 yr , anesthesiology residents ( n = 42 ) received lectures using a model/simulation design and half were also r and omly assigned to receive pathology assessment training . Posttraining performance was assessed through Kirkpatrick levels 1 to 4 outcomes based on the resident satisfaction surveys , multiple-choice tests , pathologic image evaluation , human model testing , and assessment of clinical impact via review of clinical examination data . Results : Evaluation of the curriculum demonstrated high satisfaction scores ( n = 30 ) , improved content test scores ( n = 37 ) for all tested categories ( 48 ± 16 to 69 ± 17 % , P < 0.002 ) , and improvement on human model examinations . Residents r and omized to receive pathology training ( n = 18 ) also showed higher scores compared with those who did not ( n = 19 ) ( 9.1 ± 2.5 vs. 17.4 ± 3.1 , P < 0.05 ) . Clinical examinations performed in the organization after the study ( n = 224 ) showed that POC ultrasound affected clinical management at a rate of 76 % and detected new pathology at a rate of 31 % . Conclusions : Results suggest that a whole-body POC ultrasound curriculum can be effectively taught to anesthesiology residents and that this training may provide clinical benefit . These results should be evaluated within the context of the perioperative surgical home |
11,947 | 10,796,578 | REVIEW ER 'S CONCLUSIONS There is insufficient evidence to support the use of manual therapies for patients with asthma .
Currently , there is insufficient evidence to support or refute the use of manual therapy for patients with asthma | BACKGROUND A variety of manual therapies with similar postulated biologic mechanisms of action are commonly used to treat patients with asthma .
Manual therapy practitioners are also varied , including physiotherapists , respiratory therapists , chiropractic and osteopathic physicians .
A systematic review across disciplines is warranted .
OBJECTIVES To evaluate the evidence for the effects of manual therapies for treatment of patients with bronchial asthma . | A prospect i ve r and omised single-blind study of the effects of real and sham acupuncture on exercise-induced asthma was conducted in nineteen children . Forced expiratory flow in 1st second ( FEV1 ) , forced vital capacity ( FVC ) , and peak expiratory flow rate ( PEFR ) were measured throughout acupuncture and after treadmill exercise . Neither real nor sham acupuncture affected the basal bronchomotor tone but both , when applied 20 min before exercise , attenuated exercise induced asthma : mean maximum percentage falls in FEV1 , FVC , and PEFR were 44.4 % , 33.3 % , and 49.5 % without acupuncture ; 23.8 % , 15.8 % , and 25.9 % after real acupuncture ; and 32.6 % , 26.1 % , and 34.3 % after sham acupuncture . Real acupuncture provided better protection against exercise-induced asthma than did sham acupuncture ( p less than 0.05 ) The present multicentre study evaluates the differences in efficacy between a 3 month rehabilitation programme including drug treatment , and a 3 month control period of drug treatment only , for asthmatic patients and patients with chronic obstructive pulmonary disease ( COPD ) . The programme was run by physiotherapists in eight local practice s , and included exercise training , patient education , breathing retraining , evacuation of mucus , relaxation techniques , and recreational activities . In a r and omized controlled trial with a cross-over design , the effects of rehabilitation were evaluated 3 and 6 months after baseline measurements in terms of exercise tolerance and quality of life ( QOL ) . Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min walking tests . QOL was evaluated by means of the Chronic Respiratory Disease Question naire ( CRDQ ) . After 3 months , the patients who started with rehabilitation showed significant improvements in endurance time ( 421 s ) and cardiac frequency ( 6 beats.min-1 ) during cycling , walking distance ( 39 m ) , and total CRDQ score ( 17 points ) compared to the control group . These improvements were still significant after 6 months . Additional analysis indicated that the asthmatic patients and the patients with COPD responded to rehabilitation in a similar way , with the exception that there was a greater improvement in walking distance for asthmatics . Improvements in exercise tolerance were not significantly correlated with improvements in QOL . Rehabilitation of patients with asthma or chronic obstructive pulmonary disease in local physiotherapy practice s improves exercise tolerance and quality of life A small , controlled trial of joint treatment of childhood asthma by a doctor , a physiotherapist , a psychologist , and a social worker , working together in the family setting , demonstrated an improvement in ventilatory capacity . The limited scope of this trial does not permit more general conclusions as to the effect of such treatment on the severity and frequency of attacks , but the observation that some measurable physiological improvement occurred suggests that the place of multidisciplinary nonpharmaceutical management of childhood asthma should be investigated in more detail Many asthma patients seek alternative or adjunctive therapies . One such modality is reflexology , whereby finger pressure is applied to certain parts of the body . The aim of the study was to examine the popular cl aim that reflexology treatment benefits bronchial asthma . Ten weeks of active or simulated ( placebo ) reflexology given by an experienced reflexologist , were compared in an otherwise blind , controlled trial of 20 + 20 out patients with asthma . Objective lung function tests ( peak flow morning and evening , and weekly spirometry at the clinic ) did not change . Subjective scores ( describing symptoms , beta2-inhalations and quality of life ) and also bronchial sensitivity to histamine improved on both regimens , but no differences were found between groups receiving active or placebo reflexology . However , a trend in favour of reflexology became significant when a supplementary analysis of symptom diaries was carried out . It was accompanied by a significant pattern compatible with subconscious unblinding , in that patients tended to guess which treatment they had been receiving . No evidence was found that reflexology has a specific effect on asthma beyond placebo influence The effects of chest physical therapy in acute severe asthma in children have been studied in 38 children aged 6 to 13 years in a r and omized placebo controlled trial . The study began between 6 and 24 hours after admission to hospital ; 19 children received chest physical therapy ( PT ) and 19 children received placebo visits . Each child had 4 treatments over 2 days which were preceded by nebulized salbutamol . Lung volumes and flow rates were measured in a body plethysmograph before salbutamol and before and after either PT or placebo on the first and fourth treatments . Throughout the study st and ard asthma drug therapy was given . In both groups characteristics such as sex , race , age , height , weight , severity , and baseline lung function were similar . Taking into account the baseline , lung function at the end of the study was similar in both groups . Three 12 year old children in the PT group showed improvements in flows above those seen in any children in the placebo group . We conclude that chest PT , when combined with asthma drug therapy , does not improve lung function in most children in this age group with acute severe asthma The purpose of this r and omized patient‐ and observer‐blinded cross‐over trial was to evaluate the efficacy of chiropractic treatment in the management of chronic asthma when combined with pharmaceutical maintenance therapy . The trial was conducted at the National University Hospital 's Out‐patient Clinic in Copenhagen , Denmark . Thirty‐one patients aged 18–44 years participated , all suffering from chronic asthma controlled by bronchodilators and /or inhaled steroids . Patients , or who had received chiropractic treatment for asthma within the last 5 years , who received oral steroids and immunotherapy , were not eligible . Patients were r and omized to receive either active chiropractic spinal manipulative treatment or sham chiropractic spinal manipulative treatment twice weekly for 4 weeks , and then crossed over to the alternative treatment for another 4 weeks . Both phases were preceded and followed by a 2‐week period without chiropractic treatment . The main outcome measurements were forced expiratory volume in the first second ( FEV1 ) , forced vital capacity ( FVC ) , daily use of inhaled bronchodilators , patient‐rated asthma severity and non‐specific bronchial reactivity ( n‐BR ) . Using the cross‐over analysis , no clinical ly important or statistically significant differences were found between the active and sham chiropractic interventions on any of the main or secondary outcome measures . Objective lung function did not change during the study , but over the course of the study , non‐specific bronchial hyperreactivity ( n‐BR ) improved by 36 % ( P= 0.01 ) and patient‐rated asthma severity decreased by 34 % ( P= 0.0002 ) compared with the baseline values . The results do not support the hypothesis that chiropractic spinal manipulative therapy is superior to sham spinal manipulation in the management of pharmaceutically controlled chronic asthma in adults when administered twice weekly for 4 weeks The therapeutic effectiveness of classic Chinese acupuncture was compared with " placebo " acupuncture in 15 patients with stable bronchial asthma . The patients received treatments with real and placebo acupuncture in a r and omly ordered , subject and evaluator-blind crossover fashion twice weekly for five weeks . Both real and placebo treatment periods were preceded by three week periods when no acupuncture was administered . Five patients felt better on real treatment , five patients preferred placebo and five did not feel any improvement on either of the two treatments . Treatment with real acupuncture when compared with no treatment and placebo treatment failed to provide any improvement in daily peak flow rates , asthma symptom scores , number of puffs of beta 2-agonist aerosol use , and pulmonary function results Physiotherapy is an established treatment in asthmatic children . One purpose is to increase tolerance towards physical activity , decrease broncho-obstruction and promote elimination of secretions . A positive effect of physical training in asthmatic children has been reported in many studies . An improved working capacity has e.g. been shown after supervised physical training at least twice a week for a period of three months ( 1 ) . This was not a realistic level of training intensity in our clinical practice . Therefore , the goal of this study was to test whether physiotherapy combined with physical training once a week had any effect on working capacity or lung function tests in asthmatic children Thirty patients with proved bronchial asthma receiving treatment with inhaled steroid in dosages of less than 1,000 micrograms daily were subdivided at r and om into two groups of 15 patients . One group received foot zone therapy and the other merely uniform clinical care but without " placebo foot zone therapy " . The " active " group received a total of ten foot zone therapy sessions of one hour at intervals of one week . The asthmatic symptoms , consumption of medicine and the objective pulmonary function parameters were followed-up during the subsequent six months . Decrease in consumption of beta-2-agonists and increase in peak-flow levels were observed in the group which had received foot zone therapy , but the same changes were observed in the control group . The authors do not find that this investigation demonstrates that foot zone therapy is of effect on the disease bronchial asthma . They conclude , however , that the favourable effect in both of the groups are due to increased care and control which occurred in both patient groups BACKGROUND Chiropractic spinal manipulation has been reported to be of benefit in nonmusculoskeletal conditions , including asthma . METHODS We conducted a r and omized , controlled trial of chiropractic spinal manipulation for children with mild or moderate asthma . After a three-week base-line evaluation period , 91 children who had continuing symptoms of asthma despite usual medical therapy were r and omly assigned to receive either active or simulated chiropractic manipulation for four months . None had previously received chiropractic care . Each subject was treated by 1 of 11 participating chiropractors , selected by the family according to location . The primary outcome measure was the change from base line in the peak expiratory flow , measured in the morning , before the use of a bronchodilator , at two and four months . Except for the treating chiropractor and one investigator ( who was not involved in assessing outcomes ) , all participants remained fully blinded to treatment assignment throughout the study . RESULTS Eighty children ( 38 in the active-treatment group and 42 in the simulated-treatment group ) had outcome data that could be evaluated . There were small increases ( 7 to 12 liters per minute ) in peak expiratory flow in the morning and the evening in both treatment groups , with no significant differences between the groups in the degree of change from base line ( morning peak expiratory flow , P=0.49 at two months and P=0.82 at four months ) . Symptoms of asthma and use of 3-agonists decreased and the quality of life increased in both groups , with no significant differences between the groups . There were no significant changes in spirometric measurements or airway responsiveness . CONCLUSIONS In children with mild or moderate asthma , the addition of chiropractic spinal manipulation to usual medical care provided no benefit A 5-day , non-residential exercise and living course for children with asthma is described as a feature of a programme of outpatient physiotherapy . Eleven children undertaking such a course were compared with 10 asthmatic children in a control group . The subject group showed , in the short term at least , an improvement in bronchial lability , peak flow rates , nocturnal and daytime wheeze , and activity compared with the controls . These findings were statistically significant . There was no difference between the groups in the number of days on which extra medication was taken . A short , sharp course is of benefit physically , socially and psychologically to children with asthma In this pilot study , the authors evaluated the immediate effects of osteopathic manipulative procedures compared with sham procedures on 10 subjects who were diagnosed with chronic asthma . The research followed a pretest-posttest crossover design wherein each subject served as her own control . Blinded examiners recorded respiratory excursion , peak expiratory flow rates , and subjective measures of asthma symptoms . Measurements of both upper thoracic and lower thoracic forced respiratory excursion statistically increased after osteopathic manipulative procedures compared with sham procedures . Changes in peak expiratory flow rates and asthma symptoms were not statistically significant OBJECTIVES The first objective was to determine if chiropractic spinal manipulative therapy ( SMT ) in addition to optimal medical management result ed in clinical ly important changes in asthma-related outcomes in children . The second objective was to assess the feasibility of conducting a full-scale , r and omized clinical trial in terms of recruitment , evaluation , treatment , and ability to deliver a sham SMT procedure . STUDY DESIGN Prospect i ve clinical case series combined with an observer-blinded , pilot r and omized clinical trial with a 1-year follow-up period . SETTING Primary contact , college outpatient clinic , and a pediatric hospital . PATIENTS A total of 36 patients aged 6 to 17 years with mild and moderate persistent asthma were admitted to the study . OUTCOME MEASURES Pulmonary function tests ; patient- and parent- or guardian-rated asthma-specific quality of life , asthma severity , and improvement ; am and pm peak expiratory flow rates ; and diary-based day and nighttime symptoms . INTERVENTIONS Twenty chiropractic treatment sessions were scheduled during the 3-month intervention phase . Patients were r and omly assigned to receive either active SMT or sham SMT in addition to their st and ardized ongoing medical management . RESULTS It is possible to blind the participants to the nature of the SMT intervention , and a full-scale trial with the described design is feasible to conduct . At the end of the 12-week intervention phase , objective lung function tests and patient-rated day and nighttime symptoms based on diary recordings showed little or no change . Of the patient-rated measures , a reduction of approximately 20 % in beta(2 ) bronchodilator use was seen ( P = .10 ) . The quality of life scores improved by 10 % to 28 % ( P < .01 ) , with the activity scale showing the most change . Asthma severity ratings showed a reduction of 39 % ( P < .001 ) , and there was an overall improvement rating corresponding to 50 % to 75 % . The pulmonologist-rated improvement was small . Similarly , the improvements in parent- or guardian-rated outcomes were mostly small and not statistically significant . The changes in patient-rated severity and the improvement rating remained unchanged at 12-month posttreatment follow-up as assessed by a brief postal question naire . CONCLUSION After 3 months of combining chiropractic SMT with optimal medical management for pediatric asthma , the children rated their quality of life substantially higher and their asthma severity substantially lower . These improvements were maintained at the 1-year follow-up assessment . There were no important changes in lung function or hyperresponsiveness at any time . The observed improvements are unlikely as a result of the specific effects of chiropractic SMT alone , but other aspects of the clinical encounter that should not be dismissed readily . Further research is needed to assess which components of the chiropractic encounter are responsible for important improvements in patient-oriented outcomes so that they may be incorporated into the care of all patients with asthma Thirty-two children with asthma ( 16 4- to 8-year-olds and 16 9- to 14-year-olds ) were r and omly assigned to receive either massage therapy or relaxation therapy . The children 's parents were taught to provide one therapy or the other for 20 minutes before bedtime each night for 30 days . The younger children who received massage therapy showed an immediate decrease in behavioral anxiety and cortisol levels after massage . Also , their attitude toward asthma and their peak air flow and other pulmonary functions improved over the course of the study . The older children who received massage therapy reported lower anxiety after the massage . Their attitude toward asthma also improved over the study , but only one measure of pulmonary function ( forced expiratory flow 25 % to 75 % ) improved . The reason for the smaller therapeutic benefit in the older children is unknown ; however , it appears that daily massage improves airway caliber and control of asthma |
11,948 | 26,808,540 | CRP , IL-6 and soluble vascular cell adhesion molecule ( sVCAM-1 ) were the most studied markers in relation to CIMT .
None of the inflammatory markers showed an association with CIMT .
Interpretation This review showed a relation between some inflammatory markers and CVD , however , no consistent relation is observed for CIMT . | Background In the past years many inflammatory markers have been studied in association with clinical ly manifest cardiovascular disease ( CVD ) and carotid intima-media thickness ( CIMT ) in HIV-infected patients , to obtain insights in the increased cardiovascular risk observed in HIV infection .
This systematic review provides an oversight of the current knowledge . | BACKGROUND Persons with human immunodeficiency virus ( HIV ) infection are at risk for premature cardiovascular disease ( CVD ) . Predictors of atherosclerotic disease progression in contemporary patients have not been well described . METHODS Using data from a prospect i ve observational cohort of adults infected with HIV ( Study to Underst and the Natural History of HIV/AIDS in the Era of Effective Therapy ) , we assessed common carotid artery intima-media thickness ( CIMT ) at baseline and year 2 by ultrasound . We examined HIV-associated predictors of CIMT progression after adjusting for age , sex , race/ethnicity , body mass index , smoking , hypertension , diabetes , low-density lipoprotein cholesterol level , and baseline CIMT using linear regression . RESULTS Among 389 participants ( median age at baseline , 42 years ; male sex , 77 % ; median CD4 + cell count at baseline , 485 cells/mm³ ; 78 % receiving antiretroviral therapy ) , the median 2-year CIMT change was 0.016 mm ( interquartile range , -0.003 to 0.033 mm ; P < .001 ) . Lesser CIMT progression was associated with a suppressed viral load at baseline ( -0.009 mm change ; P = .015 ) and remaining virologically suppressed throughout follow-up ( -0.011 mm change ; P < .001 ) . After adjusting for additional risk factors and a suppressed viral load during follow-up , nonnucleoside reverse transcriptase inhibitor versus protease inhibitor exposure was associated with lesser CIMT progression ( -0.011 mm change ; P = .02 ) . CONCLUSIONS Suppressing HIV replication below clinical thresholds was associated with less progression of atherosclerosis . The proatherogenic mechanisms of HIV replication and the net CVD benefit of different antiretroviral drugs should be a focus of future research BACKGROUND Human immunodeficiency virus (HIV)-infected patients are at increased risk of cardiovascular disease , which may be related to chronic inflammation and endothelial dysfunction despite virological control with antiretroviral therapy . The relationship between carotid intima-media thickness ( IMT ) , a surrogate marker for cardiovascular disease , proinflammatory cytokines , and endothelial activation markers has not been fully explored in HIV-infected patients who are receiving antiretroviral therapy . METHODS We conducted a prospect i ve , cross-sectional , observational study of treated HIV-infected patients and healthy control subjects to evaluate the relationship between carotid IMT , proinflammatory cytokines , endothelial activation biomarkers , and metabolic parameters in treated HIV-infected patients , compared with healthy control subjects . RESULTS We enrolled 73 HIV-infected patients and 21 control subjects . Common carotid artery and internal carotid artery IMT measurements , as well as tumor necrosis factor-alpha , high-sensitivity C-reactive protein , interleukin-6 , myeloperoxidase , and soluble vascular cell adhesion molecule-1 levels were higher in the HIV-infected group . High-sensitivity C-reactive protein was the only biomarker that was positively correlated with carotid IMT in both groups . In the HIV-infected group , soluble vascular cell adhesion molecule-1 was positively correlated with all inflammatory cytokine levels . In multiple regression analysis , soluble vascular cell adhesion molecule-1 , myeloperoxidase , and tumor necrosis factor-alpha levels were all associated with internal carotid artery IMT in the HIV-infected group , whereas age was associated with both common carotid artery and internal carotid artery IMT . CONCLUSIONS Enhanced endothelial activation , inflammation , and increased carotid IMT occur in HIV-infected patients despite antiretroviral therapy . Inflammatory markers are associated with endothelial activation , and both are associated with internal carotid artery IMT , supporting a potential role of inflammation in endothelial activation and cardiovascular disease in HIV infection OBJECTIVE Combined antiretroviral therapy ( cART ) has significantly improved the survival rate and quality of life for HIV-infected subjects , but it contributes to the development of metabolic complications including coronary artery disease ( CAD ) . Recent studies have reported that high plasma levels of the soluble receptor for advanced glycation end products ( sRAGE ) were associated with a lower incidence of CAD in non-HIV infected patients . However , there has been no report of an association of sRAGE and sub clinical carotid atherosclerosis in HIV-infected patients receiving cART . METHODS We examined the association of circulating sRAGE in HIV-infected patients with carotid intima-media thickness ( IMT ) and other metabolic variables . We prospect ively enrolled 76 HIV-infected patients receiving cART for ≥ 6 months . RESULTS sRAGE had a significantly negative correlation with body mass index ( r = -0.324 , p = 0.005 ) , waist-to-hip ratio ( r = -0.335 , p = 0.003 ) , systolic blood pressure ( BP ) ( r=-0.359 , p=0.002 ) , diastolic BP ( r = -0.343 , p = 0.004 ) , total cholesterol ( r = -0.240 , p = 0.037 ) , low-density lipoprotein-cholesterol ( r=-0.284 , p=0.024 ) , log(homeostasis model assessment of insulin resistance [ HOMA-IR ] ) ( r = -0.380 , p = 0.002 ) and carotid IMT including max-IMT and mean-IMT ( r = -0.358 , p = 0.001 and r = -0.329 , p = 0.004 , respectively ) . By the use of multiple stepwise regression analyses , systolic BP ( p=0.001 ) and log[HOMA-IR ] ( p = 0.001 ) remained significant independently . CONCLUSIONS These results suggest that sRAGE may have a protective effect against sub clinical atherosclerosis by preventing inflammatory responses mediated by the activation of cell surface RAGE in HIV-infected patients receiving cART BACKGROUND Marked changes in the prevalence of noncommunicable diseases such as obesity , diabetes , and cardiovascular disease have occurred in developed and developing countries in recent decades . The overarching aim of the study is to examine the relationship of societal influences on human lifestyle behaviors , cardiovascular risk factors , and incidence of chronic noncommunicable diseases . METHODS The Prospect i ve Urban Rural Epidemiology ( PURE ) study is a large-scale epidemiological study that plans to recruit approximately 140,000 individuals residing in > 600 communities in 17 low- , middle- , and high-income countries around the world . Individual data collection includes medical history , lifestyle behaviors ( physical activity and dietary profile ) , blood collection and storage for biochemistry and future genetic analysis , electrocardiogram , and anthropometric measures . In addition , detailed information is being collected with respect to 4 environmental domains of interest-the built environment , nutrition and associated food policy , psychosocial/socioeconomic factors , and tobacco environment . A minimum follow-up of 10 years is currently planned . RESULTS This report describes the design , justification , and methodology of the PURE study . The PURE study has been recruiting since 2002 and has enrolled 139,506 individuals by March 31 , 2009 . CONCLUSIONS The PURE study builds on the work and experience gained through conduct of the INTERHEART study . Its design and extensive data collection are geared toward addressing major questions on causation and development of the underlying determinants of cardiovascular disease in population s at varying stages of epidemiologic transition Rosiglitazone may be useful for the treatment of antiretroviral therapy-associated lipoatrophy , but an association with cardiovascular disease ( CVD ) has been question ed in diabetics . We evaluated rosiglitazone 's effect on surrogate markers of CVD in HIV-infected individuals with lipoatrophy . HIV(+ ) patients with lipoatrophy on thymidine-sparing regimens were r and omized to rosiglitazone vs. placebo for 48 weeks . We serially assessed carotid IMT , fasting metabolic profiles , tumor necrosis factor (TNF)-α , soluble receptors ( sTNFRI and II ) , interleukin (IL)-6 , high-sensitivity C-reactive protein ( hsCRP ) , myeloperoxidase ( MPO ) , and endothelial activation markers [ von Willebr and factor ( vWF ) , soluble intercellular cell adhesion molecules-1 ( sICAM-1 ) , and vascular cell adhesion molecules-1 ( sVCAM-1 ) ] . Seventy-one subjects enrolled : 17 % were female and 51%were white . Baseline characteristics were similar between groups except for higher total cholesterol in the placebo group ( p = 0.04 ) . At 48 weeks , common carotid artery ( CCA ) IMT changed significantly ( p ≤ 0.05 ) within but not between the groups ( p = 0.36 ) : the median ( IQR ) increase was 0.10 ( 0.05 , 0.25 ) mm and 0.15 ( 0 , 0.25 ) mm in the rosiglitazone and placebo groups , respectively . hsCRP , sTNFRI and II , sVCAM-1 , and vWF changed significantly ( p ≤ 0.02 ) within but not between groups . Total cholesterol increased significantly in the rosiglitazone group ( p = 0.008 ) . In our study of virologically controlled subjects with lipoatrophy , rosiglitazone did not independently increase carotid IMT , endothelial activation , and inflammatory cytokines Chronic HIV infection is associated with increased risk of cardiovascular disease ( CVD ) , including in patients with virological suppression . Persistent innate immune activation may contribute to the development of CVD via activation of monocytes in these patients . We investigated whether changes in monocyte phenotype predict sub clinical atherosclerosis in virologically suppressed HIV-positive individuals with low cardiovascular risk . We enroled 51 virologically suppressed HIV-positive individuals not receiving protease inhibitors or statins and 49 age-matched uninfected controls in this study . Carotid artery intima-media thickness ( cIMT ) was used as a surrogate marker for CVD , and traditional risk factors , including Framingham risk scores , were recorded . Markers of monocyte activation ( CD14 , CD16 , CCR2 , CX3CR1 , CD38 , HLA-DR and CD11b ) were measured in whole-blood sample s by flow cytometry . Associations were assessed using univariate and multivariate median regressions . Median cIMT was similar between HIV-positive and HIV-negative participants ( P=0.3 ) , although HIV-positive patients had significantly higher Framingham risk score ( P=0.009 ) and systemic inflammation . Expression of two monocyte markers , CD11b and CX3CR1 , independently predicted carotid artery thickness in HIV-positive individuals after controlling for Framingham risk score ( P=0.025 and 0.015 , respectively ) . These markers were not predictive of carotid artery thickening in controls . Our study indicates that monocyte surface markers may serve as novel predictors of CVD in HIV-positive individuals and is consistent with an important role for monocyte activation in the progression of HIV-related cardiovascular pathology BACKGROUND The relationships between soluble CD14 ( sCD14 ) , endotoxin ( lipopolysaccharide [ LPS ] ) , and progression of atherosclerosis have not been defined in human immunodeficiency virus ( HIV ) infection . METHODS We retrospectively assessed serum sCD14 and LPS levels of 91 subjects in a prospect i ve 3-year study of carotid artery intima-media thickness ( CIMT ) ( AIDS Clinical Trials Group [ ACTG ] 5078 ) , where subjects were enrolled as risk factor-controlled triads of HIV-uninfected ( n = 36 ) and HIV-infected individuals with ( n = 29 ) or without ( n = 26 ) protease inhibitor (PI)-based therapy for ≥2 years . The primary end point was the yearly rate of change of CIMT ( ΔCIMT ) . RESULTS In multivariate analysis of the HIV-infected subjects , each 1 µg/mL above the mean of baseline serum sCD14 corresponded to an additional 1.52 µm/y ( 95 % confidence interval , .07 - 2.98 ; P = .04 ) in the ΔCIMT . Every 100 pg/mL above the mean of baseline serum LPS corresponded to an additional 0.49 µm/y ( 95 % confidence interval , .18-.81 ; P = .003 ) in the ΔCIMT . However , in univariate analysis in the HIV-uninfected group sCD14 ( P = .33 ) and LPS ( P = .27 ) levels were not associated with higher ΔCIMT . HIV infection and PI therapy were not associated with baseline serum LPS and sCD14 levels ( P > .1 ) . CONCLUSIONS Our data are among the first to suggest that serum biomarkers of microbial translocation ( LPS ) and macrophage activation ( sCD14 ) predict sub clinical atherosclerosis progression in HIV-infected persons Background Interleukin-6 ( IL-6 ) may have a protective role in acute liver disease but a detrimental effect in chronic liver disease . It is unknown whether IL-6 is associated with risk of liver-related mortality in humans . Aims To determine if IL-6 is associated with an increased risk of all-cause , cardiovascular disease ( CVD ) , cancer , and liver-related mortality . Methods A prospect i ve cohort study included 1843 participants who attended a research visit in 1984–87 . Multiple covariates were ascertained including serum IL-6 . Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 as a continuous ( log transformed ) variable with all-cause , CVD , cancer , and liver-related mortality . Patients with prevalent CVD , cancer and liver disease were excluded for cause-specific mortality . Results The mean ( ± st and ard deviation ) age and body-mass-index ( BMI ) of participants was 68 ( ±10.6 ) years and 25 ( ±3.7 ) Kg/m2 , respectively . During the 25,802 person-years of follow-up , the cumulative all-cause , CVD , cancer , and liver-related mortality were 53.1 % ( N = 978 ) , 25.5 % , 11.3 % , and 1.3 % , respectively . The median ( ±IQR ) length of follow-up was 15.3±10.6 years . In multivariable analyses , adjusted for age , sex , alcohol , BMI , diabetes , hypertension , total cholesterol , HDL , and smoking , one-SD increment in log-transformed serum IL-6 was associated with increased risk of all-cause , CVD , cancer , and liver-related mortality , with hazard ratios of 1.48 ( 95 % CI , 1.33–1.64 ) , 1.38 ( 95 % CI , 1.16–1.65 ) , 1.35 ( 95 % CI , 1.02–1.79 ) , and 1.88 ( 95 % CI , 0.97–3.67 ) , respectively . CRP adjustment attenuated the effects but the association between IL-6 and all-cause and CVD mortality remained statistically significant , independent of CRP levels . Conclusions In community-dwelling older adults , serum IL-6 is associated with all-cause , CVD , cancer , and liver-related mortality BACKGROUND Carotid intima media thickness ( CIMT ) progresses faster in HIV-infected adults on antiretroviral therapy ( ART ) than the general population . It is unclear if the rate of progression is similarly faster in ART-naive , HIV-infected adults . METHODS This was a 48-week prospect i ve cohort study to compare change in CIMT and inflammation markers in ART-naive , HIV-infected adults in no immediate need of ART ( HIV-positive/ART-naive ) and age/sex/body mass index ( BMI ) -matched controls ( HIV-negative ) . RESULTS A total of 85 HIV-positive/ART-naive and 45 HIV-negative participants were enrolled . In the HIV-positive/ART-naive group , median baseline CD4 + T-cell count and HIV-1 RNA were 535 cells/mm3 and 6,916 copies/ml . Baseline common carotid artery ( CCA ) and bulb CIMTs were similar between groups . Changes in CIMT to 48 weeks at both sites were not different within- or between-groups ( median [ IQR ] change in HIV-positive/ART-naive versus HIV-negative CCA CIMT -0.0071 mm [ -0.0267 - 0.0233 ] versus 0.0113 mm [ -0.0117 - 0.0306 ] ; P = 0.19 between-groups ; and bulb CIMT 0.0017 mm [ -0.0367 - 0.06167 ] versus 0.01 mm [ -0.0383 - 0.0625 ] ; P = 0.54 ) . After adjustment for cardiovascular disease ( CVD ) risk factors , change in CCA CIMT was greater in HIV-negative participants ( -0.0046 versus 0.0177 mm for HIV-positive/ART-naive versus HIV-negative ; P = 0.01 ) . In HIV-positive/ART-naive , interleukin (IL)-6 , soluble tumour necrosis factor-α receptor (sTNFR)-II , vascular cell adhesion molecule-1 and intercellular adhesion molecule (ICAM)-1 were higher at both time points and D-dimer was higher at week 48 ( P < 0.01 for all ) . IL-6 , sTNFR-I and D-dimer increased over 48 weeks in HIV-positive/ART-naive participants ( P < 0.01 for all ) . In HIV-positive/ART-naive participants , independent predictors of greater change in CCA CIMT were higher BMI ( P = 0.05 ) and family history of CVD ( P < 0.01 ) and of greater change in bulb CIMT were higher sTNFR-I ( P = 0.03 ) and higher diastolic blood pressure ( P < 0.01 ) . CONCLUSIONS In ART-naive HIV-infected adults at low risk of HIV disease progression and low cardiovascular risk , CIMT progression rate was similar to matched controls . In addition to traditional CVD risk factors , higher levels of sTNFR-I predicted greater bulb CIMT changes Objective : To evaluate associations between traditional cardiovascular disease ( CVD ) risk factors , inflammatory markers and markers of HIV disease activity with ultrasonographic measures of CVD risk in patients with HIV who are not receiving antiretroviral therapy ( ART ) . Design : Cross-sectional , baseline evaluation of ART-naive HIV-infected individuals without known CVD or diabetes mellitus enrolled in a r and omized ART treatment trial . Methods : Prior to ART initiation , carotid artery intima – media thickness ( CIMT ) and brachial artery flow-mediated dilation ( FMD ) were measured . Additional parameters included CD4 cell count , HIV viral load , body composition , lipoproteins and inflammatory markers . Associations with common CIMT , bifurcation CIMT , presence of carotid artery lesions and brachial artery FMD were evaluated . Results : The 331 enrolled individuals were a median ( first – third quartile ) of 36 ( 28–45 ) years old . Common and bifurcation CIMT values were higher and lesions more prevalent with older age ( P < 0.001 ) . FMD was lower with older age ( P = 0.009 ) . Those with a Framingham Risk Score of at least 6 % per 10 years ( N = 44 ) had higher common and bifurcation CIMT ( P < 0.001 ) , carotid lesion prevalence ( P < 0.001 ) and lower FMD ( P = 0.035 ) . Independent associations with common CIMT were identified for increasing age , height , weight , small low-density lipoprotein ( LDL ) particles and black race ; these were similar for bifurcation CIMT . Presence of carotid artery lesions was associated with increasing age , presence of metabolic syndrome , interleukin-6 and lower HIV-1 RNA . Conclusion : In a contemporary cohort of ART-naive HIV-infected individuals , ultrasonographic measures of CVD risk were more strongly associated with traditional risk factors than CD4 cell counts , HIV replication or inflammatory markers BACKGROUND C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events . We report data from a large study of C-reactive protein and other circulating inflammatory markers , as well as up date d meta-analyses , to evaluate their relevance to the prediction of coronary heart disease . METHODS Measurements were made in sample s obtained at base line from up to 2459 patients who had a nonfatal myocardial infa rct ion or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospect i ve study of 18,569 participants . Measurements were made in paired sample s obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels . RESULTS The long-term stability of C-reactive protein values ( within-person correlation coefficient , 0.59 ; 95 percent confidence interval , 0.52 to 0.66 ) was similar to that of both blood pressure and total serum cholesterol . After adjustment for base-line values for established risk factors , the odds ratio for coronary heart disease was 1.45 ( 95 percent confidence interval , 1.25 to 1.68 ) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third , and similar overall findings were observed in an up date d meta- analysis involving a total of 7068 patients with coronary heart disease . By comparison , the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate ( 1.30 ; 95 percent confidence interval , 1.13 to 1.51 ) and the von Willebr and factor concentration ( 1.11 ; 95 percent confidence interval , 0.97 to 1.27 ) but generally stronger for established risk factors , such as an increased total cholesterol concentration ( 2.35 ; 95 percent confidence interval , 2.03 to 2.74 ) and cigarette smoking ( 1.87 ; 95 percent confidence interval , 1.62 to 2.16 ) . CONCLUSIONS C-reactive protein is a relatively moderate predictor of coronary heart disease . Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be review ed Background : AIDS-related death and disease rates have declined in the highly active antiretroviral therapy ( HAART ) era and remain low ; however , current causes of death in HAART-treated patients remain ill defined . Objective : To describe mortality trends and causes of death among HIV-infected patients in the HAART era . Design : Prospect i ve , multicenter , observational cohort study of participants in the HIV Outpatient Study who were treated from January 1996 through December 2004 . Measurements : Rates of death , opportunistic disease , and other non-AIDS-defining illnesses ( NADIs ) determined to be primary or secondary causes of death . Results : Among 6945 HIV-infected patients followed for a median of 39.2 months , death rates fell from 7.0 deaths/100 person-years of observation in 1996 to 1.3 deaths/100 person-years in 2004 ( P = 0.008 for trend ) . Deaths that included AIDS-related causes decreased from 3.79/100 person-years in 1996 to 0.32/100 person-years in 2004 ( P = 0.008 ) . Proportional increases in deaths involving liver disease , bacteremia/sepsis , gastrointestinal disease , non-AIDS malignancies , and renal disease also occurred ( P = < 0.001 , 0.017 , 0.006 , < 0.001 , and 0.037 , respectively . ) Hepatic disease was the only reported cause of death for which absolute rates increased over time , albeit not significantly , from 0.09/100 person-years in 1996 to 0.16/100 person-years in 2004 ( P = 0.10 ) . The percentage of deaths due exclusively to NADI rose from 13.1 % in 1996 to 42.5 % in 2004 ( P < 0.001 for trend ) , the most frequent of which were cardiovascular , hepatic , and pulmonary disease , and non-AIDS malignancies in 2004 . Mean CD4 cell counts closest to death ( n = 486 deaths ) increased from 59 cells/&mgr;L in 1996 to 287 cells/&mgr;L in 2004 ( P < 0.001 for trend ) . Patients dying of NADI causes were more HAART experienced and initiated HAART at higher CD4 cell counts than those who died with AIDS ( 34.5 % vs 16.8 % , respectively , received HAART for 4 of more years , P < 0.0001 ; 22.4 % vs 7.8 % , respectively , initiated HAART with CD4 cell counts of more than 350 cells/&mgr;L , P < 0.001 ) . Conclusions : Although overall death rates remained low through 2004 , the proportion of deaths attributable to non-AIDS diseases increased and prominently included hepatic , cardiovascular , and pulmonary diseases , as well as non-AIDS malignancies . Longer time spent receiving HAART and higher CD4 cell counts at HAART initiation were associated with death from non-AIDS causes . CD4 cell count at time of death increased over time Background : The effects of HIV infection and antiretroviral therapy ( ART ) on usual lipid levels have been reported . The effects of initiating versus deferring ART on high-density and low-density lipoprotein particle ( HDL-P and LDL-P , respectively ) concentrations and apolipoprotein ( Apo ) levels are not well described . Methods : In a subgroup of participants not taking ART at study entry who were r and omized in the Strategies for Management of Antiretroviral Therapy ( SMART ) trial to immediately initiate ART ( ‘ viral suppression group ’ ) or to defer it ( ‘ drug conservation group ’ ) , lipoprotein particle concentrations and ApoA1 and ApoB levels were measured at baseline and at 2 and 6 months following r and omization . Results : Compared with drug conservation group ( n = 126 ) , HDL-P and ApoA1 levels increased among viral suppression participants ( n = 128 ) after starting ART . At 6 months , viral suppression participants had 13 % higher total HDL-P ( P < 0.001 ) and 9 % higher ApoA1 ( P < 0.001 ) . LDL-P , very low density lipoprotein particle , and ApoB did not differ significantly between the viral suppression and drug conservation groups . Among viral suppression participants , predictors of HDL-P and ApoA1 increases included baseline levels of high-sensitivity C-reactive protein ( hsCRP ) and interleukin 6 ( IL-6 ) , but not HIV RNA level , CD4 cell count , or traditional cardiovascular disease risk factors . The effect of starting ART on changes in HDL-P and ApoA1 was greater for those with higher versus lower baseline levels of IL-6 ( P = 0.001 and 0.08 , respectively , for interaction ) or hsCRP ( P = 0.01 and 0.04 , respectively , for interaction ) . Conclusion : HDL-P and ApoA1 increase following ART initiation , to a degree that depends on the degree of inflammation present at entry . These findings suggest that activation of inflammatory pathways contribute to HIV-associated changes in HDL Abstract : This is a 96-week prospect i ve cohort study of antiretroviral therapy (ART)–naive HIV-infected adults and matched healthy controls to assess progression of carotid intima media thickness ( CIMT ) and its relationship to inflammation . Median common carotid artery ( CCA ) CIMT increased significantly but similarly in both groups [ CCA : 0.02 ( interquartile range : 0–0.05 ) ; P < 0.01 within HIV-infected adults vs. 0.01 ( 0–0.05 ) mm ; P < 0.01 within controls ; and P = 0.83 between groups ] . Change in bulb CIMT yielded similar results . Independent predictors of CCA CIMT progression in HIV-infected adults were higher systolic blood pressure , total cholesterol , and high sensitivity C-reactive protein . Independent predictors of bulb CIMT progression were higher non – high-density lipoprotein cholesterol and high sensitivity C-reactive protein . Other inflammation markers were not associated with CIMT progression Objectives : To compare the rate of change in intima – media thickness ( IMT ) of the carotid artery among uninfected subjects and HIV-infected subjects receiving or not receiving protease inhibitor ( PI ) regimens over a 144 week period . Design : This prospect i ve , matched cohort study enrolled 133 subjects into 45 triads ( groups of three subjects matched by age , sex , race/ethnicity , smoking status , blood pressure , and menopause ) from university based outpatient HIV clinics . Each triad consisted of one subject from each of the following groups : 1 , HIV-infected subjects with continuous use of PI therapy for ≥ 2 years ; 2 , HIV-infected subjects without prior PI use ; 3 , HIV-uninfected subjects . Methods : St and ardized ultrasound images of carotid IMT were collected at weeks 0 , 2 , 24 , 48 , 72 , 96 , and 144 . The main outcome was the yearly progression rate of carotid IMT ( mm/year ) . Results : The median yearly IMT progression rate in groups 1 , 2 , and 3 was 0.0096 , 0.0058 , and 0.0085 mm/year , respectively . There were no statistically significant differences in progression between groups 1 and 2 , or between the combined HIV-positive groups and the HIV-negative control group . A multicovariate model examining predictors of progression in carotid IMT among all subjects contained low density lipoprotein cholesterol and homocysteine . Among HIV subjects , predictors included nadir CD4 cell count and ritonavir use . Conclusions : HIV infection and PI use did not contribute substantially to the rate of carotid IMT progression in our matched study BACKGROUND Prolonged exposure to protease inhibitor (PI)- , but not non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing combination antiretroviral therapy ( CART ) has been associated with an increased cardiovascular risk , partly explained by the different effects of these drugs on plasma lipids . Most markedly , NNRTIs have been associated with increases in high density lipoprotein cholesterol ( HDL-C ) , which may be atheroprotective . METHODS In a cross-sectional study we investigated the impact of PI- vs. NNRTI-based CART in 130 HIV-1-infected patients with plasma virus suppressed to below the limit of detection , whom had been continuously exposed for at least 2 years to either one of such regimens , but not both . Carotid intima-media thickness ( C-IMT ) and fasting metabolic parameters were measured . RESULTS Mean ( + /-S.D. ) C-IMT in patients treated with PI-based CART was 0.81 ( + /-0.17 ) mm as compared to 0.71 (+/-0.14)mm in NNRTI treated patients ( p=0.0003 ) . HDL-C and apolipoprotein A-I ( apoA-I ) levels were higher in the NNRTI than in the PI group ( 1.39 mmol/L vs. 1.03 mmol/L ; p<0.0001 , and 1.44 mmol/L vs. 1.33 mmol/L ; p=0.0008 , respectively ) . Framingham Risk Score , body mass index , duration of CART , and use of PI-based CART were positively correlated with C-IMT whereas HDL-C and apoA-I were inversely correlated with C-IMT . CONCLUSIONS Treatment of HIV-1-infected patients for 2 years or more with PI-based compared to NNRTI-based CART is associated with greater C-IMT , consistent with the reported higher risk of CVD in patients using PI . However , this difference seems not fully explained by a more favorable impact of NNRTI-based CART on HDL-C and apoA-I levels |
11,949 | 28,585,933 | There were insufficient PET/SPECT receptor availability studies for meta-analyses , but a systematic review did not suggest replicable group differences in regional GABAA/BZR availability .
The current literature does not reveal consistent alterations in in vivo GABA neuroimaging measures in schizophrenia , as might be hypothesized from animal models and postmortem data . | Data from animal models and from postmortem studies suggest that schizophrenia is associated with brain GABAergic dysfunction .
The extent to which this is reflected in data from in vivo studies of GABA function in schizophrenia is unclear . | In the prefrontal cortex of subjects with schizophrenia , markers of the synthesis and re-uptake of GABA appear to be selectively altered in a subset of interneurons that includes ch and elier cells . Determining the effect of these disturbances in presynaptic GABA markers on inhibitory signaling requires knowledge of the status of GABA(A ) receptors at the postsynaptic targets of ch and elier cells , the axon initial segments ( AIS ) of pyramidal neurons . Because the alpha(2 ) subunit of the GABA(A ) receptor is preferentially localized at pyramidal neuron AIS , we quantified alpha(2 ) subunit immunoreactive AIS in tissue sections containing prefrontal cortex area 46 from 14 matched triads of subjects with schizophrenia , subjects with major depression and control subjects . Systematic , r and om sampling revealed that the mean number of alpha(2)-labeled AIS per mm(2 ) in subjects with schizophrenia was significantly ( P = 0.007 ) increased by 113 % compared to control subjects and non-significantly increased compared to subjects with major depression . Furthermore , within subjects with schizophrenia , the density of alpha(2)-labeled AIS was negatively correlated ( r = -0.49 , P = 0.038 ) with the density of ch and elier axon terminals immunoreactive for the GABA membrane transporter . These data suggest that GABA(A ) receptors are up-regulated at pyramidal neuron AIS in response to deficient GABA neuro-transmission at ch and elier axon terminals in schizophrenia . Thus , disturbances in inhibition at the ch and elier neuron-pyramidal neuron synapse may be a critical component of prefrontal cortical dysfunction in schizophrenia BACKGROUND The role of the inhibitory neurotransmitter gamma aminobutyric acid ( GABA ) in schizophrenia has previously been investigated using postmortem material . Recently , using single photon emission tomography ( SPET ) with the selective benzodiazepine antagonist 123I-Iomazenil as the radiolig and , we have demonstrated an in vivo relationship between reduced GABAA/benzodiazepine receptor binding and the severity of positive symptomatology in schizophrenia . The present study aim ed to build on this using the same in vivo scanning techniques , and relating findings to cognitive functioning . METHODS Ten nonpsychiatric control subjects and 15 schizophrenic patients , matched for age and h and edness , were scanned . A battery of neuropsychologic tests was also administered . RESULTS Correlational analysis revealed a pattern of increased correlations between GABAA/benzodiazepine receptor binding and task performance , in the schizophrenic group compared to the control group . CONCLUSIONS Findings are preliminary but suggest a relationship between reduced GABAA/benzodiazepine receptor binding and poorer cognitive functioning , involving memory and visual attention processes , in the schizophrenic group but not in the control group . A role for GABA in the pathophysiology of schizophrenia is suggested . Limitations of the present study and suggestions for future research are discussed |
11,950 | 21,861,911 | Findings revealed limited information about attributes of successful and unsuccessful team initiatives , barriers and facilitators to team initiatives , unique or combined contribution of selected interventions , or how to effectively establish these teams .
Conclusions Not unlike systematic review s of quality improvement collaboratives , this broad review revealed that while teams reported a number of positive results , there are many method ological issues . | Background The purpose of this study was to conduct a scoping review of the literature about the establishment and impact of quality and safety team initiatives in acute care . | Objective To evaluate a matrix for determining the predominant type , cause category , and rate of medication prescribing errors , and to explore the effectiveness of hospital-based improvement initiatives among pediatric intensive care units ( PICUs ) . Design This study involved the prospect i ve identification of medication errors for categorization and evaluation by using a matrix methodology . A pretest-posttest design without a control group was used to explore the impact of initiatives employed to reduce medication error rates and severity . Setting PICUs in nine freest and ing , collaborating tertiary care children ’s hospitals that participated in both baseline and postintervention analyses . Methods We evaluated 12,026 PICU medication orders at baseline and 9,187 orders postintervention for prescribing errors , excluding resuscitation orders . A st and ardized tool and process captured error type , cause category , and severity for 2 wks before and after intervention . Three levels of error detection were used and included pharmacy order entry , PICU nurse order transcription , and team-based overview . Site-specific interventions were implemented , which included predominantly provider education as well as informational ( 47 % ) and dosing “ assists ” via preprinted orders , forcing functions , or prompts ( 39 % ) . Results Of baseline orders , 11.1 % had at least one prescribing error . The interception of prescribing errors improved 30.9 % ( 1.6 % of all orders at baseline , 2.0 % post intervention ) . Preventable adverse drug events were uncommon ( 0.6 % of all medication errors ) and of low severity at baseline ; most were wrong dose errors . The implementation of improvement initiatives , specific for each facility , result ed in a 31.6 % reduction in prescribing errors from 11.1 % to 7.6 % . However , site results varied considerably . Conclusions A benchmark for medication prescribing errors in the PICU was identified among nine children ’s hospitals . The methodology was successful in accounting for site-specific differences with regard to identifying and documenting errors as well as reporting results of improvement initiatives . Furthermore , the methodology employed was generalizable in the identification of predominant prescribing error types , which helped to track individual hospital improvement initiative development and implementation . Overall improvement in prescribing error rates was noted ; however , considerable variation in the success of improvement initiatives was noted and bears further attention BACKGROUND The adherence to evidence -based treatment guidelines for acute myocardial infa rct ion ( AMI ) is still suboptimal . Therefore , we design ed a study to evaluate the effects of a collaborative quality improvement ( QI ) intervention on the adherence to AMI guidelines . The intervention used a national web-based quality registry to generate local and regular real-time performance feedback . METHODS A 12-month baseline measurement of the adherence rates was retrospectively collected , comprising the period July 1 , 2001 , through June 30 , 2002 . During the intervention period of November 1 , 2002 , through April 30 , 2003 , multidisciplinary teams from 19 nonr and omized intervention hospitals were subjected to a multifaceted QI-oriented intervention . Another 19 hospitals , unaware of their status as controls , were matched to the intervention hospitals . During the postintervention measurement period of May 1 , 2003 , through April 30 , 2004 , a total of 6726 consecutive patients were included at the intervention ( n = 3786 ) and control ( n = 2940 ) hospitals . The outcome measures comprised 5 Swedish national guideline -derived quality indicators , compared between baseline and postintervention levels in the control and QUICC intervention hospitals . RESULTS In the control and QI intervention hospitals , the mean absolute increase of patients receiving angiotensin-converting enzyme inhibitors was 1.4 % vs 12.6 % ( P = .002 ) , lipid-lowering therapy 2.3 % vs 7.2 % ( P = .065 ) , clopidogrel 26.3 % vs 41.2 % ( P = .010 ) , heparin/low-molecular weight heparin 5.3 % vs 16.3 % ( P = .010 ) , and coronary angiography 6.2 % vs 16.8 % ( P = .027 ) , respectively . The number of QI intervention hospitals reaching a treatment level of at least 70 % in 4 or 5 of the 5 indicators was 15 and 5 , respectively . In the control group , no hospital reached 70 % or more in just 4 of the 5 indicators . CONCLUSIONS By combining a systematic and multidisciplinary QI collaborative with a web-based national quality registry with functionality allowing real-time performance feedback , major improvements in the adherence to national AMI guidelines can be achieved Abstract Objective To test a multifaceted collaborative quality improvement intervention design ed to promote evidence based surfactant treatment for preterm infants of 23 - 29 weeks ' gestation . Design Cluster r and omised controlled trial Setting and participants 114 neonatal intensive care units ( which treated 6039 infants of 23 - 29 weeks gestation born in 2001 ) . Main outcome measures Process of care measures : proportion of infants receiving first surfactant in the delivery room , proportion receiving first surfactant more than two hours after birth , and median time from birth to first dose of surfactant . Clinical outcomes : death before discharge home , and pneumothorax . Intervention Multifaceted collaborative quality improvement advice including audit and feedback , evidence review s , an interactive training workshop , and ongoing faculty support via conference calls and email . Results Compared with those in control hospitals , infants in intervention hospitals were more likely to receive surfactant in the delivery room ( adjusted odds ratio 5.38 ( 95 % confidence interval 2.84 to 10.20 ) ) , were less likely to receive the first dose more than two hours after birth ( adjusted odds ratio 0.35 ( 0.24 to 0.53 ) ) , and received the first dose of surfactant sooner after birth ( median of 21 minutes v 78 minutes , P < 0.001 ) . The intervention effect on timing of surfactant was larger for infants born in the participating hospitals than for infants transferred to a participating hospital after birth . There were no significant differences in mortality or pneumothorax . Conclusion A multifaceted intervention including audit and feedback , evidence review s , quality improvement training , and follow up support changed the behaviour of health professionals and promoted evidence based practice OBJECTIVES In August 1993 a group of house staff and nursing staff at MetroHealth Medical Center formed a quality improvement team to evaluate the process of medical care on the inpatient wards . Using st and ard continuous quality improvement ( CQI ) methods , a team of medical interns , nurses , and other health professionals involved in patient care on the medicine inpatient service design ed interdisciplinary , daily work rounds to improve the care of patients on the inpatient wards . METHODS The authors conducted a r and omized , controlled firm trial of the impact of interdisciplinary rounds on the inpatient medicine services . The trial lasted 6 months ( November 1993-April 1994 ) and included 1,102 admissions r and omly assigned to experimental or control teams by the pre-existing firm system . Of the 1,102 admissions included in the study , 535 were r and omized to medical services with traditional rounds and 567 to medical services with interdisciplinary rounds . The outcomes studied included length of stay ( LOS ) , total hospital charges , provider satisfaction , and ancillary service efficiency . RESULTS Unadjusted analysis for log-transformed data showed lower length of stay and total charges for the interdisciplinary group . The mean LOS for interdisciplinary rounds was 5.46 days , compared with 6.06 days for traditional care ( P = 0.006 ) , whereas mean total charges were $ 6,681 and $ 8,090 ( P = 0.002 ) for the two groups , respectively . After multivariate regression analysis using a propensity score that included gender , age , marital status , admission source , diagnosis-related group ( DRG ) weight , and primary diagnosis by International Classification of Diseases , Ninth Revision ( ICD-9 ) cluster , these differences remained statistically significant . CONCLUSIONS Previous studies of interdisciplinary teams have failed to show statistically significant cost savings . This study involving more patients shows both cost and LOS decreases with the use of interdisciplinary teams . At the end of the 6-month trial , interdisciplinary rounds were instituted on all medicine inpatient services Background : Research into adverse events ( AEs ) has highlighted the need to improve patient safety . AEs are unintended injuries or complications result ing in death , disability or prolonged hospital stay that arise from health care management . We estimated the incidence of AEs among patients in Canadian acute care hospitals . Methods : We r and omly selected 1 teaching , 1 large community and 2 small community hospitals in each of 5 provinces ( British Columbia , Alberta , Ontario , Quebec and Nova Scotia ) and review ed a r and om sample of charts for nonpsychiatric , nonobstetric adult patients in each hospital for the fiscal year 2000 . Trained review ers screened all eligible charts , and physicians review ed the positively screened charts to identify AEs and determine their preventability . Results : At least 1 screening criterion was identified in 1527 ( 40.8 % ) of 3745 charts . The physician review ers identified AEs in 255 of the charts . After adjustment for the sampling strategy , the AE rate was 7.5 per 100 hospital admissions ( 95 % confidence interval [ CI ] 5.7– 9.3 ) . Among the patients with AEs , events judged to be preventable occurred in 36.9 % ( 95 % CI 32.0%–41.8 % ) and death in 20.8 % ( 95 % CI 7.8%–33.8 % ) . Physician review ers estimated that 1521 additional hospital days were associated with AEs . Although men and women experienced equal rates of AEs , patients who had AEs were significantly older than those who did not ( mean age [ and st and ard deviation ] 64.9 [ 16.7 ] v. 62.0 [ 18.4 ] years ; p = 0.016 ) . Interpretation : The overall incidence rate of AEs of 7.5 % in our study suggests that , of the almost 2.5 million annual hospital admissions in Canada similar to the type studied , about 185 000 are associated with an AE and close to 70 000 of these are potentially preventable In an era of chronic re source scarcity it is critical that quality improvement professionals have confidence that their project activities cause measured change . A commonly used research design , the single group pre-test/post-test design , provides little insight into whether quality improvement interventions cause measured outcomes . A re-evaluation of a quality improvement programme design ed to reduce the percentage of bilateral cardiac catheterisations for the period from January 1991 to October 1996 in three catheterisation laboratories in a north eastern state in the USA was performed using an interrupted time series design with switching replications . The accuracy and causal interpretability of the findings were considerably improved compared with the original evaluation design . Moreover , the re-evaluation provided tangible evidence in support of the suggestion that more rigorous design s can and should be more widely employed to improve the causal interpretability of quality improvement efforts . Evaluation design s for quality improvement projects should be constructed to provide a reasonable opportunity , given available time and re sources , for causal interpretation of the results . Evaluators of quality improvement initiatives may infrequently have access to r and omised design s. Nonetheless , as shown here , other very rigorous research design s are available for improving causal interpretability . Unilateral method ological surrender need not be the only alternative to r and omised experiments BACKGROUND Brigham and Women 's Hospital , in Boston , and its major health maintenance organization ( HMO ) , Harvard Community Health Plan , collected data in spring 1994 which revealed that patients were less satisfied with hospital discharge planning than with other elements of care . PROBLEM IDENTIFICATION PROCESS An interdisciplinary team , formed in November 1994 and composed of eight members from the hospital and HMO , used data from the hospital 's Patient Satisfaction Survey , flowcharting , and phone interviews with patients to identify discharge planning-related problems . For example , follow-up contact with patients after discharge was erratic and no clear signal of the successful " h and off " of care from the hospital team to the community team existed . IMPROVEMENT CYCLE 1 Eighty-three percent of the payer 's patients that received the improvement strategy developed by the interdisciplinary team-a concierge service-rated discharge planning as excellent or very good , compared to 63 % of control patients . IMPROVEMENT CYCLE 2 : PLAN SOLUTIONS/STRATEGIES FOR IMPROVING HOSPITAL DISCHARGE PLANNING : The results of the team 's Cycle 1 improvement provided information for the team to use in design ing a second cycle of incremental improvement activity . For example , to address the lack of clarity about who was responsible for making decisions about discharge and follow-up care , the attending physician was design ated the transition-of-care coordinator . Once all the improvements were implemented , Cycle 2 patients who received the intervention rated satisfaction with discharge higher ( 83 % versus 73 % ) than the control group . CONCLUSIONS Implication s of hospitalwide implementation of discharge planning-related services attempted on one unit are being considered OBJECTIVE To determine the effects of hospital quality assurance interventions on compliance with clinical st and ards , availability of essential drugs , client satisfaction , and utilization . DESIGN Quasi-experimental , prospect i ve study with four intervention hospitals and four control hospitals . All eight facilities were purposively selected and of comparable complexity . SETTING Ministry of Health secondary care facilities in Ecuador . INTERVENTIONS Facility-based quality improvement teams , job clarification , st and ards communication , refresher training , strengthening hospital pharmacy committees , monthly monitoring of compliance indicators , and formation of users ' committees . MEASURES Compliance with input and process st and ards , utilization of services , and patient satisfaction were measured monthly in both groups through review of clinical and administrative records , exit interviews , and patient satisfaction surveys . RESULTS After 12 months , the quality assurance interventions produced rapid increases in compliance with clinical st and ards in the intervention hospitals as compared with the control group . These improvements appeared as early as 2 months after the onset of the interventions . No differences were found between intervention and control groups in terms of trends in utilization patterns or client satisfaction . CONCLUSION Quality assurance interventions made a difference in technical quality of care . Patient satisfaction and utilization do not appear to be directly associated with short-term improvements in compliance with clinical st and ards . Quality improvement interventions may require longer periods and a specific aim at clients ' needs to demonstrate effects on utilization and satisfaction outcome variables PURPOSE The effects of a pharmacist-led pediatrics medication safety team ( PMST ) on the frequency and severity of medication errors reported were studied . METHODS This study was conducted in a pediatric critical care center ( PCCC ) in three phases . Phase 1 consisted of retrospective collection of medication-error reports before any interventions were made . Phases 2 and 3 included prospect i ve collection of medication-error reports after several interventions . Phase 2 introduced a pediatrics clinical pharmacist to the PCCC . A pediatrics clinical pharmacist-led PMST ( including a pediatrics critical care nurse and pediatrics intensivist ) , a new reporting form , and educational forums were added during phase 3 of the study . In addition , education focus groups were held for all intensive care unit staff . Outcomes for all phases were measured by the number of medication-error reports processed , the number of incidents , error severity , and the specialty of the reporter . RESULTS Medication-error reporting increased twofold , threefold , and sixfold between phases 1 and 2 , phases 2 and 3 , and phases 1 and 3 , respectively . Error severity decreased over the three time periods . In phases 1 , 2 , and 3 , 46 % , 8 % , and 0 % of the errors were classified as category D or E , respectively . Conversely , the reporting of near-miss errors increased from 9 % in phase 1 to 38 % in phase 2 and to 51 % in phase 3 . CONCLUSION An increase in the number of medication errors reported and a decrease in the severity of errors reported were observed in a PCCC after implementation of a PMST , provision of education to health care providers , and addition of a clinical pharmacist 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 BACKGROUND The Cooperative Cardiovascular Project ( CCP ) was initiated by the Health Care Financing Administration to improve the quality of care for Medicare beneficiaries admitted to the hospital with acute myocardial infa rct ion ( AMI ) . Four peer review organizations formed the CCP Best Practice s Working Group ( Working Group ) to identify effective intervention strategies that enable a hospital staff to improve AMI care . METHODS The peer review organization in each state was asked to identify six hospitals with exemplary quality improvement ( QI ) plans for AMI care ; 33 states responded . Data about the hospitals ' baseline performance on the CCP quality indicators and components of the QI plans were collected from each hospital . Thirty-six of 40 r and omly selected hospitals from this group were interviewed . RESULTS The Working Group identified 191 hospitals in 33 states with exemplary QI plans . Administration of thrombolytic therapy and aspirin were the quality indicators most commonly addressed . Staff education , development or revision of clinical pathways and st and ing orders , and ongoing data collection were the most common QI plan components . The need to develop interdisciplinary teams and to identify a strong physician champion for the QI efforts were the most common recommendations for other hospitals considering implementation of the CCP . CONCLUSIONS The CCP stimulated interest in QI activities for AMI care in the institutions identified for the Working Group . The characteristics of the hospitals ' improvement plans were consistent with those identified by contemporary leaders of clinical QI as central to improving care . These plans focused on changes in clinical processes , deployment of interdisciplinary teams , identification of project champions , and ongoing data collection to assess and improve quality of care Background : Adverse events are poor patient outcomes that are due to medical care . Studies of hospital patients have demonstrated that adverse events are common , but few data describe the timing of them in relation to hospital admission . We evaluated characteristics of adverse events affecting patients admitted to a Canadian teaching hospital , paying particular attention to timing . Methods : We r and omly selected 502 adults admitted to the Ottawa Hospital for acute care of nonpsychiatric illnesses over a 1-year period . Charts were review ed in 2 stages . If an adverse event was judged to have occurred , a physician determined whether it occurred before or during the index hospitalization . The review er also rated the preventability , severity and type of each adverse event . Results : Of the 64 patients with an adverse event ( incidence 12.7 % , 95 % confidence interval [ CI ] 10.1%–16.0 % ) , 24 had a preventable event ( 4.8 % , 95 % CI 3.2%–7.0 % ) , and 3 ( 0.6 % , 95 % CI 0.2%–1.7 % ) died because of an adverse event . Most adverse events were due to drug treatment , operative complications or nosocomial infections . Of the 64 patients , 39 ( 61 % , 95 % CI 49%–72 % ) experienced the adverse event before the index hospitalization . Interpretation : Adverse events were common in this study . However , only one-third were deemed avoidable , and most occurred before the hospitalization . Interventions to improve safety must address ambulatory care as well as hospital-based care A critical or clinical pathway defines the optimal care process , sequencing and timing of interventions by healthcare professionals for a particular diagnosis or procedure . It is a relatively new clinical process improvement tool that has been gaining popularity across hospitals and various healthcare organisations in many parts of the world . It is now slowly gaining momentum and popularity in Asia and Singapore . Clinical pathways are developed through collaborative efforts of clinicians , case managers , nurses , and other allied healthcare professionals with the aim of improving the quality of patient care , while minimising cost to the patient . Clinical pathways have been shown to reduce unnecessary variation in patient care , reduce delays in discharge through more efficient discharge planning , and improve the cost-effectiveness of clinical services . The approach and objectives of clinical pathways are consistent with those of total quality management ( TQM ) and continuous clinical quality improvement ( CQI ) , and is essentially the application of these principles at the patient 's bedside . However , despite the growing popularity of pathways , their impact on clinical outcomes and their clinical effectiveness remains largely untested and unproven through rigorous clinical trials . This paper begins with an overview of the nature of clinical pathways and the analysis of variances from the pathway , their benefits to the healthcare organisation , their application as a tool for CQI activities in direct relation to patient care , and their effectiveness in a variety of healthcare setting s. The paper describes an evaluation of the impact of a clinical pathway on the quality of care for patients admitted for uncomplicated acute myocardial infa rct ion ( AMI ) through an analysis of variances . The author carried out a one year evaluation of a clinical pathway on uncomplicated AMI in Changi General Hospital ( CGH ) to determine its effectiveness and impact on a defined set of outcomes . A before and after nonr and omized study of two groups of patients admitted to the Hospital for uncomplicated AMI was done . A total of 169 patients were managed on the clinical pathway compared to 100 patients in the control ( historical comparison ) group . Outcomes were compared between the two groups of patients . Restriction and matching of study subjects in both groups ensured that the patients selected were comparable in terms of severity of illness . The results showed that the patients on the clinical pathway and the comparison group were similar with respect to demographic variables , prevalence of risk factors and comorbidities . There was a statistically significant reduction in the average length of stay after implementation of the clinical pathway . This was achieved without any adverse effect on short term clinical outcomes such as in-hospital mortality , complication rate and morbidity . There were no significant difference in readmission rates at 6 months after discharge . The paper concludes that clinical pathways , implemented in the context of an acute care general hospital , is able to significantly improve care processes through better collaboration among healthcare professionals and improvements in work systems Objective : To describe the use of a multidisciplinary approach to sepsis surveillance and evaluate impact on outcome . Design : Prospect i ve clinical study or clinical audit cycle . Setting : Tertiary pediatric extracorporeal membrane oxygenation ( ECMO ) center . Patients : Patients were 215 children supported with ECMO January 1999 to December 2004 . Interventions : A multidisciplinary team met monthly to evaluate cases of bloodstream infection and mediastinitis , review trends , and up date unit policies . Changes in practice were made at the end of 2001 in order to address a perceived high rate of sepsis : a ) reeducation ; b ) introduction of electively preprimed ECMO circuits ; and c ) preference for neck rather than chest cannulation in cardiac patients . Prophylactic antibiotics were used from preprocedure for 24 hrs only throughout the study . Measurements and Main Results : Over the entire study period , 39 children had 47 septic episodes , with a rate of 24.9 per 1000 ECMO days . Multiple logistic regression analyses indicated that infection was associated with duration of ECMO support ( odds ratio 1.24 ; 95 % confidence interval 1.15 , 1.35 per day ) and case type : Closed vs. open chest was protective in cardiac patients ( odds ratio 0.08 ; 95 % confidence interval 0.01 , 0.50 ) . Infection increased the odds of death by 2.01 ( 95 % confidence interval 1.00 , 4.05 ) , but this effect was less important than case type and ECMO days . After policy changes were implemented , there was a reduction in sepsis from 29.3 to 20.1 episodes per 1000 ECMO days . There was reduced sepsis in respiratory patients : neonates from 28.0 to 6.6 and pediatric patients from 42.4 to 16.9 episodes per 1000 ECMO days . Despite policy changes , sepsis remained a problem in cardiac patients with open sternum : 65.1 per 1000 ECMO days . Conclusions : ECMO support is a high-risk setup for nosocomial infection , in particular for cardiac patients with open sternum for whom antibiotic prophylaxis is justified . Multidisciplinary surveillance offers an excellent approach for quality improvement in this challenging field BACKGROUND In 1991 Beth Israel Hospital ( Boston ) joined nine other hospitals in using the Picker/Commonwealth survey instrument to tap patients perceptions of their hospitalization experience . Beth Israel focused on one of the nine dimensions of the instrument-continuity and transition ( discharge planning ) . FOUR WORK TEAMS : In 1992 four multidisciplinary work teams were formed-for cardiac surgical patients , stroke patients , patients on a medical unit , and patients on a medical and surgical unit . Each team conducted a patient/family discussion group , during which recently discharged patients and their families were asked about their preparation for discharge and asked for input on how to improve the process . INTERVENTIONS Each work team developed interventions on the basis of information specific to their patients . The cardiac work team , for example , developed interdisciplinary practice guidelines for patient care management for the entire postoperative period ; the guidelines include a patient education component on what patients and families can expect during hospitalization . OUTCOMES Clinicians practice differently , inviting more patient feedback and other involvement in care , as a results of their involvement in the project . On the first annual patient survey , administered in 1994 , only 6 % of 1,179 r and omly selected patients ( versus 20 % of the 100 patients first surveyed in 1993 ) indicated that they did not receive the information they needed to help themselves recover . CURRENT PROGRESS AND FUTURE DIRECTIONS : A st and ardized teaching packet containing material developed during the discharge planning improvement project is now distributed . In May 1995 the nursing department launched a patient and family learning center to better meet the health education needs of patients |
11,951 | 21,713,549 | Discussion With currently available technology , and taking into account the number of embryos to be transferred , the clinical validity of PGS-FISH , although superior to that of morphological criteria , does not appear to be clinical ly relevant | Introduction Embryo selection can be carried out via morphological criteria or by using genetic studies based on Preimplantation Genetic Screening .
In the present study , we evaluate the clinical validity of Preimplantation Genetic Screening with fluorescence in situ hybridization ( PGS-FISH ) compared with morphological embryo criteria . | PGD ( preimplantation genetic diagnosis ) of aneuploidy for chromosomes X , Y , 13 , 18 and 21 was carried out on 196 embryos from 36 infertile patients classified with a poor prognosis due to ( i ) maternal age , ( ii ) repeated in-vitro fertilization ( IVF ) failures and ( iii ) mosaic karyotype . The percentage of abnormal embryos was comparable in the three groups of patients : maternal age 63 % , repeated IVF failure 57 % , and mosaic karyotype 62 % . The analysis of the overall data revealed an increased incidence of abnormal embryos in the older age categories ( predominantly due to aneuploidy ) , even in embryos at the 7- to 8-cell stage . In addition , the percentage of chromosomally abnormal embryos was directly proportional to the number of IVF failures , where the increase in chromosomal abnormalities was not correlated to aneuploidy but to other aberrations such as mosaicism and polyploidy . Following PGD , 28 patients had at least one embryo transferred that appeared normal by fluorescent in-situ hybridization ( FISH ) . Four clinical pregnancies result ed , with an implantation rate of 10 % per normal embryo . In conclusion , the high rate of chromosomally abnormal embryos in poor prognosis patients may have been the cause of implantation failure in their previous IVF cycles . Therefore , the possibility of transferring embryos with a normal FISH complement could improve the chance of pregnancy in this category of patients OBJECTIVE To assess the potential benefit of preimplantation aneuploidy testing on the outcome of in vitro fertilization ( IVF ) for women of advanced maternal age ( AMA ) . DESIGN Prospect i ve r and omized clinical trial . SETTING Private IVF clinic . PATIENT(S ) Sixty-two infertile AMA couples undergoing fertility treatment . INTERVENTION(S ) Fluorescent in situ hybridization ( FISH ) for chromosomes X , Y , 13 , 15 , 16 , 17 , 18 , 21 , and 22 . MAIN OUTCOME MEASURE(S ) Preimplantation aneuploidy testing of biopsied blastomeres on day 3 of development . RESULT ( S ) Fertilization and blastocyst developmental rates were similar for the test and control groups : 80 % versus 77.4 % and 49 % versus 48.2 % , respectively . The average number of embryos transferred was comparable at 2.2 for the test group and 2.7 for the control group . Implantation rates were also equivalent across the two groups : 37.3 % in the control group versus 36.5 % in the test group . Nevertheless , the spontaneous abortion rate was observed to be lower for the test group : 25.9 % versus 32.26 % in the control group . This result ed in an observed increase in delivery rates for the test group : 78 % versus 67.74 % in the control group . CONCLUSION ( S ) Preimplantation aneuploidy testing does not appear to statistically significantly improve outcome parameters in infertile AMA patients ; however , a trend toward a decrease in the spontaneous abortion rate with a subsequent higher delivery rate was observed BACKGROUND Single-embryo transfer is a well-accepted strategy to avoid multiple pregnancies in an assisted reproductive technology ( ART ) programme . Besides the morphological quality and embryo kinetics up to the blastocyst stage , preimplantation genetic screening ( PGS ) of aneuploidy has been advocated as an adjuvant approach to select the embryo . METHODS Couples with a female partner younger than 36 were r and omly assigned to undergo transfer of a single blastocyst in a cycle with or without PGS using FISH for the chromosomes X , Y , 13 , 16 , 18 , 21 , 22 . RESULTS After the enrolment of 120 of the projected 447 patients in each group , study recruitment was terminated prematurely on the basis of futility . The observed live birth delivery rates after ART were 30.8 versus 30.8 % per r and omized patient , 34.6 versus 34.6 % per cycle initiated , 37.8 versus 37.0 % per aspirated cycle and 41.6 versus 43.5 % per embryo transfer for the control versus the PGS group , respectively , with absolute between-group differences ( 95 % CI ; P value ) of 0 % ( -11.7 to 11.7 ; P = 1.00 ) , 0 % ( -12.7 to 12.7 ; P = 1.00 ) , -0.8 % ( -14.2 to 12.7 ; P = 0.91 ) and 2.1 % ( -12.7 to 16.7 ; P = 0.79 ) , respectively . Even in this younger age group , only 61 % of the embryos had a normal diploid status . CONCLUSIONS The absence of a beneficial treatment effect in this r and omized clinical trial provides no arguments in favour of PGS to improve live birth delivery rate following single-embryo transfer in women under the age 36 . Clinical Trials.gov : NCT00670059 BACKGROUND The data are compiled from two multicentre , prospect ively r and omized studies on the effect of follicular fluid meiosis-activating sterol ( FF-MAS ) on human oocytes . The donated oocytes were exposed either to test doses of FF-MAS or to control solutions . The data from the control groups are presented with chromosomal status of the embryos correlated to embryo morphology . METHODS The study includes 144 r and omly selected donated human oocytes . The nucleus from each blastomere was fixed separately and fluorescence in-situ hybridization ( FISH ) using seven probes ( 13 , 16 , 18 , 21 , 22 , X and Y ) was performed . RESULTS Analysis of 103 pre-embryos containing 479 blastomeres result ed in 424 blastomeres with clear FISH signals . Of these blastomeres , 55 % were normal diploid and 45 % were abnormal . At a pre-embryonic level , 53 % were classified as normal containing > or=50 % normal blastomeres while 31 % of the pre-embryos were classified as uniformly normal . Abnormality rate was significantly increased in the pre-embryos with unevenly sized blastomeres and with increasing degree of fragmentation at 68 h after fertilization . Applying criteria for good embryo quality significantly increased the rate of chromosomally normal pre-embryos from 53 to 75 % . CONCLUSIONS The data demonstrate the high degree of genetic heterogeneity in a r and omly selected pool of donated pre-embryos from an IVF programme . Further , we found that uniformity of blastomere size , degree of fragmentation and cleavage kinetics reflect the cytogenetic status of the pre-embryo and are therefore important in the selection of pre-embryos OBJECTIVE To select chromosomally euploid embryos for transfer by analyzing single biopsied blastomeres using either fluorescence in situ hybridization ( FISH ) for chromosomes 13 , 16 , 18 , 21 , and 22 or comparative genomic hybridization ( CGH ) , which provides a full karyotype . DESIGN Prospect i ve observational study . SETTING A large IVF unit and the research laboratory of a hospital clinical genetics unit . PATIENT(S ) Twenty patients with recurrent implantation failure . INTERVENTION(S ) Ovarian stimulation and IVF by intracytoplasmic sperm injection ( ICSI ) , embryo biopsy , and embryo transfer . MAIN OUTCOME MEASURE(S ) Chromosome normality of biopsied blastomeres and implantation and clinical pregnancy rates . RESULT ( S ) Comparative genomic hybridization was able to identify many chromosomal abnormalities that would have been missed if those cells had been analyzed by FISH . The clinical pregnancy rate per transfer and implantation rate was 11 % and 7 % for embryos analyzed by FISH and 21 % and 15 % for embryos analyzed by CGH . CONCLUSION ( S ) Comparative genomic hybridization is more effective than FISH for identifying chromosomally normal embryos , which may result in a higher clinical pregnancy rate and implantation rate after embryo transfer BACKGROUND It is generally accepted that the age-related increased aneuploidy rate is correlated with reduced implantation and a higher abortion rate . Therefore , advanced maternal age ( AMA ) couples are a good target group to assess the possible benefit of preimplantation genetic diagnosis for aneuploidy screening ( PGD-AS ) on the outcome after assisted reproductive technology ( ART ) . METHODS A prospect i ve r and omized controlled clinical trial ( RCT ) was carried out comparing the outcome after blastocyst transfer combined with PGD-AS using fluorescence in situ hybridization ( FISH ) for the chromosomes X , Y , 13 , 16 , 18 , 21 and 22 in AMA couples ( aged > or = 37 years ) with a control group without PGD-AS . From the 400 ( 200 for PGD-AS and 200 controls ) couples that were allocated to the trial , an oocyte pick-up was performed effectively in 289 cycles ( 148 PGD-AS cycles and 141 control cycles ) . RESULTS Positive serum HCG rates per transfer and per cycle were the same for PGD-AS and controls : 35.8 % ( 19.6 % ) [ % /per embryo transfer ( per cycle ) ] and 32.2 % ( 27.7 % ) , respectively ( NS ) . Significantly fewer embryos were transferred in the PGD-AS group than in the control group ( P<0.001 ) . The implantation rate ( with fetal heart beat ) was 17.1 % in the PGD-AS group versus 11.5 % in the control group ( not significant ; P=0.09 ) . We observed a normal diploid status in 36.8 % of the embryos . CONCLUSIONS This RCT provides no arguments in favour of PGD-AS for improving clinical outcome per initiated cycle in patients with AMA when there are no restrictions in the number of embryos to be transferred Blastocysts more commonly have a normal karyotype than cleavage-stage embryos do . Moreover , blastocysts have also made a metabolic transition from catabolism and recycling of the oocyte 's reserves and re sources , processes that fuel the first 3 days of cleavage . Although not all blastocysts are karyotypically equal , it is still to be determined to what extent a mosaic karyotype might be a normal feature among embryos , both at the cleavage stage and the blastocyst stage-- and when looking for karyotypic abnormalities by embryo biopsy might help the chance of implantation rather than harm it . It is also still impractical to look at all the chromosomes that can , through their aneuploidy , st and in the way of successful embryonic and fetal development . We report a r and omized clinical trial of blastocyst biopsy followed by preimplantation genetic screening ( PGS ) for aneuploidy using 5-colour FISH . The trial was suspended and then terminated early when we were unable to show an advantage for PGS . If we are correct in assuming that mitotic non-disjunction is common by the stage of the blastocyst ( and that it is much less ominous than meiotic non-disjunction ) , then further studies of effective PGS of blastocysts for aneuploidy require methods of analysis that cover all the chromosomes and can differentiate the triallelic and monoallelic states of meiotically derived aneuploidies from the biallelic state of mitotic aneuploidies OBJECTIVE The purpose of this study was to determine the positive predictive value ( PPV ) and negative predictive value ( NPV ) of FISH analysis and to determine which chromosomal abnormalities are most frequently confirmed . DESIGN Prospect i ve observational . SETTING IVF laboratory . PATIENT(S ) Two hundred forty-one embryos were analyzed from 98 patients . INTERVENTION(S ) FISH re analysis . MAIN OUTCOME MEASURE(S ) Embryos that would have been discarded in patients undergoing preimplantation genetic diagnosis ( PGD ) were fixed and FISH re analysis was performed . Results of re analysis were compared with the day 3 diagnosis while PPV and NPV were calculated . RESULT ( S ) Among the 241 embryos , 198 embryos were abnormal and 43 were normal by day 3 FISH analysis . The PPV was 83 % and the NPV was 81 % . PPV was also determined for specific categories of aneuploidy , and certain abnormalities such as monosomies , trisomies , tetrasomies , and polyploidies were frequently confirmed on re analysis ( PPV > 80 % ) , whereas Turner syndrome diagnosis was not ( PPV = 17 % ) . CONCLUSION ( S ) FISH analysis offers a PPV of 83 % and NPV of 81 % when evaluating a single blastomere in conjunction with PGD . FISH errors and mosaicism are primarily responsible for the errors associated with FISH analysis in PGD Preimplantation genetic diagnosis for aneuploidy screening ( preimplantation genetic screening-PGS ) has been used to detect chromosomally normal embryos from subfertile patients . The main indications are advanced maternal age ( AMA ) , repeated implantation failure , repeated miscarriages and severe male factor infertility . Many non-r and omized PGS studies have been published and report an increase in implantation rate , and /or a decrease in miscarriage rate . Recently , two r and omized controlled trials have been conducted on patients with AMA as the only indication . Neither study showed a benefit in performing PGS using live birth rate as the measure of success . The debate on the usefulness of PGS is ongoing ; the only effective way to resolve the debate is to perform more well- design ed and well-executed r and omized clinical trials OBJECTIVE To determine whether the routine use of preimplantation genetic screening ( PGS ) in " good prognosis " women improves in vitro fertilization ( IVF ) cycle outcome . DESIGN R and omized , controlled , prospect i ve clinical study . SETTING Private infertility clinic . PATIENT(S ) Infertile women predicted to have a good prognosis as defined by : age < 39 years , normal ovarian reserve , body mass index < 30 kg/m(2 ) , presence of ejaculated sperm , normal uterus , < or=2 previous failed IVF cycles . INTERVENTION(S ) Patients were r and omized to the PGS group or the control group on day 3 after oocyte retrieval ; 23 women underwent blastomere biopsy on day 3 after fertilization ( PGS group ) , and 24 women underwent routine IVF ( control group ) . All embryos were transferred on day 5 or 6 after fertilization . MAIN OUTCOME MEASURE(S ) Pregnancy , implantation , multiple gestation , and live birth rates . RESULT ( S ) No statistically significant differences were found between the PGS and control groups with respect to clinical pregnancy rate ( 52.4 % versus 72.7 % ) . However , the embryo implantation rate was statistically significantly lower for the PGS group ( 31.7 % versus 62.3 % ) as were the live birth rate ( 28.6 % versus 68.2 % ) and the multiple birth rate ( 9.1 % versus 46.7 % ) . CONCLUSION ( S ) In a " good prognosis " population of women , PGS does not appear to improve pregnancy , implantation , or live birth rates BACKGROUND Advanced maternal age ( AMA ) is an important parameter that negatively influences the clinical pregnancy rate in IVF , in particular owing to the increased embryo aneuploidy rate . It has thus been suggested that only transferring euploid embryos in this patient group would improve the pregnancy rate . The purpose of this study was to test whether employing preimplantation genetic screening ( PGS ) in AMA patients would increase the clinical pregnancy rate . METHODS We conducted a two-center , r and omized controlled trial ( RCT ) to analyze the outcome of embryo transfers in AMA patients ( > or=38 years of age ) after PGS using FISH analysis for chromosomes X , Y , 13 , 16 , 18 , 21 and 22 . The PGS group was compared with a control group . The primary outcome measure was clinical pregnancy rate after 6 - 7 weeks of gestation per r and omized patient . RESULTS The study was terminated early as an interim analysis showed a very low conditional power of superiority for the primary outcome . Of the 320 patients calculated to be included in the study , 56 and 53 patients were r and omized into the PGS and control groups , respectively . The clinical pregnancy rate in the PGS group was 8.9 % ( 95 % CI , 2.9 - 19.6 % ) compared with 24.5 % ( 95 % CI , 13.8 - 38.3 % ) in the control group , giving a difference of 15.6 % ( 95 % CI , 1.8 - 29.4 % , P = 0.039 ) . CONCLUSIONS Although the study was terminated early , this RCT study provides evidence against the use of PGS for AMA patients when performing IVF . TRIAL REGISTRATION NUMBER IS RCT N38014610 BACKGROUND The use of ICSI has been a major breakthrough in the treatment of male infertility . Even azoospermic patients with focal spermatogenesis in the testis ( not sufficient to spill over into the ejaculate ) may benefit from the technique . Previous reports suggest a higher pregnancy rate after ICSI treatment in patients with obstructive azoospermia ( OA ) compared to their non-obstructive azoospermia ( NOA ) counterparts , which could be due to a higher aneuploidy frequency in the embryos of the latter group . We therefore conducted a prospect i ve cohort study to compare the aneuploidy frequency of the screened embryos between the two groups . METHODS From May 2001 until September 2003 , we offered couples with an OA or NOA partner ICSI in combination with preimplantation genetic diagnosis for aneuploidy screening . RESULTS No difference in age ( 30.6 and 33.5 years ) or stimulation parameters was observed between the two groups ; 53 and 60 % of the embryos were abnormal in the NOA and OA groups respectively ( P = not significant ) . CONCLUSIONS The aneuploidy frequency in embryos obtained from NOA as well as OA men is similar and very high , despite the young age of their female partners A retrospective study recently showed that oocytes presenting with a high birefringence of the inner zona layer were more often associated with conception cycles . To further investigate these findings , a prospect i ve study was conducted between September 2005 and September 2006 including intracytoplasmic sperm injection ( ICSI ) cycles presenting with at least two embryos for transfer . Using a polarization imaging system , oocytes were classified prior to ICSI treatment as having either a high zona birefringence ( HZB ) or a low zona birefringence ( LZB ) of the zona pellucida . Using zona birefringence as the only selection criterion , two fertilized oocytes , preferably derived from HZB oocytes , were selected for further culture and transfer . The required criteria were met by 135 ICSI cycles ( 124 patients ; 34.9 + /- 4.1 years of age ) . Embryos for transfer were used in 20 cycles derived from HZB/HZB oocytes , in 50 cycles from HZB/LZB oocytes and in 65 from LZB/LZB oocytes . The corresponding implantation ( P < 0.025 ) , pregnancy ( P < 0.005 ) and live birth ( P < 0.025 ) rates were significantly different between HZB/HZB and HZB/LZB versus LZB/LZB group . Embryo development was superior in embryos derived from HZB oocytes . This study concludes that oocyte zona birefringence is a good selection criterion and a good predictive criterion for embryo implantation potential OBJECTIVE To improve preimplantation genetic diagnosis ( PGD ) accuracy by using " no result rescue " ( NRR ) consisting of the re analysis of dubious results with additional probes binding to a locus different from the one previously analyzed . DESIGN Prospect i ve study of PGD cycles with and without re analysis of inconclusive results . SETTING PGD laboratory . PATIENT(S ) Patients undergoing PGD for infertility or Robertsonian translocations . INTERVENTION(S ) Nuclei from day 3 biopsied embryos were analyzed with fluorescence in situ hybridization for chromosomes X , Y , 13 , 15 , 16 , 17 , 18 , 21 , and 22 . When inconclusive results were obtained , NRR was performed . In addition , 100 PGD cycles using NRR were matched to controls according to maternal age , previous failed cycles , number of zygotes , number of eggs , and date of retrieval . MAIN OUTCOME MEASURE(S ) Determination of frequency of inconclusive results and error rate after use of additional probes . Comparison of frequency of inconclusive results with prior PGD results when NRR was not used . Assisted reproductive technology outcome was compared between PGD using NRR and controls not using PGD . RESULT ( S ) After analysis of 34,831 blastomeres from 34,225 embryos , 2,609 blastomeres ( 7.5 % ) showed inconclusive results . After NRR on those 2,609 blastomeres , the number of cells with inconclusive results was reduced to 3.1 % ( P<.001 ) . After the introduction of NRR , fluorescence in situ hybridization errors , measured as discrepancies between the PGD diagnosis and the analysis of the nonreplaced embryo , decreased from 13.6 % to 4.7 % ( P<.001 ) . PGD with NRR significantly improved implantation rates , from 20 % to 31 % , and reduced spontaneous abortions from 27 % to 6 % . CONCLUSION ( S ) The use of NRR has been proven to be a powerful tool to reduce the error rate and the frequency of inconclusive results in PGD , both parameters of high importance to assess quality of PGD laboratories . Indeed , these parameters are two of the few measurable criteria to measure PGD laboratories . In a parallel controlled study , PGD with NRR significantly improved implantation rates and reduced spontaneous abortions , showing that PGD is more efficient in selecting embryos that will reach term The intent of this study was to evaluate a recent r and omized clinical trial evaluating the effect of preimplantation genetic screening ( PGS ) that reports a negative effect on pregnancy outcome . This article review s appropriate PGS techniques and how they differ from the trial in question . A closer look at the clinical trial in question reveals significant lack of expertise in biopsy , cell fixation , genetic analysis , and patient selection . At most , this trial demonstrates that in inexperienced h and s , PGS can be detrimental . No other conclusions concerning the effect of PGS on pregnancy results can be drawn from the trial BACKGROUND Pregnancy rates in women of advanced maternal age undergoing in vitro fertilization ( IVF ) are disappointingly low . It has been suggested that the use of preimplantation genetic screening of cleavage-stage embryos for aneuploidies may improve the effectiveness of IVF in these women . METHODS We conducted a multicenter , r and omized , double-blind , controlled trial comparing three cycles of IVF with and without preimplantation genetic screening in women 35 through 41 years of age . The primary outcome measure was ongoing pregnancy at 12 weeks of gestation . The secondary outcome measures were biochemical pregnancy , clinical pregnancy , miscarriage , and live birth . RESULTS Four hundred eight women ( 206 assigned to preimplantation genetic screening and 202 assigned to the control group ) underwent 836 cycles of IVF ( 434 cycles with and 402 cycles without preimplantation genetic screening ) . The ongoing-pregnancy rate was significantly lower in the women assigned to preimplantation genetic screening ( 52 of 206 women [ 25 % ] ) than in those not assigned to preimplantation genetic screening ( 74 of 202 women [ 37 % ] ; rate ratio , 0.69 ; 95 % confidence interval [ CI ] , 0.51 to 0.93 ) . The women assigned to preimplantation genetic screening also had a significantly lower live-birth rate ( 49 of 206 women [ 24 % ] vs. 71 of 202 women [ 35 % ] ; rate ratio , 0.68 ; 95 % CI , 0.50 to 0.92 ) . CONCLUSIONS Preimplantation genetic screening did not increase but instead significantly reduced the rates of ongoing pregnancies and live births after IVF in women of advanced maternal age . ( Current Controlled Trials number , IS RCT N76355836 [ controlled-trials.com ] . ) BACKGROUND Preimplantation genetic diagnosis or screening ( PGD , PGS ) involves embryo biopsy on Day 3 . Opting for one- or two-cell biopsy is a balance between the lowest risk for misdiagnosis on the one h and and the highest chance for a pregnancy on the other h and . METHODS A prospect i ve controlled trial was design ed and 592 ICSI cycles were r and omly assigned to the one-cell ( group I ) or the two-cell group ( group II ) . Primary outcomes were diagnostic efficiency and embryonic development to delivery with live birth ( analysed by cycle ) . The false-positive rate for the PCR cycles is presented as a secondary outcome ( analysed by embryo ) . RESULTS A strong significant correlation was observed between embryonic developmental stage on Day 3 and post-biopsy in vitro development on Day 5 ( P < 0.0001 ) . The influence of the intervention on Day 3 was less significant ( P = 0.007 ) : the biopsy of one cell is less invasive than the biopsy of two cells . PCR diagnostic efficiency was 88.6 % in group I and 96.4 % in group II ( P = 0.008 ) . For the fluorescence in situ hybridization ( FISH ) PGD cycles no significant difference in efficiency was obtained ( 98.2 and 97.5 % in group I and II , respectively ) . Similar delivery rates with live birth per started cycle were obtained [ 58/287 or 20.2 % in group I versus 52/303 or 17.2 % in group II , P = 0.358 ; the absolute risk reduction = 3.05 % ; 95 % confidence interval ( CI ) : -3.24 , 9.34 ] . Post-PGD PCR re analysis showed six false positives in 97 embryos ( 6.2 % ) in group II and none in group I ( 91 embryos reanalysed ) . No false negatives were found . CONCLUSIONS While removal of two blastomeres decreases the likelihood of blastocyst formation , compared with removal of one blastomere , Day 3 in vitro developmental stage is a stronger predictor for Day 5 developmental potential than the removal of one or two cells . The biopsy of only one cell significantly lowers the efficiency of a PCR-based diagnosis , whereas the efficiency of the FISH PGD procedure remains similar whether one or two cells are removed . Delivery rates with live birth per started cycle were not significantly different This r and omized , controlled trial verifies whether patients with recurrent failed implantation benefit from preimplantation genetic diagnosis for aneuploidy , as compared with conventional assisted reproduction treatment procedures . Two hundred patients with recurrent failed implantation were r and omized into two groups . A total of 139 patients underwent ovarian stimulation , and preimplantation genetic screening was performed in 72 patients . Analysis of chromosomes X , Y , 13 , 16 , 18 , 21 and 22 was carried out using fluorescence in-situ hybridization in blastomeres of day-3 cleavage-stage embryos in the study group . The primary endpoint was implantation rate . Secondary endpoints were embryonic morphology and chromosomal status , number of transferred embryos and clinical pregnancy rate . With regard to the implantation rate , there was no significant difference between the study group ( 21.4 % ) and the control group ( 25.3 % ) . The number of embryos transferred was significantly lower in the study group , namely 1.4 ( SD 1.0 ) versus 2.1 ( SD 1.0 ) in the control group ( P < 0.05 ) . The clinical pregnancy rate was not significantly different between the groups ( 25.0 % in the study group versus 40.3 % in the control group ) . It can be concluded that preimplantation genetic screening does not increase the implantation rates after IVF-intracytoplasmic sperm injection in women with repeated implantation failure OBJECTIVE To analyze the incidence of numeric chromosomal abnormalities in preimplantation embryos from women with unexplained recurrent miscarriage ( RM ) so as to seek an etiology and to determine whether the use of IVF may be indicated to treat these cases . DESIGN Prospect i ve controlled study . SETTING University laboratory of reproductive genetics and a tertiary referral center for infertility . PATIENT(S ) Nine women with a mean ( + /-SD ) of 3.9 + /- 0.6 RMs who were undergoing IVF and preimplantation genetic diagnosis , and a control group of young ( n = 10 ) and older ( n = 6 ) patients who were undergoing preimplantation genetic diagnosis because of sex-linked diseases . INTERVENTION(S ) In vitro fertilization , embryo culture for 72 hours , blastomere biopsy , and analysis of chromosomes 13 , 16 , 18 , 21 , 22 , X , and Y with the use of fluorescent in situ hybridization . Transfer of chromosomally normal embryos into the uterus . MAIN OUTCOME MEASURE(S ) Numeric chromosomal abnormalities in human embryos . RESULT ( S ) Sixty-six embryos from patients with RM were compared with 62 embryos from young patients and 41 embryos from older patients . There was a significant increase in the rate of abnormal embryos in the patients with RM and the older patients compared with the controls . Abnormalities in most of the chromosomes studied were higher in the RM group than in the control group , especially those affecting chromosome 13 . CONCLUSION ( S ) There was an increase in numeric chromosomal abnormalities in preimplantation embryos from women with RM that could be the cause of infertility in many couples with unexplained RM . The use of IVF in such circumstances may be indicated if successful preimplantation genetic diagnosis is added to the procedure BACKGROUND Evidence -based morphological embryo scoring models for ranking of implantation potential are still scarce , and the need for a precise model increases when aim ing for singleton pregnancies . METHODS Prospect ively , 2266 IVF/ICSI double-embryo , day 2 transfers were studied . The five variables scored in 3- to 5-step scales for the embryos transferred are blastomere number ( BL ) , fragmentation , blastomere size variation ( ' e quality ' , EQ ) , symmetry of the cleavage and mononuclearity in the blastomeres ( NU ) . The scoring results of embryos with an individual traceability from scoring to implantation , i.e. treatments result ing in either no implantation ( n=1385 ) or twin implantation ( n=228 ) , were studied for prognostic potential . RESULTS Although all five variables correlated highly with implantation potential , only BL , NU and EQ remained independently significant after regression analysis . The equation thus derived formed the basis for a 10-point integrated morphology cleavage ( IMC ) embryo score . A table with the scoring point for each possible combination of the embryo variables is presented . The scoring model was statistically vali date d on the singleton pregnancy group ( n=653 ) . CONCLUSIONS We suggest that this IMC embryo scoring , incorporating cleavage stage and information on the variation in blastomere size and the number of mononucleated blastomeres , may optimize embryo ranking and selection for day 2 transfers Recurrent miscarriage is a pathological condition induced by maternal and embryonic causes . This paper describes a prospect i ve study to determine the real incidence of aneuploidy for autosomes 13 , 16 , 18 , 21 , 22 , and gonosomes in preimplantation human embryos obtained from patients with recurrent pregnancy loss after ovarian stimulation in an IVF-ET programme . Our results indicate that aneuploidy for the chromosomes analysed are abnormally higher in embryos obtained after IVF from recurrent abortion patients ( 58 % ) compared to non-recurrent abortion patients undergoing IVF . Furthermore , monosomies are six times more frequent than trisomies ( 47:8 ) in preimplantation embryos from recurrent abortion patients . Based on the present study , preimplantation genetic diagnosis ( PGD ) of embryos obtained from patients with recurrent miscarriage could prove advantageous in diagnosing abnormal embryos and selecting normal embryos for transfer A r and omized clinical trial of 406 patients with advanced maternal age by Mastenbroek and co-workers recently published in the New Engl and Journal of Medicine showed a significant decrease in pregnancy outcome after preimplantation genetic screening ( PGS ) . It is our opinion that this study suffers from a number of insurmountable inaccuracies and that these are either a direct consequence of the inexperience of the team or of a general disregard of vital guidelines reported in the literature . Most importantly , the authors show that in their h and s embryo biopsy may affect as many as half the embryos . The error rate was not presented , shedding doubt on the authors ' abilities to reliably diagnose the biopsied cells . An evaluation of the study indicates that poor biopsy technique , sub st and ard fixation and FISH methods , poor IVF outcomes and inappropriate patient selection are the cause of the discouraging results obtained by these authors rather than problems inherent to PGS This prospect i ve r and omized controlled pilot trial was design ed to evaluate whether prescreening embryos for aneuploidy can improve clinical outcomes in infertile patients undergoing IVF , without limiting to poor prognosis patients . Although there was no statistically significant improvement in live birth rates or implantation rates in this pilot study , there was a trend toward improved clinical outcomes , indicating that future multicenter r and omized trials are needed OBJECTIVE To determine whether preimplantation genetic diagnosis ( PGD ) and transfer of euploid embryos would decrease spontaneous abortion rates in recurrent miscarriage ( RM ) patients . DESIGN Controlled clinical study . SETTING In vitro fertilization centers and PGD reference laboratory . PATIENT(S ) Recurrent-miscarriage patients with three or more prior lost pregnancies with no known etiology . INTERVENTION(S ) Biopsy of a single blastomere from each day 3 embryo , followed by fluorescence in situ hybridization analysis . MAIN OUTCOME MEASURE(S ) The rate of spontaneous abortions in RM subjects undergoing PGD were compared with [ 1 ] their own a priori expectations and [ 2 ] a comparison group of women undergoing PGD for advanced maternal age ( > or = 35 years ) . RESULT ( S ) Before PGD , RM patients had lost 87 % ( 262/301 ) of their pregnancies , with an expected loss rate of 36.5 % . After , they only lost 16.7 % pregnancies . This difference was mostly due to reduction in pregnancy loss in the > or = 35-years age subgroup , to 12 % from an expected 44.5 % . CONCLUSION ( S ) Preimplantation genetic diagnosis aneuploidy screening has a beneficial effect on pregnancy outcome in RM couples , especially those in which the woman is aged > or = 35 years . Our data indicate that PGD reduces the risk of miscarriage in RM patients to baseline levels Despite recent controversy , existing experience suggests that aneuploidy testing has had a significant impact on the reproductive outcome of poor prognosis IVF patients , which is based on the experience of over 20,000 cases of PGD for chromosomal disorders . The clinical impact was demonstrated in the improved implantation and pregnancy rates , reduction of spontaneous abortions and improved take-home baby rate in patients of advanced reproductive age , those with repeated IVF failures and recurrent spontaneous abortions . The lack of positive effect of aneuploidy testing in a few smaller series may be due to potential detrimental effect of two blastomere removal , reducing the implantation potential of the biopsied embryos , or exclusion from testing a few key chromosomes and poor outcome of aneuploidy testing , affecting the appropriate pre- selection of embryos for transfer . Despite the need for r and omized controlled studies to quantify in more detail the clinical impact of the pre- selection of aneuploidy-free zygotes , the positive impact of PGD is particularly obvious from the comparison of reproductive outcome in the same patients with and without PGD , revealing the actual benefits of PGD BACKGROUND Human preimplantation embryos generated through in vitro fertilization ( IVF ) or intracytoplasmic sperm injection ( ICSI ) treatments show a variable rate of numerical chromosome abnormalities or aneuploidies . Preimplantation genetic screening ( PGS ) has been design ed to screen for aneuploidies in high risk patients , with the aim of improving live birth rates in IVF/ICSI . We assessed whether the effect of PGS on live births rates differs in women of advanced maternal age with variable risks for embryonic aneuploidy , and weighed these effects against the results obtained after IVF/ICSI without PGS . METHODS The effect of PGS on live birth rates was compared between groups defined by maternal age , number of previous miscarriages , semen quality , total amount of recombinant FSH ( rFSH ) administered during ovarian stimulation and total number of top- quality embryos , using data from a r and omized controlled trial among women of advanced maternal age ( 35 - 41 years ) . RESULTS There was no significant differential effect of PGS in groups based on maternal age ( P-value of interaction 0.16 ) , the number of previous miscarriages ( P-value of interaction 0.93 ) , semen quality ( P-value of interaction 0.26 ) , rFSH dose ( P-value of interaction 0.15 ) or the number of top- quality embryos ( P-value of interaction 0.59 ) . Live birth rates after IVF/ICSI with PGS were lower in all groups when compared with live birth rates after IVF/ICSI without PGS . CONCLUSIONS The paradigm that the effect of PGS is determined by a woman 's risk for embryonic aneuploidy seems incorrect . In fact , PGS has no clinical benefit over st and ard IVF/ICSI in women of advanced maternal age regardless of their risk for embryonic aneuploidy |
11,952 | 29,736,193 | We noted no significant differences in serum ANG levels between patients and healthy controls , except in cases in which patients suffered from cancer or cardiovascular diseases .
The serum ANG concentrations were significantly higher in patients who developed colorectal cancer , acute myeloid leukemia , multiple myeloma , myelodysplastic syndromes , and heart failure than those in healthy controls .
Conclusion ANG has the potential of being a serum biomarker for cancers and cardiovascular diseases | Background Angiogenin ( ANG ) is a multifunctional angiogenic protein that participates in both normal development and diseases .
Abnormal serum ANG levels are commonly reported in various diseases .
However , whether ANG can serve as a diagnostic or prognostic marker for different diseases remains a matter of debate . | Schnitzler syndrome is a rare plasma cell disorder the pathogenesis of which is still not fully understood . We evaluated the circulating levels of four major angiogenic cytokines ( VEGF , angiogenin , angiopoietin-1 and angiopoietin-2 ) and six bone remodeling markers ( sRANKL , osteoprotegerin , dickkopf-1 , CTX , osteocalcin and bone-specific alkaline phosphatase-bALP ) in 13 patients with Schnitzler syndrome . At diagnosis , patients had elevated angiogenic cytokines . The mean VEGF levels were almost 3.5-fold higher in Schnitzler syndrome compared to controls , while 10 of 13 patients had higher VEGF than the upper control value . Successful treatment led to a significant reduction in VEGF . Patients with Schnitzler syndrome had increased bone formation ( high bALP , osteocalcin and osteoprotegerin ) which was not balanced by an increase in bone resorption ( normal CTX and sRANKL ) . These data support a role for VEGF as a new minor criterion in the diagnosis and follow up of Schnitzler syndrome , while the uncoupling of bone remodeling in favor of bone formation justifies the presence of bone densification More than half of all cases of preeclampsia occur in healthy first-time pregnant women . Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints ( SCOPE ) study of low-risk nulliparous women . Forty-seven biomarkers identified on the basis of ( 1 ) association with preeclampsia , ( 2 ) a biological role in placentation , or ( 3 ) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sample d at 14 to 16 weeks ’ gestation from 5623 women . The cohort was r and omly divided into training ( n=3747 ) and validation ( n=1876 ) cohorts . Preeclampsia developed in 278 ( 4.9 % ) women , of whom 28 ( 0.5 % ) developed early-onset preeclampsia . The final model for the prediction of preeclampsia included placental growth factor , mean arterial pressure , and body mass index at 14 to 16 weeks ’ gestation , the consumption of ≥3 pieces of fruit per day , and mean uterine artery resistance index . The area under the receiver operator curve ( 95 % confidence interval ) for this model in training and validation cohorts was 0.73 ( 0.70–0.77 ) and 0.68 ( 0.63–0.74 ) , respectively . A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio , mean arterial pressure , any pregnancy loss < 10 weeks , and mean uterine artery resistance index ( area under the receiver operator curve [ 95 % confidence interval ] in training and validation cohorts , 0.89 [ 0.78–1.0 ] and 0.78 [ 0.58–0.99 ] , respectively ) . Neither model included pregnancy-associated plasma protein A , previously reported to predict preeclampsia in population s of mixed parity and risk . In nulliparous women , combining multiple biomarkers and clinical data provided modest prediction of preeclampsia Aim /hypothesisLeptin has been shown to regulate angiogenesis in animal and in vitro studies by upregulating the production of several pro-angiogenic factors , but its role in regulating angiogenesis has never been studied in humans . Methods The potential angiogenic effect of two doses of metreleptin ( 50 and 100 ng/ml ) was evaluated in vitro , using a novel three-dimensional angiogenesis assay . Fifteen healthy , normoleptinaemic volunteers were administered both a physiological ( 0.1 mg/kg ) and a pharmacological ( 0.3 mg/kg ) single dose of metreleptin , in vivo , on two different inpatient admissions separated by 1–12 weeks . Serum was collected at 0 , 6 , 12 and 24 h after metreleptin administration . Twenty lean women , with leptin levels < 5 ng/ml , were r and omised in a 1:1 fashion to receive either physiological replacement doses of metreleptin ( 0.04–0.12 mg/kg q.d . ) or placebo for 32 weeks . Serum was collected at 0 , 8 , 20 and 32 weeks after r and omisation . Proteomic angiogenesis array analysis was performed to screen for angiogenic factors . Circulating concentrations of angiogenin , angiopoietin-1 , platelet derived endothelial factor (PDGF)-AA , matrix metalloproteinase ( MMP ) 8 and 9 , endothelial growth factor ( EGF ) and vascular EGF ( VEGF ) were also measured . Results Both metreleptin doses failed to induce angiogenesis in the in vitro model . Although leptin levels increased significantly in response to both short-term and long-term metreleptin administration , circulating concentrations of angiogenesis markers did not change significantly in vivo . Conclusions /interpretationsThis is the first study that examines the effect of metreleptin administration in angiogenesis in humans . Metreleptin administration does not regulate circulating angiogenesis related factors in humans . Clinical trial registration : Clinical Trials.gov NCT00140205 and NCT00130117 . Funding : This study was supported by National Institutes of Health-National Center for Research Re sources grant M01-RR-01032 ( Harvard Clinical and Translational Science Center ) and grant number UL1 RR025758 . Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785 , 79929 and 81913 , and AG032030 PURPOSE Accurate urine assays for bladder cancer detection would benefit patients and health care systems . Through extensive genomic and proteomic profiling of urine components we previously identified a panel of 8 biomarkers that can facilitate the detection of bladder cancer in voided urine sample s. In this study we confirmed this diagnostic molecular signature in a diverse multicenter cohort . MATERIAL S AND METHODS We performed a case-control , phase II study in which we analyzed voided urine from 102 subjects with bladder cancer and 206 with varying urological disorders . The urinary concentration of 8 biomarkers ( IL-8 , MMP-9 and 10 , PAI-1 , VEGF , ANG , CA9 and APOE ) was assessed by enzyme-linked immunosorbent assay . Diagnostic performance of the panel of tested biomarkers was evaluated using ROCs and descriptive statistical values , eg sensitivity and specificity . RESULTS Seven of the 8 urine biomarkers were increased in subjects with bladder cancer relative to those without bladder cancer . The 7 biomarkers were assessed in a new model , which had an AUROC of 0.88 ( 95 % CI 0.84 - 0.93 ) , and 74 % sensitivity and 90 % specificity . In contrast , the sensitivity of voided urine cytology and the UroVysion ® cytogenetic test in this cohort was 39 % and 54 % , respectively . Study limitations include analysis performed on banked urine sample s and the lack of voided urine cytology and cytogenetic test data on controls . CONCLUSIONS The study provides further evidence that the reported panel of diagnostic biomarkers can reliably achieve the noninvasive detection of bladder cancer with higher sensitivity than currently available urine based assays OBJECTIVE To investigate whether elevated urinary levels of vascular endothelial growth factor ( VEGF ) , carbonic anhydrase 9 ( CA9 ) , and angiogenin are associated with bladder cancer ( BCa ) . METHODS This was a case-control study in which voided urine sample s from 127 patients ( 63 control subjects and 64 patients with BCa ) were analyzed . The urinary concentrations of VEGF , CA9 , angiogenin , and bladder tumor antigen ( BTA ) were assessed using enzyme-linked immunosorbent assays . We used the area under the curve of receiver operating characteristic curves to determine the ability of VEGF , CA9 , and angiogenin to detect BCa in voided urine sample s. Data were also compared with the findings from a commercial enzyme-linked immunosorbent assay-based BCa detection assay ( BTA-Trak ) . The sensitivity , specificity , and positive and negative predictive values were calculated . RESULTS The urinary concentrations of VEGF , CA9 , angiogenin , and BTA were significantly elevated in those with BCa . VEGF was the most accurate urinary biomarker ( area under the curve 0.886 , 95 % confidence interval 0.8301 - 0.9418 ) . Furthermore , multivariate regression analysis highlighted VEGF ( odds ratio 5.90 , 95 % confidence interval 2.60 - 13.40 , P < .0001 ) as an independent variable . The sensitivity and specificity for VEGF ( 83 % sensitivity and 87 % specificity ) outperformed those for BTA ( 80 % sensitivity and 84 % specificity ) . CONCLUSION VEGF could be a valuable addition to voided urine sample analysis for the detection of BCa . Larger , prospect i ve studies are needed to determine the clinical utility of urinary VEGF and angiogenin as biomarkers in the noninvasive evaluation of patients with BCa OBJECTIVE Angiogenin ( ANG ) , a potent inducer of neovascularization , is secreted by some types of human tumor cells and appears crucial for their growth . This study was design ed with the aim to investigate any correlation between the serum angiogenin and the clinicopathological variables and furthermore evaluate the prognostic value of serum angiogenin in patients with breast cancer . MATERIAL AND METHODS Sixty-four consecutive patients with invasive breast cancer undergoing surgery were prospect ively included and evaluated . Venous blood sample s were collected before surgery . Sera were obtained by centrifugation and stored at -70 degrees C until assayed . The control group consisted of 16 patients with benign breast tumor ( 8 with fibrocystic disease and 8 with fibroadenoma ) . Serum concentration of angiogenin was measured by the quantitative s and wich enzyme immunoassay technique . The data on primary tumor staging , age , estrogen receptor , lymph node status , distant metastases and TNM staging were review ed and recorded . RESULTS The mean value of serum angiogenin in patients with invasive breast cancer was 2123.95 + /- 324.34 pg/ml and that of control group were 2108.16 + /- 398.20 pg/ml ( fibrocystic disease ) and 2010.27 + /- 318.40 pg/ml ( fibroadenoma ) . The difference was not significant ( p = 0.66 ) . Furthermore , with univariate analysis , there were no significant differences in serum angiogenin levels between the subgroups of the above-mentioned clinicopathological variables . CONCLUSION Serum angiogenin levels did not appear as a meaningful prognostic parameter for invasive breast cancer OBJECTIVE Our purpose was to compare angiogenin , lactate dehydrogenase ( LDH ) and fibronectin levels in mid-trimester amniotic fluid of patients with preterm and term deliveries and to find out their predictive values for preterm birth . STUDY DESIGN A prospect i ve cohort study was conducted in 55 pregnancies with singleton gestations that underwent amniocentesis at 15 - 20 weeks for st and ard genetic indications . Amniotic fluid angiogenin , lactate dehydrogenase and fibronectin levels were measured by enzyme-linked immunosorbent assay ( ELISA ) , radial immundiffusion technic and automated analyzer , respectively . RESULTS Five patients delivered preterm , five developed signs or symptoms of threatened preterm labor and 45 had term delivery after an uneventful pregnancy . Demographic data were not significantly different . Amniotic fluid angiogenin and lactate dehydrogenase levels were significantly higher in patients with preterm than term deliveries ( P<0.001 and 0.02 , respectively ) . Receiver-operator characteristic curve analysis showed that the amniotic fluid angiogenin had the best screening efficiency in predicting preterm delivery . An angiogenin level of 35ng/ml was the optimal cut-off value for the prediction of preterm delivery , with a sensitivity of 100 % and specificity of 91 % . CONCLUSION Second-trimester angiogenin is found to be quite effective in the prediction of preterm delivery . Preexisting intrauterine ischemia may be an important risk factor for preterm delivery and already be present in the early mid-trimester OBJECTIVE To investigate the role of the angiogenic factors , vascular endothelial growth factor ( VEGF ) and angiogenin in the pathophysiology of preeclampsia and how their concentrations correlate with the severity of the disease and fetal outcome . PATIENTS AND METHODS A prospect i ve study was carried out on 71 pregnant patients with preeclampsia and 20 pregnant normotensive controls . Maternal serum levels of VEGF and angiogenin were determined in all cases by enzyme immunoassay . Assessment of fetal well-being using the Biophysical Profile Score ( BPS ) , umbilical and uterine artery Doppler velocimetry , and infant birthweight were carried out . RESULTS Maternal serum VEGF and angiogenin levels were significantly increased in cases of mild and severe preeclampsia compared to controls . Their increase was positively correlated with elevated systolic and diastolic blood pressure , as well as poor BPS , abnormal Doppler velocimetry , and low birthweight . CONCLUSION Elevated levels of both VEGF and angiogenin could confirm the existence of vascular reactivity and endothelial disturbance in preeclampsia . Measurement of these angiogenic factors in maternal serum may be a useful as biomarkers for the assessment of the severity of the disease and of fetal outcome BACKGROUND AND METHODS Abnormal circulating endothelial cell ( CEC ) and circulating progenitor cell ( CPC ) numbers are present in cancer , but their relationship with angiogenesis , apoptosis , vascular biology , and prognosis is unclear . We prospect ively studied 160 patients with breast cancer and 63 age-matched controls free of breast cancer , measuring CECs ( CD45(-)/CD146(+)/CD34(+ ) ) and CPCs ( CD45(-)/CD133(+)/CD34(+ ) ) by flow cytometry and plasma markers of endothelial damage/dysfunction ( von Willebr and factor ) , apoptosis ( Fas/Fas-L ) and angiogenesis ( vascular endothelial growth factor [ VEGF ] , angiogenin ) by ELISA . These were compared with clinicopathophysiologic features and the Nottingham Prognostic Index ( NPI ) . An additional blood sample was taken 6 to 8 weeks after surgery from 15 women to test the effect of tumor removal . RESULTS CECs were significantly higher in the NPI poor prognostic group compared with moderate and good prognostic groups , and the cancer-free controls , whereas CPCs were lower in the poor prognosis group ( both P < .05 ) . Levels of von Willebr and factor , VEGF , angiogenin , and Fas-L ( but not soluble Fas ) were abnormal in breast cancer compared with controls ( P < .05 ) , with no relationship to prognosis groups . VEGF ( P = .04 ) and angiogenin ( P = .001 ) were markedly different after surgery . In multivariate analysis , vascular invasion ( P < .05 ) and tumor size ( P < .001 ) were independently associated with CECs . CPCs did not significantly associate with NPI in a linear regression model ; age ( P < .05 ) was a negative predictor , whereas Her-2 status ( P < .05 ) positively predicted CPCs . After adjustment , no variable independently predicted CPC levels . CONCLUSIONS CECs and CPCs demonstrate a strong relationship with NPI groups , but only CECs positively predict higher NPI scores and correlate with tumor invasiveness and size , possibly reflecting total tumor vascular volume |
11,953 | 27,287,500 | As compared with the st and ard peer review process , training did not improve the quality of the peer review report and use of a checklist did not improve the quality of the final manuscript .
Blinded peer review did not affect the quality of the peer review report or rejection rate . | Background The peer review process is a cornerstone of biomedical research .
We aim ed to evaluate the impact of interventions to improve the quality of peer review for biomedical publications .
Conclusion Despite the essential role of peer review , only a few interventions have been assessed in r and omized controlled trials . | Background Spin represents specific reporting strategies , either intentional or unintentional , to convince the reader that the beneficial effect of the experimental intervention in terms of efficacy and safety is greater than that shown by the results . The objectives of this study were to 1 ) develop a classification of spin specific to non-r and omized studies assessing an intervention and 2 ) estimate the prevalence of spin in abstract s of reports of such studies . Methods In a first step , we developed a specific classification of spin for non-r and omized studies by a literature review and pilot study . In a second step , 2 research ers trained in the field of methodology evaluated the prevalence of spin in the abstract of all non-r and omized studies assessing an intervention published in the BioMed Central Medical Series journals between January 1 , 2011 and December 31 , 2013 . All disagreements were resolved by consensus . We also determined whether the level of spin in abstract conclusions was high ( spin reported without uncertainty or recommendations for further trials ) , moderate ( spin reported with some uncertainty or recommendations for further trials ) or low ( spin reported with uncertainty and recommendations for further trials ) . Results Among the 128 assessed articles assessed , 107 ( 84 % ) had at least one example of spin in their abstract . The most prevalent strategy of spin was the use of causal language , identified in 68 ( 53 % ) abstract s. Other frequent strategies were linguistic spin , inadequate implication s for clinical practice , and lack of focus on harm , identified in 33 ( 26 % ) , 25 ( 20 % ) , and 34 ( 27 % ) abstract s respectively . Abstract conclusions of 61 ( 48 % ) articles featured a high level of spin . Conclusion Abstract of reports of non-r and omized studies assessing an intervention frequently includes spin . Efforts to reduce the prevalence of spin in abstract for such studies are needed Publication of medical research has high stakes : the communication and legitimization of medical research , the advancement of authors ' careers , priorities in funding decisions , the direction of future research , and the visibility and prestige of journals themselves . Peer review and editing play central roles in the publication process , affecting the acceptance of a manuscript and the form in which it appears . The most commonly heard justification of peer review is that it is an indispensable aid to an editor in assessing the importance of a scientific question and in assessing how well that question has been answered [ 1 , 2 ] . However , it has also been criticized as being inherently conservative , censorial , and , perhaps worst of all , arbitrary [ 3 ] . A frequently heard charge is that peer review delays the dissemination of crucial medical information without commensurate benefit [ 4 - 7 ] . During the last several years , some medical journal editors decided that the value of peer- review and editing practice s should be examined with the same rigor dem and ed for testing medical hypotheses [ 8 , 9 ] . The First International Congress on Peer Review was organized in 1989 [ 10 ] , bringing together medical journal editors and other interested scholars to present and discuss research on peer review ; a second Congress was held in 1993 . The peer- review process has two components : the assessment s by external review ers and the decisions and actions taken by editors , which are partially affected by comments from the review ers . To our knowledge , no study has evaluated the effects of peer review and editing on manuscript quality once the decision to accept has been made , and a computerized search of Index Medicus back to 1966 failed to locate any such studies . In this paper , we present the results of such a study , assessing the change in a manuscript between the times of provisional acceptance and final publication . We studied whether the quality of accepted manuscripts was improved by peer- review and editorial processes and , if it was , which aspects were most improved . Methods Setting The study was conducted at the editorial offices of Annals of Internal Medicine . Annals , a specialty journal in internal medicine , is published twice monthly and has a circulation of approximately 100 000 . Annals receives approximately 2400 manuscripts annually , of which half are reports of original research . During the period of this study , the investigators included the editors of Annals ( RHF and SWF ) and a statistical associate editor ( SNG ) . The Review Process No change was noted in the usual review and editing procedures at Annals during the time of this study . All manuscripts received at Annals were initially review ed by one of two full-time editors or one of two half-time deputy editors , as well as by one of seven associate editors , all of whom are faculty members of medical schools in Philadelphia and have subspecialty interests ( for example , infectious disease , gastroenterology ) . Half of the su bmi ssions were returned to authors without further review and half were sent to at least 2 outside review ers , selected by the associate editor from a data base of about 7000 review ers . After comments from the review ers were received , the original editor and associate editor reassessed each manuscript and chose which ones would be discussed at a weekly editorial conference of editors , deputy editors , medical associate editors , and two statistical associate editors . Factors that affected acceptance decisions included the quality of the research , the importance of the question , the contribution of the finding to its field , the utility and interest for Annals readers , the quality of the presentation , the priority relative to other articles , and available space . Authors were notified either that the editors would not accept the paper , that the editors were willing to reconsider the paper after major revisions , or that the paper was provisionally accepted , pending satisfactory revision . Approximately one third of the articles evaluated by outside review ers were accepted , 15 % of su bmi tted original research articles . Papers to be considered further were sent to authors , along with the comments of the two outside review ers , comments of one of the statistical editors , and a letter from one of the editors or deputy editors ( which summarized the discussion at the weekly conference , the ideas of the associate editor , and suggestions from the editor ) . In addition , each manuscript was review ed by a production editor , and directions for changes in manuscript wording or layout of figures and tables were included . All revised manuscripts were review ed by the editor or deputy editor in charge of the manuscript , the appropriate associate editor , the statistical editor , and the production editor . Some revised manuscripts were also reassessed by the original outside review ers . Approximately half of the revised manuscripts were returned to authors for further revision . Most revised manuscripts ( > 95 % ) were ultimately published . The time taken by this process was approximately 2 weeks for the initial decision to review or reject , 8 additional weeks to review and make an acceptance decision , 8 weeks until final acceptance , and about 4 months until publication . More than 95 % of manuscripts su bmi tted to Annals had a provisional acceptance or rejection decision sent to the authors within 3 months . The average time from su bmi ssion to publication was about 7 months , with initial peer review accounting for approximately 6 weeks . Manuscript Selection and Study Design All original research manuscripts ( articles ) accepted for publication by Annals from March 1992 to March 1993 were entered into the study after obtaining the author 's consent . Commentaries , review s , expository pieces , editorials , and brief reports were not included . This study had a beforeafter design , in which two versions of each manuscript were evaluated : the version originally su bmi tted and the version sent to the printer for publication after all modifications based on peer review , editors ' comments , and copyediting . All before and after manuscripts were in electronic form and were reformatted to make the appearance of the two versions identical . Authors ' names and affiliations were removed . The design of the study was approved by the Institutional Review Board of the University of Pennsylvania School of Medicine . Definition of Quality Manuscript quality can be separated conceptually into two components : the quality of the research itself , and the quality of the research report . The quality of the research report was evaluated in this study . It was defined as follows on the cover sheet of the quality assessment instrument : Whether the authors have described their research in enough detail and with sufficient clarity so a reader could make an independent judgment about the strengths and weaknesses of their data and conclusions . Manuscript Quality Assessment Instrument A 34- question instrument was developed to structure the assessment of the quality of a manuscript ( Appendix ) . Items were derived from published checklists [ 11 - 14 ] , articles about the contents of journal articles [ 15 - 18 ] , the authors ' editorial experience , and the comments of journal editors and method ologists who review ed drafts of the instrument . Each question could be answered on a 5-point ordinal scale , where 1 was worst and 5 was best . The instrument was organized along the same dimensions as a st and ard journal article : Title and Abstract ( 2 items ) , Introduction ( 2 items ) , Methods ( 7 items ) , Results ( 15 items ) , Discussion and Conclusions ( 4 items ) , and General Evaluation ( 4 items ) . An additional question asked for a subjective assessment of the manuscript 's overall quality on a 10-point scale . The instrument differed from previously published quality scoring schemes in several ways . It was not a checklist but rather was a set of structured judgments , grade d ordinally , allowing users the discretion not to penalize a manuscript if a detail was omitted that was not critical to the study 's interpretation . Also , in keeping with the definition of quality given above , each question was about the adequacy of the reporting rather than the quality of the research itself . Assessment A panel of 44 physicians and epidemiologists with training in research methods and in critically assessing the medical literature was recruited to serve as an independent panel of expert assessors ( experts ) . They did not receive any formal training in the use of the assessment instrument , although general guidelines were given on the cover sheet ( Appendix ) . The panel was masked to the design and aims of the study ; they were told only that they were participating in a study of manuscript quality for Annals . Before and after versions of each manuscript were r and omly assigned to different experts to prevent the bias that might have been introduced if they could infer the design of the study and thereby which manuscript had been through the editorial process . Thirty-two manuscript versions were given to two or three experts to assess the reliability of the instrument ; all others were assessed by only one expert . Statistical Analyses The study was design ed to have 90 % power to detect a 0.5 unit change in average score , assuming a within-manuscript st and ard deviation of 1 scale unit , using = 0.05 . The main outcome measure was the percentage of items that were scored 3 or higher on the 5-point scales ( percentage score ) . The average of all score components ( average score ) was also analyzed . Linear regression was used to assess the effect of revision on each of these outcome measures , with terms controlling for manuscript and review er . Item-specific analyses were done on dichotomized item scores ( 0 for ratings 2 and 1 for ratings 3 ) . The change from before revision to after revision in individual items was statistically assessed with conditional logistic regression , which allowed for variable group Objective To investigate the effectiveness of open peer review as a mechanism to improve the reporting of r and omised trials published in biomedical journals . Design Retrospective before and after study . Setting BioMed Central series medical journals . Sample 93 primary reports of r and omised trials published in BMC -series medical journals in 2012 . Main outcome measures Changes to the reporting of method ological aspects of r and omised trials in manuscripts after peer review , based on the CONSORT checklist , corresponding peer review er reports , the type of changes requested , and the extent to which authors adhered to these requests . Results Of the 93 trial reports , 38 % ( n=35 ) did not describe the method of r and om sequence generation , 54 % ( n=50 ) concealment of allocation sequence , 50 % ( n=46 ) whether the study was blinded , 34 % ( n=32 ) the sample size calculation , 35 % ( n=33 ) specification of primary and secondary outcomes , 55 % ( n=51 ) results for the primary outcome , and 90 % ( n=84 ) details of the trial protocol . The number of changes between manuscript versions was relatively small ; most involved adding new information or altering existing information . Most changes requested by peer review ers had a positive impact on the reporting of the final manuscript — for example , adding or clarifying r and omisation and blinding ( n=27 ) , sample size ( n=15 ) , primary and secondary outcomes ( n=16 ) , results for primary or secondary outcomes ( n=14 ) , and toning down conclusions to reflect the results ( n=27 ) . Some changes requested by peer review ers , however , had a negative impact , such as adding additional unplanned analyses ( n=15 ) . Conclusion Peer review ers fail to detect important deficiencies in reporting of the methods and results of r and omised trials . The number of these changes requested by peer review ers was relatively small . Although most had a positive impact , some were inappropriate and could have a negative impact on reporting in the final publication Background The analysis of clinical trials with dropout usually assumes the missing data are ` missing at r and om ' , i.e. given an individual 's past observed data , their probability of dropout does not depend on their present outcome . However , in many setting s this assumption is implausible , so it is sensible to assess the robustness of conclusions to departures from missing at r and om . Purpose To develop a practical , accessible , approach that allows expert opinions about the degree of departure from missing at r and om in the analysis of a clinical trial to be meaningfully and accurately elicited and incorporated in sensitivity analysis . Methods We elicit experts ' prior beliefs about the mean difference between missing and observed outcomes in each trial arm . Then we perform a Bayesian synthesis of the information in the trial data with that in the experts ' prior , using ( i ) a full Bayesian analysis for which we give WinBUGS code , and ( ii ) a simple approximate formula for the estimated treatment effect and its st and ard error . We illustrate our approach by re-analysing a recent trial of interventions to improve the quality of peer review . Results In the peer review trial , the approximate formula agreed well with the full Bayesian analysis , and both showed substantially larger st and ard errors than an analysis assuming missing at r and om . Limitations Strictly , the method is only applicable if the outcome is normally distributed . We did not elicit the full bivariate prior distribution , and instead used a sensitivity analysis . Our approach is not design ed to incorporate prior beliefs about the intervention effect itself . Conclusions Our proposed approach allows for the greater uncertainty introduced by missing data that are potentially informatively missing . It can therefore cl aim to be a truly conservative method , unlike methods such as ` last observation carried forward ' . It is practical and accessible to non-statisticians . It should be considered as part of the design and analysis of future clinical trials . Clinical Trials 2007 ; 4 : 125—139 . Background Prior efforts to train medical journal peer review ers have not improved subsequent review quality , although such interventions were general and brief . We hypothesized that a manuscript-specific and more extended intervention pairing new review ers with high- quality senior review ers as mentors would improve subsequent review quality . Methods Over a four-year period we r and omly assigned all new review ers for Annals of Emergency Medicine to receive our st and ard written informational material s alone , or these material s plus a new mentoring intervention . For this program we paired new review ers with a high- quality senior review er for each of their first three manuscript review s , and asked mentees to discuss their review with their mentor by email or phone . We then compared the quality of subsequent review s between the control and intervention groups , using linear mixed effects models of the slopes of review quality scores over time . Results We studied 490 manuscript review s , with similar baseline characteristics between the 24 mentees who completed the trial and the 22 control review ers . Mean quality scores for the first 3 review s on our 1 to 5 point scale were similar between control and mentee groups ( 3.4 versus 3.5 ) , as were slopes of change of review scores ( -0.229 versus -0.549 ) and all other secondary measures of review er performance . Conclusions A structured training intervention of pairing newly recruited medical journal peer review ers with senior review er mentors did not improve the quality of their subsequent review Background The extended Consoli date d St and ards of Reporting Trials ( CONSORT ) Statement for Abstract s was developed to improve the quality of reports of r and omized controlled trials ( RCTs ) because readers often base their assessment of a trial solely on the abstract . To date , few data exist regarding whether it has achieved this goal . We evaluated the extent of adherence to the CONSORT for Abstract statement for quality of reports on RCT abstract s by four high-impact general medical journals . Methods A descriptive analysis of published RCT abstract s in The New Engl and Journal of Medicine ( NEJM ) , The Lancet , The Journal of American Medical Association ( JAMA ) , and the British Medical Journal ( BMJ ) in the year 2010 was conducted by two review ers , independently extracting data from a MEDLINE / PubMed search . Results We identified 271 potential RCT abstract s meeting our inclusion criteria . More than half of the abstract s identified the study as r and omized in the title ( 58.7 % ; 159/271 ) , reported the specific objective /hypothesis ( 72.7 % ; 197/271 ) , described participant eligibility criteria with setting s for data collection ( 60.9 % ; 165/271 ) , detailed the interventions for both groups ( 90.8 % ; 246/271 ) , and clearly defined the primary outcome ( 94.8 % ; 257/271 ) . However , the method ological quality domains were inadequately reported : allocation concealment ( 11.8 % ; 32/271 ) and details of blinding ( 21.0 % ; 57/271 ) . Reporting the primary outcome results for each group was done in 84.1 % ( 228/271 ) . Almost all of the abstract s reported trial registration ( 99.3 % ; 269/271 ) , whereas reports of funding and of harm or side effects from the interventions were found in only 47.6 % ( 129/271 ) and 42.8 % ( 116/271 ) of the abstract s , respectively . Conclusions These findings show inconsistencies and non-adherence to the CONSORT for abstract guidelines , especially in the method ological quality domains . Improvements in the quality of RCT reports can be expected by adhering to existing st and ards and guidelines as expressed by the CONSORT group 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 Abstract Objective To determine the effects of training on the quality of peer review . Design Single blind r and omised controlled trial with two intervention groups receiving different types of training plus a control group . Setting and participants Review ers at a general medical journal . Interventions Attendance at a training workshop or reception of a self taught training package focusing on what editors want from review ers and how to critically appraise r and omised controlled trials . Main outcome measures Quality of review s of three manuscripts sent to review ers at four to six monthly intervals , evaluated using the vali date d review quality instrument ; number of deliberate major errors identified ; time taken to review the manuscripts ; proportion recommending rejection of the manuscripts . Results Review ers in the self taught group scored higher in review quality after training than did the control group ( score 2.85 v 2.56 ; difference 0.29 , 95 % confidence interval 0.14 to 0.44 ; P = 0.001 ) , but the difference was not of editorial significance and was not maintained in the long term . Both intervention groups identified significantly more major errors after training than did the control group ( 3.14 and 2.96 v 2.13 ; P < 0.001 ) , and this remained significant after the review ers ' performance at baseline assessment was taken into account . The evidence for benefit of training was no longer apparent on further testing six months after the interventions . Training had no impact on the time taken to review the papers but was associated with an increased likelihood of recommending rejection ( 92 % and 84 % v 76 % ; P = 0.002 ) . Conclusions Short training packages have only a slight impact on the quality of peer review . The value of longer interventions needs to be assessed INTRODUCTION Research into the peer review process has previously been conducted in English- language journals . This study deals with a Danish general medical journal with a relatively small pool of both review ers and readers . The aim of the study was to compare the quality of review s produced by identifiable and anonymous review ers , and further to characterize authors ' and review ers ' attitudes towards different peer review systems . MATERIAL AND METHODS The study was conducted as a blinded , r and omised controlled trial . Each manuscript was review ed by an identifiable and an anonymous review er . Review quality was subsequently assessed by two blinded editors , using the vali date d Review Quality Instrument . Review ers ' and authors ' attitudes towards different peer review systems were characterized using question naires . RESULTS The study included 364 review s. There was no statistically significant difference in quality between anonymous and identifiable review ers ' evaluations . 55 % of the authors preferred the evaluation produced by the identifiable review er ( p < 0.05 ) . 26 % of the identifiable review ers found it unpleasant that authors knew their identities ; 43 % of the anonymous review ers found it reassuring that authors did not know their identities . Regarding review ers ' preferences for different peer review systems , 38 % preferred a double-blinded , 34 % preferred a single-blinded and 28 % preferred an open system . For authors , the corresponding proportions were 43 % , 19 % and 37 % . CONCLUSION Implementing open peer review will not affect review quality , but lack of anonymity may cause review ers , already limited in number , to decline when asked to review . Even though this would be a serious implication for a national journal like the Ugeskrift for Læger , the implementation of an open system should be discussed . FUNDING not relevant . TRIAL REGISTRATION not relevant CONTEXT The quality of a process can only be tested against its agreed objectives . Editorial peer- review is widely used , yet there appears to be little agreement about how to measure its effects or processes . METHODS To identify outcome measures used to assess editorial peer review as performed by biomedical journals , we analyzed studies identified from 2 systematic review s that measured the effects of editorial peer review on the quality of the output ( ie , published articles ) or of the process itself ( eg , review ers ' comments ) . RESULTS Ten studies used a variety of instruments to assess the quality of articles that had undergone peer review . Only 1 , nonr and omized study compared the quality of articles published in peer- review ed and non-peer- review ed journals . The others measured the effects of variations in the peer- review process or used a before- and -after design to measure the effects of st and ard peer review on accepted articles . Eighteen studies measured the quality of review ers ' reports under different conditions such as blinding or after training . One study compared the time and cost of different review processes . CONCLUSIONS Until we have properly defined the objectives of peer- review , it will remain almost impossible to assess or improve its effectiveness . The research needed to underst and the broader effects of peer review poses many method ologic problems and would require the cooperation of many parts of the scientific community Background The peer review process is a cornerstone of biomedical research publications . However , it may fail to allow the publication of high- quality articles . We aim ed to identify and sort , according to their importance , all tasks that are expected from peer review ers when evaluating a manuscript reporting the results of a r and omized controlled trial ( RCT ) and to determine which of these tasks are clearly requested by editors in their recommendations to peer review ers . Methods We identified the tasks expected of peer review ers from 1 ) a systematic review of the published literature and 2 ) recommendations to peer review ers for 171 journals ( i.e. , 10 journals with the highest impact factor for 14 different medical areas and all journals indexed in PubMed that published more than 15 RCTs over 3 months regardless of the medical area ) . Participants who had peer- review ed at least one report of an RCT had to classify the importance of each task relative to other tasks using a Q-sort technique . Finally , we evaluated editors ’ recommendations to authors to determine which tasks were clearly requested by editors in their recommendations to peer review ers . Results The Q-sort survey was completed by 203 participants , 93 ( 46 % ) with clinical expertise , 72 ( 36 % ) with method ological/statistical expertise , 17 ( 8 % ) with expertise in both areas , and 21 ( 10 % ) with other expertise . The task rated most important by participants ( evaluating the risk of bias ) was clearly requested by only 5 % of editors . In contrast , the task most frequently requested by editors ( provide recommendations for publication ) , was rated in the first tertile only by 21 % of all participants . Conclusions The most important tasks for peer review ers were not congruent with the tasks most often requested by journal editors in their guidelines to review ers CONTEXT Anxiety about bias , lack of accountability , and poor quality of peer review has led to questions about the imbalance in anonymity between review ers and authors . OBJECTIVE To evaluate the effect on the quality of peer review of blinding review ers to the authors ' identities and requiring review ers to sign their reports . DESIGN R and omized controlled trial . SETTING A general medical journal . PARTICIPANTS A total of 420 review ers from the journal 's data base . INTERVENTION We modified a paper accepted for publication introducing 8 areas of weakness . Review ers were r and omly allocated to 5 groups . Groups 1 and 2 received manuscripts from which the authors ' names and affiliations had been removed , while groups 3 and 4 were aware of the authors ' identities . Groups 1 and 3 were asked to sign their reports , while groups 2 and 4 were asked to return their reports unsigned . The fifth group was sent the paper in the usual manner of the journal , with authors ' identities revealed and a request to comment anonymously . Group 5 differed from group 4 only in that its members were unaware that they were taking part in a study . MAIN OUTCOME MEASURE The number of weaknesses in the paper that were commented on by the review ers . RESULTS Reports were received from 221 review ers ( 53 % ) . The mean number of weaknesses commented on was 2 ( 1.7 , 2.1 , 1.8 , and 1.9 for groups 1 , 2 , 3 , and 4 and 5 combined , respectively ) . There were no statistically significant differences between groups in their performance . Review ers who were blinded to authors ' dentities were less likely to recommend rejection than those who were aware of the authors ' identities ( odds ratio , 0.5 ; 95 % confidence interval , 0.3 - 1.0 ) . CONCLUSIONS Neither blinding review ers to the authors and origin of the paper nor requiring them to sign their reports had any effect on rate of detection of errors . Such measures are unlikely to improve the quality of peer review reports Background Although peer review is widely considered to be the most credible way of selecting manuscripts and improving the quality of accepted papers in scientific journals , there is little evidence to support its use . Our aim was to estimate the effects on manuscript quality of either adding a statistical peer review er or suggesting the use of checklists such as CONSORT or STARD to clinical review ers or both . Methodology and Principal Findings Interventions were defined as 1 ) the addition of a statistical review er to the clinical peer review process , and 2 ) suggesting reporting guidelines to review ers ; with “ no statistical expert ” and “ no checklist ” as controls . The two interventions were crossed in a 2 × 2 balanced factorial design including original research articles consecutively selected , between May 2004 and March 2005 , by the Medicina Clinica ( Barc ) editorial committee . We r and omized manuscripts to minimize differences in terms of baseline quality and type of study ( intervention , longitudinal , cross-sectional , others ) . Sample -size calculations indicated that 100 papers provide an 80 % power to test a 55 % st and ardized difference . We specified the main outcome as the increment in quality of papers as measured on the Goodman Scale . Two blinded evaluators rated the quality of manuscripts at initial su bmi ssion and final post peer review version . Of the 327 manuscripts su bmi tted to the journal , 131 were accepted for further review , and 129 were r and omized . Of those , 14 that were lost to follow-up showed no differences in initial quality to the followed-up papers . Hence , 115 were included in the main analysis , with 16 rejected for publication after peer review . 21 ( 18.3 % ) of the 115 included papers were interventions , 46 ( 40.0 % ) were longitudinal design s , 28 ( 24.3 % ) cross-sectional and 20 ( 17.4 % ) others . The 16 ( 13.9 % ) rejected papers had a significantly lower initial score on the overall Goodman scale than accepted papers ( difference 15.0 , 95 % CI : 4.6–24.4 ) . The effect of suggesting a guideline to the review ers had no effect on change in overall quality as measured by the Goodman scale ( 0.9 , 95 % CI : −0.3–+2.1 ) . The estimated effect of adding a statistical review er was 5.5 ( 95 % CI : 4.3–6.7 ) , showing a significant improvement in quality . Conclusions and Significance This prospect i ve r and omized study shows the positive effect of adding a statistical review er to the field-expert peers in improving manuscript quality . We did not find a statistically significant positive effect by suggesting review ers use reporting guidelines CONTEXT Some journals routinely query potential referees before sending manuscripts ( " askfirst " ) , whereas others just send manuscripts and allow referees to opt out ( " justsend " ) . It is not known which protocol results in more completed review s or shorter review time . METHODS Trial to assess proportion of referee turndowns and length of review process , conducted at editorial office of Obstetrics & Gynecology and involving 283 consecutive qualifying manuscripts . For each , a referee was r and omly assigned to askfirst ( manuscript sent only after affirmative response within 3 days ) and another to justsend ( manuscript sent with request to review ; could opt out ) . RESULTS Only 64 % of askfirst referees assented initially ( 15 % declined [ vs 8 % for justsend , P = .008 ] and 21 % failed to respond within 3 working days , necessitating a replacement ) . But once manuscript was mailed , mean time to file a review was significantly shorter for askfirst ( 21.0 vs 25.0 days , P<.001 ) ; thus , overall time to receipt of review did not differ significantly ( 24.7 vs 25.9 days , P = .19 ) , nor did review quality ( P = .39 ) . CONCLUSION Askfirst led to a higher rate of referee turndown than did justsend , but assenting askfirst referees completed review s faster . The overall time for the review process did not differ between the 2 protocol Objective To investigate the effect of an additional review based on reporting guidelines such as STROBE and CONSORT on quality of manuscripts . Design Masked r and omised trial . Population Original research manuscripts su bmi tted to the Medicina Clínica journal from May 2008 to April 2009 and considered suitable for publication . Intervention Control group : conventional peer review s alone . Intervention group : conventional review plus an additional review looking for missing items from reporting guidelines . Outcomes Manuscript quality , assessed with a 5 point Likert scale ( primary : overall quality ; secondary : average quality of specific items in paper ) . Main analysis compared groups as allocated , after adjustment for baseline factors ( analysis of covariance ) ; sensitivity analysis compared groups as review ed . Adherence to review er suggestions assessed with Likert scale . Results Of 126 consecutive papers receiving conventional review , 34 were not suitable for publication . The remaining 92 papers were allocated to receive conventional review s alone ( n=41 ) or additional review s ( n=51 ) . Four papers assigned to the conventional review group deviated from protocol ; they received an additional review based on reporting guidelines . We saw an improvement in manuscript quality in favour of the additional review group ( comparison as allocated , 0.25 , 95 % confidence interval –0.05 to 0.54 ; as review ed , 0.33 , 0.03 to 0.63 ) . More papers with additional review s than with conventional review s alone improved from baseline ( 22 ( 43 % ) v eight ( 20 % ) , difference 23.6 % ( 3.2 % to 44.0 % ) , number needed to treat 4.2 ( from 2.3 to 31.2 ) , relative risk 2.21 ( 1.10 to 4.44 ) ) . Authors in the additional review group adhered more to suggestions from conventional review s than to those from additional review s ( average increase 0.43 Likert points ( 0.19 to 0.67 ) ) . Conclusions Additional review s based on reporting guidelines improve manuscript quality , although the observed effect was smaller than hypothesised and not definitively demonstrated . Authors adhere more to suggestions from conventional review s than to those from additional review s , showing difficulties in adhering to high method ological st and ards at the latest research phases . To boost paper quality and impact , authors should be aware of future requirements of reporting guidelines at the very beginning of their study . Trial registration and protocol Although registries do not include trials of peer review , the protocol design was su bmi tted to sponsored research projects ( Instituto de Salud Carlos III , PI081903 ) CONTEXT Previous studies indicate that the interpretation of trial results can be distorted by authors of published reports . OBJECTIVE To identify the nature and frequency of distorted presentation or " spin " ( ie , specific reporting strategies , whatever their motive , to highlight that the experimental treatment is beneficial , despite a statistically nonsignificant difference for the primary outcome , or to distract the reader from statistically nonsignificant results ) in published reports of r and omized controlled trials ( RCTs ) with statistically nonsignificant results for primary outcomes . DATA SOURCES March 2007 search of MEDLINE via PubMed using the Cochrane Highly Sensitive Search Strategy to identify reports of RCTs published in December 2006 . STUDY SELECTION Articles were included if they were parallel-group RCTs with a clearly identified primary outcome showing statistically nonsignificant results ( ie , P > or = .05 ) . DATA EXTRACTION Two readers appraised each selected article using a pretested , st and ardized data abstract ion form developed in a pilot test . RESULTS From the 616 published reports of RCTs examined , 72 were eligible and appraised . The title was reported with spin in 13 articles ( 18.0 % ; 95 % confidence interval [ CI ] , 10.0%-28.9 % ) . Spin was identified in the Results and Conclusions sections of the abstract s of 27 ( 37.5 % ; 95 % CI , 26.4%-49.7 % ) and 42 ( 58.3 % ; 95 % CI , 46.1%-69.8 % ) reports , respectively , with the conclusions of 17 ( 23.6 % ; 95 % CI , 14.4%-35.1 % ) focusing only on treatment effectiveness . Spin was identified in the main-text Results , Discussion , and Conclusions sections of 21 ( 29.2 % ; 95 % CI , 19.0%-41.1 % ) , 31 ( 43.1 % ; 95 % CI , 31.4%-55.3 % ) , and 36 ( 50.0 % ; 95 % CI , 38.0%-62.0 % ) reports , respectively . More than 40 % of the reports had spin in at least 2 of these sections in the main text . CONCLUSION In this representative sample of RCTs published in 2006 with statistically nonsignificant primary outcomes , the reporting and interpretation of findings was frequently inconsistent with the results OBJECTIVE To study whether review ers aware of author identity are biased in favor of authors with more previous publications . DESIGN R and omized controlled trial . SETTING Editorial office of the Journal of Developmental and Behavioral Pediatrics . PARTICIPANTS Two " blinded " and two " nonblinded " review ers assigned to 57 consecutive manuscripts su bmi tted between September 1991 and March 1992 . OUTCOME MEASURES Spearman rank correlation coefficients were used to compare the sum of rating scores of 1 to 5 ( 1 , accept ; 5 , reject ) given by the two blinded review ers , the two nonblinded review ers , and the editors to the number of articles published previously by the first and senior authors ( as determined from requested curricula vitae ) . Blinded review ers were sent a question naire asking whether they could determine the identity of the authors , how they knew , and whether they thought binding changed the quality or difficulty of their review . RESULTS The Wilcoxon Sign Rank Test disclosed no differences between blinded and nonblinded scores . The number of previous articles by the senior author was significantly correlated ( P < .01 ) with blinded scores ( r = -.45 ) and editors ' decisions ( r = -.45 ) , but not with nonblinded scores ; the number of articles by the first author was correlated ( P < .05 ) with editors ' decisions ( r = -.35 ) but not with blinded or nonblinded scores . Fifty ( 46 % ) of 108 blinded review ers correctly guessed the identity of the authors , mostly from self-references and knowledge of the work ; 86 % believed blinding did not change the quality of their review , and 73 % believed it did not change the difficulty of performing a review . CONCLUSIONS Blinded review ers and editors in this study , but not nonblinded review ers , gave better scores to authors with more previous articles . These results suggest that blinded review ers may provide more unbiased review s and that nonblinded review ers may be affected by various types of bias The objectives of this study were to see whether , in the opinion of authors , blinding or unmasking or a combination of the two affects the quality of review s and to compare authors ’ and editors ’ assessment s. In a trial conducted in the British Medical Journal , 527 consecutive manuscripts were r and omized into one of three groups , and each was sent to two review ers , who were r and omized to receive a blinded or an unblinded copy of the manuscript . Review quality was assessed by two editors and the corresponding author . There was no significant difference in assessment between groups or between editors and authors . Review s recommending publication were scored more highly than those recommending rejection Objectives To see whether telling peer review ers that their signed review s of original research papers might be posted on the BMJ ’s website would affect the quality of their review s. Design R and omised controlled trial . Setting A large international general medical journal based in the United Kingdom . Participants 541 authors , 471 peer review ers , and 12 editors . Intervention Consecutive eligible papers were r and omised either to have the review er ’s signed report made available on the BMJ ’s website alongside the published paper ( intervention group ) or to have the report made available only to the author — the BMJ ’s normal procedure ( control group ) . The intervention was the act of revealing to review ers — after they had agreed to review but before they undertook their review —that their signed report might appear on the website . Main outcome measures The main outcome measure was the quality of the review s , as independently rated on a scale of 1 to 5 using a vali date d instrument by two editors and the corresponding author . Authors and editors were blind to the intervention group . Authors rated review quality before the fate of their paper had been decided . Additional outcomes were the time taken to complete the review and the review er ’s recommendation regarding publication . Results 558 manuscripts were r and omised , and 471 manuscripts remained after exclusions . Of the 1039 review ers approached to take part in the study , 568 ( 55 % ) declined . Two editors ’ evaluations of the quality of the peer review were obtained for all 471 manuscripts , with the corresponding author ’s evaluation obtained for 453 . There was no significant difference in review quality between the intervention and control groups ( mean difference for editors 0.04 , 95 % CI −0.09 to 0.17 ; for authors 0.06 , 95 % CI −0.09 to 0.20 ) . Any possible difference in favour of the control group was well below the level regarded as editorially significant . Review ers in the intervention group took significantly longer to review ( mean difference 25 minutes , 95 % CI 3.0 to 47.0 minutes ) . Conclusion Telling peer review ers that their signed review s might be available in the public domain on the BMJ ’s website had no important effect on review quality . Although the possibility of posting review s online was associated with a high refusal rate among potential peer review ers and an increase in the amount of time taken to write a review , we believe that the ethical arguments in favour of open peer review more than outweigh these disadvantages CONTEXT All authors may not be equal in the eyes of review ers . Specifically , well-known authors may receive less objective ( poorer quality ) review s. One study at a single journal found a small improvement in review quality when review ers were masked to author identity . OBJECTIVES To determine whether masking review ers to author identity is generally associated with higher quality of review at biomedical journals , and to determine the success of routine masking techniques . DESIGN AND SETTING A r and omized controlled trial performed on external review s of manuscripts su bmi tted to Annals of Emergency Medicine , Annals of Internal Medicine , JAMA , Obstetrics & Gynecology , and Ophthalmology . INTERVENTIONS Two peers review ed each manuscript . In one study arm , both peer review ers received the manuscript according to usual masking practice . In the other arm , one review er was r and omized to receive a manuscript with author identity masked , and the other review er received an unmasked manuscript . MAIN OUTCOME MEASURE Review quality on a 5-point Likert scale as judged by manuscript author and editor . A difference of 0.5 or greater was considered important . RESULTS A total of 118 manuscripts were r and omized , 26 to usual practice and 92 to intervention . In the intervention arm , editor quality assessment was complete for 77 ( 84 % ) of 92 manuscripts . Author quality assessment was complete on 40 ( 54 % ) of 74 manuscripts . Authors and editors perceived no significant difference in quality between masked ( mean difference , 0.1 ; 95 % confidence interval [ CI ] , -0.2 to 0.4 ) and unmasked ( mean difference , -0.1 ; 95 % CI , -0.5 to 0.4 ) review s. We also found no difference in the degree to which the review influenced the editorial decision ( mean difference , -0.1 ; 95 % CI,-0.3 to 0.3 ) . Masking was often unsuccessful ( overall , 68 % successfully masked ; 95 % CI , 58%-77 % ) , although 1 journal had significantly better masking success than others ( 90 % successfully masked ; 95 % CI , 73%-98 % ) . Manuscripts by generally known authors were less likely to be successfully masked ( odds ratio , 0.3 ; 95 % CI , 0.1 - 0.8 ) . When analysis was restricted to manuscripts that were successfully masked , review quality as assessed by editors and authors still did not differ . CONCLUSIONS Masking review ers to author identity as commonly practice d does not improve quality of review s. Since manuscripts of well-known authors are more difficult to mask , and those manuscripts may be more likely to benefit from masking , the inability to mask review ers to the identity of well-known authors may have contributed to the lack of effect BACKGROUND AND OBJECTIVE The statistical review of biomedical articles should result in an improved quality . The objective of this study was to compare the effects of clinical review and joint clinical and statistical review on manuscript quality , in articles su bmi tted to Medicina Clínica ( Barcelona ) , a Spanish weekly journal of internal medicine . METHOD Original papers arriving between May 2000 and February 2001 were r and omized either to a clinical review group or a clinical and statistical review group . Two evaluators , blinded to the paper 's group , assessed the quality improvement in both groups , from su bmi ssion to publication using a modified version ot the Goodman et al. scale . The protocol required that final versions arrived before the end of May 2001 . RESULTS Final sample size was 43 manuscripts , evaluated before and after peer review . On the intention to treat analysis , the estimated effect of statistical review was 1.35 ( 95 % CI : -0.45 to 3.16 ) positive , but not statistically significant . The analysis of the review ers ' comments revealed some protocol deviations . Taking into account the spontaneous inclusion of statistical experts in the clinical group , the estimated effect was statistically significant , with a confidence interval of 0.3 to 3.7 . CONCLUSION The inclusion of a statistical expert in the peer review process improves manuscript quality , although in the intention to treat analysis the improvement was not statistically significant As recently as 10 years ago we had almost no evidence on peer review , a process at the heart of science . Then a small group of editors and research ers began to urge that peer review could itself be examined using scientific methods . The result is a rapidly growing body of work , much of it presented at the third international congress on peer review held in Prague last week . The central message from the conference was that there is something rotten in the state of scientific publishing and that we need radical reform . The problem with peer review is that we have good evidence on its deficiencies and poor evidence on its benefits . We know that it is expensive , slow , prone to bias , open to abuse , possibly anti-innovatory , and unable to detect fraud . We also know that the published papers that emerge from the process are often grossly deficient . Research presented at the conference showed , for instance , that reports of r and omised controlled trials often fail to mention previous trials and do not place their work in the context of what has gone before ; that routine review s rarely have adequate methods and are hugely biased by specialty and geography in the references they quote ( p 766 ) ; and that systematic review s rarely define a primary outcome measure . Perhaps because scientific publishing without peer review seems unimaginable , Abstract Objectives : To examine the effect on peer review of asking review ers to have their identity revealed to the authors of the paper . Design : R and omised trial . Consecutive eligible papers were sent to two review ers who were r and omised to have their identity revealed to the authors or to remain anonymous . Editors and authors were blind to the intervention . Main outcome measures : The quality of the review s was independently rated by two editors and the corresponding author using a vali date d instrument . Additional outcomes were the time taken to complete the review and the recommendation regarding publication . A question naire survey was undertaken of the authors of a cohort of manuscripts su bmi tted for publication to find out their views on open peer review . Results : Two editors ' assessment s were obtained for 113out of 125manuscripts , and the corresponding author 's assessment was obtained for 105 . Review ers r and omised to be asked to be identified were 12 % ( 95 % confidence interval 0.2 % to 24 % ) more likely to decline to review than review ers r and omised to remain anonymous ( 35 % v 23 % ) . There was no significant difference in quality ( scored on a scale of 1to 5 ) between anonymous review ers ( 3.06(SD 0.72 ) ) and identified review ers ( 3.09(0.68 ) ) ( P=0.68 , 95 % confidence interval for difference −align = baseline>0.19 to 0.12 ) , and no significant difference in the recommendation regarding publication or time taken to review the paper . The editors ' quality score for review s ( 3.05(SD 0.70 ) ) was significantly higher than that of authors ( 2.90(0.87))(P<0.005 , 95%confidence interval for difference − align = baseline>0.26 to − align = baseline>0.03 ) . Most authors were in favour of open peer review . Conclusions : Asking review ers to consent to being identified to the author had no important effect on the quality of the review , the recommendation regarding publication , or the time taken to review , but it significantly increased the likelihood of review ers declining to review CONTEXT Better peer review is needed , but proven methods to improve quality are unknown . Our objective was to determine whether written feedback to review ers improves subsequent review s. METHODS Eligible review ers were r and omized to intervention or control ( receiving other review ers ' unscored review s and the editor 's decision letter ) . Study 1 ( September 1998-September 2000 ) included review ers with a median quality score of 3 or lower ; study 2 ( April 2000-January 2002 ) , review ers with median score of 4 or lower . Study 1 was design ed with a power of 0.80 to detect a difference in score of 1 ; study 2 , with a power of 0.80 to detect a difference of 0.5 . All review ers were at a peer- review ed journal ( Annals of Emergency Medicine ) . The main outcome measure was the editor 's routine quality rating ( 1 - 5 ) of all review s ( blinded to study enrollment ) . RESULTS For study 1 , 51 review ers were eligible and r and omized and 35 had sufficient data ( 182 review s ) for analysis . The mean individual review er rating change was 0.16 ( 95 % confidence interval [ CI ] , -0.26 to 0.58 ) for control and -0.13 ( -0.49 to 0.23 ) for intervention . For study 2 , 127 review ers were eligible and r and omized , and 95 had sufficient data ( 324 review s ) . Controls had a mean individual rating change of 0.12 ( 95 % CI , -0.20 to 0.26 ) and intervention review ers , 0.06 ( -0.19 to 0.31 ) . CONCLUSIONS In study 1 , minimal feedback from editors on review quality had no effect on subsequent performance of poor- quality review ers , and the trend was toward a negative effect . In study 2 , feedback to average review ers was more extensive and supportive but produced no improvement in review er performance . Simple written feedback to review ers seems to be an ineffective educational tool Peer review ers are blinded sometimes to authors ' and institutions ' names , but the effects of blinding on review quality are not known . We , therefore , conducted a r and omized trial of blinded peer review . Each of 127 consecutive manuscripts of original research that were su bmi tted to the Journal of General Internal Medicine were sent to two external review ers , one of whom was r and omly selected to receive a manuscript with the authors ' and institutions ' names removed . Review ers were asked , but not required , to sign their review s. Blinding was successful for 73 % of review ers . Quality of review s was higher for the blinded manuscripts ( 3.5 vs 3.1 on a 5-point scale ) . Forty-three percent of review ers signed their review s , and blinding did not affect the proportion who signed . There was no association between signing and quality . Our study shows that , in our setting , blinding improves the quality of review s and that research on the effects of peer review is possible Peer review is a cornerstone of scientific publication . However , it is time consuming for review ers and contributors , and must be balanced with editorial oversight for balance and bias . To test a more efficient method of review ing manuscripts , we performed a r and omized trial comparing traditional peer review for all manuscripts received by the Annals of Neurology with an early screening approach in which six editors rejected a manuscript without external review when the chance of acceptance was deemed very low . Of the 351 manuscripts entered into the trial , 88 were r and omized to traditional external review and 263 to early screening . Rates of final acceptance were similar in the two groups ( p = 0.41 ) . Final decisions were more delayed for traditional review ( mean 48 days versus 18 days with early screening ; p < 0.0001 ) and more review ers were required for each manuscript ( mean 2.3 versus 0.7 with early screening ; p < 0.0001 ) . Among accepted manuscripts , review er ratings of scientific and clinical impact were similar . We conclude that a method of early screening of manuscripts for appropriateness for publication results in substantial decreases in the time between manuscript su bmi ssion and publication decisions , and reduces the burden on review ers with minimal impact on the quality of accepted manuscripts . Editorial screening is now journal policy . Ann Neurol 2007;61:A10–A12 BACKGROUND The quality of peer review ing in developing countries is thought to be poor . To examine whether this was so , we compared the performance of Indian and non-Indian review ers who were sent original and review articles su bmi tted to The National Medical Journal of India . We also tested whether informing review ers that their comments would be exchanged improved the quality of their review s. METHODS In a prospect i ve , r and omized , blinded study , we sent 100 manuscripts to pairs of peer review ers ( Indian and non-Indian ) of which 78 pairs of completed replies were available for analysis . Thirty-eight pairs of review s were exchanged and 40 were not . The quality of the review s was assessed by two editors who were unaware of the review ers ' nationality and whether they had been told that their review s would be exchanged . The quality of the review s was scored out of 100 ( based on a pre design ed evaluation proforma ) . We also measured the time taken to return a manuscript . RESULTS Overall , non-Indian review ers scored higher than Indians ( mean scores non-Indians first , 56.7 v. 48.6 , p < 0.001 ) , especially those in the non-exchanged group ( 58.4 v. 47.3 , p < 0.001 ) but not the exchanged group ( 54.8 v. 50.0 , p < 0.06 ) . Being informed that review s would be exchanged did not affect the quality of review s by non-Indians ( 54.8 exchanged v. 58.4 non-exchanged ) or of review s by Indians ( 50.0 exchanged v. 47.3 non-exchanged ) . The editors ' assessment of the review ers matched well ( r = 0.59 , p < 0.001 ) . Non-Indians took the same amount of time as Indians to return their review s , although the postage time was at least eight days longer . CONCLUSIONS We found that non-Indian peer review ers were better than Indians and informing them that their views would be exchanged did not seem to affect the quality of their review s. We suggest that Indian editors should also use non-Indian review ers and start training programmes to improve the quality of peer review s in India STUDY OBJECTIVE We sought to determine whether peer review ers who attend a formal interactive training session produce better review s. METHODS Peer review ers were invited to attend a formal , 4-hour , highly interactive workshop on peer review . Attendees received a sample manuscript to read and review in writing in advance . The workshop included presentations on analyzing a study and the journal 's expectations for a quality review , discussion of the sample manuscript 's flaws and how to address them in a review , discussion of the review s written by the attendees , and discussion of real review s of other manuscripts illustrating key points . The performance of attendees on the basis of st and ard editor quality ratings ( 1 to 5 ) was assessed for the 2 years after workshop attendance . Control review ers matched for previous review quality and volume were selected from nonattendees of the workshop . In study 1 , all average review ers received a st and ard written invitation . In study 2 , 75 r and omly selected average review ers were personally and actively recruited with intensive follow-up by means of e-mail and telephone calls in an effort to reduce self- selection bias . RESULTS In study 1 , 25 review ers volunteered for the course , were eligible for study , attended , and were compared with 25 matched control review ers . Of attendees filling out evaluations , 19 % thought it somewhat and 81 % thought it very helpful . All thought it would improve their subsequent review s , and 85 % thought it would improve their review ratings . The mean change in rating after the workshop was 0.11 ( 95 % confidence interval [ CI ] -0.25 to 0.48 ) for control review ers and 0.10 ( 95 % CI -0.20 to 0.39 ) for attendees . In study 2 , of 75 review ers intensively recruited , only 12 ( 41 % ) of those who said they would attend did . All of the participants thought the workshop would improve their performance and ratings . Test scores at the end of the workshop improved in 73 % of participants compared with scores on pretests . The control review ers ' average rating changed by -0.10 ( 95 % CI -0.49 to 0.29 ) versus 0.06 ( 95 % CI -0.34 to 0.23 ) for attendees . CONCLUSION Among invited peer review ers , voluntary attendance at a highly structured and interactive workshop was low and did not improve the quality of subsequent review s , contrary to the predictions of attendees . Efforts to aggressively recruit average review ers to a second workshop were time consuming , had low success rates , and showed a similar lack of effect on ratings , despite improvement in scores on a test instrument . Workshop teaching formats , although traditional , are of unproven efficacy |
11,954 | 17,725,834 | Conclusion The significant association between CAS characteristics and effectiveness of reported outcomes for patients with Type II diabetes suggests that complexity science may provide an effective framework for design ing and implementing interventions that lead to improved patient outcomes | Background Despite the development of several models of care delivery for patients with chronic illness , consistent improvements in outcomes have not been achieved .
These inconsistent results may be less related to the content of the models themselves , but to their underlying conceptualization of clinical setting s as linear , predictable systems .
The science of complex adaptive systems ( CAS ) , suggests that clinical setting s are non-linear , and increasingly has been used as a framework for describing and underst and ing clinical systems .
The purpose of this study is to broaden the conceptualization by examining the relationship between interventions that leverage CAS characteristics in intervention design and implementation , and effectiveness of reported outcomes for patients with Type II diabetes . | BACKGROUND African Americans suffer disproportionately from diabetes complications , but little research has focused on how to improve diabetic control in this population . There are also few or no data on a combined primary care and community-based intervention approach . METHODS We r and omly assigned 186 urban African Americans with type 2 diabetes ( 76 % female , mean A SD age 59 A 9 years ) to 1 of 4 parallel arms : ( 1 ) usual care only ; ( 2 ) usual care + nurse case manager ( NCM ) ; ( 3 ) usual care + community health worker ( CHW ) ; ( 4 ) usual care + nurse case manager/community health worker team . Using the framework of the Precede-Proceed behavioral model , interventions included patient counseling regarding self-care practice s and physician reminders . RESULTS The 2-year follow-up visit was completed by 149 individuals ( 84 % ) . Compared to the Usual care group , the NCM group and the CHW group had modest declines in HbA(1c ) over 2 years ( 0.3 and 0.3 % , respectively ) , and the combined NCM/CHW group had a greater decline in HbA(1c ) ( 0.8 % . P = 0.137 ) . After adjustment for baseline differences and /or follow-up time , the combined NCM/CHW group showed improvements in triglycerides ( -35.5 mg/dl ; P = 0.041 ) and diastolic blood pressure , compared to the usual care group ( -5.6 mmHg ; P = 0.042 ) . CONCLUSIONS Combined NCM/CHW interventions may improve diabetic control in urban African Americans with type 2 diabetes . Although results were clinical ly important , they did not reach statistical significance . This approach deserves further attention as a means to reduce the excess risk of diabetic complications in African Americans The effect of pharmaceutical care on the prevention , detection , and resolution of medication-related problems in high-risk patients in a rural community was studied . Adult patients who received care at clinics in a medically underserved area of Alabama and who were identified as being at high risk of medication-related adverse events were r and omly assigned to a control group or an intervention group . The control group received st and ard medical care , and the intervention group received pharmaceutical care , including a medical record review , a medication history review , pharmacotherapeutic evaluation , and patient medication education and monitoring over a one-year period . A total of 69 patients completed the study ( 33 in the intervention group and 36 in the control group ) . The percentage of patients responding to hypertension , diabetes , dyslipidemia , and anticoagulation therapy increased significantly in the intervention group and declined in the control group . Ratings for inappropriate prescribing improved in all 10 domains evaluated in the intervention group but worsened in 5 domains in the control group . There were no significant differences between the groups at 12 months in health-related quality of life or medication misadventures . Medication compliance scores improved in the intervention group but not in the control group . Medication knowledge increased in the intervention group and decreased in the control group . Pharmaceutical care in a rural , community-based setting appeared to reduce inappropriate prescribing , enhance disease management , and improve medication compliance and knowledge without adversely affecting health-related quality of life A decision support system for the management of oral hypoglycaemic therapy in type II diabetes was evaluated . The ruleset contained therein forms the basis of a prototype computer programme , but in order to assess the robustness of the individual rules , it was decided it was necessary to use a paper-based form of the ruleset . A nurse with no previous experience of managing type II diabetes was trained to use the system and then undertook the exclusive management of half of all new type II diabetics , from a district population of 300,000 , over a 16-month period . General practice s within this area were divided into two groups , study and control , matching for size , geographical area and st and ards of existing diabetes care . Patients ( n = 102 ) from the study group practice s were then assigned to her care . Those patients ( n = 116 ) in the control group of practice s were treated according to their normal procedures . The decision support system for oral hypoglycaemic therapy was based on the following criteria : the current type of treatment ( six levels ) ; current glycaemic control ( HbA1 and FBS)-whether improving , steady or worsening ; and weight-%IBW , whether rising , steady or falling . Each of these parameters was carefully defined on the basis of established practice and clinical experience . Patients after initial education were seen at their usual clinic by the nurse only , on a monthly basis , until satisfactory glycaemic control was established and thereafter review ed 3 monthly . She was also responsible for ensuring the organisation of Diabetes Annual Review procedures . The medical records of the control group patients were examined at the end of the study and data on glycaemic control and Annual Review s extracted . In the study group 98 % patients achieved HbA1 levels within the normal range and all patients had full annual review s performed . The control practice s achieved much poorer degrees of metabolic control ( P < 0.01 ) and completed fewer annual review s. The study group did not demonstrate a significantly increased frequency of clinical hypoglycaemia consequent upon better blood sugar control . No exceptions to the ruleset , as initially defined , were detected . In conclusion , this decision support system was successful at achieving st and ards of diabetes control and care equal to or better than conventional structures of diabetes care . Implementation of such a system , on a simple computer platform , could greatly assist and possibly improve diabetes management in general practice PURPOSE This study was conducted to evaluate the impact of a provider problem-based learning ( PBL ) intervention on screening for complications of diabetes in community health centers . METHODS A successive sampling design was used to compare selected st and ards of diabetes care delivered preintervention with the care delivered postintervention at 2 community health centers and 1 comparison centers . Two r and omly assigned intervention sites received a PBL intervention focused on care guidelines for prevention of diabetes complications , with telephone follow-up over 12 months . Effects of the intervention were determined from an audit of 200 charts from each site . RESULTS The odds of having a glycosylated hemoglobin test more than doubled from preintervention to postintervention , and the odds of having a foot examination more than tripled across centers . Measurement of creatinine and glycosylated hemoglobin were associated ; the odds of having one test tripled when the other had been measured . Rates for documentation of patient education were significantly lower at the intervention site where free patient education booklets were distributed . CONCLUSIONS Improvements in diabetes care were not consistent among community health centers . Interventions involving system and policy changes may be more effective in implementing and sustaining improvements than just provider education STUDY OBJECTIVE : To study the clinical and cost outcomes of providing nutritional counselling to patients with one or more of the following conditions : overweight , hypertension and type 2 diabetes . DESIGN : The study was design ed as a r and om controlled trial . Consecutive patients were screened opportunistically for one or more of the above conditions and r and omly allocated to one of two intervention groups ( doctor/dietitian or dietitian ) or a control group . Both intervention groups received six counselling sessions over 12 months from a dietitian . However , in the doctor/dietitian group it was the doctor and not the dietitian who invited the patient to join the study and the same doctor also review ed progress at two of the six counselling sessions . SETTING : The study was conducted in a university group general practice set in a lower socioeconomic outer suburb of Perth , Western Australia . PATIENTS : Of the 273 patients r and omly allocated to a study group , 198 were women . Age ranged from 25 to 65 years . Seventy eight per cent of patients resided in the lower two socioecnomic quartiles , 56 per cent described their occupation as home duties and 78 per cent were partnered . RESULTS : Both intervention groups reduced weight and blood pressure compared with the control group . Patients in the doctor/dietitian group were more likely to complete the 12 month programme than those in the dietitian group . Patients in the doctor/dietitian group lost an average of 6.7 kg at a cost of $ A9.76 per kilogram , while the dietitian group lost 5.6 kg at a cost of $ A7.30 per kilogram . CONCLUSION : General practitioners , in conjunction with a dietitian , can produce significant weight and blood pressure improvement by health promotion methods Prerequisites for translating intervention research findings into practice are maintenance of results , generalization of effects and consistency of implementation . This report presents 12 months follow-up information on a r and omized 2x2 factorial trial evaluating the incremental effects of adding ( 1 ) telephone follow-up or ( 2 ) a community re sources utilization component to a basic touchscreen computer-assisted dietary goal - setting intervention for 320 type 2 diabetes patients . All conditions evidence d significant improvement from baseline to the 12 months follow-up across behavioral , biological and psychosocial measures . There were few consistent differences between conditions , but results were robust across interventionists and clinics . The telephone follow-up component appeared to enhance long-term results on some measures . When considered along with earlier results from a r and omized trial that included a control condition without goal setting , it is concluded that this basic goal - setting intervention can be consistently implemented by a variety of interventionists and produce lasting improvements BACKGROUND Despite clear evidence for the efficacy of lowering cholesterol levels , there is a deficiency in its real-world application . There is a need to explore alternative strategies to address this important public health problem . This study aim ed to determine the effect of a program of community pharmacist intervention on the process of cholesterol risk management in patients at high risk for cardiovascular events . METHODS A r and omized controlled trial conducted in 54 community pharmacies ( 1998 - 2000 ) included patients at high risk for cardiovascular events ( with atherosclerotic disease or diabetes mellitus with another risk factor ) . Patients r and omized to pharmacist intervention received education and a brochure on risk factors , point-of-care cholesterol measurement , referral to their physician , and regular follow-up for 16 weeks . Pharmacists faxed a simple form to the primary care physician identifying risk factors and any suggestions . Usual care patients received the same brochure and general advice only , with minimal follow-up . The primary end point was a composite of performance of a fasting cholesterol panel by the physician or addition or increase in dose of cholesterol-lowering medication . RESULTS The external monitoring committee recommended early study termination owing to benefit . Of the 675 patients enrolled , approximately 40 % were women , and the average age was 64 years . The primary end point was reached in 57 % of intervention patients vs 31 % in usual care ( odds ratio , 3.0 ; 95 % confidence interval , 2.2 - 4.1 ; P<.001 ) . CONCLUSIONS A community-based intervention program improved the process of cholesterol management in high-risk patients . This program demonstrates the value of community pharmacists working in collaboration with patients and physicians OBJECTIVE To evaluate the effectiveness of a managed care approach to health care delivery , group visits , in the management of uninsured or inadequately insured patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 120 patients with uncontrolled type 2 diabetes were r and omly assigned to receive their care in group visits or usual care for 6 months . After 6 months , concordance with 10 process-of-care indicators recommended by the American Diabetes Association ( ADA ) st and ards of care was evaluated through chart abstract ion . The 10 items evaluated were up-to- date HbA(1c ) levels and lipid profiles , urine for microalbumin , appropriate use of ACE inhibitor or angiotensin receptor blockers , use of lipid-lowering agents where indicated , daily aspirin use , annual foot examinations , annual referrals for retinal examinations , and immunizations against streptococcal pneumonia and influenza . RESULTS Patients who received care in group visits showed statistically significant improvement in concordance with these 10 process-of-care indicators ( P < 0.001 ) . Of the patients , 76 % who received care in group visits had at least 9 of these 10 items up to date , as compared with 23 % of control patients ; 86 % of patients in group visits had at least 8 of the 10 indicators compared with 47 % of control patients . CONCLUSIONS Group visits proved more effective in promoting concordance with ADA st and ards of care than usual care in the treatment of uninsured or inadequately insured patients with type 2 diabetes OBJECTIVE To evaluate the impact of primary care group visits ( chronic care clinics ) on the process and outcome of care for diabetic patients . RESEARCH DESIGN AND METHODS We evaluated the intervention in primary care practice s r and omized to intervention and control groups in a large-staff model health maintenance organization ( HMO ) . Patients included diabetic patients > or = 30 years of age in each participating primary care practice , selected at r and om from an automated diabetes registry . Primary care practice s were r and omized within clinics to either a chronic care clinic ( intervention ) group or a usual care ( control ) group . The intervention group conducted periodic one-half day chronic care clinics for groups of approximately 8 diabetic patients in their respective doctor 's practice . Chronic care clinics consisted of st and ardized assessment s ; visits with the primary care physician , nurse , and clinical pharmacist ; and a group education/peer support meeting . We collected self-report question naires from patients and data from administrative systems . The question naires were mailed , and telephoned interviews were conducted for nonrespondents , at baseline and at 12 and 24 months ; we queried the process of care received , the satisfaction with care , and the health status of each patient . Serum cholesterol and HbA1c levels and health care use and cost data was collected from HMO administrative systems . RESULTS In an intention-to-treat analysis at 24 months , the intervention group had received significantly more recommended preventive procedures and helpful patient education . Of five primary health status indicators examined , two ( SF-36 general health and bed disability days ) were significantly better in the intervention group . Compared with control patients , intervention patients had slightly more primary care visits , but significantly fewer specialty and emergency room visits . Among intervention participants , we found consistently positive associations between the number of chronic care clinics attended and a number of outcomes , including patient satisfaction and HbA1c levels . CONCLUSIONS Periodic primary care sessions organized to meet the complex needs of diabetic patients imrproved the process of diabetes care and were associated with better outcomes OBJECTIVE We evaluated automated telephone disease management ( ATDM ) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs ( VA ) clinics . We also compared the results with those of a prior ATDM trial conducted in a county health care system . RESEARCH DESIGN AND METHODS A total of 272 VA patients with diabetes using hypoglycemic medications were r and omized . During the 1-year study period , intervention patients received biweekly ATDM health assessment and self-care education calls , and a nurse educator followed up with patients based on their ATDM assessment reports . Telephone surveys were used to measure patients ' self-care , symptoms , and satisfaction with care . Outpatient service use was evaluated using electronic data bases and self-reports , and glycemic control was measured by HbA1c and serum glucose testing . RESULTS At 12 months , intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics . Intervention patients also were more likely than control patients to have had a cholesterol test . Among patients with baseline HbA1c levels > or = 8 % , mean end-point values were lower among intervention patients than control patients ( 8.7 vs. 9.2 % , respectively ; P = 0.04 ) . Among intervention and control patients with baseline values > or = 9 % , mean end-point values were 9.1 and 10.2 % , respectively ( P = 0.04 ) . At follow-up , intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care . CONCLUSIONS This intervention improved the quality of VA diabetes care . Intervention effects for most end points replicated findings from the prior county clinic trial , although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study 's enrollees Abstract OBJECTIVE : A previous study described the effect of a collaborative care intervention on improving adherence to antidepressant medications and depressive and functional outcomes of patients with persistent depressive symptoms 8 weeks after the primary care physician initiated treatment . This paper examined the 28-month effect of this intervention on adherence , depressive symptoms , functioning , and health care costs . DESIGN : R and omized trial of stepped collaborative care intervention versus usual care . SETTING : HMO in Seattle , Wash. PATIENTS : Patients with major depression were stratified into severe and moderate depression groups prior to r and omization . INTERVENTIONS : A multifaceted intervention targeting patient , physician , and process of care , using collaborative management by a psychiatrist and a primary care physician . MEASURES AND MAIN RESULTS : The collaborative care intervention was associated with continued improvement in depressive symptoms at 28 months in patients in the moderate-severity group ( F1,87=8.65 ; P=.004 ) , but not in patients in the high-severity group ( F1,51=0.02 ; P=.88 ) Improvements in the intervention group in antidepressant adherence were found to occur for the first 6 months ( χ2(1)=8.23 ; P<.01 ) and second 6-month period ( χ2(1)=5.98 ; P<.05 ) after r and omization in the high-severity group and for 6 months after r and omization in the moderate-severity group(χ2(1)=6.10 ; P<.05 ) . There were no significant differences in total ambulatory costs between intervention and control patients over the 28-month period ( F1,180=0.77 ; P=.40 ) . CONCLUSIONS : A collaborative care intervention was associated with sustained improvement in depressive outcomes without additional health care costs in approximately two thirds of primary care patients with persistent depressive symptoms OBJECTIVE To compare the effectiveness of a nurse-led hypertension clinic with conventional community care in general practice in the management of uncontrolled hypertension in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We studied 120 men and women outpatient attendees ( 61 % non-Caucasian ) with type 2 diabetes and a seated blood pressure ( BP ) > or=140/80 mmHg . All patients were being treated for hypertension , and 71 % had increased urinary albumin excretion ( UAE ) . Patients were allocated to either a nurse-led hypertension clinic or conventional primary care . The primary outcome measure was a change in systolic BP . Secondary outcome measures were total cholesterol , HDL cholesterol , total triglycerides , HbA(1c ) , UAE , serum creatinine , and changes in absolute stroke and coronary heart disease ( CHD ) risk scores . RESULTS The mean ( 95 % CI ) difference in the decrement of systolic BP was 12.6 mmHg ( 5.9 - 19.3 ) ( P = 0.000 ) in favor of the nurse-led group , whose patients were three times more likely to a reach target systolic BP < 140 mmHg compared with conventional care ( P = 0.003 ) . A significant fall in 10-year CHD ( P = 0.004 ) and stroke risk ( P = 0.000 ) scores occurred only in the nurse-led group . There were no significant differences in the reduction of diastolic BP or any of the other secondary outcome measures at 6 months . CONCLUSIONS Compared with conventional care , a nurse-led hypertension clinic is a more effective intervention for patients with type 2 diabetes and uncontrolled hypertension . A target systolic BP < 140 mmHg is more readily achieved and may be associated with significant reductions in 10-year cardiovascular disease risk scores BACKGROUND / OBJECTIVES Glycosylated hemoglobin ( HbA1C ) measurements in patients with diabetes mellitus contribute to glycemic control , and , therefore to lower diabetic complication rates . Determine if an intervention that includes cl aims -based feedback about patterns of HbA1C measurement results in more frequent monitoring of HbA1C in diabetic Medicare beneficiaries . SUBJECTS Primary care physicians in a single Southern state treating Medicare beneficiaries with diabetes mellitus . METHODS A group-r and omized evaluation of an intervention that included cl aims -based feedback about patterns of HbA1C measurement , educational material s , and practice aids . RESULTS Rates for each quality indicator increased from 1996 to 1998 for both the intervention and comparison groups , although increases were larger for intervention counties . HbA1C testing rates increased in intervention counties 16.8 % compared to 13.0 % in the comparison counties , an absolute difference of 4.0 % ( 95 % CI , 0.7 to 7.3 ) . Differences for other indicators were small , although positive and favoring the intervention , and lacked statistical significance . CONCLUSIONS Physician interventions that included practice -level feedback about monitoring of glycemic control successfully led to improved care of diabetic Medicare beneficiaries PURPOSE Clinical guidelines are design ed to assist in the management of specific diseases ; however , these guidelines are often neglected in the delivery of care . The purpose of this study was to determine whether clinician use of an clinical practice guideline would increase in response to having , at the patient visit , a decision support system based on a practice guideline that generates a customized management protocol for the individual patient using data from the patient 's electronic medical record . SUBJECTS AND METHODS In a 6-month controlled trial at a primary care clinic , 58 primary care clinicians were r and omized to receive either a special encounter form with the computer-generated guideline recommendations or a st and ard encounter form . The effect of computer-generated advice on clinician behavior was measured as rate of compliance with guideline recommendations . Data from 30 clinicians were analyzed ; data from 28 clinicians were excluded because these clinicians did not meet predefined criteria for minimum exposure to diabetic patient care . RESULTS Availability of patient management recommendations generated by the decision support system result ed in a two-fold increase in clinician compliance with care guidelines for diabetes mellitus ( P = 0.01 ) . Median compliance for the group receiving the recommendations was 32.0 % versus 15.6 % for the control group . CONCLUSION Decision support based on a clinical practice guideline is an effective tool for assisting clinicians in the management of diabetic patients . This decision support system provides a model for how a clinical practice guideline can be integrated into the care process by computer to assist clinicians in managing a specific disease through helping them comply with care st and ards . Use of decision support systems based on clinical practice guidelines could ultimately improve the quality of medical care BACKGROUND A new diabetes shared care service was introduced in North Dublin . It was design ed as a r and omized controlled trial with a complex intervention comprising education of participating practitioners , the introduction of a community-based diabetes nurse specialist , local agreement on clinical protocol s and structured communication across the primary - secondary care interface . OBJECTIVES Our aim was to assess the feasibility and effectiveness of a structured diabetes shared care service in a mixed health care system and to analyse the impact on total patient care . METHODS A Cluster r and omized controlled trial lasting 18 months was carried out in 183 patients with type 2 diabetes from 30 general practice s in North Dublin . Biophysical outcomes ( HbA1c , blood pressure , body mass index ) , psychosocial measures ( smoking status and Diabetes Clinic Treatment Satisfaction and Diabetes Well-being scores ) and process outcomes were collected . RESULTS There were significant improvements in diabetes care delivery and in psychosocial outcomes , but no significant improvements in biomedical outcomes . Process data collection revealed a significant increase in diabetes care-related activity for participating patients with an increase in structured annual review s and fewer patients defaulting from care . There were also significant improvements in information exchange between primary and secondary care . CONCLUSION Structured diabetes shared care , in a mixed health care system , can produce significant improvements in diabetes care delivery and in psychosocial outcomes for patients , with improved information exchange across the primary - secondary care interface Both physicians and diabetic persons must be educated about the need for regular ophthalmologic examinations to prevent blindness . A large population -based study of diabetic persons living in Southern Wisconsin ( Wisconsin Epidemiologic Study of Diabetic Retinopathy ) , design ed to evaluate the incidence and associated risk factors for diabetic retinopathy , provided the opportunity to evaluate an intervention to increase ophthalmologic care . As part of this study , a sample of persons less than 80 years of age with older onset diabetes of less than 15 years duration was identified and examined in both 1980 - 1982 and 1984 - 1986 ( n = 619 ) using st and ardized protocol s. Study subjects received educational material on diabetic eye disease , and examination findings were conveyed to each participant and their primary physician . To evaluate the effect of this intervention , a r and om representative sample of diabetic persons who were not selected for examination ( a nonintervention control group ) was identified and interviews were completed with 241 ( 80 % ) of the surviving subjects . The two study groups were similar with respect to demographic factors , employment status , medical history , and frequency of physician visits and hospitalizations , but not for income . Self- assessment s of general health were also identical between the selected and nonintervention groups . Overall , both groups reported very similar patterns of ophthalmologic care , visual impairment , and knowledge of retinopathy . These results suggest that a more intensive intervention is needed to improve the ophthalmologic care patterns of the diabetic population at risk of eye disease OBJECTIVE Accurate and reliable HbA1c results can be obtained at the time of the office visit by using benchtop analyzers . We tested the hypothesis that immediately available HbA1c results could improve glycemic control by changing physician or patient behavior or both . RESEARCH DESIGN AND METHODS A r and omized controlled trial was conducted in 201 type 1 and insulin-treated type 2 diabetic patients attending an academic diabetes center . HbA1c levels , changes in insulin therapy , and use of health care re sources were assessed during a 12-month follow-up period . RESULTS HbA1c levels decreased significantly at 6 and 12 months in the immediate assay group ( -0.57 + /- 1.44 and -0.40 + /- 1.65 % , respectively ; P < 0.01 ) but did not change in the control group ( -0.11 + /- 0.79 and -0.19 + /- 1.16 % , respectively ; NS ) . The changes were similar for both type 1 and type 2 diabetic patients . There were no differences in the rates of hypoglycemic events or use of health care re sources . CONCLUSIONS In the setting of a controlled r and omized trial , the immediate feedback of HbA1c results at the time of patient encounters result ed in a significant improvement of glycemic control at 6-month follow-up and persisted for the 12-month study . The introduction of this assay was positively received by both patients and physicians AIMS To evaluate the effectiveness of a multifaceted intervention to improve the clinical decision making of general practitioners ( GPs ) for patients with diabetes . To identify practice characteristics which predict success . METHODS Cluster r and omized controlled trial with 124 practice s and 185 GPs in The Netherl and s. The intervention group received feedback reports and support from a facilitator ; the control group received no special attention . Outcome measures were the compliance rates with evidence -based recommendations pertaining to discussion of body weight control , discussion of problems with medication , blood pressure measurement , foot examination , eye examination , initiating anti-diabetic medication or increasing the dosage in cases of uncontrolled blood glucose , and scheduling a follow-up appointment . RESULTS The GPs reported on their clinical decision making in 1410 consultations with Type 2 diabetic patients at baseline and 1449 consultations after the intervention period . The intervention result ed in statistically significant improvement for two of the seven outcome measures : foot examination ( odds ratio 1.68 ; 95 % confidence interval 1.19 - 2.39 ) and eye examination ( 1.52 ; 1.07 - 2.16 ) . Discussion of problems with medication showed a near significant trend towards increased benefit for the intervention group ( 1.52 ; 0.99 - 2.32 ) . Practice characteristics were not found to be related to the success of the intervention . CONCLUSIONS Feedback reports with support from facilitators appear to increase rates of foot examination and eye examination in general practice . Alternative interventions should be explored to improve the pursuit of metabolic control by GPs We set out to evaluate a clinical foot-screening programme in terms of primary outcomes ( reductions in the incidence of ulcers and lower limb amputation ) and process outcomes ( compliance with screening , the number of patients not completing the programme and the use of chiropody services and prescribed footwear and cost ) . All but 4 of 2001 patients attending a general diabetic out-patient clinic were allocated r and omly to index and control groups . The exceptions were patients who presented with active ulcers and were placed in the index group . Primary and secondary screening programmes identified 128 high risk patients in the index group and these were admitted to the foot protection programme . At 2-year follow-up , 11 fewer ulcers were reported from the index group . There were 7 amputations ( 1 major , 6 minor ) in the index group and 23 ( 12 major and 13 minor ) in the control group . The differences were not statistically significant for ulceration or minor amputations but significant for major amputations ( p < 0.01 ) . The total cost of the 2-year programme was pounds sterling 100,372 ( 1991 - 92 costs ) , with a mean cost per patient of approximately pounds sterling 100 . Taking pounds sterling 12,000 as a conservative estimate of the cost of a major amputation , the foot clinic was cost-effective in terms of amputations averted . The process outcomes were much less satisfactory . Cost-effectiveness could have been improved if it had been possible to improve patient compliance PURPOSE We sought to evaluate the effect of automated telephone assessment and self-care education calls with nurse follow-up on the management of diabetes . SUBJECTS AND METHODS We enrolled 280 English- or Spanish-speaking adults with diabetes who were using hypoglycemic medications and who were treated in a county health care system . Patients were r and omly assigned to usual care or to receive an intervention that consisted of usual care plus bi-weekly automated assessment and self-care education calls with telephone follow-up by a nurse educator . Outcomes measured at 12 months included survey-reported self-care , perceived glycemic control , and symptoms , as well as glycosylated hemoglobin ( Hb A1c ) and serum glucose levels . RESULTS We collected follow-up data for 89 % of enrollees ( 248 patients ) . Compared with usual care patients , intervention patients reported more frequent glucose monitoring , foot inspection , and weight monitoring , and fewer problems with medication adherence ( all P -0.03 ) . Follow-up Hb A , , levels were 0.3 % lower in the intervention group ( P = 0.1 ) , and about twice as many intervention patients had Hb A1c levels within the normal range ( P = 0.04 ) . Serum glucose levels were 41 mg/dL lower among intervention patients than usual care patients ( P = 0.002 ) . Intervention patients also reported better glycemic control ( P = 0.005 ) and fewer diabetic symptoms ( P < 0.0001 ) , including fewer symptoms of hyperglycemia and hypoglycemia . CONCLUSIONS Automated calls with telephone nurse follow-up may be an effective strategy for improving self-care behavior and glycemic control , and for decreasing symptoms among vulnerable patients with diabetes CONTEXT Although there has been enormous interest in continuous quality improvement ( CQI ) as a measure to improve health care , this enthusiasm is based largely on its apparent success in business rather than formal evaluations in health care . OBJECTIVE To determine whether a managed care organization can increase delivery of eight clinical preventive services by using CQI . DESIGN Primary care clinics were r and omly assigned to improve delivery of preventive services with CQI ( intervention group ) or to provide usual care ( control group ) . INTERVENTION Through leadership support , training , consulting , and networking , each intervention clinic was assisted to use CQI multidisciplinary teams to develop and implement systems for delivery of preventive services . SETTING 44 primary care clinics in greater Minneapolis-St . Paul . PATIENTS Patients 19 years of age and older completed surveys at baseline ( n = 6830 ) and at follow-up ( n = 6431 ) . Medical chart audits were completed on 4777 patients at baseline and 4546 patients at follow-up . MAIN OUTCOME MEASURES The proportion of patients who were up-to- date ( according to chart audit ) and the proportion of patients who were offered a service if not up-to- date ( according to patient report ) for 8 preventive services . RESULTS Compared with the control group , based on the proportion of patients who were up-to- date , use of only one preventive service -- pneumococcal vaccine -- increased significantly in the intervention group ( 17.2 % absolute increase from baseline to follow-up compared with a 0.3 % absolute increase in the control group , P = 0.003 ) . Similarly , based on patient report of being offered a service if not up-to- date , delivery of only one preventive service -- cholesterol testing -- significantly increased in the intervention group compared with the control group ( 4.6 % increase vs. 0.4 % absolute decrease in the control group ; P = 0.006 ) . CONCLUSION In this trial , CQI methods did not result in clinical ly important increases in preventive service delivery rates BACKGROUND Disease registries are powerful tools with the potential to transform the way chronic diseases are managed . To date , however , little work has been done to determine how to optimize the implementation of a chronic disease registry in practice . METHODS Twenty-nine physicians and their nurse teams in a large community internal medicine practice participated in this 6-month prospect i ve r and omized trial in 2000 . Teams were assigned to one of three implementation strategies using information from a diabetes registry . Process and outcome measures for diabetes management were analyzed . Process measures included the percentage of patients completing glycosylated hemoglobin ( Hgb ) testing within 6 months and low-density lipoprotein ( LDL ) testing within 12 months . Outcome measures included the percentage of patients with a glycosylated Hgb > 9.3 % ( equivalent to a HgbA1c > 8.0 % ) , the percentage of patients with an LDL cholesterol > 130 mg/dl , and the percentage of patients with controlled blood pressure , defined as < 130/85 millimeters of mercury . Mean change in LDL and glycosylated Hgb values was also measured . RESULTS Teams r and omized to an intervention strategy that included direct letters to patients showed significant improvement across a number of measures . The improvement was most apparent among patients without recent testing or with poorly controlled disease . The two interventions that did not include direct patient letters result ed in limited improvement . DISCUSSION Disease registries can be used to improve outcomes in the management of diabetes and other chronic diseases . Better outcomes were seen in patients who received letters based on registry-generated data . This strategy should be included as part of a comprehensive chronic disease management plan . Further refinements in the use of registries should result in further incremental improvement OBJECTIVE in an academic family practice clinic , we performed a controlled trial of a multifaceted intervention versus usual care for managing diabetes . Providers received didactic training and computerized compliance feedback to support staged diabetes management , an evidence d-based approach to diabetes care . RESEARCH DESIGN AND METHODS one firm of the clinic practice received the intervention , the other served as the control group during a 14-month baseline period and a 14-month study period . HbA1(c ) was the principal outcome measure . RESULTS there was a significant 0.71 % difference in change in HbA1(c ) values between the intervention and control firms ( P=0.02 ) . The subgroup with the greatest improvement in HbA1(c ) was those subjects who started the intervention with a HbA1(c ) above 8 % . The overall improvement in glycemic control could not be explained by differences in visit frequency or the aggressiveness of drug therapy . There were no changes in healthcare utilization or costs between the two firms . CONCLUSION in an academic family practice clinic , a multifaceted intervention in support of diabetes treatment guidelines modestly improved glycemic control without incurring additional costs . The improvement was mostly due to mitigation of the natural deterioration in control usually seen . Further efforts are required to involve all patients in co-managing their diabetes Introduction : Hypertension should be aggressively treated , especially in diabetic patients . But studies of physician prescribing habits reveal that physicians often delay making medication changes or initiating antihypertensive therapy . A chart‐based reminder was design ed to improve physician medication prescribing in this clinical situation . Methods : A r and omized controlled trial was conducted at the Veterans Affairs Medical Center in Richmond , Virginia . Patients with diabetes and hypertension were selected . A highly visible chart reminder was applied to the front of outpatient charts in the intervention group practice . A chart review was conducted to assess physician‐directed medication changes . A successful outcome was defined as any antihypertensive medication increase or addition at that same visit . Results : Physicians were more likely to intensify antihypertensive medication as the blood pressure increased regardless of the reminder . Overall , only 33 % of visits result ed in a medication change , even though 93 % of patients had elevations over target blood pressure at the follow‐up visit . Physicians in the intervention and control groups made changes to medication at similar rates ( χ2 = 0.621 , p = .511 ) . Discussion : In this study , a chart reminder failed to improve physician compliance with the clinical guideline for hypertension management in diabetics , Sixth Report of the Joint National Committee on the Detection , Evaluation , Prevention and Treatment of High Blood Pressure . To inform the design of effective intervention strategies , further research should explore specific barriers to guideline adherence in this clinical situation Given that 14 million Americans have diabetes [ 1 ] , the common complications of this disorder , such as foot ulcers and lower extremity amputations , are of major concern to the medical community . Approximately 20 % of all diabetic patients hospitalized in the United States are admitted because of foot complications [ 2 , 3 ] . Furthermore , about 50 % of all nontraumatic amputations in the United States are done in patients with diabetes [ 1 , 4 ] . This proportion equates to about 55 000 amputations a year [ 1 ] or 59.7 amputations for every 10 000 persons with diabetes [ 5 ] . Patients who undergo an amputation are at greater risk for a second similar procedure on either the same or the other leg [ 6 , 7 ] . Yet , it has been estimated that about one half of the amputations in patients with diabetes , or about one fourth of the total amputations done in the United States , are preventable [ 1 , 4 ] . Recently , the focus has been on preventive strategies that minimize foot damage in diabetic patients and thereby reduce the rates of ulcers and amputations . These preventive strategies are based on two observations : first , that simple efforts on the part of the health care provider or patient can reduce the likelihood of subsequent amputation due to diabetes-associated foot disease [ 8 ] ; and second , that many of these simple procedures are not being systematic ally applied by health care providers or patients [ 9 ] . For example , studies indicate that physicians infrequently examine the feet of patients with diabetes [ 9 , 10 ] . Also , most patients with diabetes do not engage in simple foot-care assessment s to identify lesions requiring early treatment [ 11 ] . Preventive strategies are not systematic ally applied for several reasons : First , patients may not be aware of foot-care procedures or how to do them , or they may not believe that such procedures can make a difference ; second , podiatry and orthopedics services that could assist in foot salvage in diabetic patients may not be available ; and , finally , the health care system may make it difficult for patients or health care providers to examine the feet of patients with diabetes [ 10 ] . Several uncontrolled studies found that implementation of improved foot-care programs can significantly reduce lower extremity complications in patients with diabetes ; these studies showed a 44 % to 85 % reduction in the rate of lower extremity amputations [ 4 , 12 - 14 ] . A recent casecontrol study also supports the implementation of preventive strategies , such as foot care , use of protective footwear , and aggressive treatment of foot infection by patients or health care providers , to decrease the risk for lower extremity amputation [ 15 ] . The intervention in our study was design ed to reduce the prevalence of risk factors for lower extremity amputations in patients with noninsulin-dependent diabetes and involved the three major elements of a prevention program : the patient , health care providers , and the health care system . Specifically , we did a r and omized , controlled trial to determine whether a comprehensive foot-care intervention could improve patients ' knowledge and performance of appropriate foot care ; increase the number of referrals to specialty clinics such as the podiatry clinic ; increase the frequency of foot examinations by health care providers and the documentation of risk factors in the medical record ; and improve short-term patient outcomes such as skin and nail conditions known to be risk factors for ulcers and amputations . Methods Setting Our study , the design of which is summarized in Figure 1 , was done from April 1989 to March 1991 in the academic general medicine practice of the Regenstrief Health Center in Indianapolis , Indiana [ 16 ] . The practice is subdivided into four primary care teams ( labeled A , B , C , and D ) , each with its own nursing and clerical staff . Each team sees patients for eight half-day sessions per week , with each session staffed by one or two faculty internists and two to four housestaff . Teams A and C were r and omly assigned to the intervention group ; teams B and D were assigned to the control group . Previous studies in which this method of r and omization was used have shown no baseline interteam differences in patient characteristics and physician practice behavior and no effect of the team on the study outcome [ 16 - 19 ] . Figure 1 . Summary of the study design . Patient Identification and Recruitment The computerized Regenstrief Medical Record System [ 20 ] was used to identify approximately 3000 patients with noninsulin-dependent diabetes , as well as the date and time of their next appointment . Only patients with noninsulin-dependent diabetes who were seen at least two times in the preceding year by the same provider were included in the study . Additional criteria for inclusion were as follows : an age greater than 40 years ; a diagnosis of diabetes after 30 years of age ; a diagnosis of diabetes based on National Diabetes Data Group criteria [ 21 ] or the presence of disease requiring medication for the control of hyperglycemia ; an intention to obtain care at the general medicine practice for the next 2 years ; and a body weight that was either ideal or heavier than ideal . Exclusion criteria included pregnancy ; major psychiatric illness , including dementia ; terminal illness likely to cause death within 1 year ; renal failure ( serum creatinine > 440 mol/L ) ; previous bilateral amputations above or below the knee ; or an inability to provide any self-care . Patients of investigators involved in the protocol were also excluded from the study . Of the 728 eligible patients , 244 refused to participate , 89 enrolled in the study but failed to keep their appointments for assessment , and 395 were assessed by trained nurse-clinicians . Of the 395 patients assessed , 352 ( 89 % ) completed the study ; 43 patients ( 11 % ) did not complete the study for the following reasons : death ( 11 patients ) ; change of residence ( 15 patients ) ; illness ( 6 patients ) ; transportation problems ( 3 patients ) ; and miscellaneous reasons ( 8 patients ) . Patient Assessment Sample s for determining fasting plasma glucose , cholesterol , triglyceride , high-density lipoprotein , hemoglobin A1C , and C-peptide levels were obtained from enrolled patients and immediately transported to a certified laboratory for analysis . Patients gave a history and had a physical examination at study entry and approximately 1 year later ( mean , 11.8 1.5 months ) . These examinations focused on risk factors for amputation and were administered by two trained nurse-clinicians who were blinded to the patients ' experimental conditions . Foot-related data derived from the history and physical examination included the patient 's self-reported foot-care behaviors ; the quality of the patient 's examination of his or her feet ; the severity of any foot lesions ; and the presence of musculoskeletal abnormalities , dermatologic conditions , peripheral vascular disease , and peripheral neuropathy ( the neuropathy assessment included quantitative measures of pressure and temperature sensation ) . Patients were question ed about their regular foot-care routine and were asked to show how they examined their feet . During this self-examination , nurse-clinicians observed whether patients ' scrutinized the toenails , the soles of the feet , and the area between toes . Musculoskeletal and dermatologic abnormalities were assessed using st and ard definitions of findings such as callus , hammer toe , and Charcot foot [ 3 , 22 ] . The nurse-clinicians palpated the dorsalis pedis , posterior tibial , and femoral pulses bilaterally in their assessment for peripheral vascular disease . If a pulse was absent at any one of the six sites palpated , the assessment was considered abnormal . Foot lesions were rated for severity using the Seattle Wound Classification System [ 23 ] , which ranges from a grade of 1.1 ( absence of lesions ) to a grade of 10 ( entire foot or leg is gangrenous ) . In our study , a foot lesion was defined as any wound , with or without functional interruption of the protective cutaneous barrier , ranging from a superficial scratch to an ulcer involving the epidermis . A serious foot lesion was defined by a severity grade of at least 1.3 , which indicates a minor , nonulcerated lesion with clinical evidence of healing sufficient to close previous interruption of the cutaneous barrier [ 23 ] or a blister . Pressure and temperature sensations were measured using the 5.07-log ( 0.1 mg)-force Semmes-Weinstein monofilament and the thermal sensitivity testing apparatus , according to st and ard techniques [ 24 - 26 ] . Thermal sensitivity was considered abnormal if the patient had a value greater than 2 st and ard deviations from the mean value for a group of healthy persons without diabetes ( warm > 2.04 C ; cool > 1.58 C ) . Practice Patterns of Health Care Providers Immediately after each scheduled visit , study patients had a structured interview [ 10 ] with a research assistant , who asked about foot self-examination and foot-care education given by health care providers ( the primary care physician or nursing personnel ) . In addition , a chart audit was conducted by a nurse-clinician who was blinded to the patients ' experimental condition . Information abstract ed from the medical record included the physician 's documentation of the findings from the history and physical examination ; any referral to podiatry , orthopedics , or vascular surgery clinics ; and diagnostic-test ordering related to the evaluation and treatment of diabetes-associated foot problems . Intervention The intervention cohort was exposed to several risk-reduction strategies . The nurse-clinicians conducted the patient education session with one to four patients , covering appropriate foot-care behaviors and footwear , using a commercially available slide and audiotape presentation [ 27 ] and pamphlets [ 28 ] . Behavioral contracts regarding desired foot-care behaviors were negotiated with each patient . Follow-up was done by telephone 2 weeks after the education sessions to remind patients This study was performed to investigate the effect of a telephone-delivered intervention on glycemic control and body mass index in Korean type 2 diabetic patients . 38 patients were r and omly selected , with 20 assigned to a telephone group and 18 to a control group . The goal of the intervention was to keep blood glucose concentrations close to the normal range . The intervention was applied to the telephone group for 12 weeks . It consisted of continuous education and reinforcement of diet , exercise and medication adjustment , as well as frequent self-monitoring of blood glucose levels . Telephone intervention was performed twice per week for the first month , and then weekly for the second and third months . Subjects were requested to write self- management logs , including blood glucose , diet and an exercise diary . The diet diaries were analyzed by a dietitian , and subjects instructed about the results by telephone counseling or mail . All medication adjustments were communicated to the subjects ' diabetes specialist . Glycosylated hemoglobin ( HbA1c ) , fasting blood glucose ( FBG ) and 2-hour postpr and ial glucose were measured before , and after , the intervention . Patients in the telephone group had a mean decrease of 1.2 % , with those in the control group having a mean increase of 0.6 % , in HbA1c . There were no significant differences in the body mass index ( BMI ) between the two groups . These findings indicated that a telephone-delivered intervention would improve HbA1c , but would not affect BMI PURPOSE To measure the quality of care for hypertensive and diabetic elderly Medicaid beneficiaries enrolled in managed care versus fee-for-service ( FFS ) plans . METHODS Individuals enrolled in the Medicaid Demonstration Project in Hennepin County , Minnesota , were r and omly assigned to receive their care either in one of seven managed care health plans in which the Medicaid payment for their care was capitated or in an FFS plan . Two hundred ninety-one hypertensives and 96 diabetics who were aged 65 years or over at the beginning of the evaluation were interviewed at baseline and followed for 1 year . Drug and nondrug therapy , monitoring , monthly medication costs , and access to medications were assessed . RESULTS The prepaid and FFS did not differ in drug or nondrug therapy , with the exception that slightly more FFS enrollees were on human insulin after 1 year . Mean monthly medication costs and access to medications were similar for both groups . CONCLUSIONS In this r and omized trial , we were unable to detect differences in the process of care for hypertensive and diabetic Medicaid enrollees OBJECTIVE To study differences in diabetes-related parameters in type 2 diabetic patients treated with the support of a Diabetes Service compared to conventional general practice care . DESIGN Parallel clinical trial with r and omisation at practice level . SETTING Fifteen general practice s. PATIENTS Type 2 diabetic patients , aged < 76 years , treated by a GP . MAIN OUTCOME MEASURES Level of glycated haemoglobin ( HbA1c ) . RESULTS 246 patients entered the study . Final mean HbA1c of all evaluable patients allocated to the intervention ( n = 84 ) was 7.1+/-1.2 % , vs 7.5+/-1.8 % in the controls ( n = 140 ) ( p = 0.06 ) . Patients who were initially poorly controlled ( Fasting Blood Glucose > 10 mmol/l ) had a significantly lower final HbA1c if they were in an intervention practice ( p=0.001 ) . Fewer patients in intervention practice s were referred to hospital specialists ( 1 vs 14 ) . CONCLUSIONS Support by the Dutch Diabetes Service did not significantly influence glycated haemoglobin . The subgroup of initially poorly controlled patients developed a significantly lower HbA1c in intervention practice s ( supported by a Diabetes Service ) than in control practice PURPOSE To assess the efficacy of a pharmacist-led , primary care-based , disease management program to improve cardiovascular risk factors and glycated hemoglobin ( A(1C ) ) levels in vulnerable patients with poorly controlled diabetes . METHODS A r and omized controlled trial of 217 patients with type 2 diabetes and poor glycemic control ( A(1C ) level > or=8.0 % ) was conducted at an academic general medicine practice from February 2001 to April 2003 . Intervention patients received intensive management from clinical pharmacists , as well as from a diabetes care coordinator who provided diabetes education , applied algorithms for managing glucose control and decreasing cardiovascular risk factors , and addressed barriers to care . Control patients received a one-time management session from a pharmacist followed by usual care from their primary care provider . Outcomes were recorded at baseline and at 6 and 12 months . Primary outcomes included blood pressure , A(1C ) level , cholesterol level , and aspirin use . Secondary outcomes included diabetes knowledge , satisfaction , use of clinical services , and adverse events . RESULTS For the 194 patients ( 89 % ) with 12-month data , the intervention group had significantly greater improvement than did the control group for systolic blood pressure ( -9 mm Hg ; 95 % confidence interval [ CI ] : -16 to -3 mm Hg ) and A(1C ) level ( -0.8 % ; 95 % CI : -1.7 % to 0 % ) . Change in total cholesterol level was not significant . At 12 months , aspirin use was 91 % in the intervention group versus 58 % among controls ( P < 0.0001 ) . Intervention patients had greater improvements in diabetes knowledge and satisfaction than did control patients . There were no significant differences in use of clinical services or adverse events . CONCLUSION Our comprehensive disease management program reduced cardiovascular risk factors and A(1C ) levels among vulnerable patients with type 2 diabetes and poor glycemic control OBJECTIVE To evaluate a system for improving diabetes care in remote Indigenous communities . DESIGN R and omised , unblinded cluster trial over one year ( 1 March to 29 February 2000 ) . PARTICIPANTS AND SETTING Primary healthcare staff in 21 primary healthcare centres in the Torres Strait and Northern Peninsula Area ( NPA ) Health Service District , north Queensl and , and 678 people with diabetes , mostly Torres Strait Isl and ers . INTERVENTION Diabetes recall system established at eight of the 21 sites , as well as staff training in basic diabetes care , regular phone calls from the project officer , a two-monthly newsletter and a mid-project workshop . MAIN OUTCOME MEASURES Regular checks of weight , blood pressure , eye and foot care , serum lipid levels and glucose monitoring and control , urinary albumin to creatinine ratio and serum creatinine levels , and administration of recommended vaccines ; hospitalisation in the previous 12 months . RESULTS There was improvement in most measures at most sites , except for blood pressure monitoring and control , and vaccination status . Intervention sites showed greater improvement in most indicators than control sites ( combined relative risk [ RR ] , 1.21 ; 95 % CI , 1.03 - 1.43 ) . The intervention group showed a 32 % reduction in hospital admissions for diabetes-related conditions over the study period ( P=0.012 ) . At follow-up , patients in intervention sites were 40 % less likely to be hospitalised for a diabetes-related condition than those in control sites ( RR , 0.60 ; 95 % CI , 0.41 - 0.86 ; P=0.007 ) . CONCLUSION A simple recall system , managed by local healthcare workers and supported by a diabetes outreach service , achieved significant improvements in diabetes care and reduced hospitalisations in a high-risk population BACKGROUND Type 2 diabetes mellitus is increasing in incidence and research has shown that normalization of blood glucose levels can moderate the risk of microvascular and neurological complications . AIM The purpose of this study was to investigate the effect of nurse telephone calls on glycosylated haemoglobin ( HbA1c ) levels and adherence to diabetes control recommendations . METHODS A r and omized design with control and experimental groups being assessed pre- and post intervention was used to assess the effectiveness of nurse telephone calls . Twenty patients were r and omly assigned to an intervention group and 16 to a control group . The goal of the intervention was to keep blood glucose concentrations close to the normal range ( HbA1c < 7 % ) . The intervention was applied to the intervention group for 12 weeks , and consisted of continued education and reinforcement of diet , exercise , medication adjustment recommendations , as well as frequent self-monitoring of blood glucose levels . Telephone intervention was performed twice per week for the first month and then weekly for the second and third month . Participants were requested to write self-management logs including blood glucose levels , diet and an exercise diary . A dietitian analysed the diet diaries and participants were informed about their results by telephone or mail . All medication adjustments were communicated to participants ' doctors . The HbA1c and diabetes adherence were measured before and after the intervention . RESULTS Patients in the intervention group had a mean decrease of 1.2 % in HbA1c levels and those in the control group had a mean increase of 0.6 % in HbA1c levels . The intervention group had greater diet and blood glucose testing adherence than the control group . CONCLUSION These findings indicate that a nurse telephone intervention can improve HbA1c , and diet and blood glucose testing adherence This project tested the importance of enhanced information transfer of home monitoring results to health care providers . The study tested whether computer-assisted communication of medical information between the chronic care patient and the physician can result in health care benefit . The information tools were constructed/adapted as a test of this hypothesis for diabetes mellitus . Patients connected a glucometer to an intelligent modem weekly for six to nine months . Graphical and mathematical tools extracted and emphasized the information content of the home monitoring data arriving at the central site . Data smoothing , trend analysis , and calculation of quality control statistics were incorporated into a graphical time series oriented report that was used by the health care provider during an outpatient visit . The integrated home monitoring system was tested on 20 patients with diabetes in a double cross-over design over a 15-month period . A significant improvement in serum glucose control as measured by glycated hemoglobin was shown in the study group , but not in the control group OBJECTIVES This study evaluated a multicomponent educational intervention to increase ophthalmic examination rates among African Americans with diabetes . METHODS A r and omized trial was conducted with 280 African Americans with diabetes , enrolled from outpatient departments of 5 medical centers in the New York City metropolitan area , who had not had a dilated retinal examination within 14 months of r and omization ( 65.7 % female , mean age = 54.7 years [ SD = 12.8 years ] ) . RESULTS After site differences were controlled , the odds ratio for receiving a retinal examination associated with the intervention was 4.3 ( 95 % confidence interval = 2.4 , 7.8 ) . The examination rate pooled across sites was 54.7 % in the intervention group and 27.3 % in the control group . CONCLUSIONS The intervention was associated with a rate of ophthalmic examination double the rate achieved with routine medical care |
11,955 | 24,060,218 | Conclusions Adjuvant IFN therapy may significantly reduce the recurrence rates of patients with viral hepatitis-related HCC and improve the survival of patients after surgical resection or TACE .
The ideal dose mostly selected is 3 MIU/ml , three times per week , which can make patients tolerate the adverse reactions of IFN better and maintain effective concentrations for a long time | Objective To evaluate the efficacy and safety of adjuvant IFN therapy for viral hepatitis-related hepatocellular carcinoma ( HCC ) after treatment with surgical resection or transarterial chemoembolization ( TACE ) . | Context Hepatocellular carcinoma often follows hepatitis C virus infection . Currently available treatments for hepatocellular carcinoma are unsatisfactory . Percutaneous ethanol injection therapy into tumor nodules shows some promise , but recurrence rates are high . Contribution In a carefully selected group of 74 patients with multicentric hepatocellular carcinoma , mild hepatitis C , and mild cirrhosis , patients r and omly assigned to receive interferon in addition to ethanol injections showed improved survival at 5 and 7 years , particularly among patients with a sustained virologic response . Caution s Combined treatment of multicentric hepatocellular carcinoma offers the possibility of enhanced survival for carefully selected patients ; this study is small , however , and enrolled only patients with low virus levels and mild cirrhosis . The Editors Chronic hepatitis C virus ( HCV ) infection is a common , frequently asymptomatic disease . Despite the clinical ly quiescent course of HCV infection , it may slowly progress to cirrhosis and , eventually , to hepatocellular carcinoma ( 1 , 2 ) . Cirrhosis is a major risk factor for the development of hepatocellular carcinoma ( 3 , 4 ) , and 70 % to 80 % of patients with hepatocellular carcinoma in Japan have HCV infection ( 5 ) . Current strategies for treating hepatocellular carcinoma include surgical resection , transarterial embolization , percutaneous ethanol injection therapy , radiofrequency wave ablation , and chemotherapy ( 6 - 9 ) . Recent studies have shown that percutaneous ethanol injection therapy is effective for hepatocellular carcinoma when the tumors are small ( <3 to 5 cm in diameter ) and limited in number ; survival rates are similar to those obtained with surgery ( 10 - 12 ) . Five-year survival rates , however , are poor ( 30 % to 60 % for both hepatectomy and percutaneous ethanol injection therapy ) . Poor prognosis may be the result of the high incidence of tumor recurrence ; the cumulative recurrence rate at 5 years is 60 % to 100 % ( 10 - 13 ) . Several studies have evaluated the factors that contribute to the recurrence of hepatocellular carcinoma ( 12 , 13 ) . Occasionally , early recurrence develops adjacent to the treated lesion ( local recurrence , 6 % to 33 % depending on tumor size ) ( 14 ) , but most tumors ( 80 % to 90 % ) recur at different sites ( 15 ) . Because hepatocellular carcinoma recurrence and decompensation of underlying liver disease are major problems after medical or surgical treatment , liver transplantation is another option for treating small , unresectable hepatocellular carcinomas in patients with cirrhosis . Studies report 5-year survival rates as high as 75 % with liver transplantation ( 16 - 18 ) . Interferon therapy has beneficial effects in chronic HCV infection ( 19 , 20 ) . In long-term follow-up studies , sustained virologic responders have remained in remission with normal liver function and improved histologic features of inflammation ; in some of these responders , fibrosis even regresses ( 21 , 22 ) . Recently , the frequency of hepatocellular carcinoma in patients receiving interferon therapy has substantially decreased , especially in patients with sustained virologic and biochemical responses ( 23 - 25 ) . This decreased frequency has occurred even in patients with cirrhosis ( 25 , 26 ) . Our study evaluated whether complete ablation of neoplastic nodules and administration of antiviral therapy could increase survival rates . Methods Study Design Our prospect i ve study was design ed by an eight-member committee in December 1992 . The Ethics Committee of the University of Tokyo approved the study . We obtained informed consent from each patient in accordance with the Helsinki declaration . Patients with compensated cirrhosis , three or fewer nodules of hepatocellular carcinoma , and low HCV RNA loads were recruited after complete ablation of the lesions . Eligibility Criteria Inclusion Criteria Hepatitis C virus infection was diagnosed on the basis of identification of anti-HCV antibody using the passive hemagglutination test ( Dinabbot , Tokyo , Japan ) or enzyme-linked immunosorbent assay ( ELISA ; Ortho Diagnostic Systems , Tokyo , Japan ) . Hepatitis C virus RNA was identified by reverse transcriptase polymerase chain reaction ( RT-PCR ) . The serum HCV RNA level was measured by competitive reverse transcriptase (CRT)-PCR according to the method of Kato and colleagues ( 27 ) ; HCV genotype was determined by the method of Okamoto and colleagues ( 28 ) . Hepatocellular carcinoma was suspected on the basis of several imaging methods , including abdominal ultrasonography , dynamic computed tomography ( CT ) , magnetic resonance imaging ( MRI ) , and arteriography . We confirmed the diagnosis by histologic examination of tumor biopsy specimens obtained from all patients . Evaluation was based on the criteria of the International Working Party ( 29 ) . In addition , we obtained and evaluated biopsy specimens from non-neoplastic lesions according to the methods of Desmet and colleagues ( 30 ) . Hepatocellular carcinoma was treated with percutaneous ethanol injection therapy ( 7 , 8 , 10 ) . Real-time linear-array scanners were used with 3.5-MHz transducers for the sonographic guidance of needles [ 21-gauge with a 15-cm or 20-cm needle ; Hanako , Tokyo , Japan ] into the tumors . Two to 10 mL of 99.5 % ethanol was injected into each lesion . Ethanol injection was repeated several times at different sessions . Complete destruction of the nodules was confirmed on dynamic CT 1 month after ethanol injection according to the following criteria : 1 ) The destructive area was larger than the area of the tumor nodule shown on pretreatment dynamic CT and 2 ) dynamic CT showed no early-phase contrast enhancement of nodules ( 7 , 8 , 10 ) . Inclusion criteria were as follows : 1 ) hepatocellular carcinoma with three or fewer lesions [ verified by histologic examination ] and dynamic CTconfirmed complete ablation of hepatocellular carcinoma lesions by percutaneous ethanol injection therapy , 2 ) detection of HCV RNA by RT-PCR and an HCV RNA load of 2 106 copies/mL or less by CRT-PCR ( the cutoff value was based on unpublished data indicating that interferon treatment was effective in patients with HCV RNA loads of 105 copies/50 L of serum by CRT-PCR [ 27 ] ] , 3 ) platelet count of 50 109 cells/L , 4 ) leukocyte count of 3 109 cells/L or greater , 5 ) compensated cirrhosis in ChildPugh stage A , 6 ) age younger than 70 years , 7 ) no previous treatment with interferon , and 8) su bmi ssion of informed consent . Exclusion Criteria Exclusion criteria were as follows : 1 ) liver diseases due to other causes , such as hepatitis B or primary biliary cirrhosis ; 2 ) HCV RNA load of 2 106 copies/mL or greater by CRT-PCR ; 3 ) severe comorbid diseases , such as heart disease , lung disease , or diabetes mellitus ; 4 ) decompensated cirrhosis in ChildPugh stage B or C ; and 5 ) failure to obtain informed consent . R and omization Patients who enrolled in the study were r and omly assigned in a 2:1 ratio to the interferon group or the control group by the controller . We assigned patients to the treatment group or control group by using a r and omization list . Interferon Therapy and Follow-up of Patients Interferon Therapy We started interferon therapy with natural interferon- ( Sumitomo Pharmaceuticals , Tokyo , Japan ) 2 to 3 months after tumor ablation was confirmed . Patients received 6 million U of interferon by intramuscular injection three times weekly for 48 weeks as out patients . If patients could not tolerate this dose , the interferon dose was reduced to 3 million U. If HCV RNA in serum was still detected by RT-PCR ( detection limit , 102 copies/mL ) after 24 weeks of interferon therapy and serum alanine aminotransferase ( ALT ) levels were higher than pretreatment ALT levels , therapy was discontinued . Criteria for Interferon Response We defined the efficacy of interferon therapy virologically and biochemically . Patients who were negative for HCV RNA ( as determined by RT-PCR ; detection limit , 102 copies/mL ) more than 6 months after the completion of interferon therapy were classified as showing a sustained virologic response . Patients with persistently normal ALT levels after the completion of interferon therapy were classified as showing a sustained biochemical response ; patients with abnormal ALT levels were classified as showing a nonsustained biochemical response . Follow-up Patients attended a monthly medical consultation at the University of Tokyo Hospital outpatient clinic . Blood biochemical measures , including -fetoprotein ( AFP ) tumor markers , were measured every 1 to 2 months ; ultrasonography was performed every 2 to 3 months ; and dynamic CT was performed every 6 months . Recurrence of hepatocellular carcinoma was detected by the finding of abnormal nodules with low or high echogenic appearance on abdominal ultrasonography or by the finding of abnormal density on dynamic CT . The diagnosis was confirmed histologically through ultrasonography-guided fine-needle biopsy of the tumor . Recurrent nodules were divided into two categories [ 14 , 15 ] : 1 ) local recurrence , in which the nodule appeared adjacent to the previously treated nodules , suggesting that residual tumor cells had not been completely ablated by percutaneous ethanol injection therapy , or 2 ) new foci developing at a distant site . New foci of hepatocellular carcinoma , as well as local recurrent nodules at tumor , node , metastasis ( TNM ) stage I , II , and III , were mainly treated by a second course of percutaneous ethanol injection therapy ; local recurrent nodules at TNM stage IV were treated with transarterial chemoembolization or chemotherapy . New development of hepatocellular carcinoma and survival of the patients ( tumor recurrence rate and survival rate ) were analyzed in relation to the time interval after initial treatment . Statistical Analysis When estimating the sample size , we assumed that 5-year survival in the control group would be 40 % according to the data of our previous unpublished study . We predicted that 5-year survival would be increased by 35 % as a result of Lamivudine is widely used to treat patients with hepatitis B. However , the outcomes in patients with hepatocellular carcinoma ( HCC ) treated with lamivudine have not been established . This study was conducted to evaluate the outcomes of lamivudine treatment for patients with HCC using an untreated , matched control group . Thirty patients with controlled HCC orally received lamivudine . As controls , 40 patients with HCC who were not treated with lamivudine and matched for clinical features were selected . The lamivudine-treated and untreated groups were compared with respect to changes in liver function , HCC recurrence , survival , and cause of death . In the lamivudine-treated group , there was significant improvement in the Child-Pugh score at 24 months after starting treatment , while no improvement was observed in the untreated group . There was no significant difference in the cumulative incidence of HCC recurrence and survival between the groups . However , there was a significant difference in the cumulative incidence of death due to liver failure ( P= 0.043 ) . A significant improvement in liver function was achieved by lamivudine treatment , even in patients with HCC . These results suggest that lamivudine treatment for patients with HCC may prevent death due to liver failure . Further prospect i ve r and omized studies using a larger number of patients are required BACKGROUND / AIMS Recurrence after resection of hepatocellular carcinoma ( HCC ) is a frequent event . This study evaluated the effect of postoperative interferon alpha ( IFN alpha ) treatment on recurrence and survival in patients with hepatitis B virus (HBV)-related HCC . METHOD Two hundred and thirty six patients were r and omized after resection into IFN alpha treatment ( 5 micro i.m . tiw for 18 months ) and control groups . Treatment was terminated if recurrence was diagnosed , and recurrence was managed the same way in both groups . Statistical analysis was based on the method of intent-to-treat . RESULTS The two groups were comparable in all clinicopathological parameters . The median overall survival was 63.8 months in the treatment group and 38.8 months in the control group ( P=0.0003 ) ; the median disease-free survival period was 31.2 versus 17.7 months ( P=0.142 ) . Fever , leucocytopenia , and thrombocytopenia were adverse effects in the treatment group , but were mostly manageable . CONCLUSIONS IFN alpha treatment improved the overall survival of patients with HBV-related HCC after curative resection , probably by postponing recurrence Because hepatocellular carcinoma often recurs after surgical resection or ethanol injection therapy , we conducted a prospect i ve r and omized controlled trial of interferon ( IFN ) in patients with chronic liver disease caused by hepatitis C virus ( HCV ) . Twenty eligible patients with cirrhosis were r and omized into two groups : 10 patients treated with 6 million units of natural IFN-beta twice a week for 36 months and 10 patients without IFN therapy . One patient within the treatment group discontinued interferon therapy after 19 months of treatment because of a mild degree of retinopathy . None of the patients in either group lost HCV-RNA until the end of the observation . Although 7 ( 70.0 % ) of 10 patients in the nontreatment group showed tumor recurrence , only 1 ( 10.0 % ) of 10 patients with IFN therapy developed tumor recurrence during a median observation period of 25.0 months . Cumulative recurrence rates of the treated and untreated groups were 0 % and 62.5 % at the end of the first year , and 0 % and 100 % at the second year , respectively ( log-rank test , P = .0004 ) . In conclusion , intermittent administration of IFN suppressed tumor recurrence after treatment with surgery or ethanol injection in patients with HCV-related chronic liver disease Objective : We conducted a r and omized controlled trial of adjuvant interferon therapy in patients with predominantly hepatitis B-related hepatocellular carcinoma ( HCC ) to investigate whether the prognosis after hepatic resection could be improved . Summary Background Data : Recurrence is common after hepatic resection for HCC . Interferon possesses antiviral , immunomodulatory , antiproliferative , and antiangiogenic effects and may be an effective form of adjuvant therapy . Patients and Methods : Since February 1999 , patients with no residual disease after hepatic resection for HCC were r and omly assigned with stratification by pTNM stage to receive no treatment ( control group ) , interferon alpha-2b 10 MIU/m2 ( IFN-I group ) or 30 MIU/m2 ( IFN-II group ) thrice weekly for 16 weeks . Enrollment to the IFN-II group was terminated from January 2000 because adverse effects result ed in treatment discontinuation in the first 6 patients . By June 2002 , 40 patients each had been enrolled into the control group and IFN-I group . The baseline clinical , laboratory , and tumor characteristics of both groups were comparable . Results : The 1- and 5-year survival rates were 85 % and 61 % , respectively , for the control group and 97 % and 79 % , respectively , for the IFN-I group ( P = 0.137 ) . After adjusting for the confounding prognostic factors in a Cox model , the relative risk of death for interferon treatment was 0.42 ( 95 % CI , 0.17–1.05 ; P = 0.063 ) . Exploratory subset analysis showed that adjuvant interferon had no survival benefit for pTNM stage I/II tumor ( 5-year survival 90 % in both groups ; P = 0.917 ) but prevented early recurrence and improved the 5-year survival of patients with stage III/IVA tumor from 24 % to 68 % ( P = 0.038 ) . Conclusion : In a group of patients with predominantly hepatitis B-related HCC , adjuvant interferon therapy showed a trend for survival benefit , primarily in those with pTNM stage III/IVA tumors . Further larger r and omized trials stratified for stage are needed OBJECTIVE The authors report on the surgical techniques and protocol for perioperative care that have yielded a zero hospital mortality rate in 110 consecutive patients undergoing hepatectomy for hepatocellular carcinoma ( HCC ) . The hepatectomy results are analyzed with the aim of further reducing the postoperative morbidity rate . SUMMARY BACKGROUND DATA In recent years , hepatectomy has been performed with a mortality rate of < 10 % in patients with HCC , but a zero hospital mortality rate in a large patient series has never been reported . At Queen Mary Hospital , Hong Kong , the surgical techniques and perioperative management in hepatectomy for HCC have evolved yearly into a final st and ardized protocol that reduced the hospital mortality rate from 28 % in 1989 to 0 % in 1996 and 1997 . METHODS Surgical techniques were design ed to reduce intraoperative blood loss , blood transfusion , and ischemic injury to the liver remnant in hepatectomy . Postoperative care was focused on preservation and promotion of liver function by providing adequate tissue oxygenation and immediate postoperative nutritional support that consisted of branched-chain amino acid-enriched solution , low-dose dextrose , medium-chain triglycerides , and phosphate . The pre- , intra- , and postoperative data were collected prospect ively and analyzed each year to assess the influence of the evolving surgical techniques and perioperative care on outcome . RESULTS Of 330 patients undergoing hepatectomy for HCC , underlying cirrhosis and chronic hepatitis were present in 161 ( 49 % ) and 108 ( 33 % ) patients , respectively . There were no significant changes in the patient characteristics throughout the 9-year period , but there were significant reductions in intraoperative blood loss and blood transfusion requirements . From 1994 to 1997 , the median blood transfusion requirement was 0 ml , and 64 % of the patients did not require a blood transfusion . The postoperative morbidity rate remained the same throughout the study period . Complications in the patients operated on during 1996 and 1997 were primarily wound infections ; the potentially fatal complications seen in the early years , such as subphrenic sepsis , biliary leakage , and hepatic coma , were absent . By univariate analysis , the volume of blood loss , volume of blood transfusions , and operation time were correlated positively with postoperative morbidity rates in 1996 and 1997 . Stepwise logistic regression analysis revealed that the operation time was the only parameter that correlated significantly with the postoperative morbidity rate . CONCLUSION With appropriate surgical techniques and perioperative management to preserve function of the liver remnant , hepatectomy for HCC can be performed without hospital deaths . To improve surgical outcome further , strategies to reduce the operation time are being investigated Hepatocellular carcinoma ( HCC ) recurrence after ablation therapy for primary tumors is common Background The role of antiviral therapy for patients in the immune-active phase of hepatitis B virus ( HBV ) infection who underwent partial hepatectomy for hepatocellular carcinoma ( HCC ) is unknown . Methods From January 2004 to June 2007 , a nonr and omized comparative study for postoperative antiviral treatment was conducted on patients who underwent curative hepatectomy for advanced HCC . Patients in the treatment group ( n = 43 ) received lamivudine with or without adefovir dipivoxil , while the control group ( n = 36 ) received no antiviral treatment . Results The treatment group had a significantly higher HBeAg seroconversion rate ( 57.2 % vs. 5.6 % ) and a higher HBV DNA suppression rate ( 87.2 % vs. 2.8 % ) after 12 months of antiviral treatment . The treatment group also had a significantly greater increase in residual liver volume per unit surface area following hepatectomy ( 78.0 ± 40.1 cm3/m2 vs. 35.8 ± 56.0 cm3/m2 ) at 6-month postoperation . After a median follow-up of 12 months , there was no significant difference in recurrence rate after surgery between the treatment group and the control group ( 76.7 % and 91.7 % ) . There was a significant difference in the overall survival rate but not in the disease-free survival rate . The 1- and 2-year overall survival rates were 41.9 % and 7.0 % , respectively , for the treatment group , and 33.3 % and 0 % , respectively , for the control group . The 1- and 2-year disease-free survival rates were 23.3 % and 2.3 % , respectively , for the treatment group , and 8.3 % and 0 % , respectively , for the control group . Conclusion Although nucleoside analogs did not reduce short-term recurrence rate , they promoted postoperative viral clearance and increased residual liver volume , which significantly enhanced tolerance to subsequent therapy for disease recurrence BACKGROUND AND AIMS The present study was carried out to test the hypothesis that interferon-alpha ( IFN-alpha ) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization ( TACE ) treatment of hepatitis B virus ( HBV ) related unresectable hepatocellular carcinoma ( HCC ) . METHODS 216 patients with unresectable HBV-related HCC were r and omized into a TACE group and a TACE-IFN group , each group had 108 patients . In the TACE-IFN group , patients received IFN-alpha1b at a dose of 3 million units ( mu ) three times a week by intramuscular injection one week after/before TACE treatment , for 48 weeks . RESULTS The median disease-free survival in the TACE-IFN treatment group was 23.6 months ( 95 % CI : 21.4 - 25.8 ) and 20.3 months ( 95 % CI : 15.8 - 24.8 ) in the TACE group ( P = 0.027 ) . The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group ( 39.8 % vs 59.3 % , P = 0.004 ) . The median overall survival was 29 months ( 95 % CI : 27.5 - 32.1 ) in the TACE-IFN group and 26 months ( 95 % CI : 20.1 - 31.9 ) in the TACE group ( P = 0.003 ) . The 2-year overall survival in the TACE-IFN group was higher than in the TACE group ( 72.2 % vs 52.8 % , P = 0.003 ) . CONCLUSIONS IFN-alpha treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC , with acceptable toxicities OBJECTIVE To investigate whether quantifiable changes in serum levels of hepatitis B e antigen ( HBeAg ) in response to 24 weeks of pegylated-interferon alfa-2a ( Peg-IFN-a 2a ) treatment are predictive of therapeutic efficacy at 48 weeks of treatment in HBeAg-positive chronic hepatitis B ( CHB ) patients and to investigate the efficacy of using an individualized antiviral treatment strategy . METHODS Ninety-six HBeAg-positive CHB patients with detectable HBeAg at week 24 of Peg-IFN-a 2a treatment were categorized according to the quantitative change in HBeAg ( vs. pre-treatment baseline ) : group A , HBeAg decline more than 2 log ; group B , HBeAg decline between 1 - 2 log ; group C , HBeAg decline less than 1 log , which was then r and omly divided into two sub-groups : C1 and C2 . Group A , B , and C1 patients continued the original therapy for an additional 24 weeks , while group C2 patients were supplemented with lamivudine ( 3TC + Peg-IFN-a 2a ) for the additional 24 weeks of treatment . All patients underwent liver biopsy at the end of treatment ( week 48 ) , and HBV covalently-closed circular (ccc)DNA was quantified as a measure of therapeutic efficacy . A , B , and C1 between-group multiple comparisons were made by the Nemenyi test ; C1 and C2 between-group comparison was made by the Mann-Whitney U test . The significance of between-group differences in decreased HBV cccDNA vs. HBeAg/anti-HBe seroconversion was made by the Chi-squared test . RESULTS At week 48 , the mean decrease of serum HBV cccDNA in each group was : A , 5.8 log10 copy/ml ; B , 3.8 log10 copy/ml ; C1 , 2.8 log10 copy/ml ; C2 , 5.7 log10 copy/ml . Statistically significant differences were observed for group A vs. B and C1 ( P less than 0.01 ) and C1 vs. C2 ( P less than 0.01 ) ; however , the difference between group B and C1 did not reach statistical significance ( P = 0.19 ) . The mean decrease of HBeAg in each group was : A , 2.7 log10 S/CO ; B , 1.9 log10 S/CO ; C1 , 0.9 log10 S/CO ; C2 , 1.6 log10 S/CO . Statistically significant differences were observed for group A vs. B and C1 ( P less than 0.01 ) and C1 vs. C2 ( P less than 0.01 ) . The rate of patients who achieved undetectable HBV DNA in each group was : A , 87.5 % ; B , 34.5 % ; C1 , 17.4 % ; C2 , 85.0 % . Statistically significant differences were observed for group A vs. B and C1 ( P less than 0.01 ) and C1 vs. C2 ( P less than 0.01 ) . The HBeAg seroconversion rates were : A , 75.0 % ; B , 24.1 % ; C1 , 13.0 % ; C2 , 25.0 % . Statistically significant differences were observed only for group A vs. B and C1 ( P less than 0.01 ) . Finally , group A achieved greater reduction in levels of cccDNA in liver tissues than B or C1 ( P less than 0.01 ) ; however , the differences between B and C1 and between C1 and C2 did not reach statistical significance . CONCLUSION CHB patients who showed an HBeAg decline of more than 2 log at week 24 of Peg-IFN-a 2a treatment had better treatment outcome at week 48 than those who showed HBeAg decline less than 2 log at week 24 . Augmenting the Peg-IFN-a 2a treatment with 3TC can improve the clinical response . A change of quantifiable HBeAg at week 24 of Peg-IFN-a 2a treatment may be a useful predictor of therapeutic efficacy of a 48-week antiviral regimen AIMS The aim of the present study was to examine the catalytic domains of the polymerase gene , the basal core promoter and the precore and core regions of the hepatitis B virus ( HBV ) genome for specific mutations . These may account for the response to interferon alpha ( IFN-alpha ) treatment , which may have prognostic value . METHODS Multiple serum sample s were collected prospect ively from 30 patients with chronic active hepatitis B who were treated with IFN-alpha . Patients were assigned to one of three groups : group A ( n = 11 ) and group B ( n = 10 ) individuals were hepatitis B e antigen (HBeAg)-positive prior to treatment . Group A patients underwent HBeAg seroconversion after treatment while group B patients did not . Group C ( n = 9 ) patients were HBeAg-negative prior to treatment . The HBV DNA was extracted from the sera collected before , during and after treatment and the various genomic regions were amplified , sequenced and examined for mutations . RESULTS During IFN-alpha therapy , multiple changes were found in the catalytic domains of the HBV polymerase gene in all groups . The frequency of mutations and associated amino acid changes were highest in virus from group C patients and lowest in group A patients . The interdomain regions of the viral polymerase were the most affected . Multiple mutations were also found in the precore , core and core promoter regions . However , no specific mutations were associated with clinical response or outcome . CONCLUSIONS During IFN-alpha treatment , multiple mutations occurred in the HBV genome , including the catalytic domains of the polymerase gene . Changes that did occur could not be correlated to the clinical response or treatment outcome . However , no mutations were found that have been linked to lamivudine escape , indicating that lamivudine therapy would be effective in IFN-alpha non-responder patients Tumor recurrence after resection of hepatocellular carcinoma ( HCC ) can occur early ( < 2 years ) or late ( > 2 years ) as metastases or de novo tumors . Interferon ( IFN ) has the potential for chemoprevention against hepatitis C virus (HCV)‐related cirrhosis . A predetermined group of 150 HCV RNA – positive patients undergoing resection of early‐ to intermediate‐stage HCC was stratified into 80 HCV‐pure ( hepatitis B anticore antibody [anti‐HBc]–negative ) and 70 mixed HCV+hepatitis B virus ( HBV ) ( anti‐HBc – positive ) groups , then r and omized to IFN‐α ( 3 million units 3 times every week for 48 weeks [ n = 76 ] ) versus control ( n = 74 ) . The primary end point was recurrence‐free survival ( RFS ) ; secondary end points were disease‐specific and overall survival . Intention‐to‐treat and subgroup analysis on adherent patients were conducted . Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis . No patient experienced life‐threatening adverse events . There were 28 adherent patients ( 37 % ) . After 45 months of median follow‐up , overall survival was 58.5 % , and no significant difference in RFS was detectable between the two study arms ( 24.3 % vs. 5.8 % ; P = .49 ) . HCC recurred in 100 patients ( 48 IFN‐treated , 52 controls ) , with a 50 % reduction in late recurrence rate in the treatment arm . HCC multiplicity and vascular invasion were significantly related to recurrence ( P = .01 and .0003 ) . After viral status stratification , while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences ( 72 events ) , there was a significant benefit on late recurrences ( 28 events ) in HCV‐pure patients adherent to treatment ( HR : 0.3 ; 95 % CI : 0.09–0.9 ; P = .04 ) . In conclusion , IFN does not affect overall prevention of HCC recurrence after resection , but it may reduce late recurrence in HCV‐pure patients receiving effective treatment . ( HEPATOLOGY 2006;44:1543–1554 . Interferon therapy seems to decrease the incidence of recurrence after resection of hepatitis C virus (HCV)‐related hepatocellular carcinoma ( HCC ) . Effects of postoperative interferon therapy on the survival rate after resection of such HCC are still unclear |
11,956 | 28,899,506 | The effects of green tea can not be attributed to a single constituent of the beverage .
This is exemplified in the finding that beneficial green tea effects on cognition are observed under the combined influence of both caffeine and l-theanine , whereas separate administration of either substance was found to have a lesser impact | BACKGROUND Green tea ( Camellia sinensis ) is a beverage consumed for thous and s of years .
Numerous cl aims about the benefits of its consumption were stated and investigated .
As green tea is experiencing a surge in popularity in Western culture and as millions of people all over the world drink it every day , it is relevant to underst and its effects on the human brain .
PURPOSE To assess the current state of knowledge in the literature regarding the effects of green tea or green tea extracts , l-theanine and epigallocatechin gallate both components of green tea-on general neuropsychology , on the sub-category cognition and on brain functions in humans . | L-Theanine is an amino acid found naturally in tea . Despite the common consumption of L-theanine , predominantly in combination with caffeine in the form of tea , only one study to date has examined the cognitive effects of this substance alone , and none have examined its effects when combined with caffeine . The present r and omised , placebo-controlled , double-blind , balanced crossover study investigated the acute cognitive and mood effects of L-theanine ( 250 mg ) , and caffeine ( 150 mg ) , in isolation and in combination . Salivary caffeine levels were co-monitored . L-Theanine increased ' headache ' ratings and decreased correct serial seven subtractions . Caffeine led to faster digit vigilance reaction time , improved Rapid Visual Information Processing ( RVIP ) accuracy and attenuated increases in self-reported ' mental fatigue ' . In addition to improving RVIP accuracy and ' mental fatigue ' ratings , the combination also led to faster simple reaction time , faster numeric working memory reaction time and improved sentence verification accuracy . ' Headache ' and ' tired ' ratings were reduced and ' alert ' ratings increased . There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time . These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state . The bulk of this research has focused on either L-theanine or caffeine ingested alone ( mostly the latter ) and has been limited to behavioral testing , subjective rating , or neurophysiological assessment s during resting . Here , we investigated the effects of both L-theanine and caffeine , ingested separately or together , on behavioral and electrophysiological indices of tonic ( background ) and phasic ( event-related ) visuospatial attentional deployment . Subjects underwent 4 d of testing , ingesting either placebo , 100 mg of L-theanine , 50 mg of caffeine , or these treatments combined . The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination . In addition to behavioral measures , we examined overall , tonic attentional focus as well as phasic , cue-dependent anticipatory attentional biasing , as indexed by scalp-recorded alpha-b and ( 8 - 14 Hz ) activity . We found an increase in hit rate and target discriminability ( d ' ) for the combined treatment relative to placebo , and an increase in d ' but not hit rate for caffeine alone , whereas no effects were detected for L-theanine alone . Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment , similar to previous findings at a larger dosage of L-theanine alone . This may signify a more generalized tonic deployment of attentional re sources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea OBJECTIVE L-theanine is a unique amino acid present almost exclusively in the tea plant . It possesses neuroprotective , mood-enhancing , and relaxation properties . This is a first study design ed to evaluate the efficacy and tolerability of L-theanine augmentation of antipsychotic treatment of patients with chronic schizophrenia and schizoaffective disorder . METHOD 60 patients with DSM-IV schizophrenia or schizoaffective disorder participated in an 8-week , double-blind , r and omized , placebo-controlled study . 400 mg/d of L-theanine was added to ongoing antipsychotic treatment from February 2006 until October 2008 . The outcome measures were the Positive and Negative Syndrome Scale ( PANSS ) , the Hamilton Anxiety Rating Scale ( HARS ) , the Cambridge Neuropsychological Test Automated Battery ( CANTAB ) for neurocognitive functioning , and additional measures of general functioning , side effects , and quality of life . RESULTS 40 patients completed the study protocol . Compared with placebo , L-theanine augmentation was associated with reduction of anxiety ( P = .015 ; measured by the HARS scale ) and positive ( P = .009 ) and general psychopathology ( P < .001 ) scores ( measured by the PANSS 3-dimensional model ) . According to the 5-dimension model of psychopathology , L-theanine produced significant reductions on PANSS positive ( P = .004 ) and activation factor ( P = .006 ) scores compared to placebo . The effect sizes ( Cohen d ) for these differences ranged from modest to moderate ( 0.09 - 0.39 ) . PANSS negative and CANTAB task scores , general functioning , side effect , and quality of life measures were not affected by L-theanine augmentation . L-theanine was found to be a safe and well-tolerated medication . CONCLUSIONS L-theanine augmentation of antipsychotic therapy can ameliorate positive , activation , and anxiety symptoms in schizophrenia and schizoaffective disorder patients . Further long-term studies of L-theanine are needed to substantiate the clinical ly significant benefits of L-theanine augmentation Tea ingredients L-theanine and caffeine have repeatedly been shown to deliver unique cognitive benefits when consumed in combination . The current r and omized , placebo-controlled , double-blind , cross-over study compared a combination of L-theanine ( 97 mg ) and caffeine ( 40 mg ) to a placebo on two attention tasks and a self-report question naire before , and 10 and 60 min after consumption . The combination of L-theanine and caffeine significantly improved attention on a switch task as compared to the placebo , while subjective alertness and intersensory attention were not improved significantly . The results support previous evidence that L-theanine and caffeine in combination can improve attention Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Objective : Ingestion of the nonproteinic amino acid theanine ( 5-N-ethylglutamine ) has been shown to increase oscillatory brain activity in the so-called alpha b and ( 8 - 14 Hz ) during resting electroencephalographic recordings in humans . Independently , alpha b and activity has been shown to be a key component in selective attentional processes . Here , we set out to assess whether theanine would cause modulation of anticipatory alpha activity during selective attentional deployments to stimuli in different sensory modalities , a paradigm in which robust alpha attention effects have previously been established . Methods : Electrophysiological data from 168 scalp electrode channels were recorded while participants performed a st and ard intersensory attentional cuing task . Results : As in previous studies , significantly greater alpha b and activity was measured over parieto-occipital scalp for attentional deployments to the auditory modality than to the visual modality . Theanine ingestion result ed in a substantial overall decrease in background alpha levels relative to placebo while subjects were actively performing this dem and ing attention task . Despite this decrease in background alpha activity , attention-related alpha effects were significantly greater for the theanine condition . Conclusion : This increase of attention-related anticipatory alpha over the right parieto-occipital scalp suggests that theanine may have a specific effect on the brain 's attention circuitry . We conclude that theanine has clear psychoactive properties , and that it represents a potentially interesting , naturally occurring compound for further study , as it relates to the brain 's attentional system OBJECTIVE The aim of this study was to investigate green tea flavan-3-ol catabolism and plasma pharmacokinetic and urinary excretion by high-performance liquid chromatography with t and em mass spectrometry to evaluate their absolute bioavailability by taking into account all known and some unknown catabolites deriving from their interaction with the gastrointestinal tract and its host microflora . METHODS A feeding study was carried out in 20 healthy human volunteers who ingested 400 mL of a ready-to-drink green tea containing approximately 400 μmol of flavan-3-ols . Urine and plasma were collected for 4 and 24h , respectively , and 39 relevant catabolites were identified in these biological fluids by t and em mass spectrometry . RESULTS In biological fluids , 39 relevant flavan-3-ol catabolites were identified . In plasma , (-)-epigallocatechin-3-gallate was the only unmetabolized compound and the highest in absolute concentration compared with (-)-epigallocatechin and (-)-epicatechin conjugates . Colonic microflora-derived polyhydroxyphenyl-γ-valerolactones were by far the main urinary catabolites , averaging 10 times greater concentratin than flavan-3-ol conjugates . The calculated bioavailability was equal to 39 % and it is interesting to notice the great variability in urinary excretion of colonic metabolites among participants , probably related to differences in their own colonic microflora . CONCLUSION This study demonstrates that green tea catechins are more bioavailable than previously observed when colonic ring fission metabolites are taken into consideration . Regular consumption of ready-to-drink green tea containing flavan-3-ols allows a non-marginal exposure of the human body to these catabolites , somehow justifying the numerous beneficial actions described as linked to green tea intake |
11,957 | 25,150,465 | This review up date found no evidence from r and omised trials to suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS .
The number of oocytes retrieved appeared similar for both monitoring protocol s. The data suggest that both these monitoring methods are safe and reliable . | BACKGROUND Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation ( IVF ) and intra-cytoplasmic sperm injection ( ICSI ) treatment has included transvaginal ultrasonography ( TVUS ) plus serum estradiol levels to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome ( OHSS ) whilst achieving the good ovarian response needed for assisted reproduction treatment .
The need for combined monitoring ( using TVUS and serum estradiol ) during ovarian stimulation in assisted reproduction is controversial .
It has been suggested that combined monitoring is time consuming , expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered .
OBJECTIVES To assess the effect of monitoring controlled ovarian hyperstimulation ( COH ) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration , with respect to rates of live birth , pregnancy and OHSS . | Abstract In a non-r and omized , comparative prospect i ve study ( 416 patients ) we compared the outcome of IVF/ICSI in two parallel control groups : one in which patients were followed up using combined monitoring ( ultrasound plus serum estradiol monitoring , the UHM group ) and one in which only ultrasound monitoring was used ( the UM group ) . This study has taken the number of mature oocytes at the moment of egg retrieval as its primary end variable . After adjustment for age , gravidity , antagonist protocol , AMH and infertility diagnosis , the average difference in number of mature oocytes between the UHM group and the UM group was −0.4 ( 95 % CI : −1.7 to 1.0 ) , which met our definition of clinical equivalence ( 95 % CI for the adjusted mean difference between −2 and 2 ) . Larger studies are still needed to evaluate the differences in the live birth rates per cycle and to further confirm that blood sampling definitively has no added value in monitoring ovarian stimulation for IVF/ICSI . Chinese abstract 我们在一项非随机、对照、前瞻性研究中（416例患者）比较了IVF/ICSI中两个平行对照组的结果：一组患者应用超声联合血雌二醇进行监测（ultrasound plus serum estradiol monitoring，UHM），一组患者仅应用超声监测（ultrasound monitoring，UM）。本研究以取卵时成熟卵母细胞的数量为主要研究终点。在对年龄、孕次、拮抗剂方案、AMH水平、不孕症诊断进行校正后，UHM组和UM组的成熟卵母细胞数量的平均差异是-0.4（(95 % CI ： -1.7- 1.0），这与临床等效的定义相符（调整后的平均差的95 % CI介于-2到2之间）。仍需要更大型的研究来评估周期活产率及进一步确定IVF/ICSI中采血检测对卵巢刺激监测的最终结果无附加价值 St and ard monitoring of controlled ovarian hyperstimulation ( COH ) includes hormone assays ( estradiol , LH , progesterone ) and regular pelvic ultrasound examination . We report a r and omized study on an attempt to simplify monitoring of COH . Ultrasound monitoring of the cycle alone did not affect pregnancy rates and did not increase the risks of OHSS . These results encourage the future simplification of stimulation protocol Objective : To evaluate if monitoring patients by ultrasound ( US ) only during in vitro fertilization ( IVF ) treatment is safe . Design : R and omized prospect i ve study . Intervention : Patients undergoing their first IVF treatment were r and omized into two groups . The ultrasound only group ( study group ) was monitored by US for follicle size and endometrial thickness without blood tests . In this group , only one blood test was taken before human chorionic gonadotropin ( hCG ) injection , to ensure a safe level of estradiol ( E2 ) regarding ovarian hyperstimulation syndrome ( OHSS ) risk . The control group was monitored by ultrasound plus serum estradiol and progesterone concentration at each visit . Main outcome measure : Clinical pregnancy rate . Results : No differences were found between the groups in the parameters of IVF treatment , induction days , number of ampoules , E2 level of hCG , as well as embryo quality . The clinical pregnancy rate was not statistically different between the groups , 57.5 % vs. 40.0 % , respectively ( p = 0.25 ) . No OHSS cases were found among the study or control groups . Conclusion : Ultrasound as a single monitoring tool for IVF cycles is reliable , safe , patient friendly , and reduces treatment expenses . In an era of cost effectiveness awareness , this regimen should be considered for routine management in IVF programs OBJECTIVE To determine if there is an optimum time for the administration of human chorionic gonadotropin ( hCG ) after pituitary desensitization with gonadotropin-releasing hormone agonists ( GnRH-a ) has been achieved before ovarian stimulation for in vitro fertilization ( IVF ) . DESIGN Prospect i ve r and omized study . PATIENTS Two hundred forty-seven patients undergoing an IVF treatment cycle who were r and omly divided into three groups . INTERVENTIONS All patients were administered subcutaneously buserelin acetate 500 micrograms/d from day 1 of the menstrual cycle . After pituitary desensitization had been achieved at least 14 days later , ovarian stimulation with human menopausal gonadotropin was commenced . Ovarian stimulation , cycle monitoring , oocyte recovery , and IVF and embryo transfer ( ET ) techniques were identical in all three groups . Patients in group 1 ( n = 79 ) had hCG administered when the mean diameter of the largest follicle had reached 18 mm , at least two other follicles were greater than 14 mm , and serum estradiol ( E2 ) levels were consistent with the number of follicles observed on ultrasound . Patients in groups 2 ( n = 84 ) and 3 ( n = 84 ) had hCG administered 1 day and 2 days , respectively , after the above criteria had been reached . RESULTS The mean day of hCG administration ( P less than 0.01 ) , maximum serum E2 concentration ( P = 0.06 ) , number of days of serum E2 rise ( P = 0.03 ) , and mean diameter of the largest follicle ( P less than 0.0001 ) were significantly different . There were , however , no significant differences in the mean number of preovulatory and medium size follicles , number of oocytes recovered or embryos transferred . There were also no significant differences in the oocyte recovery , fertilization and cleavage rates , in the number of embryos frozen , or in the pregnancy rates per initiated cycle and per ET . CONCLUSIONS There is no significant advantage in the precise timing of hCG administration after pituitary desensitization with GnRH-a OBJECTIVE To determine whether cycle monitoring using both serum E(2 ) and ultrasound findings yields superior clinical pregnancy rates during IVF-embryo transfer ( ET ) compared to monitoring with ultrasound alone . DESIGN Prospect i ve , r and omized , multicenter , patient-blinded study . SETTING Four assisted conception units in the United Kingdom . PATIENT(S ) Two hundred ninety-seven women believed to be normal responders undergoing IVF treatment . INTERVENTION(S ) Patients were r and omly allocated on day 7 of stimulation to one of the two hCG administration criteria : [ 1 ] the E(2)-to-follicle > or = 11 mm ratio was between 250 and 500 pmol/L/follicle and at least 2 follicles reached a mean diameter of 18 mm or [ 2 ] at least 2 follicles reached a mean diameter of 18 mm and the endometrium thickness was > or = 8 mm . MAIN OUTCOME MEASURE(S ) Duration and cumulative dose of recombinant human FSH , total number of growing follicles , oocytes retrieved , number and quality of embryos , pregnancy rates , and ovarian hyperstimulation syndrome ( OHSS ) rates . RESULT ( S ) Two hundred ninety-seven patients were r and omized to one of the two criteria groups . Of these , 288 ( 97 % ) received urinary (u)-hCG ( 143 in group A and 145 in group B ) . One hundred three women in group A ( 72 % ) met both criteria for hCG administration . Pregnancy and OHSS rates were similar ( 34.3 % vs. 31.4 % and 4.9 % vs. 4.1 % , respectively ) . CONCLUSION ( S ) The addition of E(2)/follicle criteria to ultrasound monitoring of IVF cycles in normal responders seldom changes the timing of hCG , and does not increase pregnancy rates or the risk of OHSS OBJECTIVE To evaluate the effect of a new automated technique of follicle measurement ( Sono automated volume calculation [ SonoAVC ] ) on the timing of oocyte maturation and subsequent oocyte retrieval . DESIGN Prospect i ve r and omized controlled trial . SETTING University-based Assisted Conception Unit . PATIENT(S ) Seventy-two women undergoing their first cycle of assisted reproduction treatment . INTERVENTION(S ) The timing of final follicle maturation and oocyte retrieval based on follicle tracking with use of either conventional two-dimensional ( 2D ) ultrasound or SonoAVC . MAIN OUTCOME MEASURE(S ) The number of mature oocytes retrieved and clinical pregnancy rate . RESULT ( S ) The number of the mature oocytes collected ( 10.70 + /- 6.08 vs. 11.43 + /- 6.17 ) , the number of fertilized oocytes ( 7.27 + /- 4.78 vs. 7.97 + /- 5.25 ) , and the clinical pregnancy rates ( 42 % vs. 43 % ) were similar with both 2D ultrasound and SonoAVC methods . CONCLUSION ( S ) Automated follicle tracking using SonoAVC identifies a comparable number of follicles to real-time 2D ultrasound in this preliminary study . Timing final follicle maturation and egg retrieval on the basis of these automated measures does not appear to improve the clinical outcome of assisted reproduction treatment OBJECTIVE To investigate the feasibility of IVF treatment with minimal monitoring during ovarian hyperstimulation . DESIGN Retrospective analysis and prospect i ve study with real-time control group . SETTING Transport IVF program with transport clinic and satellite clinics . PATIENTS One hundred consecutive IVF cycles monitored at a transport clinic and 100 concurrent consecutive cycles monitored at satellite clinics , using the same stimulation-monitoring protocol and result ing in oocyte aspiration , are compared retrospectively for the number of ultrasound ( US ) measurements carried out during monitoring and for results of IVF treatment . No patient selection took place . After introduction of a minimal monitoring protocol at a transport clinic , a prospect i ve study was started comparing 100 minimal monitoring cycles at a transport clinic with 100 concurrent conventional monitoring cycles at satellite clinics , all result ing in oocyte aspiration . Patients entered the retrospective or prospect i ve study only once . In all cases the same laboratory facility was used . Monitoring of ovarian hyperstimulation was done with US measurements only . Cycles were canceled for impending ovarian hyperstimulation syndrome ( OHSS ) when > 35 follicles were seen to develop during hyperstimulation . RESULTS Retrospective analysis shows no difference for the average number of US measurements at transport and satellite clinics ( 2.8 + /- 0.9 and 3.0 + /- 1.0 ; mean + /- SD ) . No differences were found in the number of ongoing pregnancies obtained in the two groups : 22 and 18 , respectively . One case of severe OHSS occurred in the satellite clinic group . Introduction of minimal monitoring at the transport clinic gives a significant reduction of the average number of US measurements at the transport clinic compared with satellite clinics , where conventional monitoring continued to be used ( 1.5 + /- 0.8 versus 2.8 + /- 0.9 ) . Ongoing pregnancies at transport and satellite clinics numbered 33 and 26 , respectively . In both groups one patient developed severe OHSS . Sixty-two percent of cycles at the transport clinic were monitored with one US measurement only . No cancellations for impending OHSS occurred during the study period . CONCLUSION A large group of patients need only one US measurement during monitoring of ovarian hyperstimulation . Minimal monitoring gives a useful further simplification of the clinical phase of IVF treatment , without adverse effects on treatment outcome and incidence of OHSS OBJECTIVE To assess prospect ively the appropriateness of follicular sonography alone for monitoring ovarian stimulation and to compare it to ovarian monitoring with both follicular sonography and hormone level determinations . STUDY DESIGN Prospect i ve , blind , clinical study in which the investigator made cycle management decisions based on follicular sonography only . RESULTS Follicular sonography alone predicted 88 % of the decisions made by the combination of follicular sonography , luteinizing hormone ( LH ) , estradiol ( E2 ) and progesterone measurements . Follicular sonography was unable to predict abnormal E2 patterns in eight ( 8 % ) of the patients ' scans . Follicular sonography did not detect three ( 3 % ) patients with a premature LH surge . CONCLUSION Follicular sonograms alone performed during ovarian stimulation predicted 88 % of cycle decisions . One could argue that hormone measurements could be either reduced or eliminated during ovarian stimulation for assisted reproductive technology and that follicular sonography only would be a cost-effective compromise . The effect of such simplified monitoring on pregnancy rates would require further prospect i ve evaluation A total of 114 patients admitted to an in-vitro fertilization-embryo transfer programme for the first time , were r and omly assigned to the study group or controls . Gonadotrophin-releasing hormone analogue ( GnRHa ) and human menopausal gonadotrophin ( HMG ) were used for ovulation induction . The study patients were followed up merely by ultrasonography and the controls by ultrasonography and serum determinations of oestradiol , progesterone and luteinizing hormone ( LH ) . There was no significant difference in the duration and total amount of HMG used for ovulation induction ( 10.9 versus 11.5 days and 34.8 versus 37.9 ampoules , respectively ) . The number of oocytes retrieved ( 11.7 versus 13.4 ) and the numbers of embryos replaced ( 2.6 versus 2.8 ) and cryopreserved ( 1.9 versus 3.3 ) were also similar . Pregnancy rates were similar . Pregnancy rate per ovum retrieval was 22.2 versus 25 % and per embryo transfer 27.2 versus 26.5 % . Oestradiol patterns were also similar . The rate and severity of ovarian hyperstimulation syndrome were virtually identical . We conclude that ' ultrasound-only ' monitoring of ovulation induction in IVF cycles treated by GnRHa-HMG in the long protocol is as effective and safe as the conventional ultrasound and hormone determination , but far simpler , swifter and more cost-effective |
11,958 | 22,895,930 | Some measures of speech monotoni city and articulation were investigated ; however , all these results were non-significant .
Although improvements in speech impairments were noted in these studies , due to the small number of patients examined , method ological flaws , and the possibility of publication bias , there is insufficient evidence to conclusively support or refute the efficacy of SLT for speech problems in Parkinson 's disease . | BACKGROUND Parkinson 's disease patients commonly suffer from speech and vocal problems including dysarthric speech , reduced loudness and loss of articulation .
These symptoms increase in frequency and intensity with progression of the disease ) .
Speech and language therapy ( SLT ) aims to improve the intelligibility of speech with behavioural treatment techniques or instrumental aids .
OBJECTIVES To compare the efficacy of speech and language therapy versus placebo or no intervention for speech and voice problems in patients with Parkinson 's disease . | BACKGROUND Several previous studies have examined the health of carers , but they have usually focused on elderly subjects and have often not had representative control sample s. AIM To determine whether caring for a partner with Parkinson 's disease is associated with a worsening social , psychological and physical well-being than people with partners who do not suffer with Parkinson 's disease . METHOD One hundred and fifty-four carer spouses of subjects with Parkinson 's disease , and 124 non-carer spouses of r and omly selected population controls recruited from a national case-control study of early-onset Parkinson 's disease in the Republic of Irel and , between 1992 - 1994 , were studied . Outcome was measured along three dimensions : social functioning , assessed by the frequency of social contacts , outings and holidays ; psychological well-being , measured by the General Health Question naire ; and physical health , measured by the career 's use of medical services , medications and episodes of chronic illness . RESULTS Carer spouses were less likely to get out of the house once a week at least ( odds ratio 1.79 , 95 % confidence intervals 1.00 - 3.20 ) or to have had a holiday in the last year ( odds ratio 1.71 , 95 % confidence intervals 1.01 - 2.90 ) . Contact with friends and neighbours decreased with increasing care provision . For spouses providing a lot of care , there was an almost fivefold increase in psychiatric morbidity ( odds ratio 4.86 , 95 % confidence intervals 1.5 - 15.9 ) after adjusting for other variables . Most of the medical outcomes were less favourable among carers , but only the use of tranquilizers ( odds ratio 3.73 , 95 % confidence intervals 1.18 - 11.8 ) and episodes of chronic illness ( odds ratio 2.96 , 95 % confidence intervals 1.27 - 6.94 ) were significant . CONCLUSIONS Overall , career spouses have slightly worse social , psychological and physical profiles . For social outcomes , increasing care provision is associated with fewer contacts , outings and holidays . For psychological and physical measures , carers providing a lot of care experience worse health . These results have implication s for targeting appropriate interventions The aim of this study was to evaluate the effects of orofacial physiotherapeutic treatment ( OPT ) on the facial mobility of Parkinson 's disease ( PD ) sufferers . Sixteen participants with PD were allocated r and omly to either the Treatment group or the Control group . A short interview between the physiotherapist and each subject was videotaped , and 10 r and om frames of the videotape were selected to be used in the facial expression assessment . The quantification of facial expressions was achieved by using an objective microcomputer-based measurement system , based on a mathematical model of the face ( FACEM ) . A facial outline is obtained , as well as 12 facial measures , which represent distances between key facial l and marks . The facial assessment was performed on 3 separate occasions , that is , baseline ( pretreatment ) , posttreatment , and follow-up ( 4 weeks later ) . A repeated measures analysis of variance ( MANOVA ) revealed a significant main effect of Time and a significant interaction effect between Time and Group for the Mouth-Opening Measure , suggesting that after treatment , members of the Treatment group opened their mouths to a greater degree than members of the Control group . Within the Treatment group , significant differences between pretreatment and posttreatment scores ( MANOVA ) were found for Mouth-Opening Measure and Mid-Top-Lip Measure . Similarly , Mouth-Opening Measure , Mid-Top-Lip Measure , Lower-Lip Thickness Measure , Top Eyelid/Iris Intersect Measure and Lower Eyelid/Iris Intersect Measure were significant across time from baseline to follow-up in the Treatment group only . No significant differences were found on any of the facial measures during the same period for members of the Control group . These findings suggest that OPT can improve facial movement and that this benefit extends in time , beyond the period of OPT itself . Such an increase in facial mobility can be expected to modify the " Parkinsonian facies " and facilitate the display of facial expressions Respiratory symptoms are recognized as sequelae of motor dysfunction in idiopathic Parkinson 's disease ( IPD ) and these symptoms have the potential to cause problems with swallow , cough , voice and speech . Specifically , maneuvers that require rapid activation and coordination of upper airway and chest wall musculature become progressively impaired as motor dysfunction progresses during the natural course of the disease . This study reports on the maximum inspiratory and expiratory pressures produced by 28 participants ( average age 64 ) diagnosed with moderate to severe IPD ( average stage 2.5 with a range of 2.0 - 3.0 ) . All measures were collected during the " medication on " state . Outcomes of a specific respiratory muscle strength training technique for improving maximum expiratory pressure are reported for three of the patients in this study . Techniques that focus on strengthening the respiratory muscles in patients with IPD ( other than with low load breathing exercises ) , have not been previously reported . The results of this pilot study demonstrate that respiratory muscle weakness may be an important factor in the respiratory complications in IPD and that respiratory muscle strength training has the potential to improve expiratory muscle strength for this population . This improvement has the potential to positively impact high forced respiratory activities , such as forced breathing maneuvers , swallow , cough and speech functions that require greater magnitude and duration of expiration We studied the effect of clonazepam in a double-blind trial on 12 parkinsonian patients with hypokinetic dysarthria . Speech sample s were judged on 14 of the dimensions used in the Mayo Clinic dysarthria study . Of the 11 patients who completed the study , 10 showed improvement . The effective dosage of clonazepam was 0 . 25 to 0 . 5 mg/d with higher dosage than that less effective . Clonazepam has a definite role in the management of perkinsonian dysarthria A study was set up to judge the efficacy and long term effects of intensive speech therapy in patients with Parkinson 's Disease . A total of 22 patients entered the study but only 18 completed it . Twelve patients were r and omly allocated to a treatment group and participated in a two week intensive speech therapy programme . Ten patients were r and omly allocated to a control group and received no therapy . Six of the control group and all twelve of the treatment group patients were available for follow-up assessment s . It is concluded that a course of intensive speech therapy is of value to patients with speech and voice problems arising out of their Parkinson 's Disease and that the effects of speech therapy can be maintained for up to a period of three months at least |
11,959 | 11,687,021 | REVIEW ER 'S CONCLUSIONS No studied intervention has been shown to eliminate the need to treat maternal hypotension during spinal anaesthesia for caesarean section .
We are unable to draw any conclusions regarding adverse effects of the studied interventions , due to their probable low incidence and the small number of women studied . | BACKGROUND Maternal hypotension is the most frequent complication of a spinal anaesthetic for caesarean section with an incidence approaching 100 % .
Most workers define hypotension as a maternal systolic blood pressure below 70 - 80 % of baseline recordings and /or an absolute value of < 90 -100mmHg .
The frequent occurrence and rapid onset of hypotension during spinal anaesthesia has encouraged anaesthetists to try and prevent or minimise the associated maternal symptoms of nausea and vomiting during the establishment of the block .
Untreated , severe hypotension can also pose serious risks to both mother ( unconsciousness , pulmonary aspiration , apnoea or even cardiac arrest ) and baby ( impaired placental perfusion leading to hypoxia , fetal acidosis and neurological injury ) .
A range of strategies is currently used to prevent or minimise hypotension but there is no established ideal technique .
OBJECTIVES To assess the relative efficacy and side effects of prophylactic interventions for hypotension following spinal anaesthesia for caesarean section . | Ninety‐seven parturients undergoing elective Caesarean section were allocated r and omly to have their legs elevated to approximately 30 ° on pillows or elevated and wrapped with elasticated Esmarch b and ages or neither ( controls ) following spinal anaesthesia . All patients received intravenous crystalloid ( 20 ml.kg−1 over 20 min ) prior to spinal injection and were placed in the left lateral tilt position . Significant hypotension was treated with intravenous ephedrine in 5 mg bolus doses . Leg wrapping result ed in a significant reduction in the incidence ofpostspinal hypotension in comparison to the control group ( 18 % compared to 53 % , p = 0.004 ) . This represents a five‐fold reduction in the likelihood ofpostspinal hypotension ( odds ratio 5.3 , 95 % CI 1.7–16.3 ) . Leg elevation alone did not significantly reduce the incidence of hypotension ( 39 % ) . There was no significant difference in the time of onset of hypotension between the groups . For those patients requiring ephedrine , there was no significant difference in mean dose requirements between the groups . The use of leg compression immediately postspinal provides a simple means of reducing the accompanying hypotension and should be used more widely Seventy-eight pregnant women at term , scheduled for elective cesarean section , were enrolled in this multicenter trial to compare the analgesic efficacy and side effect profile of a spinal block with hyperbaric bupivacaine alone ( Group B ) or combined with 75 [ micro sign]g of clonidine ( Group BC ) or with clonidine 75 [ micro sign]g and fentanyl 12.5 [ micro sign]g ( Group BCF ) . Intraoperatively , clonidine increased the spread of the sensory block and decreased pain ( pain scores 23 + /- 7 mm vs 17 + /- 6 and 2 + /- 1 mm for Group B versus Groups BC and BCF ; P < 0.05 ) and analgesic supplementation . This improved analgesia was best with the clonidine-fentanyl combination ( Group BC versus Group BCF ; P < 0.05 ) . Postoperative analgesia was prolonged only in Group BCF ( 215 + /- 79 min vs 137 + /- 35 and 183 + /- 80 min for Group BCF versus Groups B and BC ; P < 0.05 ) . Blood pressure and heart rate changes were not significantly different among groups , whereas sedation and pruritus were significantly more frequent in Group BCF . Nausea and vomiting were decreased in Groups BC and BCF . Apgar scores and umbilical artery blood pH were not different among groups . We conclude that adding a small dose of intrathecal clonidine to bupivacaine increases the quality of intraoperative analgesia and decreases pain during cesarean section . Combining clonidine with fentanyl further improved analgesia . Implication s : In this study , we demonstrate improved intraoperative spinal analgesia by adding 75 [ micro sign]g of clonidine to bupivacaine ; side effects were not increased . The combination of clonidine and fentanyl further improved analgesia but moderately increased sedation and pruritus . ( Anesth Analg 1998;87:609 - 13 Abstract Purpose . This study aim ed to compare low-molecular weight hydroxyethyl starch containing 1 % dextrose ( HES ) infusion and lactated Ringer 's solution ( LR ) in the prevention of hypotension associated with spinal anesthesia for cesarean section . Methods . Sixty-seven patients scheduled for cesarean section under spinal anesthesia were r and omly allocated to receive either LR ( n= 35 ) or HES ( n= 32 ) infusion before cesarean delivery . Infusion of the fluid was started immediately after arrival at the operating room , through two fully open i.v . routes of 18 or 16 gauge . The two groups were compared in terms of the incidence of hypotension ; ephedrine dose ; cord and maternal blood gas , hemoglobin , and glucose ; and Apgar scores . Results . Intravenous fluid volume until delivery in the LR group was significantly greater than that in the HES group ( 1298 ± 503 and 973 ± 339 ml , respectively ) in spite of the similar periods of intravenous infusion ( 18.1 ± 3.9 and 18.2 ± 4.1 min ) . The incidence of hypotension , and the ephedrine dose , blood gas analyses , and Apgar scores were not significantly different between the groups . The ephedrine dose correlated with the anesthesia level by spinal anesthesia ( P < 0.05 ) . Conclusion . This study did not show an advantage of HES compared with LR in the prevention of hypotension or in the reduction of ephedrine dose during cesarean section under spinal anesthesia . The anesthesia level , rather than the choice of intravenous fluid solution , might be related to the ephedrine dose We r and omized women having elective Caesarean section to receive either no preload ( control group , n=33 ) or 4 % gelatin solution ( Gelofusine ) 15 ml kg(-1 ) ( colloid group , n=35 ) i.v . before spinal anaesthesia . Intravenous metaraminol was titrated at 0.25 - 0.75 mg min(-1 ) to maintain systolic arterial pressure ( SAP ) in the target range 90 - 100 % of baseline after the spinal injection . The control group required more vasopressor in the first 10 min [ median 1.7 ( range 0 - 2.9 ) mg vs 1.4 ( 0 - 2.8 ) , P=0.02 ] at a greater maximum infusion rate [ 0.5 ( 0 - 0.75 ) vs 0.25 ( 0 - 0.5 ) mg min(-1 ) , P=0.0005 ] and had a lower minimum SAP [ 90 ( 51 - 109 ) vs 101 ( 75 - 127 ) mm Hg , P=0.006 ] than the colloid group . Nausea was less frequent in the colloid group ( 6 vs 24 % ) but neonatal outcome was similar in the two groups . Colloid preload improved haemodynamic stability but did not affect neonatal outcome when arterial pressure was maintained with an infusion of metaraminol during spinal anaesthesia for Caesarean section Abstract We have routinely applied an extra-strong graduated compression stocking to cesarean section patients to reduce the incidence of spinal anesthesia hypotension . Because bupivacaine has recently become available in Japan , we compared the incidence of spinal hypotension using either 2.0 ml of hyperbaric 0.3 % dibucaine or 0.5 % bupivacaine . There were 98 full-term parturients wearing the stocking who received 2.0 ml injection of dibucaine or bupivacaine for elective cesarean section . When systolic blood pressure decreased to 90–100 mm Hg or to less than 70 % of the pre-anesthesia value , ephedrine was injected intravenously . There was no significant difference in systolic blood pressure or heart rate during spinal anesthesia between the dibucaine and bupivacaine groups . Although the demographic data and various data related to anesthesia or surgery were similar in the groups , the fluid volume and the dose and incidence of ephedrine injection during anesthesia showed significant differences : the mean dose was 3.6 and 1.5 mg and the incidence was 41 % and 19 % in the dibucaine and bupivacaine groups , respectively . Spinal anesthesia using bupivacaine results in a lower incidence of spinal hypotension compared with dibucaine and , in combination with fitting the extra-strong stockings onto both legs , is clinical ly useful for cesarean sections Maternal and neonatal catecholamine concentrations , following the use of either phenylephrine or ephedrine to treat a drop in maternal blood pressure after spinal anaesthesia for caesarean delivery , were compared . Patients were r and omly assigned to one of two groups : Group 1 patients ( n = 20 ) were treated with ephedrine given as 5 mg intravenous bolus injections ; Group 2 patients ( n = 20 ) were treated with phenylephrine given as 40 μg intravenous bolus injections , for decreases in maternal systolic blood pressure to maintain maternal systolic blood pressure above 100 mmHg . Maternal vein ( MV ) , umbilical vein ( UV ) , and umbilical artery ( UA ) blood sample s were taken at the time of delivery . Sample s were analyzed for catecholamine concentrations and blood gas values The value of intravenous crystalloid administration in preventing spinal-induced hypotension in the parturient has recently been question ed . Also , the association between increasing crystalloid volume and decreasing postpartum colloid osmotic pressure ( COP ) raises concern regarding the risk of maternal and fetal pulmonary edema . To study the dose-response effect of varying amounts of crystalloid volume prior to spinal anesthesia , we measured maternal hemodynamic variables and maternal and fetal COP in three groups of healthy parturients receiving spinal anesthesia for elective cesarean delivery . Fifty-five parturients were r and omized in a double-blind fashion to receive one of 10 , 20 , or 30 mL/kg of crystalloid volumes prior to induction of spinal anesthesia . Measurements included mean arterial blood pressure ( MAP ) , cardiac index ( CI ) , and systemic vascular resistance index ( SVRI ) recorded using noninvasive thoracic impedance monitoring until delivery . Maternal and neonatal COP were measured . All groups showed declines in MAP and SVRI from baseline at 5 min after spinal anesthesia , but the amount of decline did not differ among groups . Total ephedrine and additional intravenous ( IV ) fluid administered did not differ among groups . The 20- and 30- mL/kg groups showed a larger decline in maternal COP than the 10-mL/kg group ; no differences in neonatal COP were seen with varying preload . We conclude that increasing the amount of IV crystalloid administered to 30 mL/kg in the healthy parturient does not significantly alter maternal hemodynamics or ephedrine requirements after spinal anesthesia and has no apparent benefit . ( Anesth Analg 1996;83:299 - 303 Purpose To study how the body h and les fluid given intravenously during the onset of spinal anaesthesia in women scheduled for Caesarean section . Methods The effect of spinal anaesthesia on the volume kinetics of a constant-rate infusion of 25 ml · kg−1 of Ringer ’s solution ( n = 11 ) and 10 ml · kg−1 of dextran 3 % 60 ( n = 8) was studied before elective Caesarean section , Measurements of the blood haemoglobin concentration and urine excretion served as input variables in calculations of the size(s ) of the body fluid spaces exp and ed by the infused fluid . The blood glucose level was also monitored . Results When a one-volume kinetic model were fitted to the data , spinal anaesthesia reduced the size of the exp and ed body fluid space by 30 % ( Ringer ’s ) and 58 % ( dextran ) ( P < 0.02 ) When a two-volume model was statistically justified , anaesthesia reduced the rate of fluid equilibration between the two exp and ed body fluid spaces by 47 % and 19 % , respectively ( P < 0.04 ) The baseline volume for the primary ( central ) fluid space was smaller than the expected plasma volume ; 1.5 l for Ringer ’s solution and 0.9 l for dextran . Only small changes in the blood glucose concentration were found . Conclusion The onset of spinal anaesthesia induces acute changes in the body ’s h and ling of infused fluid that can be described by volume kinetic analysis .RésuméObjectifÉtudier le devenir des liquides administrés par voie intraveineuse durant l’induction de l’anesthésie rachidienne chez des parturientes subissant une césarienne . MéthodesLes effets de la rachianesthésie sur la cinétique volumétrique d’une infusion à débit constant de 25 ml · kg−1 de solution de Ringer ( n= 11 ) ou de 10 ml · kg−1 de dextran 60 en solution à 3 % ( n = 8) ont été étudiés avant la césarienne élective . Les mesures du taux d’hémoglobine sanguin et du débit urinaire ont servi comme entrées variables dans le calcul de l’expansion volémique par le liquide infusé des différents compartiments corporels . La glycémie a aussi été mesurée . RésultatsLorsque les données étaient rapportées à un modèle cinétique à un seul compartiment , l’anesthésie rachidienne entraînait une réduction du compartiment corporel déjà distendu de 30 % pour le Ringer et de 58 % pour le dextran ( P 0.02 ) . Lorsqu’un modèle à deux compartiments apparaissait justifié d’un point de vue statistique , l’anesthésie entraînait une réduction du taux d’équilibration entre les deux compartiments corporels déjà distendus de 47 % et de 19 % respectivement ( P 0.04 ) . Le volume de base pour le compartiment primaire ( central ) était plus petit que le volume plasmatique prévu : 1.5L pour le Ringer et 0.9L pour le dextran . La glycémie a peu varié . Conclusion Linduction de l’anesthésie rachidienne entraîne des modification aiguës de la gestion par le corps humain des liquides infusés , ces modifications pouvant être décrites par des analyses de cinétique volumétrique Serial haemodynamic investigations were performed in 32 women who were allocated r and omly to receive either spinal or extradural anaesthesia for elective Caesarean section . Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic valve . Doppler flow velocity waveforms were recorded also from the umbilical artery . Preloading with Ringer lactate solution 1 litre increased cardiac output in both groups . After injection of bupivacaine , cardiac output remained increased in the extradural group , but decreased in the spinal group . This was associated with an increase in umbilical artery pulsatility index in the spinal group . Umbilical artery pH was less in the spinal group ( 7.22 vs 7.27 ) , although no neonate was depressed at birth . The maximum percentage change in cardiac output and umbilical artery pulsatility index correlated with umbilical artery pH ( r = 0.54 , r = 0.72 , respectively ) . There was no significant correlation with change in arterial pressure A prospect i ve survey of anaesthesia for caesarean section was performed for the year 1 January to 31 December , 1997 . Two hundred and fifty maternity hospitals were sent question naires from which 129 responses were obtained . The data provided information on anaesthesia for 60 455 caesarean sections . Overall 78 % of sections were performed with regional anaesthesia : 47 % single shot spinal ; 22 % epidural ; 9 % combined spinal epidural ( CSE ) ; 22 % general anaesthesia . For elective caesarean sections ( 39 % of all sections ) regional anaesthesia was used for 87 % of cases : 68 % single shot spinal ; 3 % epidural ; 15 % CSE ; 13 % general anaesthesia . For emergency procedures regional anaesthesia was used for 72 % of cases : 34 % single shot spinal ; 34 % epidural ; 4 % CSE ; 28 % general anaesthesia . There was a wide range of regional anaesthesia use among the units , varying from an overall rate of 95 % at one extreme to 41 % at the other . Similarly , there was a wide range of conversion of regional anaesthesia to general anaesthesia , varying from 0 % to 88 % . Overall , 10.6 % of the general anaesthetics were the result of regional to general anaesthesia conversion Background : The study tested the hypothesis that the incidence of hypotension during spinal anaesthesia for caesarean section is less in parturients who remain in the sitting position for 3 min compared with parturients who are placed in the modified supine position immediately after induction of spinal anesthesia Maternal cardiovascular changes and neonatal acid-base status , including lactate levels , were assessed in 30 healthy women undergoing elective caesarean section under spinal anaesthesia . Patients were allocated r and omly to receive IV ephedrine infusion ( n=15 ) ( 5 mg.min -1 ) immediately after the spinal injection or bolus administration of IV ephedrine ( n=15 ) ( 10 mg ) in case of development of hypotension . Maternal and neonatal blood pressure , heart rate and acid-base status including lactate levels were compared between the groups . Systolic blood pressure in the bolus group was significantly lower when compared to the infusion group . Nausea was observed in one patient ( 6 % ) in the infusion group and nausea and vomiting were observed in 10 patients ( 66 % ) in the bolus group . Although umbilical arterial pH values were significantly lower in the bolus group , lactate levels were similar . In conclusion , ephedrine infusion prevented maternal hypotension , reduced the incidence of nausea and vomiting and led to improved umbilical blood pH during spinal anaesthesia for caesarean section Twenty-six parturients scheduled to receive spinal anaesthesia for caesarean section were r and omized to receive either isotonic saline 750 ml plus 20 ml/kg ( group A ) or 750 ml plus 500 ml ( group B ) before subarachnoid administration of bupivacaine 13 mg . Ephedrine 0.15 mg/kg i.v . followed by an infusion 0.4 mg.kg(-1 ) h(-1 ) were then administered in group B. In both groups ephedrine 10 mg/min i.v . was given if the mean arterial blood pressure decreased more than 10 mmHg . Despite the fluid preload and large doses of ephedrine noted { median ( range ) , group A 30 mg ( 10 - 80 ) , group B 92 mg ( 25 - 194 ) } , hypotension , sometimes accompanied by nausea , still occurred . Mean maternal arterial was significantly lower in group A than in group B 5 - 10 min after induction of spinal anaesthesia ( P < 0.05 ) . There was no difference in the frequency of nausea or vomiting , Apgar score , or pH in umbilical cord blood . One neonate in group A and 2 in group B were acidotic . In conclusion , a reduced volume loading could be compensated with an increased ephedrine administration after induction of spinal anaesthesia , without increasing the incidence of hypotension or other maternal or neonatal complications . However , the fluid volumes and /or ephedrine doses used were not sufficient to prevent hypotension altogether Induction of spinal anesthesia for cesarean delivery in the left lateral ( LL ) decubitus position combined with intraoperative left uterine displacement may result in pooling of local anesthetic onto one side of the body . We studied the effect of the right lateral ( RL ) and LL decubitus positions during placement of spinal anesthesia on the intrathecal spread of 0.5 % hyperbaric bupivacaine plus fentanyl in 60 term parturients . Though all parturients acquired a loss of cold sensation at T4 15 min after intrathecal injection , more parturients in the LL group than in the RL group did so at 5 min ( P < 0.05 ) . The maximum levels of sensory blockades , amounts of fluid , vasopressor , and supplementary analgesia used , and the incidence of postoperative complications were similar . We conclude that the two positions can be used equally well when hyperbaric bupivacaine and fentanyl are used in cesarean delivery under spinal anesthesia To investigate the safety and efficacy of 0.25 % hyperbaric bupivacaine for spinal anaesthesia in Caesarean section , we studied 60 parturients allocated r and omly to one of three groups . According to the patient 's height , groups 1 , 2 and 3 received 3.2 - 3.6 ml ( 8 - 9 mg ) , 3.6 - 4.0 ml ( 9 - 10 mg ) and 4.0 - 4.4 ml ( 10 - 11 mg ) of 0.25 % bupivacaine in 5 % glucose , respectively . Subarachnoid injection was performed in the right lateral decubitus position , and parturients were then turned immediately supine with left uterine displacement . Mean spread of sensory analgesia was significantly higher in group 3 ( T2 - 3 ) than in groups 1 and 2 ( T4 - 5 in each group ) . Duration of sensory analgesia was significantly longer in groups 2 and 3 than in group 1 . Complete motor block of the lower extremities occurred in all patients but in only one in group 1 . Onset time and duration of motor block were not significantly different between the three groups . The incidence of hypotension was significantly higher in group 3 ( 75 % ) than in groups 1 and 2 ( 40 % in each group ) . The efficacy of intraoperative analgesia was significantly greater in groups 2 and 3 than in group 1 . The incidence of patients requiring analgesics during operation was significantly lower in groups 2 ( 25 % ) and 3 ( 10 % ) than in group 1 ( 70 % ) . There was no difference in neonatal condition between the three groups . Spinal anaesthesia with 3.6 - 4.0 ml of 0.25 % bupivacaine in 5 % glucose was satisfactory for Caesarean section We have compared the protective effect of 1000 ml preload with 200 ml preload of crystalloid solution , administered during the 10 min before spinal anaesthesia was induced , in 60 healthy women with no fetal compromise undergoing elective Caesarean section . The spinal anaesthetic was managed identically in both groups by an anaesthetist who was unaware of the volume of fluid administered . A prophylactic infusion of ephedrine 60 mg in Hartmann 's solution 500 ml was given according to maternal arterial pressure . Hypotension was defined as > or = 30 % reduction from baseline or < 90 mm Hg , and was treated by i.v . ephedrine bolus doses . There was no significant difference in ephedrine requirements between the two groups or in the incidence , severity or duration of hypotension : 10 women in the 1000-ml group , five episodes lasting > or = 3 min compared with nine women in the 200-ml group , four lasting > or = 3 min . There was no difference between neonates in each group . We have now ab and oned the routine of preloading before regional anaesthesia This study was design ed to determine whether preoperative administration of 6 % hetastarch decreases the incidence and severity of hypotension after spinal anesthesia for cesarean section . Forty nonlaboring ASA class I and II women having nonurgent cesarean sections were r and omized to receive either 500 mL of 6 % hetastarch plus 1 L lactated Ringer 's solution ( LR ) ( n = 20 ) , or 2 L of LR ( n = 20 ) prior to induction of spinal anesthesia . Hypotension occurred in 45 % of patients who received hetastarch vs 85 % of those who received only LR ( P < 0.05 ) , and minimum systolic blood pressure was lower in the LR group than in the hetastarch group ( 85 + /- 12 vs 93 + /- 12 mm Hg [ mean + /- SD ] ; P < 0.05 ) . In addition , the LR group had a higher maximum heart rate ( 115 + /- 17 vs 104 + /- 16 bpm ) , a shorter mean time to hypotension ( 7 + /- 4 vs 10 + /- 7 min ) , and required more 5-mg doses of ephedrine for treatment of hypotension ( 0 vs 2 [ median ] ; P < 0.05 ) than the hetastarch group . Neonatal outcome , as determined by Apgar scores and cord blood gas analyses , was good and similar in both groups . We conclude that 6 % hetastarch plus LR is more effective than LR alone and that its routine use before spinal anesthesia for cesarean section should be considered . ( Anesth Analg 1995;81:838 - 42 We studied 90 patients undergoing elective Caesarean section under spinal anaesthesia who received lactated Ringer 's solution 1000 ml with up to 1000 ml of modified gelatin , lactated Ringer 's solution 1000 ml with up to 1000 ml of 6 % hydroxyethylstarch or only up to 1000 ml of 6 % hydroxyethylstarch . Lumbar puncture was performed as soon as 500 ml of the colloid were infused . The incidence of hypotension , number of patients requiring a vasopressor and doses of ephedrine required to restore arterial pressure were significantly lower in favour of those receiving the crystalloid-hydroxyethylstarch combination . In both groups receiving the 2000 ml preload , packed cell volume ( PCV ) values decreased by more than 20 % , which may be of concern in patients already presenting with mild anaemia . In patients who received the colloid without the crystalloid , PCV values decreased by 14 % but the risk of severe hypotension was comparable with the crystalloid-gelatin combination We conducted a r and omised controlled trial to compare the severity of hypotension and ephedrine requirements following spinal anaesthesia for elective caesarean section in women pretreated with either i.v . glycopyrrolate 4.0 microg/kg ( group G ) or saline ( group S ) . Data were analysed using sequential analysis which allowed us to terminate the study after data from 40 patients had been analysed ( 20 in each group ) . There were no differences between the two groups in the severity of hypotension ( mean + /- SD decrease from baseline 35 + /- 14 % in group G and 29 + /- 15 % in group S ) or ephedrine requirements ( 15 + /- 11 mg in group G and 18 + /- 12 mg in group S ) . Intra-operative heart rate increased by a greater amount in group G than in group S ( 58 + /- 26 % vs 35 + /- 21 % mean + /- SD;P = 0.002 ) and there was a greater incidence of dry mouth ( 75 % vs 15%;P = 0.0006 ) but no difference in the incidence of nausea and vomiting ( 30 % vs 50%;P = 0.33 ) . Pretreatment with glycopyrrolate did not confer an advantage in this study We induced spinal anaesthesia in 100 women presenting for elective Caesarean section with the mother in the right lateral position . Patients were allocated r and omly to have the side eye of the 24-gauge Sprotte spinal needle pointing in one of four directions : group A , cephalad ; group B , right lateral ; group C , left lateral ; group D , caudad . Isobaric bupivacaine 0.5 % ( 2.5 ml ) was injected over 30 s before the mother was placed supine with a 15 degree left lateral tilt . Onset time and height of the subsequent analgesic and anaesthetic blocks were assessed by a blinded observer . Onset of sensory block to T4 was significantly faster in group A ( P = 0.001 ) . There were no differences in final block height , incidence of hypotension , nausea and vomiting or ephedrine requirements A novel positioning technique was tested to see whether the unpredictability of block height and haemodynamic instability during spinal anaesthesia for caesarean section could be reduced . In this ' Oxford ' position , the woman is placed left lateral with an inflated bag under the shoulder and pillows supporting the head . Following spinal injection the woman is turned to an identical right lateral position . This is maintained until just before incision to minimise aorto-caval compression , when she is placed in the wedged supine position . Sixty women undergoing elective caesarean section were r and omised to receive spinal anaesthesia using hyperbaric bupivacaine in either the Oxford ( group O ) , or the sitting position followed immediately by the wedged supine position ( group S ) . Ephedrine 6 mg was given every minute that systolic blood pressure was less than 80 % of baseline . In group S , 9/30 women lost pinprick sensation up to T4 at 5 minutes compared with 2/30 in group O ( chi2 test , P = 0.04 ) . Block height was more variable in group S than in group O ( f test , P = 0.001 ) . Blood pressure decreased by a greater amount initially : group S women required more ephedrine ( 15.5 + /- 12.9 versus 9.2 + /- 7.7 mg , t test , P = 0.03 ) . Block height with spinal anaesthesia for caesarean section is more predictable and haemodynamically stable if the Oxford position is used whilst anaesthesia develops Spinal anaesthesia provides rapid , safe anaesthesia for Caesarean section . The pencil-point spinal needles ( Sprotte and Whitacre ) are reported to have a low incidence of post-dural puncture headache ( PDPH ) . As the 25 G Whitacre is less expensive than the 24 G Sprotte needle , this prospect i ve , r and omized , doubleblind study was design ed to compare the incidence of PDPH and ease of insertion of these needles in 304 ASA 1 and 2 women having elective Caesarean section under spinal anaesthesia . Each patient was assessed daily for five consecutive days following Caesarean section by an investigator blinded to the needle used . The results indicate that the two needles have a similar ease of insertion , number of failed insertions , and failed subarachnoid blockade . An inability to insert the spinal needles occurred in two patients in each group . Therefore , 150 patients in each group completed the study . The incidence of PDPH with the 24 G Sprotte needle was 4.0 % ( 6/150 ) compared with 0.66 % ( 1/150 ) with the 25 G Whitacre ( NS ) . There was no correlation between the occurrence of PDPH and the difficulty of needle insertion , presence of transient hypotension or the effectiveness of anaesthesia delivered . This study indicates that both needles are comparable with respect to ease of insertion and incidence of PDPH . As the Whitacre needle is less expensive it is a reasonable alternative to the more expensive Sprotte needle . RésuméLa rachianesthésie administrée pour la césarienne offre les avantages d’une installation rapide et d’une gr and e sécurité . L’incidence de la céphalée post-rachidienne avec l’utilisation d’aiguilles à extrémité conique ( Sprotte et Whitacre ) est faible . Toutefois , l’aiguille Whitacre 25 G coûte moins cher que la Sprotte 24 G . Cette étude r and omisée , prospect i ve et à double insu vise à comparer pour ces deux aiguilles l’incidence de céphalée post-rachidienne et leur facilité d’insertion chez 304 parturientes ASA 1 et 2 programmées pour césarienne non urgente sous rachianesthésie . Après l’intervention , chaque patiente est évaluée pendant cinq jours consécutifs par un observateur ignorant du type d’aiguille utilisé . Les résultats montrent que les deux aiguilles s’introduisent avec la même facilité ; la fréquence des insertions impossibles et des anesthésies ratées est la même pour les deux aiguilles . L’impossibilité d’insérer l’aiguille rachidienne survient deux fois dans chaque groupe . Cent cinquante patientes de chaque groupe ont donc pu compléter l’étude . L’incidence de céphalée post-rachidienne avec l’aiguille Sprotte 24 G est de 4,0 % ( 6/150 ) comparativement à 0,66 % ( 1/150 ) avec la Whitacre 25 G ( NS ) . On ne trouve pas de corrélation entre la céphalée post-rachidienne et l’insertion difficile , l’hypotension transitoire ou la qualité de l’anesthésie . Cette étude montre que les deux aiguilles sont comparables au regard de la facilité d’insertion et de l’incidence de céphalée post-rachidienne . Le prix moins élevé de l’aiguille de Whitacre constitue un avantage sur l’aiguille Sprotte Pre-emptive intramuscular ( i.m . ) vasopressors were evaluated in 108 patients undergoing elective Caesarean section under spinal anaesthesia , assigned to four groups in a r and omized , double-blind , placebo-controlled study . Group 1 received pre-emptive phenylephrine 4 mg i.m . , group 2 received phenylephrine 2 mg i.m . , group 3 received ephedrine 45 mg i.m . , while controls received an i.m . injection of saline , all given immediately after induction of spinal anaesthesia . Hypotension was defined as a 25 % decrease in mean arterial pressure ( MAP ) . Rescue intravenous ( i.v . ) boluses of ephedrine were given if the patient was hypotensive or reported nausea , vomiting or dizziness . The incidence of hypotension was 33 % in the phenylephrine 4 mg group compared with 70 % in the control and phenylephrine 2 mg groups ( P=0.03 ) , and 48 % in the ephedrine 45 mg group . The phenylephrine 4 mg and ephedrine 45 mg groups had a significantly lower percentage reduction in MAP ( -21 ( SD 14)% and -22 (14)% ) compared with controls ( -32 (18)% , P=0.04 ) . They also had a lower total dose of rescue i.v . ephedrine ( 15.7 ( 15.7 ) mg and 15.8 ( 15.6 ) mg ) compared with controls ( 28.8 ( 20.6 ) mg , P=0.02 ) . We conclude that pre-emptive i.m . phenylephrine 4 mg and ephedrine 45 mg reduce the severity of hypotension and the total dose of rescue i.v . ephedrine during spinal anaesthesia for Caesarean section BACKGROUND AND OBJECTIVE To evaluate the efficacy and optimal dose of prophylactic intravenous ephedrine for the prevention of maternal hypotension associated with spinal anaesthesia for Caesarean section . METHODS After patients had received an intravenous preload of 0.5 L of lactated Ringer 's solution , spinal anaesthesia was administered in the sitting position with hyperbaric bupivacaine 2.5 mL 0.5 % combined with 25 microg fentanyl . A total of 68 patients were r and omized to receive a simultaneous 2 mL bolus intravenously of either 0.9 % saline ( Group C , n = 20 ) , ephedrine 6 mg ( Group E-6 , n = 24 ) , or ephedrine 12 mg ( Group E-12 , n = 22 ) . Further rescue boluses of ephedrine 6 mg were given if systolic arterial pressure fell to below 90 mmHg , greater than 30 % below baseline , or if symptoms suggestive of hypotension were reported . RESULTS There was a significantly higher incidence of hypotension in Group C ( 60 % patients ) compared to Group E-12 ( 27 % ) , but not in Group E-6 ( 50 % ) . The 95 % Confidence Interval for the difference in proportions between Groups C and E-12 was 6 - 60 % , P < 0.05 . Fewer rescue boluses of ephedrine were required in Group E-12 compared with Group C ( 1.8 + /- 1.2 vs. 3.3 + /- 2.1 , P < 0.05 ) . There were no significant differences in the incidence of maternal nausea or vomiting , or of neonatal acidaemia between groups . CONCLUSION A prophylactic bolus of ephedrine 12 mg intravenously given at the time of intrathecal block , plus rescue boluses , leads to a lower incidence of hypotension following spinal anaesthesia for elective Caesarean section compared to intravenous rescue boluses alone We conducted a prospect i ve double‐blind r and omised trial to compare bupivacaine 0.5 % ; a 50 : 50 mixture of bupivacaine 0.5%/lignocaine 2 % with 1 : 200 000 adrenaline ( final concentration ) ; and lignocaine 2 % with 1 : 200 000 adrenaline for converting a low‐dose labour epidural into a block adequate for emergency Caesarean section . Ninety patients were studied , 30 in each group . There was no difference between the groups in the time taken for bilateral loss of cold sensation to reach T4 . Onset time was unaffected by the existing sensory level pre‐Caesarean section top‐up ; the number of low‐dose top‐ups in labour ; the total dose of bupivacaine in labour ; or maternal weight or height . Three patients in the lignocaine with adrenaline group had blocks that reached the cervical dermatomes and three in the same group required general anaesthesia for inadequate anaesthesia , compared with none in the other groups ( both p = 0.04 ) Hypotension commonly accompanies induction of spinal anesthesia for cesarean section . To determine whether intravenous ephedrine prophylaxis would benefit prehydrated obstetrical patients presenting for elective cesarean section , we studied 30 patients r and omly assigned to one of three experimental groups . All patients were preloaded with crystalloid ( 15 ml/kg ) , given spinal anesthesia and positioned with left uterine displacement ( LUD ) . During induction , all patients received a 2 ml intravenous bolus and intravenous infusion of the study drug or placebo . The control group ( n=10 ) received a saline bolus and saline infusion , the bolus group ( n=10 ) received an ephedrine bolus ( 10 mg ) and a saline infusion and the infusion group ( n=10 ) received a saline bolus and a two-stage ephedrine infusion ( 20 mg over 12 min ) . After induction of anesthesia , systolic blood pressure decreased in the first 5 min in all groups . Hypotension occurred in 6/10 control patients , 5/10 bolus patients and 5/10 infusion patients . The amount of supplemental ephedrine required to treat hypotension did not differ among groups . Although the efficacy of ephedrine prophylaxis for hypotension associated with spinal anesthesia for elective cesarean section can not be established by the small number of patients studied , this practice does not appear to be clinical ly relevant at the doses studied Forty women presenting for elective Caesarean section under spinal anaesthesia were r and omly assigned to have anaesthesia induced in either the sitting or right lateral positions ; 2.5 ml 0.5 % hyperbaric bupivacaine was injected over 10 s before the mother was placed in a supine position with a 20 ° lateral tilt . The onset time and height of the subsequent analgesic and anaesthetic block was measured . It took longer to site spinal needles in the lateral position ( 240 vs 115 s , p < 0.001 ) . There was a faster onset of sensory block to the sixth thoracic dermatomal level ( 8 vs 10 min , p < 0.001 ) , in the lateral group , although onset time to T4 was comparable . There was no difference in maximum block height or degree of motor block . Mothers in the lateral group required more ephedrine in the first 10 m after siting the spinal ( 13.5 vs 10.5 mg , p < 0.05 ) BACKGROUND The role of crystalloid preloading to prevent hypotension associated with spinal anesthesia in parturients during cesarean section has been challenged . Direct measurement of blood volume should provide insight regarding the volume-exp and ing effects . The aim of the current study was to clarify the effects of volume preload with either crystalloid or colloid solution on the changes in blood volume of parturients undergoing spinal anesthesia for cesarean section . METHODS Thirty-six healthy parturients scheduled for elective cesarean section during spinal anesthesia were allocated r and omly to one of three groups receiving 1.5 l lactated Ringer 's solution ( LR ; n = 12 ) , 0.5 l hydroxyethylstarch solution , 6 % ( 0.5 l HES ; n = 12 ) , and 1.0 l hydroxyethylstarch solution , 6 % ( 1.0 l HES ; n = 12 ) , respectively . Blood volume and cardiac output were measured before and after volume preloading with indocyanine green ( ICG ) , and the indocyanine green blood concentrations were monitored by noninvasive pulse spectrophotometry . RESULTS After volume preload , the blood volume significantly increased in all three groups ( P < 0.01 ) . The volume of infused solution remaining in the vascular space in the LR , 0.5-l HES , and 1.0-l HES groups were 0.43+/-0.20 l , 0.54+/-0.14 l , and 1.03+/-0.21 l , respectively , corresponding to 28 % of lactated Ringer 's solution and 100 % of hydroxyethylstarch solution infused . Significant increases in cardiac output were observed in the 0.5-l and 1.0-l HES groups ( P < 0.01 ) . A significant correlation between the percentage increase in blood volume and that of cardiac output was observed by volume preloading ( r2 = 0.838 ; P < 0.001 ) . The incidence of hypotension was 75 % for the LR group , 58 % for the 0.5-l HES group , and 17 % for the 1.0-l HES group , respectively . CONCLUSIONS The incidence of hypotension developed in the 1.0-l HES group was significantly lower than that in the LR and 0.5-l HES groups , showing that greater volume expansion results in less hypotension . This result indicates that the augmentation of blood volume with preloading , regardless of the fluid used , must be large enough to result in a significant increase in cardiac output for effective prevention of hypotension Purpose : To compare the preloading effect of 500 ml hydroxyethylstarch ( HES ) 10 % with I L Lactated Ringer ’s solution ( LR ) . Methods : In 40 healthy women undergoing elective Cesarean section HES , 500 ml ( n=20 ) , or LR , IL ( n=20 ) , was administered during 10 min before spinal anesthesia . The incidence of hypotension , ( systolic blood pressure < 80 % of baseline and < 100 mm Hg ) , and the amount of ephedrine used to treat it were compared . Also , the incidence of nausea and /or vomiting were recorded . Neonatal outcome was assessed using Apgar scores and umbilical venous and arterial blood gases . Results : The incidence of hypotension was higher in the LR than in HES group ( 80%vs 40 % ) . Mean minimum systolic blood pressure was lower in the LR than in the HES group ( 86.1±12.7 mm Hgvs 99.6±9.7 mm HgP<0.05 ) . Systolic blood pressure < 90 mmHg occurred in two of 20 patients ( 10 % ) who received HESvs 11 of 20 patients ( 55 % ) who received LR ( P<0.05 ) . More doses of ephedrine were required to treat hypotension in the Lr than in the HES group ( 35.3±18.4 mgvs 10.6±8.6 mg;P<0.05 ) . The incidence of nausea and /or vomiting was lower in the HES than in the crystalloid group . Neonatal outcome was good and similar in both groups . Conclusion : Preloading patients undergoing elective Cesarean section with 500 ml HES 10 % , decreases the incidence and severity of spinal-induced hypotension more than preloading with I L of LR solution . RésuméObjectif : Comparer l’effet d’une précharge de 500 ml d’hydroxyéthylamidon ( HEA ) à 10 % avec celui de I L de solution de lactate de Ringer (LR).Méthode : Pendant 10 min avant la rachianesthésie , on a administré chez 40 femmes qui devaient subir une césarienne 500 ml d’HEA ( n=20 ) ou I L de LR ( n=20 ) . L’incidence d’hypotension ( tension artérielle < 80 % de la mesure de base et < 100 mmHg ) et la quantité d’éphédrine utilisée pour la traiter ont été comparées . De plus , l’incidence de nausées et/ou de vomissements a été enregistrée . L’indice d’Apgar et l’analyse des gaz du sang veineux et artériel ombilical ont permis d’évaluer les nouveau-nés . Résultats : On a noté une plus gr and e incidence d’hypotension avec le LR qu’avec l’HEA ( 80 % vs 40 % ) . La moyenne des mesures de tension artérielle systolique minimale était plus basse dans le groupe LR que dans le groupe HEA ( 86,1±12,7 mmHgvs 99,6±9,7 mmHgP < 0,05 ) . La tension artérielle systolique < 90 mmHg est survenue chez deux des 20 patientes ( 10 % ) qui ont reçu de l’HEAvs 11 des 20 patientes ( 55 % ) qui ont reçu du LR ( P < 0,05 ) . Le traitement de l’hypotension a nécessité plus d’éphédrine dans le groupe LR que dans le groupe HEA ( 35,3±18,4 mgvs 10,6±8,6 mg;P < 0,05 ) . L’incidence de nausées et/ou de vomissements a été plus faible avec l’HEA qu’avec le cristalloïde . L’évaluation néonatale a été satisfaisante et similaire dans les deux groupes . Conclusion : Une précharge de 500 ml d’HEA à 10 % chez des patientes qui vont subir une césarienne diminue plus l’incidence et la sévérité de l’hypotension induite par la rachianesthésie qu’une précharge avec I L de solution de LR Summary Eighty‐seven pregnant mothers undergoing elective Caesarean section were r and omly allocated either to the full left lateral position ( n = 45 ) or to the supine position with 12 ° left lateral tilt ( n = 42 ) after a combined spinal – epidural ( CSE ) in the sitting position and an initial 2 min in the full right lateral position . Fewer mothers were hypotensive while in the study position [ 29 ( 64 % ) in lateral group vs. 38 ( 90 % ) in the tilted supine group ; p = 0.03 ] . Mothers in the lateral group tended to become hypotensive after turning them back to the tilted supine position immediately before surgery ; hence the number of mothers who were hypotensive from the insertion of the CSE until delivery were similar [ 36 ( 80 % ) vs. 38 ( 90 % ) ] . Mothers in the lateral group needed a lower dose of ephedrine to treat their hypotension while in their study position { median ( interquartile range [ range ] ) 6 ( 0–12 [ 0–36 ] ) mg vs. 12 ( 6–18 [ 0–36 ] ) mg , respectively ; p = 0.04 } but ephedrine requirements were similar overall { 12 ( 6–12 [ 0–36 ] ) mg vs. 12 ( 6–18 [ 0–36 ] ) mg } , respectively . The full left lateral position reduces the incidence of early hypotension compared with the tilted supine position with tilt , and makes it easier to treat Forty women presenting for elective Caesarean section under spinal anaesthesia were r and omly assigned to have anaesthesia induced in the right lateral position either in the horizontal position or with 10 ° head‐up tilt . Hyperbaric bupivacaine 2 ml 0.5 % with 0.1 mg of morphine was injected intrathecally before the parturients were placed in the supine position with 15 ° left lateral tilt . Blood pressure and heart rate were monitored every minute and the sensory level ( loss of sharp sensation to pinprick ) was monitored every 3 min until clamping of the umbilical cord . Ephedrine 6 mg was given every minute that the systolic blood pressure decreased below 90 mmHg . The mean systolic blood pressure during the first 5 min after induction of spinal anaesthesia was lower in the control group compared to the tilted group ( 99 mmHg vs. 109 mmHg ; p = 0.043 ) . The upper limit of block was higher in the control group compared to the tilted group ( p = 0.002 ) . The use of 10 ° head‐up tilt result ed in a reduced incidence of hypotension initially and less extensive sensory block Background In our routine practice , we observed a reduced incidence of fetal acidosis ( umbilical artery p H < 7.20 ) at cesarean delivery during spinal anesthesia when a combination of phenylephrine and ephedrine was used as first line vasopressor therapy , compared with using ephedrine alone . Methods The study was r and omized and double blind . It compared phenylephrine 100 & mgr;g/ml ( phenylephrine group ) , ephedrine 3 mg/ml ( ephedrine group ) , and phenylephrine 50 & mgr;g/ml combined with ephedrine 1.5 mg/ml ( combination group ) , given by infusion , to maintain maternal systolic arterial pressure at baseline during spinal anesthesia for elective cesarean delivery . Results Fetal acidosis was less frequent in the phenylephrine group ( 1 of 48 ) ( P = 0.004 ) and less frequent in the combination group ( 1 of 47 ) ( P = 0.005 ) than in the ephedrine group ( 10 of 48 ) . The mean systolic arterial pressure was similar for the three groups : Phenylephrine group median 98 % ( IQR 94–103 ) of baseline , ephedrine group 100 % ( 96–106 ) and combination group 101 % ( 97–108 ) ( P = 0.11 ) . The mean heart rate was higher in the ephedrine group ( median 107 % [ IQR 99–118 ] of baseline ) than in the phenylephrine group ( 88 % [ 82–98 ] ) ( P < 0.0001 ) , or the combination group ( 96 % [ 86–102 ] ) ( P < 0.0001 ) . Nausea and vomiting were less frequent in the phenylephrine group ( nausea 17 % , vomiting 0 % ) than in the ephedrine group ( nausea 66 % , vomiting 36 % ) ( P < 0.0001 ) , or the combination group ( nausea 55 % , vomiting 18 % ) ( P < 0.0001 ) . Conclusions Giving phenylephrine alone by infusion at cesarean delivery was associated with a lower incidence of fetal acidosis and maternal nausea and vomiting than giving ephe-drine alone . There was no advantage to combining phenylephrine and ephedrine because it increased nausea and vomiting , and it did not further improve fetal blood gas values , compared with giving phenylephrine alone Background Because ephedrine infusion ( 2 mg/min ) does not adequately prevent spinal hypotension during cesarean delivery , the authors investigated whether adding phenylephrine would improve its efficacy . Methods Thirty-nine parturients with American Society of Anesthesiologists physical status I – II who were scheduled for cesarean delivery received a crystalloid preload of 15 ml/kg . Spinal anesthesia was performed using 11 mg hyperbaric bupivacaine , 2.5 & mgr;g sufentanil , and 0.1 mg morphine . Maternal heart rate and systolic blood pressure were measured at frequent intervals . A vasopressor infusion was started immediately after spinal injection of either 2 mg/min ephedrine plus 10 & mgr;g/min phenylephrine or 2 mg/min ephedrine alone . Treatments were assigned r and omly in a double-blind fashion . The infusion rate was adjusted according to systolic blood pressure using a predefined algorithm . Hypotension , defined as systolic blood pressure less than 100 mmHg and less than 80 % of baseline , was treated with 6 mg ephedrine bolus doses . Results Hypotension occurred less frequently in the ephedrine – phenylephrine group than in the ephedrine-alone group : 37%versus 75 % ( P = 0.02 ) . Ephedrine ( 36 ±16 mg , mean ± SD ) plus 178 ±81 & mgr;g phenylephrine was infused in former group , whereas 54 ±18 mg ephedrine was infused in the latter . Median supplemental ephedrine requirements and nausea scores ( 0–3 ) were less in the ephedrine – phenylephrine group ( 0 vs. 12 mg , P = 0.02 ; and 0 vs. 1.5 , P = 0.01 , respectively ) . Umbilical artery p H values were significantly higher in the ephedrine – phenylephrine group than in the group that received ephedrine alone ( 7.24 vs. 7.19 ) . Apgar scores were similarly good in both groups . Conclusion Phenylephrine added to an infusion of ephedrine halved the incidence of hypotension and increased umbilical cord p Combined spinal-epidural anesthesia ( CSE ) is a popular technique for cesarean delivery . Regional blocks in obstetrics are often performed with the parturient in the sitting position because the midline may be recognized more easily than in the lateral decubitus position . When conventional spinal anesthesia is performed in the sitting position , the patient is placed supine immediately after drug injection . In contrast , when CSE is performed with the woman sitting , there is a delay in assuming the supine position because of epidural catheter placement , which may affect the incidence of hypotension . Healthy women , at term of pregnancy , about to undergo an elective cesarean section under CSE , were r and omly assigned to the sitting or lateral recumbent position for initiation of the block . All parturients were given 1000 mL of lactated Ringer 's solution in the 15 min preceding induction and an additional 300 - 500 mL while the actual block was being performed . On completion of the CSE , they were turned to the supine position with left uterine displacement . A second anesthesiologist , blinded to the woman 's position during CSE , evaluated the sensory level of anesthesia , maternal heart rate , blood pressure , oxygen saturation , need for ephedrine , and occurrence of nausea and vomiting . Results are expressed as mean + /- SD . Twelve women were studied in the sitting group and 10 were studied in the lateral recumbent group . The severity and duration of hypotension were greater in those parturients who had CSE induced in the sitting ( 47 % + /- 7 % and 6 + /- 3 min , respectively ) compared with the lateral recumbent position ( 32 % + /- 14 % and 3 + /- 2 min , respectively ) . Women in the sitting group also required twice as much ephedrine ( 38 + /- 18 mg ) to correct hypotension compared with the other group ( 17 + /- 12 mg ) . In conclusion , the severity and duration of hypotension were greater when CSE was induced in the sitting compared with the lateral decubitus position . Implication s : We studied the induction of combined spinal-epidural anesthesia ( CSE ) in the sitting versus lateral recumbent positions in healthy women undergoing a scheduled cesarean delivery . The severity and duration of hypotension were greater when CSE was induced in the sitting position . Thus , the position used for induction of CSE should be among the factors considered when there is greater maternal or fetal risk from hypotension . ( Anesth Analg 1998;87:614 - 8 Background : In 1981 , with support from the American Society of Anesthesiologists and the American College of Obstetricians and Gynecologists , anesthesia and obstetric providers were surveyed to identify the personnel and methods used to provide obstetric anesthesia in the United States . The survey was exp and ed and repeated in 1992 with support from the same organizations . Methods : Comments and questions from the American Society of Anesthesiologists Committee on Obstetrical Anesthesia and the American College of Obstetricians and Gynecologists Committee on Obstetric Practice were added to the original survey instrument to include newer issues while allowing comparison with data from 1981 . Using the American Hospital Association registry of hospitals , hospitals were differentiated by number of births per year ( stratum I , > or= to 1,500 births ; stratum II , 500–1,499 births ; stratum III , < 500 births ) and by U.S. census region . A stratified r and om sample of hospitals was selected . Two copies of the survey were sent to the administrator of each hospital , one for the chief of obstetrics and one for the chief of anesthesiology . Results : Compared with 1981 data , there was an overall reduction in the number of hospitals providing obstetric care ( from 4,163 to 3,545 ) , with the decrease occurring in the smallest units ( 56 % of stratum III hospitals in 1981 compared with 45 % in 1992 ) . More women received some type of labor analgesia , and there was a 100 % increase in the use of epidural analgesia . However , regional analgesia was unavailable in 20 % of the smallest hospitals . Spinal analgesia for labor was used in 4 % of parturients . In 1981 , obstetricians provided 30 % of epidural analgesia for labor ; they provided only 2 % in 1992 . Regional anesthesia was used for 78–85 % ( depending on strata ) of patients undergoing cesarean section , result ing in a marked decrease in the use of general anesthesia . Anesthesia for cesarean section was provided by nurse anesthetists without the medical direction of an anesthesiologist in only 4 % of stratum I hospitals but in 59 % of stratum III hospitals . Anesthesia personnel provided neonatal resuscitation in 10 % of cesarean deliveries compared with 23 % in 1981 . Conclusions : Compared with 1981 , analgesia is more often used by parturients during labor , and general anesthesia is used less often in patients having cesarean section deliveries . In the smallest hospitals , regional analgesia for labor is still unavailable to many parturients , and more than one half of anesthetics for cesarean section are provided by nurse anesthetists without medical direction by an anesthesiologist . Obstetricians are less likely to personally provide epidural analgesia for their patients . Anesthesia personnel are less involved in newborn resuscitation Nausea and vomiting occur frequently during cesarean section under spinal anesthesia . Metoclopramide reduces intraoperative nausea and vomiting , but not without potential side effects . Acupressure , a noninvasive variation of acupuncture that involves constant pressure on the wrist , has been suggested as an alternative method to prevent nausea and vomiting . The aim of this study was to compare acupressure and intravenous ( IV ) metoclopramide for the prevention of nausea and vomiting during elective cesarean section under spinal anesthesia . Seventy-five patients were studied in a r and omized , prospect i ve , double-blind comparative trial . Group I patients received acupressure b and s + 2 mL IV saline , Group II patients received placebo wrist b and s + 10 mg IV metoclopramide , and Group III patients received placebo wrist b and s + 2 mL IV saline . Patients who received either acupressure or metoclopramide prior to initiation of spinal anesthesia for cesarean section had much less nausea than patients in the placebo group . Acupressure is an effective , nonpharmacologic method to reduce intraoperative nausea during elective cesarean section in the awake patient . ( Anesth Analg 1997;84:342 - 5 We studied 160 patients undergoing elective Caesarean section under spinal anaesthesia who received a preloading volume of 15 ml kg-1 of 10 % pentastarch in 0.9 % saline , or Hartmann 's solution , in a prospect i ve , r and omized , double-blind study . We compared the incidence of spinal-induced hypotension in each group . Hypotension was defined as a decrease in systolic arterial pressure to less than 70 % of baseline values or < or = 90 mm Hg , whichever was the greater . The groups were comparable in physical characteristics and there was no serious morbidity . Fetal outcome was similar in both groups . Significantly more patients in the Hartmann 's group ( n = 38 , 47.5 % ) developed hypotension than in the pentastarch group ( n = 10 , 12.5 % ) ( P < 0.0001 ) . Linear regression analysis showed that the only significant variable was type of fluid used . Blood glucose concentrations were not related to the presence of hypotension . We conclude that starches may be suitable for preloading in Caesarean section under spinal anaesthesia and provide an alternative to the aggressive use of vasoconstrictors Sixty healthy women undergoing elective Caesarean section were r and omly allocated to either a measured 15 ° left table tilt position ( n = 31 ) or full left lateral position ( n = 29 ) for a 15‐min period after spinal blockade . Arm and leg blood pressure , ephedrine requirements , symptoms , fetal heart rate , cord gases and Apgar scores were recorded . Mean ephedrine requirements and incidence of hypotension were similar in the two groups . Arm systolic arterial pressure over time was similar in both groups , but leg systolic arterial pressure over time was significantly lower in the tilt group ( p < 0.001 ) ; the mean leg systolic arterial pressure was lower for all 15 sequential recordings in the tilt group , reaching statistical significance ( p < 0.05 ) at 4 , 5 , 6 and 8 min . Differences in maternal nausea , vomiting and bradycardia and fetal outcome were not statistically significant . Following spinal anaesthesia , even a true 15 ° left table tilt position is associated with aortic compression BACKGROUND This study investigated the use of a Sequential Compression Device ( SCD ) with thigh-high sleeves and a preset pressure of 50 mm Hg that recruits blood from the lower limbs intermittently , as a method to prevent spinal hypotension during elective Caesarean section . Possible association of arterial pressure changes with maternal , fetal , haemodynamic , and anaesthetic factors were studied . METHODS Fifty healthy parturients undergoing elective Caesarean section under spinal anaesthesia were r and omly assigned to either SCD ( n=25 ) or control ( n=25 ) groups . A st and ardized protocol for pre-hydration and anaesthetic technique was followed . Hypotension was defined as a decrease in any mean arterial pressure ( MAP ) measurement by more than 20 % of the baseline MAP . Systolic ( SAP ) , MAP and diastolic ( DAP ) arterial pressure , pulse pressure ( PP ) , and heart rate ( HR ) were noted at baseline and every minute after the spinal block until delivery . RESULTS A greater than 20 % decrease in MAP occurred in 52 % of patients in the SCD group vs 92 % in the control group ( P=0.004 , odds ratio 0.094 , 95 % CI 0.018 - 0.488 ) . There were no significant differences in SAP , DAP , HR , and PP between the groups . CONCLUSION SCD use in conjunction with vasopressor significantly reduced the incidence of a 20 % reduction of MAP Aortocaval compression may not be completely prevented by the supine wedged or tilted positions . It is commonly believed , however , that the unmodified full lateral position after induction of spinal anaesthesia might allow excessive spread of the block . We therefore compared baseline arterial pressures in the supine wedged , sitting , tilted and full lateral positions in 40 women who were about to undergo elective caesarean section . They were then given spinal anaesthesia in the left lateral position and r and omised to be turned to the right lateral or the supine wedged position , after which speed of onset and spread of blockade to cold sensation were measured every 2 min for 10 min and mean arterial pressure and ephedrine requirement were recorded every minute for 20 min . Baseline mean arterial pressure was 9 mmHg ( 95 % CI 3 to 14 ) lower in the left lateral ( measured in the upper arm ) than in the sitting position ; those in the supine wedged and tilted positions were intermediate . Following spinal anaesthesia , hypotension ( defined as a reading < /=80 % of the baseline value in the same position ) lasted 2.4 min longer ( CI + 0.6 to + 4.1 ) in the supine wedged group , but there was no significant difference between the groups in maximum fall or ephedrine requirement . The upper level of block rose more rapidly in the supine wedged than in the lateral group and showed less variability . There is therefore no reason to fear the unmodified lateral group position , which may offer better protection against hypotension Hypotension is a common side effect of spinal anaesthesia for caesarean section . We have performed a r and omised , controlled study to determine the efficacy of a sequential compression device ( SCD ) ( Kendall ) in combination with thromboembolic deterrent ( TED ) stockings ( Kendall ) to reduce the incidence of hypotension in this setting . Within 20 min of spinal injection , there was no statistically significant difference in the incidence of hypotension ( defined as less than 100 mmHg and less than 80 % of baseline blood pressure ) ( TED/SCD group 65 % , control 80 % , P = 0.12 ) . However , there was a trend for those receiving TED/SCD prophylaxis to require less ephedrine to maintain normotension than the control group ( median TED/SCD 3 mg , control 6 mg , P = 0.08 ) . The administration of ephedrine deviated from protocol on a total of 46 occasions ( 2.3 % of recordings ) . To try to reduce the influence of this , we reinspected our data using time to first episode of hypotension with a Kaplan-Meier survival analysis . This showed that the instantaneous risk ( hazard ) of developing hypotension was 1.8 ( 95 % CI : 1.1 - 2.9 ) times higher in controls than those receiving TED/SCD prophylaxis ( P = 0.02 ) . Despite demonstrating some benefit of TED/SCD prophylaxis to prevent hypotension , we do not consider that the magnitude of this benefit warrants their routine use The ability of glycopyrronium to reduce the severity of hypotension following subarachnoid block in parturients with a relative bradycardia was evaluated in a double‐blind r and omised controlled study . Women with a resting heart rate of ≤ 80 beat.min−1 presenting for elective Caesarean section were r and omly allocated to receive either glycopyrronium 2 µg.kg−1 or normal saline intravenously once positioned for combined spinal‐epidural anaesthesia . Following spinal injection of 2.6 ml hyperbaric bupivacaine 0.5 % and fentanyl 15 µg , women r and omly allocated to the saline group were given 6 mg ephedrine so that all parturients received some prophylaxis against hypotension other than the fluid preload . Further ephedrine and fluid boluses were administered if mean arterial pressure fell 20 % or more from resting values . Using a sequential analysis technique , analysis after the first 20 subjects indicated the study should be stopped , with no difference in ephedrine requirements or hypotension between the groups . We conclude that pretreatment with glycopyrronium 2 µg.kg−1 is no more effective than 6 mg ephedrine in preventing hypotension following subarachnoid block in parturients with relatively low resting heart rates Twenty parturients undergoing elective Caesarean section were allocated r and omly to receive crystalloid preload 20 ml kg-1 over either 20 min or 10 min before spinal anaesthesia . Significant hypotension ( systolic arterial pressure less than 100 mm Hg and less than 80 % of baseline value ) occurred in six of the 10 patients in the 20-min preload group and seven of 10 patients in the 10-min preload group ( ns ) . Both groups had a significant ( P less than 0.05 ) increase in central venous pressure during the preload period . The mean central venous pressure in the 10-min group was 11.9 mm Hg ( range 6 - 19 mm Hg ) , which was significantly greater ( P less than 0.05 ) than that in the 20-min group ( mean 7.3 mm Hg , range 2 - 13 mm Hg ) . Three patients in the 10-min group had clinical ly unacceptable increases in central venous pressure . This study has demonstrated that rapid administration of crystalloid preload before spinal anaesthesia did not decrease the incidence or severity of hypotension , and questions the role of crystalloid preload Maternal position during induction of intrathecal anaesthesia for caesarean section influences block height and haemodynamic stability . In a r and omised study of 90 women presenting for elective caesarean section using combined spinal-epidural anaesthesia , three positions were compared -- the Oxford position ( group O ) , the right lateral to supine wedged ( group R ) and the sitting to supine wedged ( group S ) . Hyperbaric bupivacaine 12.5 mg with fentanyl 12.5 microg was injected intrathecally using a needle-through-needle CSE technique . Intravenous ephedrine 6 mg was given every minute that systolic blood pressure fell below 80 % of baseline . Time required for block height to reach T5 as assessed by light touch , was similar in the three groups . There were no significant differences in blood pressure although ephedrine requirements were less in group R. There were no significant differences in the incidence of maternal nausea and vomiting or in neonatal outcome as assessed by Apgar scores and umbilical cord blood gas analysis . Although the study failed to show any significant differences in block height between the groups , no women in group O had a block above T2 compared with three in group R and three in group Background In recent years , the concept of prophylactic volume expansion to prevent hypotension caused by spinal anesthesia has been challenged . Investigators have reevaluated the concept of prehydration in the obstetric patient and the physiologic mechanisms involved . This article addresses whether the hypotensive effects attributed to the atrial natriuretic factor are the reason for the apparent failure of prehydration . Methods Atrial natriuretic factor was measured before ( baseline ) and 10 min after spinal anesthetic drug injection ( control ) in 48 healthy pregnant patients scheduled for elective cesarean section . Sixteen patients received hydration with 15 ml/kg crystalloid immediately before spinal anesthesia , 16 patients received the same volume starting with the spinal anesthetic injection , and the remaining 16 patients received no prehydration ( control ) . Blood pressure , heart rate , ephedrine requirements , infused fluids , and urine output were measured . Results Atrial natriuretic factor concentrations increased significantly in prehydrated patients but not in the control group . There was a significant correlation in the change in atrial natriuretic factor concentrations and urine output but no correlation in the control atrial natriuretic factor concentrations and blood pressure or ephedrine requirements . Ephedrine requirements and blood pressure did not differ significantly among study groups . Conclusions Atrial natriuretic factor is a potent endogenous diuretic in the pregnant patient but does not appear to be involved in short-term cardiovascular homeostasis after spinal anesthesia . Prehydration appears to prevent hypotension after spinal anesthesia in the obstetric patient Background and Objectives . The effect of the head‐down tilt position after induction of spinal anesthesia for cesarean delivery on blood pressure and level of sensory block was examined . Methods . Patients were allocated r and omly into two groups , the head‐down tilt group ( n = 17 ) and the horizontal group ( n = 17 ) . In the head‐down tilt group , patients were positioned with a 10 ° head‐down tilt immediately after supine positioning , while those in the horizontal group were maintained in a horizontal position . All patients received 500 mL of lactated Ringer 's solution intravenously over 10 minutes prior to spinal injection , a wedge was placed under the patient 's right hip , and the operating table was rotated 5 ° in a counterclockwise direction to provide left uterine displacement . Hypotension ( defined as systolic blood pressure below 100 mm Hg ) was treated with 5 mg ephedrine intravenously and an increase in the infusion rate of lactated Ringer 's solution . The change in systolic blood pressure was expressed as percent change from the baseline value . Results . Systolic blood pressure decreased 20 % at 3 minutes after spinal block in both groups but recovered to half of this decrease . The incidence of postspinal hypotension was not different between the two groups . The total amount of ephedrine and lactated Ringer 's solution administered during the first 20 minutes of spinal block did not differ between the two groups nor did the extent of the cephalad spread of analgesia 20 minutes after spinal block ( T4 ± 2 vs T4 ± 1 for the headdown and horizontal groups , respectively ) . Conclusions . The head‐down position is concluded to have no effect on the incidence of hypotension during spinal anesthesia for cesarean delivery The recovery of 16 infants born by elective caesarean section with spinal anaesthesia , in which either ephedrine or fluid load was used to prevent maternal hypotension , were studied using Scanlon 's neurobehavioural tests and a computerized EEG . Neurobehavioural testing showed no differences between the ephedrine and the non‐ephedrine groups of infants at ages of 3 h , 1 day , 2 days and 4–5 days , whereas the spectral EEG showed significant differences between the two groups during the first 2 h after delivery , which had disappeared 24 h later . It is suggested that small doses of ephedrine given to the mother i.v . to prevent hypotension during spinal anaesthesia have short‐lived effects on the neonate 's central nervous system , which will be detected in the spectral EEG , but not in neurobehavioural tests We performed a r and omized , double-blinded dose-finding study of IV ephedrine for prophylaxis for hypotension in 80 women who received an IV crystalloid preload and spinal anesthesia for elective cesarean delivery . One minute after the intrathecal injection , patients were given saline control or ephedrine 10 , 20 , or 30 mg IV for 30 s. Systolic arterial pressure ( SAP ) in the first 12 min after the spinal injection was greater in the 30-mg group compared with other groups ( P < 0.05 ) . Hypotension occurred in 7 patients ( 35 % ) in the 30-mg group compared with 19 ( 95 % ) , 17 ( 85 % ) , and 16 ( 80 % ) patients in the control and 10- and 20-mg groups , respectively ( P < 0.0001 ) . Maximum decrease in SAP was smaller in the 30-mg group ( mean lowest SAP 87 % of baseline , range 58%–105 % ) compared with other groups ( P < 0.01 ) . Reactive hypertension occurred in 9 patients ( 45 % ) in the 30-mg group ( mean highest SAP 120 % of baseline , range 104%–143 % ) compared with 2 ( 10 % ) , 1 ( 5 % ) , and 5 ( 25 % ) patients in the other groups ( P = 0.009 ) . Heart rate changes , total ephedrine requirement , incidence of nausea and vomiting , and neonatal outcome were similar among groups . The proportion of patients with umbilical arterial pH < 7.2 was 10.5 % , 25 % , 42 % , and 22 % in the control , 10- , 20- , and 30-mg groups , respectively ( P = 0.12 ) . We conclude that the smallest effective dose of ephedrine to reduce the incidence of hypotension was 30 mg . However , this dose did not completely eliminate hypotension , nausea and vomiting , and fetal acidosis , and it caused reactive hypertension in some patients . Implication s We investigated different doses of IV ephedrine as prophylaxis for hypotension during spinal anesthesia for cesarean delivery and found that the smallest effective dose was 30 mg . However , this dose did not completely eliminate hypotension , caused reactive hypertension in some patients , and did not improve neonatal outcome STUDY OBJECTIVE Phenylephrine and ephedrine were compared in the prevention of maternal hypotension following spinal anesthesia for elective cesarean delivery . DESIGN R and omized , double-blind trial . SETTING Obstetric suite at a university-affiliated hospital . PATIENTS Sixty healthy patients electively scheduled for cesarean delivery under spinal anesthesia . INTERVENTIONS Patients were r and omly assigned to receive either ephedrine ( n = 29 ) in 10 mg intravenous ( IV ) bolus injections or phenylephrine ( n = 31 ) in 80 microgram IV bolus injections to maintain systolic blood pressure ( SBP ) above 100 mmHg . MEASUREMENTS AND MAIN RESULTS Maternal venous , umbilical artery , and umbilical vein blood gases were measured , and neonatal Apgar scores and Early Neonatal Neurobehavior Scale scores were assessed . In the ephedrine group , umbilical artery pH was 7.28 + /- 0.01 ( mean + /- SEM ) , umbilical artery partial pressure of carbon dioxide ( PCO2 ) was 56.6 + /- 1.4 mmHg , and umbilical artery base deficit was 2.2 + /- 0.04 meq . In the phenylephrine group , umbilical artery pH was 7.32 + /- 0.01 , umbilical artery PCO2 was 52.1 + /- 1.3 torr , and umbilical artery base deficit was 0.38 + /- 0.35 meq . There were significant differences between the groups in mean umbilical artery pH , PCO2 , and base deficit , although all values obtained were within normal limits . There were no significant differences between the groups in the remaining acid-base values , neonatal Apgar scores , Early Neonatal Neurobehavior Scale scores , or frequency of maternal nausea and vomiting . CONCLUSIONS Phenylephrine is as effective as ephedrine in the treatment of maternal hypotension , and when used in small incremental bolus injections , it appears to have no adverse neonatal effects in healthy , nonlaboring parturients Background Angiotensin II may prove useful in treating regional anesthesia‐induced hypotension in obstetric patients , because it causes less uterine vasoconstriction than do other vasoconstrictor drugs ( such as phenylephrine ) . This study compared ( 1 ) maternal blood pressure and heart rate and ( 2 ) fetal status at delivery in parturients given either prophylactic angiotensin II or ephedrine infusion during spinal anesthesia for elective cesarean delivery . Methods Fifty‐four women were r and omized to receive either angiotensin II or ephedrine infusion intravenously during spinal anesthesia for elective cesarean section delivery . Simultaneous with subarachnoid injection , infusion of angiotensin II ( 2.5 [ micro sign]g/ml ) or ephedrine ( 5 mg/ml ) was initiated at 10 ng [ middle dot ] kg‐1 [ middle dot ] min‐1 and 50 [ micro sign]g [ middle dot ] kg‐1 [ middle dot ] min‐1 , respectively . The rate of each infusion was adjusted to maintain maternal systolic blood pressure at 90–100 % of baseline . Results Cumulative vasopressor doses ( mean + /‐ SD ) through 10 , 20 , and 30 min were 150 + /‐ 100 , 310 + /‐ 180 , and 500 + /‐ 320 ng/kg in the angiotensin group and 480 + /‐ 210 , 660 + /‐ 390 , and 790 + /‐ 640 [ micro sign]g/kg in the ephedrine group . Maternal heart rate was significantly higher ( P < 0.001 ) during vasopressor infusion in the ephedrine group than in the angiotensin group . Umbilical arterial and venous blood pH and base excess were all significantly higher ( P < 0.05 ) in the angiotensin group than in the ephedrine group . Conclusions Angiotensin II infusion maintained maternal systolic blood pressure during spinal anesthesia without increasing maternal heart rate or causing fetal acidosis We have tested the hypotheses that glycopyrrolate , administered immediately before induction of subarachnoid anaesthesia for elective Caesarean section , reduces the incidence and severity of nausea , with no adverse effects on neonatal Apgar scores , in a double-blind , r and omized , controlled study . Fifty women received either glycopyrrolate 200 micrograms or saline ( placebo ) i.v . during fluid preload , before induction of spinal anaesthesia with 2.5 ml of 0.5 % isobaric bupivacaine . Patients were question ed directly regarding nausea at 3-min intervals throughout operation and asked to report symptoms as they arose . The severity of nausea was assessed using a verbal scoring system and was treated with increments of i.v . ephedrine and fluids . Patients in the group pretreated with glycopyrrolate reported a reduction in the frequency ( P = 0.02 ) and severity ( P = 0.03 ) of nausea . Glycopyrrolate also reduced the severity of hypotension , as evidence d by reduced ephedrine requirements ( P = 0.02 ) . There were no differences in neonatal Apgar scores between groups A r and omized double-blind study of 40 women was performed to compare blood pressure changes between two groups of women following induction of spinal anaesthesia for elective caesarean section . One group received a 1 L Ringer 's solution preload , administered over 10 min , before spinal anaesthesia while the other group received no preload . In both groups a prophylactic infusion of ephedrine ( 60 mg in Ringer 's solution 1000 ml ) was started immediately following intrathecal injection of local anaesthetic . There was no significant difference either in the ephedrine requirements or the incidence of hypotension between the two groups . There were no differences between the groups in terms of neonatal outcome as assessed by Apgar score , umbilical arterial and venous blood pH , and Neonatal Adaptive Capacity Scores . When ephedrine is infused prophylactically immediately following spinal anaesthesia for elective caesarean section , a 1000 ml crystalloid preload confers no advantages in terms of maternal blood pressure control or neonatal outcome This study was carried out to determine whether the use of thrombo-embolic deterrent ( TED ) stockings , in combination with an intravenous crystalloid preload , would prevent hypotension following spinal anaesthesia for caesarean section . Fifty parturients undergoing elective caesarean section under spinal anaesthesia were r and omly allocated into two groups . TED stockings were applied to the study group 1 h before spinal anaesthesia but none were applied to the control group . Both groups received a crystalloid preload of 15 ml kg(-1 ) over 15 min before spinal injection . Significant hypotension , defined as an absolute value of systolic arterial pressure ( SAP ) of less than 90 mmHg and a decrease of more than 20 % from baseline SAP was treated with 3 mg bolus of ephedrine as required . The difference in SAO between the two groups was not statistically significant . In the control group , 80 % of parturients required ephedrine as opposed to 56 % in the TED group ; a difference that was also not statistically significant The effects of i.v . vasopressors on Doppler velocimetry of the maternal uterine and placental arcuate arteries and the fetal umbilical , renal and middle cerebral arteries were studied during spinal anaesthesia in 19 healthy parturients undergoing elective caesarean section . Fetal myocardial function was investigated at the same time by M-mode echocardiography . The patients were r and omized into two groups , to be given either ephedrine or phenylephrine as a prophylactic infusion supplemented with minor boluses if systolic arterial pressure decreased by more than 10 mmHg from the control value . Both the vasopressors restored maternal arterial pressure effectively . The ephedrine group showed no significant differences in any of the Doppler velocimetry recordings relative to the baseline values , but during the phenylephrine infusion the blood flow velocity waveform indices for the uterine and placental arcuate arteries increased significantly and vascular resistance decreased significantly in the fetal renal arteries . Healthy fetuses seem to tolerate these changes in uteroplacental circulation well , however , since the Apgar scores for the newborns and the acid-base values in the umbilical cord were within the normal range in both groups . The results suggest that some caution is required when selecting the specific vasopressor agent , the dosage and the mode of administration for the treatment of maternal hypotension secondary to spinal anaesthesia for caesarean section This prospect i ve study recorded levels of analgesia ( loss of sharp pin prick sensation ) and anaesthesia ( loss of touch sensation ) in 220 women during caesarean section under regional anaesthesia ( 70 epidurals , 150 spinals ) . At delivery the difference between analgesia and anaesthesia varied from 0 - 7 segments for epidurals and 0 - 9 segments for spinals . During surgery the level of anaesthesia at the time pain was experienced varied between T5 and T10 . No patient with a level of anaesthesia which remained above T5 experienced pain . These results indicate that assessing the adequacy of block by sharp pin prick may be misleading and that in the absence of spinal or epidural narcotics a level of anaesthesia up to and including T5 is required to prevent pain during caesarean section We compared the efficacy of prophylactic ephedrine infusion over fluid preloading in prevention of maternal hypotension during spinal anaesthesia for Caesarean section . Forty‐six women undergoing elective Caesarean section at term were allocated r and omly to receive either intravenous fluid preloading with Hartmann 's solution 20 ml.kg−1 ( fluid group ) or prophylactic intravenous ephedrine 0.25 mgkg−1 ( ephedrine group ) . Moderate hypotension was defined as ≥ 20 % reduction in systolic blood pressure and severe hypotension as ≥ 30 % reduction in systolic blood pressure . Maternal uterine circulation was measured using Doppler ultrasound in 11 parturients before and after spinal anaesthesia . There was a lower incidence of severe hypotension in the ephedrine group compared with the fluid group ( 35 % vs. 65 % , p = 0.04 ) , although the incidence of moderate hypotension was similar . Mean umbilical venous pH was higher in the ephedrine group than in the fluid group ( 7.33 vs. 7.29 , p = 0.02 ) and the number of patients shivering was lower in the ephedrine group ( 2 vs. 9 , p = 0.02 ) . No difference was found between pre‐ and postspinal uterine artery pulsatility indices in either group . We conclude that prophylactic ephedrine infusion alone is at least as good as fluid preload alone in combating the hypotension associated with spinal anaesthesia for Caesarean section OBJECTIVE To assess the benefits of performing the cesarean section in lateral tilt during active labor . SETTING University Hospital . PATIENTS 204 unselected women undergoing cesarean section ( 21.1 % fetal distress , 45.6 % cephalo-pelvic disproportion , 26.0 % induction failure , 7.4 % abnormal presentation ) under general ( 86.8 % ) or spinal anesthesia ( 13.2 % ) . DESIGN R and omized study . INTERVENTION During anesthesia induction and cesarean section 103 women were in partial left lateralization ( 20 degrees ) , whereas the remaining 101 remained in the supine position . MAIN OUTCOME MEASURES Internal cardiotocography during cesarean section . Umbilical artery acid-base analysis . Newborn evaluation . Maternal hemodynamic parameters . RESULTS Fetal heart rate during cesarean section was similar in both groups , except for a baseline heart rate which was slightly higher in the lateral tilt group ( 137.5 + /- 19.2 vs 131.1 + /- 20 ) . The umbilical artery pH values , as well as pCO2 , base deficit , CO3H and oxygen saturation were similar in both groups . The pO2 value was significantly lower in the lateral tilt group ( 14.03 + /- 6.04 Hg mm vs 16.02 + /- 7.65 ) . Newborn evaluation was similar in both groups . The blood pressure and heart rate of the mother during the cesarean section were also similar in both groups . CONCLUSIONS No benefits were found in performing cesarean section in left lateral tilt To evaluate the effectiveness of prophylactic ephedrine for the prevention of hypotension associated with spinal anesthesia , 50 parturients undergoing cesarean delivery received either ephedrine 5 mg or saline IV in a double-blinded fashion immediately after the induction of spinal anesthesia . Spinal anesthesia was performed with hyperbaric bupivacaine 6.6 mg combined with sufentanil 3.3 & mgr;g as part of a combined spinal-epidural technique . All patients received 1000 mL of lactated Ringer ’s solution and 500 mL of hydroxyethylstarch 6 % before the spinal injection . Additional ephedrine boluses ( 5 mg ) were administered IV when the systolic blood pressure or heart rate decreased by more than 30 % from baseline values , when systolic blood pressure became < 100 mm Hg , or when patients complained of nausea or feeling faint . The height of the block was equal in the groups ; however , more patients in the placebo group were found to develop hypotension ( 58 % vs 25 % , P < 0.05 ) . Only 2 ( 8 % ) patients in the ephedrine group developed hypotension with systolic blood pressure values < 90 mm Hg , whereas 10 patients ( 42 % ) in the saline group experienced hypotension of this severity ( P < 0.05 ) . In addition , there was a higher incidence of nausea in the placebo-treated patients . The total amount of ephedrine administered did not differ between groups . These findings suggest that the incidence and severity of hypotension are significantly reduced by the IV administration of a prophylactic dose of 5 mg ephedrine in patients receiving small-dose spinal anesthesia for cesarean delivery . Implication s Ephedrine is the drug most often used to correct hypotension during spinal anesthesia for cesarean delivery in healthy patients . A single IV dose of 5 mg decreases the occurrence and limits the severity of hypotension in prehydrated subjects receiving a small-dose spinal local anesthetic-opioid combination The endogenous release of the vasoactive peptides atrial natriuretic peptide and endothelin‐1 may modify maternal haemodynamic responses to a rapid intravenous volume load used to prevent hypotension at elective Caesarean delivery under spinal anaesthesia . Twenty‐two healthy pregnant women were examined during elective Caesarean section at term pregnancy . They were r and omly assigned to receive either 2000ml of Ringer lactate solution ( crystalloid group ) or 500ml of 6 % hydroxyethyl starch + 1000 ml of Ringer lactate solution ( colloid group ) . The mean ( SEM ) concentration of atrial natriuretic peptide in plasma increased from 10.9 ( 1.5 ) to 24.7 (5.1)pmol.l‐1 during crystalloid infusion and from 10.3 ( 1.4 ) to 28.2 (5.6)pmol.l‐1 during colloid infusion . A slight decrease in endothelin‐1 levels was found during colloid infusion . A significant increase in the release of atrial natriuretic peptide in response to volume load may decrease vascular tone and initiate diuresis , thereby attenuating the effect of volume load on blood pressure during elective Caesarean delivery The effects of two types of uterine displacement , on uterine and umbilical artery blood flow waveforms were investigated in 22 healthy parturients undergoing elective caesarean section . Displacement was accomplished with either a wedge under the right hip or a mechanical displacer plus 5 degrees left lateral tilt of the operating table . The first 14 patients were assigned r and omly into one of the two displacement methods and the left ( underlying ) uterine and umbilical artery blood flow waveforms were recorded . In a further 8 patients the displacer was used and flow velocity waveforms for both the right and left uterine arteries and the umbilical artery were recorded . Arterial resistance was expressed in terms of the pulsatility index ( PI ) . There were no significant changes in Doppler velocimetry recordings after preloading in either group , but blood flow velocity waveform indices for the underlying left uterine artery increased significantly ( P < 0.001 ) following spinal anaesthesia when the mechanical device was used . This finding indicates increased vascular resistance in the left uterine artery and is probably due to mechanical compression . A wedge as a method for displacing the gravid uterus seems preferable since its use had no effect on the blood flow indices . The unaltered umbilical artery index values in the groups suggest a great tolerance of minor changes in maternal uterine circulation on the part of the fetus Objective : Effects of volume preloading during spinal anaesthesia for elective caesarean section on maternal blood pressure , feto-maternal circulation and fetal outcome . Patients and Methods : In a pilot study a r and omised trial was performed in 22 healthy women with uncomplicated , singleton pregnancies at 36–40 weeks of gestation undergoing elective caesarean section under spinal anaesthesia . In the low volume group ( group A ) patients received 150 ml of crystalloid solution for preloading , in the high volume group ( group B ) they were given 15 ml/kg of crystalloid solution for preloading before the initiation of spinal anaesthesia . Maternal blood pressure was monitored intermittently . Hypotension was defined as a decrease in systolic pressure to less than 80 % of the baseline value . The Doppler flow evaluation consisted of measurements from the uterine artery at the placental site , fetal umbilical artery and fetal middle cerebral artery . Pulsatility indices were derived before and after fluid preloading , and when spinal anaesthesia was established . The neonatal outcome was assessed by Apgar scores , arterial acid base status and neurologic and adaptive capacity scores ( NACS ) . Results : The incidence of maternal hypotension in both groups was 45.5 % ( n = 10 ) ; 3 cases occurred in group A compared to 7 cases in group B ( n.s . ) . There was no evidence that the high dose volume is useful in preventing maternal hypotension . The pulsatility indices of uterine arteries , umbilical arteries and middle cerebral arteries were not altered . Statistical analysis showed no changes in neonatal outcome concerning umbilical arterial pH , Apgar score and NACS ( n.s . ) between groups A and B. Conclusions : Our preliminary results suggest that high dose crystalloid volume preloading has no preventive function in the avoidance of maternal hypotension in healthy parturients undergoing elective caesarean section under spinal anaesthesia , and shows no harmful effects on neonatal outcome as long as maternal hypotension is corrected immediately . However , the statistical significance may reflect the small sample size , and larger series are needed before changing the current management AIM To compare the quality of anesthesia produced by the intrathecal administration of equivalent doses of 0.5 % and 1 % hyperbaric bupivacaine in patients undergoing cesarian section . EXPERIMENTAL DESIGN A prospect i ve , comparative and r and omised clinical study . SETTING Anesthesia Unit-Non-university civil hospital . PATIENTS 50 patients undergoing elective or emergency cesarian section r and omly assigned to two groups of 25 patients each . SURGERY After prehydration , subarachnoid access was achieved through space L2-L3 or L3-L4 using a 24 G Sprotte 's needle with patients in right h and lateral decubitus . Patients in group A were injected with 1.25 ml of 1 % hyperbaric bupivacaine and those in group B with 2.5 ml of 0.5 % hyperbaric bupivacaine ( 12.5 mg ) . Patients were positioned immediately in partial decubitus on their left h and sides and ephedrine infusion , or if required i.v . bolus , was commenced to counter hypotension ( SAP < 80 % basal ) . MEASUREMENTS ECG , pulse measurement , arterial pressure with non-invasive method , metameric level of analgesia ( pin prick ) , motor block of lower limbs ( Bromage 's scale ) , time lapsed between induction of anesthesia and extraction of neonate , Apgar score , quantity of ephedrine used , duration of surgery , respiratory complications , insufficient analgesia , resolution of motor block , any postspinal cephalea . STATISTICAL ANALYSIS Variance analysis , Student 's t-test , chi 2 . RESULTS Both solutions guaranteed satisfactory intraoperative analgesia in 96 % of cases . No statistically significant differences were noted between the two groups relating to the maximum duration of analgesia , the extent of motor block , induction times and regression , incidence of complications . CONCLUSIONS No important difference was observed in the quality of the anesthesia obtained using the intrathecal administration of equivalent doses of 1 % and 0.5 % solutions of hyperbaric bupivacaine in patients undergoing cesarian section . In view of the possible relationship between the neurotoxicity of local anesthetics and the concentration of the solution used for spinal anesthesia , it is to be hoped that less concentrated solutions of hyperbaric bupivacaine will be introduced in Italy compared to the 1 % solution currently available STUDY OBJECTIVE To evaluate the hemodynamic effects of an intravenous ( IV ) ephedrine bolus given simultaneously with spinal anesthesia for cesarean delivery . DESIGN R and omized , prospect i ve , double-blind study . SETTING Tertiary-care academic medical center . PATIENTS 40 ASA physical status I and II nonlaboring women undergoing elective cesarean delivery of term , uncomplicated , singleton pregnancies . INTERVENTIONS After a 10 mL/kg IV lactated Ringers bolus given over 15 minutes , patients simultaneously received an IV dose of 2 mL ( 10 mg ) ephedrine or 2 mL saline , and an intrathecal dose of 12 mg ( 1.6 mL 0.75 % ) bupivacaine with 10 microg of fentanyl . Hypotension , defined as a 20 % decrease in mean arterial pressure ( MAP ) , was treated with 10-mg IV doses of ephedrine . MEASUREMENTS Hemodynamic ( heart rate and MAP ) and non-invasive thoracic impedance ( cardiac index , stroke index , and systemic vascular resistance index ) measurements at baseline and at 1-minute intervals until the time of delivery . Total fluid , supplemental ephedrine , and Apgar scores were recorded . Data were evaluated using analysis of variance ( ANOVA ) , ANOVA for repeated measures , and Mann-Whitney U-tests where appropriate , with p < 0.05 considered significant . MAIN RESULTS Significant changes from baseline in MAP , systemic vascular resistance index , heart rate , and cardiac index were observed in both groups after spinal anesthesia . However , there were no differences between the ephedrine and saline groups in the incidence and severity of change from the baseline . The overall incidence of hypotension was 70 % in both groups . No difference in total fluid or supplemental ephedrine use was observed . CONCLUSIONS 10 mg of IV ephedrine given at the time of spinal anesthesia , and after a 10 mL/kg lactated Ringers fluid bolus , does not diminish the incidence or severity of hypotension in parturients undergoing cesarean delivery BACKGROUND This study was design ed to compare the efficacy of 10 % dextran 40 with lactated Ringer 's ( LR ) solution in reducing the incidence and severity of hypotension after spinal anesthesia for Cesarean section . METHODS Sixty ASA grade I patients scheduled for Cesarean section were r and omized into two groups in a double-blind fashion to receive either 500 ml of dextran 40 or 1000 ml of LR solution prior to induction of spinal anesthesia . RESULTS The incidence of hypotension was 16 in 30 ( 53.3 % ) in the LR solution group and 8 in 30 ( 26.7 % ) in the dextran group ( P < 0.05 ) . The required dose of ephedrine for treatment of hypotension was significantly greater in the LR solution group than in the dextran group ( 15.5 mg versus 3.2 mg , P < 0.05 ) . Neonatal outcome , as determined by Apgar score , was good and similar in both groups . CONCLUSIONS We concluded that 500 ml of dextran 40 is more effective than 1000 ml of lactated Ringer 's solution in reducing the incidence of hypotension induced by spinal anesthesia Purpose To determine if preoperative intravenous dextrose affects the incidence and ease of treatment of spinalinduced hypotension in parturients having elective Cesarean section under spinal anesthesia . Methods In this prospect i ve , double-blind study , following informed consent , 119 ASA I , II parturients for elective Cesarean section were r and omized to receive intravenously either dextrose 5 % in normal saline ( Group D ) or normal saline ( Group NS ) at 125 ml·hr−1 for two hours prior to delivery . Following a bolus of 15 ml·kg−1 normal salineiv , spinal anesthesia was induced with hyperbaric bupivacaine 0.75 % , fentanyl and morphine . Hypotension ( systolic blood pressure < 100 mm Hg or > 20 % decrease ) was treated with fluids and /or vasopressor . Data collected : demographics , blood glucose concentrations ( fasting , time of spinal , delivery ) , blood pressure ( baseline , one minute intervals from spinal to delivery ) , neonatal Apgar scores , umbilical blood gas analyses , glucose and lactate concentrations . Results There was no difference between the two groups in the rate of hypotension ( P=0.272 ) . All parturients who experienced hypotension received fluids , and there was also no difference between the groups in vasopressor requirement [ mean dose of ephedrine : Group D = 21.6 mg ( 95 % Cl 15.1–28.2 ) , Group NS = 16 mg ( 95 % Cl 12.0–20.5 ) ] . Conclusion The routine administration of dextrose 5 % at a rate of 5.22 g·hr−1 preoperatively does not affect the hypotension rate , or make it easier to treat . RésuméObjectif : Déterminer si l’administration intraveineuse préopératoire de dextrose modifie l’incidence d’hypotension à induction rachidienne et la facilité de son traitement chez des parturientes qui subissent une césarienne élective sous rachianesthésie . MéthodeAyant accordé leur consentement éclairé , 119 parturientes ASA I et II ont participé à une étude prospect i ve à double insu . Réparties au hasard , elles ont reçu pendant deux heures avant la césarienne prévue une perfusion intraveineuse de dextrose 5 % dans une solution salée ( Groupe D ) , ou d’une solution salée ( Groupe S ) , de 125 ml·hr−1 . Après l’administration iv d’un bolus de 15 ml·kg−1 de solution salée , la rachianesthésie a été induite avec de la bupivacaïne hyperbare à 0,75 % , du fentanyl et de la morphine . On a traité l’hypotension ( la tension artérielle systolique < 100 mmHg ou une baisse > 20 % ) avec des liquides et/ou un vasopresseur . On a noté : des renseignements personnels , les concentrations de glucose sanguin ( à jeun , au moment de la rachianesthésie , lors de l’accouchement ) , la tension artérielle ( une mesure de base , des mesures à intervalles d’une minute de la rachianesthésie à l’accouchement ) , l’indice d’Apgar , la gazométrie ombilicale , les concentrations de glucose et de lactate . RésultatsIl n’y a pas eu de différence intergroupe quant à la fréquence d’hypotension ( P = 0,272 ) . Toutes les parturientes qui ont souffert d’hypotension ont reçu des liquides . Il n’y a pas eu de différence intergroupe pour la dem and e de vasopresseur [ dose moyenne d’éphédrine : Groupe D = 21,6 mg ( IC 95 % ; 15 , 1–28,2 ) ; Groupe NS= 16 mg(IC 95 % ; 12,0–20,5 ) ] . Conclusion L’administration préopératoire de routine de dextrose à 5 % selon un débit de 5,22 g·hr−1 n’a pas d’effet sur la fréquence d’hypotension et ne facilite pas son traitement Twenty-four parturients undergoing elective Caesarean section were allocated r and omly to have the legs wrapped with elasticated Esmarch b and ages immediately following spinal anaesthesia or to serve as controls . Significant hypotension ( systolic arterial pressure less than 100 mm Hg and less than 80 % of baseline value ) was treated with i.v . ephedrine in 5-mg boluses . Leg wrapped patients had a significantly ( P = 0.0033 ) lower incidence ( 16.7 % ) of hypotension than controls ( 83.3 % ) . Only two patients in the leg wrapped group required ephedrine compared with 10 in the control group . Systolic arterial pressure was significantly ( P less than 0.05 ) less in control subjects at 4 , 5 and 6 min following spinal injection . No patient in the leg wrapped group became hypotensive following removal of the elasticated b and ages Maternal cardiovascular changes and neonatal acid-base status were assessed in 29 healthy women undergoing elective lower segment Caesarean section under spinal anaesthesia . The patients were allocated r and omly to one of three groups to receive an i.v . infusion of one of the following : ephedrine 1 mg min-1 ( group E1 : n = 10 ) , ephedrine 2 mg min-1 ( group E2 : n = 9 ) , or phenylephrine 10 micrograms min-1 ( group P : n = 10 ) . Invasive arterial pressure was monitored continuously and if hypotension occurred ( defined as a 20 % decrease from baseline , taken after i.v . preload administration ) , bolus doses of either ephedrine ( 6 mg in groups E1 and E2 ) or phenylephrine ( 20 micrograms in group P ) were given . Only four patients became hypotensive in group E2 , compared with eight patients in group E1 and nine patients in group P. The total time that the patients remained hypotensive was greatest in group P ( P < 0.005 ) , less in group E1 and least in group E2 . Neonatal Apgar scores and acid-base profiles were similar in all three groups . In this study , an infusion of phenylephrine 10 micrograms min-1 with bolus doses of 20 micrograms was shown to be significantly less effective in maintaining systolic arterial pressure within 20 % limits of baseline compared with an infusion of ephedrine 1 or 2 mg min-1 with bolus doses of 6 mg OBJECTIVE Our purpose was to study the efficacy of ephedrine versus angiotensin II prophylactic infusions to counter maternal hypotension that occurs during spinal anesthesia at cesarean delivery . STUDY DESIGN Healthy pregnant women undergoing elective repeat cesarean delivery at term with spinal anesthesia were r and omized either to a control group ( n = 10 ) or to one of two prophylactic infusion groups : angiotensin II ( n = 10 ) or ephedrine ( n = 10 ) . Prophylactic infusions were titrated to a maternal diastolic blood pressure 0 to 10 mm Hg above baseline . Maternal and fetal blood sample s for angiotensin II levels and acid-base status were obtained . Student 's t test , chi 2 , and analysis of variance were used . RESULTS Mean arterial pressures were maintained after spinal anesthesia in the ephedrine and angiotensin II groups but decreased ( p < 0.05 ) in the control group . Maternal angiotensin II levels rose with angiotensin II infusions but were unaltered in the other groups . Umbilical artery and vein angiotensin II levels were unaltered by angiotensin II infusions . Mean umbilical artery blood pH was lower ( p < 0.05 ) in the ephedrine group than in the angiotensin II and control groups . CONCLUSIONS In the healthy term fetus there is an advantage in using angiotensin II to maintain maternal blood pressure during regional anesthesia Inflatable splints and wrapping of the legs have been shown to be effective against hypotension during spinal anaesthesia for Caesarean section . The aim of this study was to investigate if compression stockings could have a similar effect . Thirty healthy mothers scheduled for elective Caesarean section were r and omised to have either compression stockings or no stockings on before spinal anaesthesia . The stockings had a pressure effect of 54 mmHg . The women were preloaded with 20 ml isotonic NaCl one hour preoperatively . Hypotension was defined as either a decrease in systolic blood pressure to 80 % of preoperative values or systolic blood pressure under 100 mmHg . Blood pressure was measured every second minute , and ephedrine 5 mg was given in the presence of hypotension . Two patients were excluded in the control group . There were no differences in demographic data , extension of blockade , and spinal injection to delivery time . Nine patients in the group with stockings had either no fall in blood pressure or a fall in blood pressure corrected with only 5 mg ephedrine . In the control group the corresponding number was four patients ( p < 0.12 ) . Ephedrine dose between zero and 20 minutes and total ephedrine dose was significantly lower in the group with stockings than in the control group ( p < 0.038 ) . Five patients in the control group experienced nausea , no patients in the study group had nausea ( p < 0.013 ) . In conclusion , compression stockings stabilised the blood pressure during Caesarean section in spinal anaesthesia and led to a significant smaller need for ephedrine St and ard textbooks advocate epidural rather than spinal anaesthesia for caesarean section in severe preeclampsia . The basis for this recommendation is the theoretical risk of severe hypotension but no published scientific studies have been identified to support this assertion . We therefore design ed a prospect i ve study to compare spinal versus epidural anaesthesia in severely pre-eclamptic patients requiring hypotensive therapy . Following ethics committee approval , 28 women with preeclampsia requiring hypotensive medication who were scheduled for urgent ( not emergency ) or elective caesarean section consented to receive epidural or spinal anaesthesia by r and om assignment . Seven patients were excluded due to protocol violations . Four of these were in the epidural group of which two were excluded due to inadequate analgesia . No spinal patient was excluded because of inadequate analgesia . Mean ephedrine dosage was 5.2 mg ( range 0 - 24 mg ) in the spinal group and 6.3 mg ( range 0 - 27 mg ) in the epidural group . Six of the 11 patients in the spinal group required no ephedrine as did five of 10 in the epidural group . One patient in the spinal group suffered from mild intraoperative pain . By contrast in the epidural group three patients had mild pain and four others had pain severe enough to warrant intraoperative analgesia . There were no differences in neonatal outcomes . These findings support recent studies suggesting the safety and efficacy of spinal anaesthesia in this group of patients |
11,960 | 31,237,873 | RESULTS QoL and glycaemic control was significantly better in CSII subjects at baseline and follow-up .
No significant differences in adverse events were found between study groups .
No significant changes over time could be shown for either QoL or glycaemic control .
CONCLUSION CSII proved to provide similar or slightly better outcomes in all analysed fields .
This is consistent with previous research . | BACKGROUND In 2017 , more than 1.1 million children were living with type 1 diabetes mellitus ( T1DM ) globally .
The goal in paediatric diabetes therapy is reaching optimal glycaemic control as early as possible in order to avoid complications and early mortality without compromising the quality of life ( QoL ) of children .
Several different insulin regimens are available for T1DM patients to reach this goal .
AIMS This review set out to analyse whether continuous subcutaneous insulin infusion ( CSII ) regimens are superior to multiple daily injection ( MDI ) therapy in T1DM youth regarding QoL. Additionally , it assessed glycaemic control and adverse events as secondary outcomes and discussed potential future public health implication s and justifications for using CSII as a first-line therapy in diabetic youth . | OBJECTIVE Effects of pump treatment vs. four times daily injections were explored in children with diabetes with regard to quality of life and impact of disease as well as adverse effects and parameters of metabolic control . METHODS An open , parallel , r and omized controlled prospect i ve comparative study lasting 14 months was completed by 38 type 1 children with diabetes ( age 4 - 16 yr ) following a 3.5-months run-in phase . St and ardized quality -of-life Pediatric Quality of life Inventory ( PedsQL ) and impact of disease scores were obtained every 3.5 months as well as regular medical parameters . Parallel treatment group data and longitudinal within-patient data were analysed for each treatment modality . RESULTS Within-patient comparisons of the two treatment modalities showed significant improvement in PedsQL and impact scores after pump treatment . Treatment group comparisons did not show significant improvement . Pump treatment result ed in decreased symptomatic hypoglycaemia and lowered haemoglobin A1c by 0.22 % after run in . CONCLUSIONS Within-patient comparison suggests that metabolic control , frequency of severe hypoglycaemia ( a threefold decrease ) , quality of life and impact of disease scores are improved by pump treatment in comparison to regular treatment with four daily insulin injections BACKGROUND The management of diabetes in preschool children poses unique difficulties for both the families and the medical team . OBJECTIVE To test the feasibility and safety of insulin pump therapy in the 1 - 6 year age group in order to improve quality of life and metabolic control . METHODS The study group comprised 15 type 1 diabetic children aged 1 - 6 years old ( mean + /- SD , 3.8 + /- 1.2 years ) from three diabetes centers . Insulin pump therapy was applied for 12 months . Data , including insulin dose , hemoglobin A1c , hypoglycemic events , as well as scores on the Diabetes Quality of Life Measure Question naire and the Diabetes Treatment Satisfaction Question naire , were collected and compared with the multiple daily injection treatment prior to entry into the study , RESULTS HbA1c was measured at the beginning of the study and at 2 , 4 , 8 and 12 months later ; the respective levels ( mean + /- SD ) were 8.82 + /- 0.98 , 8.45 + /- 1.05 , 8.37 + /- 0.85 , 8.32 + /- 0.71 , 8.18 + /- 0.90 % . HbA1c measurements after 12 months were significantly lower than at the beginning of the study ( P < 0.05 ) . There were no significant differences in insulin dose and the total number of hypoglycemic events . In both the DQOL and DTSQ scales there were significant differences in scores in favor of the insulin pump period ( 43.7 + /- 8.0 versus 33.7 + /- 7.9 , P < 0.001 ; and 10.9 + /- 2.3 versus 14.5 + /- 2.3 , P < 0.001 ) , respectively . CONCLUSIONS For very young diabetic children , insulin pump therapy improves quality of life and is feasible and safe . It should be considered as an optional mode of therapy for this age group OBJECTIVE Our goals were to determine if continuous subcutaneous insulin infusion ( CSII ) , compared with those continuing multiple daily injections ( MDIs ) , can be safely used in young children , if those on CSII will have superior glycemic control , if subjects using CSII will have less hypoglycemia for their level of control , and if families using CSII will report an improved quality of life . RESEARCH DESIGN AND METHODS We conducted a r and omized 1-year feasibility trial comparing CSII with continuing MDIs in preschool children with a history of type 1 diabetes for at least 6 months ' duration . Prospect i ve outcomes included measures of overall glycemic control ( HbA1c and continuous glucose monitoring system ) , the incidence of severe hypoglycemia and diabetic ketoacidosis , the percent of glucose values below 3.9 mmol/l , and the parents ' report of quality of life . RESULTS The 19 subjects ' ages ranged from 1.7 to 6.1 ( mean 3.6 ) years , duration of diabetes ranged from 0.6 to 2.6 ( mean 1.4 ) years , and baseline HbA1c ranged from 6.7 to 9.6 % ( mean 7.9 % ) . Seven subjects were male . Nine subjects were r and omized to start CSII and 10 to continue on MDI . All baseline characteristics were well balanced . Overall metabolic control , diabetes quality of life , and the incidence of hypoglycemia were similar in the two groups . No subject had diabetic ketoacidosis , while one subject in each group had an episode of severe hypoglycemia . No CSII subject discontinued using the pump during or after the study . CONCLUSIONS CSII can be a safe and effective method to deliver insulin in young children 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 Intensive therapy for type 1 diabetes mellitus ( DM ) is usually provided by either multiple daily injections of insulin ( MDI ) or by insulin pump ( continuous subcutaneous insulin infusion CSII ) . We design ed an open , r and omized , crossover trial to compare CSII with MDI for glycemic control , dose requirements , weight change , incidence of adverse events , quality of life and satisfaction in adolescents Purpose : To review research design s for rehabilitation . Summary of Key Points : Single-case , observational , and qualitative design s are highlighted in terms of recent advances and ability to answer important scientific questions about rehabilitation . Statement of Conclusions : Single-case , observational , and qualitative design s can be conducted in a systematic and rigorous manner that provides important information that can not be acquired using more common design s , such as r and omized controlled trials . These less commonly used design s may be more feasible and effective in answering many research questions in the field of rehabilitation . Recommendations for Clinical Practice : Research ers should consider these design s when selecting the optimal design to answer their research questions . We should improve education about the advantages and disadvantages of existing research design s to enable more critical analysis of the scientific literature we read and review to avoid undervaluing studies not within more commonly used categories OBJECTIVE To compare the efficacy and feasibility of continuous subcutaneous insulin infusion ( CSII ) with multiple daily insulin injections ( MDI ) in children with type 1 diabetes . METHODS The study sample included 23 children ( 10 males ) aged 9.4 to 13.9 years with type 1 diabetes . An open r and omized crossover design was used to compare 3.5 months of CSII to 3.5 months of MDI therapy for the following variables : diabetic control , incidence of adverse events , daily insulin requirement , body mass index st and ard deviation scores , treatment satisfaction , and quality of life . RESULTS The changes in HbA(1c ) and fructoseamine values were similar in the 2 arms over time . At the end of the study , mean HbA(1c ) level measured 8.05 + /- 0.78 % . There were no differences between the treatment modes in frequency of symptomatic hypoglycemic or hyperglycemic events . There was 1 event of severe hypoglycemia during pump therapy and 3 during MDI , yielding a rate of 0.26 events per patient-year . There were no episodes of diabetic ketoacidosis . Body mass index st and ard deviation scores decreased during CSII and increased during MDI , as did mean insulin dose . Patients expressed a higher treatment satisfaction from CSII than MDI , although there was no difference in quality of life between the 2 modes . CONCLUSIONS Intensive insulin therapy by either insulin pump or MDI is safe in children and young adolescents with type 1 diabetes , with similar diabetes control and a very low rate of adverse events . We suggest that both modes be available to the diabetic team to better tailor therapy BACKGROUND The risk of developing long-term complications of type 1 diabetes ( T1D ) is related to glycaemic control and is reduced by the use of intensive insulin treatment regimens : multiple daily injections ( MDI ) ( ≥ 4 ) and continuous subcutaneous insulin infusion ( CSII ) . Despite a lack of evidence that the more expensive treatment with CSII is superior to MDI , both treatments are used widely within the NHS . OBJECTIVES ( 1 ) To compare glycaemic control during treatment with CSII and MDI and ( 2 ) to determine safety and cost-effectiveness of the treatment , and quality of life ( QoL ) of the patients . DESIGN A pragmatic , open-label r and omised controlled trial with an internal pilot and 12-month follow-up with 1 : 1 web-based block r and omisation stratified by age and centre . SETTING Fifteen diabetes clinics in hospitals in Engl and and Wales . PARTICIPANTS Patients aged 7 months to 15 years . INTERVENTIONS Continuous subsutaneous insulin infusion or MDI initiated within 14 days of diagnosis of T1D . DATA SOURCES Data were collected at baseline and at 3 , 6 , 9 and 12 months using paper forms and were entered central ly . Data from glucometers and CSII were downloaded . The Health Utilities Index Mark 2 was completed at each visit and the Pediatric Quality of Life Inventory ( PedsQL , diabetes module ) was completed at 6 and 12 months . Costs were estimated from hospital patient administration system data . OUTCOMES The primary outcome was glycosylated haemoglobin ( HbA1c ) concentration at 12 months . The secondary outcomes were ( 1 ) HbA1c concentrations of < 48 mmol/mol , ( 2 ) severe hypoglycaemia , ( 3 ) diabetic ketoacidosis ( DKA ) , ( 4 ) T1D- or treatment-related adverse events ( AEs ) , ( 5 ) change in body mass index and height st and ard deviation score , ( 6 ) insulin requirements , ( 7 ) QoL and ( 8) partial remission rate . The economic outcome was the incremental cost per quality -adjusted life-year ( QALY ) gained . RESULTS A total of 293 participants , with a median age of 9.8 years ( minimum 0.7 years , maximum 16 years ) , were r and omised ( CSII , n = 149 ; MDI , n = 144 ) between May 2011 and January 2015 . Primary outcome data were available for 97 % of participants ( CSII , n = 143 ; MDI , n = 142 ) . At 12 months , age-adjusted least mean squares HbA1c concentrations were comparable between groups : CSII , 60.9 mmol/mol [ 95 % confidence interval ( CI ) 58.5 to 63.3 mmol/mol ] ; MDI , 58.5 mmol/mol ( 95 % CI 56.1 to 60.9 mmol/mol ) ; and the difference of CSII - MDI , 2.4 mmol/mol ( 95 % CI -0.4 to 5.3 mmol/mol ) . For HbA1c concentrations of < 48 mmol/mol ( CSII , 22/143 participants ; MDI , 29/142 participants ) , the relative risk was 0.75 ( 95 % CI 0.46 to 1.25 ) , and for partial remission rates ( CSII , 21/86 participants ; MDI , 21/64 ) , the relative risk was 0.74 ( 95 % CI 0.45 to 1.24 ) . The incidences of severe hypoglycaemia ( CSII , 6/144 ; MDI , 2/149 participants ) and DKA ( CSII , 2/144 participants ; MDI , 0/149 participants ) were low . In total , 68 AEs ( 14 serious ) were reported during CSII treatment and 25 AEs ( eight serious ) were reported during MDI treatment . Growth outcomes did not differ . The reported insulin use was higher with CSII ( mean difference 0.1 unit/kg/day , 95 % CI 0.0 to 0.2 unit/kg/day ; p = 0.01 ) . QoL was slightly higher for those r and omised to CSII . From a NHS perspective , CSII was more expensive than MDI mean total cost ( £ 1863 , 95 % CI £ 1620 to £ 2137 ) with no additional QALY gains ( -0.006 QALYs , 95 % CI -0.031 to 0.018 QALYs ) . LIMITATIONS Generalisability beyond 12 months is uncertain . CONCLUSIONS No clinical benefit of CSII over MDI was identified . CSII is not a cost-effective treatment in patients representative of the study population . FUTURE WORK Longer-term follow-up is required to determine if clinical outcomes diverge after 1 year . A qualitative exploration of patient and professional experiences of MDI and CSII should be considered . TRIAL REGISTRATION Current Controlled Trials IS RCT N29255275 and EudraCT 2010 - 023792 - 25 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 22 , No. 42 . See the NIHR Journals Library website for further project information . The cost of insulin pumps and consumables supplied by F. Hoffman-La Roche AG ( Basel , Switzerl and ) for the purpose of the study were subject to a 25 % discount on st and ard NHS costs OBJECTIVE Continuous subcutaneous insulin infusion ( CSII ) is on the rise among pediatric patients with type 1 diabetes mellitus . Metabolic effects alone can not explain this rising popularity . From the patient 's perspective , the main benefits of CSII may be found in subjective psychosocial health outcomes ( patient-reported outcomes [ PRO ] ) . SUBJECTS AND METHODS In a multicenter open r and omized controlled trial , children and adolescents aged 6 to16 years currently treated with multiple daily injections ( MDI ) were r and omized 1:1 , stratified by center , to either starting with CSII immediately after the baseline interview or to continuing MDI while waiting 6 months for transmission to CSII . The primary outcomes were patient-reported diabetes-specific health-related quality of life ( DHRQOL ) and diabetes burden of the main caregiver . Secondary outcomes were caregiver stress , fear of hypoglycemia , satisfaction with treatment , and HbA1c . RESULTS Two-hundred and eleven patients were r and omized between February 2011 and October 2014 , and 186 caregivers and 170 patients were analyzed using the intention-to-treat principle for primary outcomes . Children 8 to 11 years in the CSII group reported improved DHRQOL at follow-up compared to MDI ( median difference [ MD ] 9.5 , 95 % confidence interval [ CI ] 3.6 - 16.7 , P = 0.004 ) . There were no treatment differences in the adolescent age-group 12 to 16 years ( MD 2.7 ; 95 % CI -3.2 - 9.5 ; P = 0.353 ) . The main caregivers of the CSII group reported a significant decline of overall diabetes burden at follow-up compared to the MDI group ( MD 0 ; 95 % CI -1 - 0 ; P = 0.029 ) . Secondary PROs also were in favor of CSII . CONCLUSIONS CSII has substantial psychosocial benefits . PROs demonstrate these benefits . Registered as NCT01338922 at clinical trials.gov Importance Insulin pump therapy may improve metabolic control in young patients with type 1 diabetes , but the association with short-term diabetes complications is unclear . Objective To determine whether rates of severe hypoglycemia and diabetic ketoacidosis are lower with insulin pump therapy compared with insulin injection therapy in children , adolescents , and young adults with type 1 diabetes . Design , Setting , and Participants Population -based cohort study conducted between January 2011 and December 2015 in 446 diabetes centers participating in the Diabetes Prospect i ve Follow-up Initiative in Germany , Austria , and Luxembourg . Patients with type 1 diabetes younger than 20 years and diabetes duration of more than 1 year were identified . Propensity score matching and inverse probability of treatment weighting analyses with age , sex , diabetes duration , migration background ( defined as place of birth outside of Germany or Austria ) , body mass index , and glycated hemoglobin as covariates were used to account for relevant confounders . Exposures Type 1 diabetes treated with insulin pump therapy or with multiple ( ≥4 ) daily insulin injections . Main Outcomes and Measures Primary outcomes were rates of severe hypoglycemia and diabetic ketoacidosis during the most recent treatment year . Secondary outcomes included glycated hemoglobin levels , insulin dose , and body mass index . Results Of 30 579 patients ( mean age , 14.1 years [ SD , 4.0 ] ; 53 % male ) , 14 119 used pump therapy ( median duration , 3.7 years ) and 16 460 used insulin injections ( median duration , 3.6 years ) . Patients using pump therapy ( n = 9814 ) were matched with 9814 patients using injection therapy . Pump therapy , compared with injection therapy , was associated with lower rates of severe hypoglycemia ( 9.55 vs 13.97 per 100 patient-years ; difference , −4.42 [ 95 % CI , −6.15 to −2.69 ] ; P < .001 ) and diabetic ketoacidosis ( 3.64 vs 4.26 per 100 patient-years ; difference , −0.63 [ 95 % CI , −1.24 to −0.02 ] ; P = .04 ) . Glycated hemoglobin levels were lower with pump therapy than with injection therapy ( 8.04 % vs 8.22 % ; difference , −0.18 [ 95 % CI , −0.22 to −0.13 ] , P < .001 ) . Total daily insulin doses were lower for pump therapy compared with injection therapy ( 0.84 U/kg vs 0.98 U/kg ; difference , −0.14 [ −0.15 to −0.13 ] , P < .001 ) . There was no significant difference in body mass index between both treatment regimens . Similar results were obtained after propensity score inverse probability of treatment weighting analyses in the entire cohort . Conclusions and Relevance Among young patients with type 1 diabetes , insulin pump therapy , compared with insulin injection therapy , was associated with lower risks of severe hypoglycemia and diabetic ketoacidosis and with better glycemic control during the most recent year of therapy . These findings provide evidence for improved clinical outcomes associated with insulin pump therapy compared with injection therapy in children , adolescents , and young adults with type 1 diabetes OBJECTIVE To compare two intensified insulin therapy regimens - continuous subcutaneous insulin infusion ( CSII ) against multiple daily insulin injection ( MDI ) - in Danish adolescents examined in a prospect i ve , matched controlled study design . RESEARCH DESIGN AND METHODS Thirty type 1 diabetic adolescents at CSII and 26 matched MDI controls were included in this open intention-to-treat study . Actrapid was used in both groups . Before study entry , all participants followed a brush-up course in order to minimize study effect . At each visit , the following parameters were recorded : hemoglobin A1c ( HbA1c ) , insulin dose , weight , number of hypoglycemic and diabetic ketoacidosis ( DKA ) events , and the time re sources used . At entry and exit of the study , diet registration and vali date d quality -of-life ( QoL ) question naires were filled by the participants . RESULTS A non-significant decline in HbA1c was seen in both groups ( p = 0.468 ) ; HbA1c decreased from 9.5 to 8.9 % and from 9.7 to 9.5 % in the CSII and MDI group , respectively . The insulin dose and the number of severe hypoglycemic events per patient were lower ( non-significant ) in the CSII group . Both groups showed increased body mass index - highest in the CSII group - and mild to moderate DKA episodes were only seen among CSII users . No differences could be demonstrated within the QoL or diet registration s. CONCLUSIONS CSII treatment is beneficial as an intensified insulin therapy for selected type 1 diabetic patients and both MDI and CSII can be offered by the professional diabetes team to better tailor therapy . In future , there is a strong need to identify the characteristics of responders to CSII treatment in order to increase the efficacy and safety of CSII treatment |
11,961 | 18,254,042 | However , for the latter two outcomes , this was not clearly reflected in an increase in any other hypertensive complications .
AUTHORS ' CONCLUSIONS Evidence from this review does not support routine antioxidant supplementation during pregnancy to reduce the risk of pre-eclampsia and other serious complications in pregnancy | BACKGROUND Oxidative stress has been proposed as a key factor involved in the development of pre-eclampsia .
Supplementing women with antioxidants during pregnancy may help to counteract oxidative stress and thereby prevent or delay the onset of pre-eclampsia .
OBJECTIVES To determine the effectiveness and safety of any antioxidant supplementation during pregnancy and the risk of developing pre-eclampsia and its related complications . | Objective To determine whether antioxidant therapy alters the disease process in severe early onset pre‐eclampsia , in support of the hypothesis that increased lipid peroxides and reactive oxygen species production play an important role in the pathogenesis of the disease To study the effect of calcium and vitamin D supplementation on the incidence of toxaemia of pregnancy , 200 r and omly selected pregnant women ( supplemented group ) , were put on calcium ( 375 mg/day ) and vitamin D ( 1,200 IU/day ) supplements at 20 - 24 weeks of pregnancy onwards . Another 200 pregnant women constituted the non-supplemented group . At 32 and 36 weeks of pregnancy the systolic and diastolic blood pressure of non-toxemic women was significantly lower in the supplemented group than in the non-supplemented group . However , the incidence of toxaemia in the supplemented group ( 6 % ) was not significantly different from that in the non-supplemented group ( 9 % ) Hypertension during pregnancy increases fetal growth retardation , preterm deliveries , and perinatal deaths , and yet its causes remain unclear . In HIV-infected women , preterm birth additionally increases the risk of HIV transmission to the infant . Oxidative stress and endothelial cell dysfunction of the placenta have been implicated in the development of hypertension during pregnancy . Vitamin intake can reduce oxidative stress and improve endothelial function . We therefore evaluated the effect of multivitamin ( 20 mg thiamine , 20 mg riboflavin , 25 mg B-6 , 50 microg B-12 , 500 mg C , 30 mg E , and 0.8 mg folic acid ) and vitamin A supplements ( 30 mg beta-carotene plus 5000 IU preformed vitamin A ) in relation to hypertension during pregnancy ( systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg at any time during pregnancy ) . In a double-blind , placebo-controlled , r and omized , clinical trial , conducted among 1078 HIV-positive pregnant Tanzanian women , those who received multivitamins were 38 % less likely to develop hypertension during pregnancy than those who did not [ relative risk ( RR ) = 0.62 , 95 % CI 0.40 - 0.94 , P = 0.03 ] . There was no overall effect of vitamin A on hypertension during pregnancy ( RR = 1.00 , 95 % CI 0.66 - 1.51 , P = 0.98 ) . Hypertension during pregnancy was more likely in women with high baseline systolic blood pressure ( > 120 vs. < or = 120 mm Hg ) ( RR = 6.02 , 95%CI 2.59 - 13.97 , P < 0.001 ) , and those with higher mid-upper arm circumference ( RR = 1.12 , 95 % CI 1.04 - 1.19 , P = 0.002 ) . Taking multivitamins containing vitamins B , C , and E during pregnancy may be an inexpensive and effective strategy to improve the health of the mother and baby BACKGROUND Vitamin C is involved in the synthesis and degradation of collagen and is important for maintenance of the chorioamniotic membranes . Inadequate availability of ascorbic acid during pregnancy has been proposed as a risk factor for premature rupture of the chorioamniotic membranes ( PROM ) . OBJECTIVE The objective of the study was to evaluate the effectiveness of 100 mg vitamin C/d in preventing PROM . DESIGN A controlled double-blind trial was performed . Pregnant women ( n = 126 ) in their 20th wk of gestation were invited ; 120 accepted and were r and omly assigned to 2 groups ( 100 mg vitamin C/d or placebo ) . Every 4 wk , plasma and leukocyte vitamin C concentrations were measured , and each subject was evaluated for cervicovaginal infection . The incidence of PROM was recorded for each group as an indicator of the protective effect of vitamin C supplementation . RESULTS One hundred nine patients finished the study . Mean plasma vitamin C concentrations decreased significantly throughout the pregnancy in both groups ( P = 0.001 ) , and there were no significant differences between groups . Between weeks 20 and 36 , mean leukocyte vitamin C concentrations decreased from 17.5 to 15.23 microg/10(8 ) cells in the placebo group and increased from 17.26 to 22.17 microg/10(8 ) cells in the supplemented group ( within- and between-group differences : P = 0.001 ) . The incidence of PROM was 14 per 57 pregnancies ( 24.5 % ) in the placebo group and 4 per 52 pregnancies ( 7.69 % ) in the supplemented group ( relative risk : 0.26 ; 95 % CI : 0.078 , 0.837 ) . CONCLUSION Daily supplementation with 100 mg vitamin C after 20 wk of gestation effectively lessens the incidence of PROM CONTEXT Pregnant women who are positive for thyroid peroxidase antibodies [ TPOAb(+ ) ] are prone to develop postpartum thyroid dysfunction ( PPTD ) and permanent hypothyroidism . Selenium ( Se ) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis . OBJECTIVE We examined whether Se supplementation , during and after pregnancy , influences the thyroidal autoimmune pattern and function . DESIGN This was a prospect i ve , r and omized , placebo-controlled study . SETTING The study was conducted in the Department of Obstetrics and Gynecology and Department of Endocrinology . PATIENTS A total of 2143 euthyroid pregnant women participated in the study ; 7.9 % were TPOAb(+ ) . INTERVENTIONS During pregnancy and the postpartum period , 77 TPOAb(+ ) women received selenomethionine 200 microg/d ( group S1 ) , 74 TPOAb(+ ) women received placebo ( group S0 ) , and 81 TPOAb(- ) age-matched women were the control group ( group C ) . MAIN OUTCOME MEASURES We measured the prevalence of PPTD and hypothyroidism . RESULTS PPTD and permanent hypothyroidism were significantly lower in group S1 compared with S0 ( 28.6 vs. 48.6 % , P<0.01 ; and 11.7 vs. 20.3 % , P<0.01 ) . CONCLUSION Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism OBJECTIVE Rates of pre-eclampsia in women with type 1 diabetes are two to four times higher than in normal pregnancies . Diabetes is associated with antioxidant depletion and increased free radical production , and an increasing body of evidence suggests that oxidative stress and endothelial cell activation may be relevant to disease pathogenesis in pre-eclampsia . The Diabetes and Pre-eclampsia Intervention Trial ( DAPIT ) aims to establish if pregnant women with type 1 diabetes supplemented with vitamins C and E have lower rates of pre-eclampsia and endothelial activation compared with placebo treatment . METHODS DAPIT is a r and omised multicentre double-blind placebo-controlled trial that will recruit 756 pregnant women with type 1 diabetes from 20 metabolic-antenatal clinics in the UK over 4 years . Women are r and omised to daily vitamin C ( 1000 mg ) and vitamin E ( 400 IU ) or placebo at 8 - 22 weeks of gestation until delivery . Maternal venous blood is obtained at r and omisation , 26 and 34 weeks , for markers of endothelial activation and oxidative stress and to assess glycaemic control . The primary outcome of DAPIT is pre-eclampsia . Secondary outcomes include endothelial activation ( PAI-1/PAI-2 ) and birthweight centile In a previous study from this institution , patients at high risk for preterm labour were screened for the presence of bacterial vaginosis ( BV ) . When BV was present , they were r and omised to receive either treatment ( metronidazole ) or placebo ( vitamin C ) . There were significantly more patients with preterm labour in the metronidazole group . The aim of this double-blind r and omised placebo-controlled trial study was to determine whether vitamin C could indeed reduce the recurrence risk of preterm labour . Patients with a history of preterm labour in a preceding pregnancy were r and omised to receive 250 mg vitamin C or a matching placebo twice daily until 34 weeks ' gestation . They attended a dedicated premature labour clinic . Significantly more women delivered before term in the group that received vitamin C , but there was no difference in the outcome of the babies between the two groups . Supplementation with vitamin C did not prevent premature labour We studied the effect of VIBOVITmama ( Polfa Kutno S.A. ) supplementation on the course of pregnancy duration , delivery and puerperium and also the status of zinc , copper and selenium in the blood of matched maternal-cord pairs . Healthy pregnant women ( n=138 ) were divided by a double blinded trial into a test group taking vitamin and mineral supplementation containing 15 mg of zinc , 2 mg of copper and 20 microg of selenium and a control group taking placebo . Course of pregnancy , delivery and puerperium were analyzed , as well as concentration of bioelements in the blood serum of pregnant women in the I , II , and II trimester and in umbilical cord blood of their children . In the study group we noted fewer by 1.45 % cases of pregnancy induced hypertension and a much higher rate of natural deliveries ( 75 % ) in comparison to the control group ( 53 % ) . During pregnancy in the supplemented group a 1 % increase of zinc serum concentration was found . In the control group zinc concentration decreased by 7 % ( p < 0.005 ) . Insignificant differences in serum concentration of copper and selenium was observed between the study group and controls . In umbilical cord blood the differences in the concentration of the above microelements were also insignificant . The results allow for the statement that VIBOVITmama supplementation stabilizes the zinc , copper and selenium levels in blood of pregnant women without the risk of overdosing , especially with reference to selenium OBJECTIVE To determine whether supplementation with vitamins C and E after preterm premature rupture of membranes ( PPROM ) is associated with an increased latency period . METHODS In this double-blind , r and omized , controlled trial , 60 women with singleton pregnancies of 26 to 34 weeks ' duration and PPROM were r and omly assigned to vitamin C ( 500 mg/day ) and vitamin E ( 400 IU/day ) or placebo until delivery . All women received 2 doses of betamethasone in the first 24 h after admission as well as broad-spectrum antibiotic prophylaxis . RESULTS Important demographic , as well as clinical characteristics such as number of cases of chorioamnionitis , early neonatal sepsis , and respiratory distress syndrome , were similar in the 2 groups . A statically significant difference in the mean+/-S.D. number of days of latency was found between the groups ( 10.5+/-5.2 days vs. 3.5+/-4.0 days ( P = 0.03 ) . CONCLUSION Vitamins C and E supplementation of after PPROM is associated with a longer latency before delivery BACKGROUND Oxidative stress could play a part in pre-eclampsia , and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder . Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors . METHODS We did a r and omised , placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals . We assigned the women 1000 mg vitamin C and 400 IU vitamin E ( RRR alpha tocopherol ; n=1199 ) or matched placebo ( n=1205 ) daily from the second trimester of pregnancy until delivery . Our primary endpoint was pre-eclampsia , and our main secondary endpoints were low birthweight ( < 2.5 kg ) and small size for gestational age ( < 5th customised birthweight centile ) . Analyses were by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 62368611 . FINDINGS Of 2404 patients treated , we analysed 2395 ( 99.6 % ) . The incidence of pre-eclampsia was similar in treatment placebo groups ( 15 % [ n=181 ] vs 16 % [ n=187 ] , RR 0.97 [ 95 % CI 0.80 - 1.17 ] ) . More low birthweight babies were born to women who took antioxidants than to controls ( 28 % [ n=387 ] vs 24 % [ n=335 ] , 1.15 [ 1.02 - 1.30 ] ) , but small size for gestational age did not differ between groups ( 21 % [ n=294 ] vs 19 % [ n=259 ] , 1.12 [ 0.96 - 1.31 ] ) . INTERPRETATION Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk , but does increase the rate of babies born with a low birthweight . As such , use of these high-dose antioxidants is not justified in pregnancy This double-blinded , r and omized , controlled study was design ed to study the effect of dietary supplementation with red palm oil during pregnancy on maternal and neonatal vitamin A status . A total of 170 women were recruited at 16 to 24 weeks of gestation and r and omly assigned to an experimental group that received red palm oil to supply approximately one recommended dietary amount ( RDA ) ( 2,400 micrograms ) of beta-carotene or to a control group that received an equivalent volume of groundnut oil . The women received the oils for a period of 8 weeks , starting at 26 to 28 weeks of gestation and extending to 34 to 36 weeks of gestation . The mean postintervention ( 34 to 36 weeks ) levels of serum retinol were 1.20 + /- 0.22 ( SD ) mumol/L ( 95 % CI , 1.15 - 1.25 ) in women receiving red palm oil and 0.73 + /- 0.15 mumol/L ( 95 % CI , 0.69 - 0.77 ) in their infants ; these levels were significantly higher than those in women receiving groundnut oil ( 1.07 + /- 0.26 mumol/L ; 95 % CI , 1.01 - 1.13 ; p < .01 ) and their infants ( 0.62 + /- 0.17 mumol/L ; 95 % CI , 0.57 - 0.67 ; p < .001 ) . A significantly lower proportion of women in the red palm oil group than in the control group had vitamin A deficiency ( serum retinol levels < 0.7 mumol/L ) after intervention ( 1.5 % vs. 9.7 % ) . The proportion of women having anemia was significantly lower ( p < .01 ) in the red palm oil-supplemented group ( 80.6 % ) than in the control group ( 96.7 % ) . The mean birthweight and gestational age of the infants did not differ significantly between the two groups . An increased risk of low birth-weight ( p = .003 ) and preterm delivery ( p = .000 ) was observed with decreasing serum retinol levels in the third trimester of pregnancy . These results show that red palm oil supplementation significantly improved maternal and neonatal vitamin A status and reduced the prevalence of maternal anemia . Maternal vitamin A status in the later part of pregnancy is significantly associated with fetal growth and maturation . Hence red palm oil , a rich source of bioavailable vitamin A , could be used as a diet-based approach for improving vitamin A status in pregnancy OBJECTIVE We have previously reported a reduced incidence of preeclampsia in women who were at risk and were taking vitamin C ( 1000 mg/d ) and vitamin E ( 400 IU/d ) supplements . In this study , we determined whether supplementation in the same cohort was associated with an improvement in indices of placental dysfunction and oxidative stress toward values determined in women who were at low risk of preeclampsia . STUDY DESIGN Seventy-nine women who were at high risk and who were taking vitamin supplements and 81 who were taking placebos were compared with 32 women who were at low risk and who were not taking supplements who were studied simultaneously . RESULTS Indices of oxidative stress and placental function were abnormal in the placebo group . When the placebo group was compared with the women who were at low risk , ascorbic acid , plasminogen activator inhibitor-2 , and placenta growth factor concentrations were decreased ; and 8-epi-prostagl and in F(2alpha),leptin , and the plasminogen activator inhibitor-1/-2 ratio were increased . In the group that received vitamin supplements , ascorbic acid , 8-epi-prostagl and in F(2alpha ) , leptin , and plasminogen activator inhibitor-1/-2 values were similar to women who were at low risk . CONCLUSION Antioxidant supplementation in women who were at risk of preeclampsia was associated with improvement in biochemical indices of the disease The New Zeal and environment is low in selenium and iodine , and is therefore ideally suited for the study of these anionic trace elements . The aim of this study was to determine urinary excretion of selenium and iodine during pregnancy and postpartum as part of an investigation of the influence of pregnancy and lactation on selenium metabolism in women of low selenium status . In a double-blind placebo-controlled study , 35 women in the earliest stages of pregnancy and 17 non-pregnant women were recruited in Dunedin , New Zeal and . Eighteen pregnant women received 50 microg selenium as L-selenomethionine , while the others received a placebo daily during pregnancy and 12 months postpartum . The non-pregnant women received the supplement , serving as a positive control . Blood sample s and twenty-four hour urine sample s were collected monthly during pregnancy and at 3 , 6 , and 12 months postpartum for analysis of selenium and iodine . Selenium content in plasma and urinary excretion of selenium fell during pregnancy ; however , total excretion of selenium was greater during pregnancy than postpartum . Urinary iodine excretion was much lower than reported previously in New Zeal and . Due to large intra- and inter-subject variability , no trends in iodide excretion were observed . Factors which influence urinary excretion of selenium include dietary intake , but more closely , plasma concentrations of selenium ( which is probably related to total selenium pool ) , creatinine excretion and therefore lean body mass , and glomerular filtration rate . The exact mechanism and sequence of events remains unclear and future studies incorporating new speciation techniques are necessary Determinants of the recommended dietary allowance ( RDA ) for vitamin C include the relationship between vitamin C dose and steady-state plasma concentration , bioavailability , urinary excretion , cell concentration , and potential adverse effects . Because current data are inadequate , an in-hospital depletion-repletion study was conducted . Seven healthy volunteers were hospitalized for 4 - 6 months and consumed a diet containing < 5 mg of vitamin C daily . Steady-state plasma and tissue concentrations were determined at seven daily doses of vitamin C from 30 to 2500 mg . Vitamin C steady-state plasma concentrations as a function of dose displayed sigmoid kinetics . The steep portion of the curve occurred between the 30- and 100-mg daily dose , the current RDA of 60 mg daily was on the lower third of the curve , the first dose beyond the sigmoid portion of the curve was 200 mg daily , and complete plasma saturation occurred at 1000 mg daily . Neutrophils , monocytes , and lymphocytes saturated at 100 mg daily and contained concentrations at least 14-fold higher than plasma . Bioavailability was complete for 200 mg of vitamin C as a single dose . No vitamin C was excreted in urine of six of seven volunteers until the 100-mg dose . At single doses of 500 mg and higher , bioavailability declined and the absorbed amount was excreted . Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses . Based on these data and Institute of Medicine criteria , the current RDA of 60 mg daily should be increased to 200 mg daily , which can be obtained from fruits and vegetables . Safe doses of vitamin C are less than 1000 mg daily , and vitamin C daily doses above 400 mg have no evident value OBJECTIVE We sought to determine the effect of supplemental antioxidant vitamins C and E on the rate of preeclampsia in high-risk pregnant women . STUDY DESIGN Women at risk for preeclampsia ( previous preeclampsia , chronic hypertension , pregestational diabetes , or multifetal gestation ) were recruited at 14 to 20 weeks ' gestation and r and omly assigned to receive either 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily in addition to their regular prenatal vitamins . The primary outcome was the occurrence of preeclampsia . An estimated sample size of 220 women in each arm was determined to be necessary to demonstrate a 50 % reduction in the rate of preeclampsia . RESULTS Funding was terminated after 109 women had been recruited ; 9 were lost to follow-up or withdrew . We analyzed data from the remaining 100 women to look for differences in outcome and to estimate the required sample size for future studies . The rate of preeclampsia was not different : 17.3 % in women who received supplemental vitamins C and E , versus 18.8 % in the placebo group . Assuming a baseline rate of preeclampsia in the placebo group between 15 % and 20 % , we can estimate that 500 to 950 women in each arm will be required to show a clinical ly important reduction in the rate of preeclampsia . CONCLUSION The potential benefit of vitamin C and E supplementation to prevent preeclampsia in women with clinical risk factors is smaller than we estimated . Future studies of antioxidant vitamin supplementation in this population will require more than 500 women in each arm OBJECTIVE The possibility of reducing pregnancy-induced hypertension and preeclampsia in primigravidas with low doses of nutritional factors and relative rest in the left lateral position was investigated in a r and omized controlled , double-blind trial . METHOD Seventy-four normotensive women at 28 - 29 weeks ' gestation , judged to be at risk of PIH or pre-eclampsia because they presented with a mean blood pressure of 80 mmHg or higher and a positive roll-over test , were studied . The treatment protocol was received by 37 women and the other 37 women received st and ard antenatal control until delivery . RESULT Twenty-nine ( 78.3 % ) women in the control group developed PIH and /or pre-eclampsia , as opposed to only 4 ( 10.8 % ) cases in the treatment group ( P < 0.001 ) . There were no adverse effects of treatment in mothers or in infants . CONCLUSION This protocol reduces PIH and pre-eclampsia in primigravidas judged to be at risk of hypertension . Further studies are required to evaluate prostacyclin and prostagl and in E2 changes OBJECTIVE We sought to determine whether vitamins C and E could be delivered to the fetal-placental unit through maternal oral supplementation . STUDY DESIGN In a r and omized , double-blind study , 20 women received a daily prenatal vitamin with or without 400 IU of vitamin E and 500 mg of vitamin C , starting at 35 weeks ' gestation . At r and omization , a nutritional question naire , plasma vitamin C and E and red blood cell ( RBC ) vitamin E levels were determined . At delivery , concentrations of maternal and fetal plasma vitamin C and E , maternal and fetal RBC vitamin E , amniotic fluid vitamin C , and chorioamnion vitamin E and tensile strength were determined . RESULTS Maternal plasma vitamin E levels increased in the supplemented women but not in the control subjects . No changes in maternal vitamin C levels were noted . Maternal plasma vitamin C concentrations at delivery correlated closely with amniotic fluid vitamin C levels . Similarly , maternal plasma vitamin E levels at delivery correlated with the chorioamnion concentration of vitamin E. CONCLUSIONS Maternal plasma vitamin E levels are increased by oral supplementation . Maternal plasma vitamin C and E concentrations correlate with the concentration of vitamin C in the amniotic fluid and vitamin E in the chorioamnion , respectively OBJECTIVES To observe the effect of the antioxidant lycopene on the occurrence of pre-eclampsia and intrauterine growth retardation in primigravida women . METHODS A total of 251 primigravida women were enrolled in this prospect i ve , r and omized controlled study in the second trimester . A total of 116 women were given oral lycopene ( Group I ) in a dose of 2 mg twice daily while 135 women were given a placebo ( Group II ) in the same dose until delivery . The criteria for recruitment included gestational age of 16 - 20 weeks , singleton pregnancy , absence of any medical complication and willingness on the part of the women to participate in the study . The women were followed-up until delivery for development of pre-eclampsia , mode of delivery and fetal outcome . RESULTS The two groups were comparable in their maternal characteristics . Pre-eclampsia developed in significantly less women in the lycopene group than in the placebo group ( 8.6 % vs. 17.7 % , P=0.043 by chi-square test ) . Mean diastolic blood pressure was significantly higher in the placebo group ( 92.2+/-5.98 mmHg vs. 86.7+/-3.80 mmHg , P=0.012 ) . Mean fetal weight was significantly higher in the lycopene group ( 2751.17+/-315.76 g vs. 2657+/-444.30 g , P=0.049 ) . The incidence of intrauterine growth retardation was significantly lower in the lycopene group than in the placebo group ( 12 % vs. 23.7 % , P=0.033 ) . CONCLUSIONS The results of the present study suggest that the antioxidant lycopene reduces the development of pre-eclampsia and intrauterine growth retardation in primigravida women Much data have accrued in support of the concept that oxidation of LDL is a key early step in atherogenesis . The most consistent data with respect to micronutrient antioxidants and atherosclerosis appear to relate to alpha-tocopherol ( AT ) , the predominant lipid-soluble antioxidant in LDL . There are scant data on the direct comparison of RRR-AT and all-racemic (rac)-AT on LDL oxidizability . Hence , the aim of the present study was to examine the relative effects of RRR-AT and all-rac-AT on plasma antioxidant levels and LDL oxidation in healthy persons in a dose-response study . The effect of RRR-AT and all-rac-AT at doses of 100 , 200 , 400 , and 800 IU/d on plasma and LDL AT levels and LDL oxidation was tested in a r and omized , placebo-controlled study of 79 healthy subjects . Copper-catalyzed oxidation of LDL was monitored by measuring the formation of conjugated dienes and lipid peroxides over an 8-hour time course at baseline and again after 8 weeks . Plasma AT , lipid-st and ardized AT , and LDL AT levels rose in a dose-dependent fashion in both the RRR-AT and all-rac-AT groups compared with baseline . There were no significant differences in plasma , lipid-st and ardized , and LDL AT levels between RRR-AT and all-rac-AT supplementation at any dose comparison . The lag phases of oxidation were significantly prolonged with doses > or = 400 IU/d of RRR-AT and all-rac-AT , as measured by conjugated-dienes assay and at 400 IU/d of RRR-AT and 800 IU/d of both forms of AT by lipid peroxide assay . Again , there were no significant differences in the lag phase of oxidation at each dose for RRR-AT when compared with all-rac-AT . Also , there were no significant differences in LDL oxidation after in vitro enrichment of LDL with RRR-AT and all-rac-AT . Thus , supplementation with either RRR-AT or all-rac-AT result ed in similar increases in plasma and LDL AT levels at equivalent IU doses , and the degree of protection against copper-catalyzed LDL oxidation was only evident at doses > or = 400 IU/d for both forms BACKGROUND Oxidative stress has been implicated in the pathophysiology of pre-eclampsia . This r and omised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia . METHODS 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were r and omly assigned vitamin C ( 1000 mg/day ) and vitamin E ( 400 IU/day ) or placebo at 16 - 22 weeks ' gestation . Plasma markers of endothelial activation ( plasminogen-activator inhibitor 1 [ PAI-1 ] ) and placental dysfunction ( PAI-2 ) were measured every month until delivery . Pre-eclampsia was assessed by the development of proteinuric hypertension . Analyses were done by intention to treat , and in the cohort who completed the study . FINDINGS Supplementation with vitamins C and E was associated with a 21 % decrease in the PAI-1/PAI-2 ratio during gestation ( 95 % CI 4 - 35 , p=0.015 ) . In the intention-to-treat cohort , pre-eclampsia occurred in 24 ( 17 % ) of 142 women in the placebo group and 11 ( 8 % ) of 141 in the vitamin group ( adjusted odds ratio 0.39 [ 0.17 - 0.90 ] , p=0.02 ) . In the cohort who completed the study ( 81 placebo group , 79 vitamin group ) , the odds ratio for pre-eclampsia was 0.24 ( 0.08 - 0.70 , p=0.002 ) . INTERPRETATION Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease . Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different population Objective : To investigate maternal and neonatal outcomes after antioxidant supplementation relatively early in pregnancy ( 8 to 12 weeks ) for pregnant women with low antioxidant status . Methods : A r and omized , double-blind , placebo-controlled trial of daily antioxidant supplementation was performed on pregnant women screening positive for low antioxidant status at 8 to 12 weeks of gestation . Low antioxidant status was defined as a superoxidedismutase ( SOD ) level below 1102 U/g Hb or 164 U/mL. The supplementation group received the following antioxidants daily : vitamins A ( 1000 IU ) , B6 ( 2.2 mg ) , B12 ( 2.2 μg ) , C ( 200 mg ) , and E ( 400 IU ) , folic acid ( 400 μg ) , N-acetylcysteine ( 200 mg ) , Cu ( 2 mg ) , Zn ( 15 mg ) , Mn ( 0.5 mg ) , Fe ( 30 mg ) , calcium ( 800 mg ) , and selenium ( 100 μg ) . The control group received Fe ( 30 mg ) and folic acid ( 400 μg ) . Maternal ( preeclampsia , abortion , and hypertension ) and perinatal outcomes were assessed . Results : In the supplementation group ( 29 subjects ) , we observed 2 cases of preeclampsia ( 6.8 % , 1 mild and 1 severe ) , 1 of IUGR ( birth weight 2300 g at 38 weeks ) , and 1 preterm delivery . In the control group ( 31 subjects ) , there were 8 abortions , 9 cases of preeclampsia ( 29 % , 6 mild and 3 severe ) with perinatal outcome : 3 preterm delivery cases and 1 IUGR ( birth weight 2030 g at 39 weeks ) . Preeclampsia was significantly less frequent in the supplementation group when compared to the control group ( 2 vs. 9 cases , p = 0.043 , OR = 0.18 [ 95 % CI : 0.03 , 0.92 ] ) . Finally we focused on the prediction of preeclampsia at 8 to 12 weeks . Combined sensitivity of markers of antioxidant status ( SOD slutathione peroxidase , [ GPx ] , and total anti-oxidant status [ TAS ] ) was 33 % ( false-positive rate of 4.5 % ) . Conclusion : Antioxidant supplementation was associated with better maternal and perinatal outcome in pregnant women with low antioxidant status than control supplementation with iron and folate alone . In a selected population already screened positive for low SOD , preeclampsia can be detected in 33 % of asymptomatic cases in the first trimester using SOD , GPx , and TAS . It seems feasible that panels of both biochemical and molecular markers may be clinical ly useful in the prediction of this disease BACKGROUND Preterm infants are at increased risk of oxidative stress and free-radical mediated diseases partly related to deficient antioxidant state . The purpose of this study was to investigate if maternal supplementation of antioxidant vitamins prior to delivery would reduce the oxidative stress in the mothers and their infants . STUDY DESIGN A pilot case-control study . PATIENTS AND METHODS Five mothers at risk of preterm delivery between 30 and 36 weeks were given a daily oral dose of betacarotene 20 mg , vitamin E 167.8 mg and vitamin C 1000 mg until delivery . Plasma levels of MDA and vitamins A , E and beta-carotene were measured prior to treatment in mothers and at delivery in both mothers and neonates . Seven mother-infant pairs comparable in gestation and birthweight acted as controls . RESULTS In the supplemented group , median maternal plasma MDA at delivery was significantly lower compared to the pretreatment level ( 1.9 vs. 3.2 micromol/l , p=0.04 ) and it was also lower than the control group ( 1.9 vs. 3.65 micromol/l , p<0.001 ) . In the supplemented group , median maternal plasma vitamin E at delivery was significantly higher than the levels prior to treatment ( 46 vs. 31 micromol/l , p=0.007 ) in the same group and those at delivery in the control group ( 46 vs. 30 micromol/l , p=0.03 ) . There was a trend of lower plasma MDA and higher vitamin E at birth in infants born to supplemented mothers , but it did not reach statistical significance . CONCLUSION A short supplementation of multiple antioxidant vitamins to a small sample of preterm pregnant women reduced the oxidative stress at delivery in mothers and probably in their neonates . Larger studies probably using larger doses are needed to evaluate the efficacy of this strategy The effect of selenium ( Se ) supplement on pregnancy was studied in 52 pregnant women with high risk factors of pregnancy induced hypertension ( PIH ) . They were given natural Se dietetic liquid ( 100 micrograms/d ) for 6 - 8 weeks during late pregnancy , and 48 controls were given placebo . They received similar routine prenatal care . The results revealed that Se supplement on the pregnant women prevented and decreased the incidence of PIH and gestational edema , and elevated the mother 's blood Se level by 0.1008 + /- 0.091 ppm in the treated group while decreased by 0.0402 + /- 0.046 ppm in the control group ( P < 0.01 ) . The umbilical blood Se level was 0.2756 + /- 0.100 ppm in the treated group and 0.1544 + /- 0.051 ppm in the control ( P < 0.01 ) . The differences of the neonatal birth weight and the amount of postpartum hemorrhage between the two groups were not significant A potential role for oxidative stress in the pathophysiology of pre-eclampsia was first proposed by Stark in 1993 . Synthesis of free radicals by a dysfunctional placenta , and possibly by maternal leucocytes and endothelium , seems to play a central role in this association . Free radicals , through oxidative damage of biomolecules and lipid peroxidation , can initiate maternal vascular endothelial dysfunction and leucocyte activation . A comprehensive review of the role of oxidative stress in pre-eclampsia has been recently published . Antioxidants such as vitamin C and vitamin E have been proposed as potential therapeutic or prophylactic treatment for pre-eclampsia . This suggestion was supported by the observation that women with pre-eclampsia have lower plasma vitamin C concentrations . Both in vitro and in vivo studies suggest that there is an interaction between vitamin C and vitamin E , with vitamin C possibly exerting a ‘ redox ’ recycling effect on oxidised vitamin E within lipoproteins and membranes . The vitamin C to E ratio may be of central importance in protecting against the damaging effects of reactive oxygen species . To date , three placebo-controlled trials have assessed the effect of vitamins C and E on pre-eclampsia . Although no benefits were found when supplementation was given to women with diagnosed pre-eclampsia , a combination of 1 g/day of vitamin C and 400 IU/day of vitamin E given as prophylaxis to high risk women demonstrated a reduction in the risk of pre-eclampsia from 17 % in the control group to 8 % in the active treatment group . In this same double-masked r and omised controlled trial , women receiving vitamins C and E showed a reduction in biological markers of oxidative stress . Since this report , a number of multicentre r and omised clinical trials have been initiated both in low risk and in high risk population s , with the goal of testing the hypothesis that antioxidants reduce the incidence of pre-eclampsia ( Table 1 ) . In the UK , a multicentre trial is currently recruiting pregnant women with diabetes . The NIH has funded two antioxidant trials , one that is under way in Brazil and the second that is being conducted among nulliparous women in the NICHD Maternal Fetal Medicine Network . The International Trial of Antioxidants for the Prevention of Preeclampsia ( INTAPP ) , funded by the Canadian Institutes of Health Research , is enrolling nulliparas without additional risk factors ( Stratum I ) and multiparas and nulliparas with clinical risk factors for gestational hypertension ( Stratum II ) . Collectively , these trials should provide an answer to the question of the role of antioxidants in the prevention of pre-eclampsia and its related disorders . Recently , a meta- analysis of 19 clinical trials of vitamin E , for the most part secondary prevention trials , conducted in elderly population s at increased risk for a number of diseases ranging from lung or gastrointestinal cancer to cardiovascular disease , Alzheimer ’s disease or cataract , was published in the Annals of Internal Medicine . The authors of the meta- analysis concluded that high doses of vitamin E may be associated with an increased risk of all-cause mortality . What are the implication s of this meta- analysis for the ongoing pre-eclampsia prevention trials ? It is the responsibility of the Principal Investigators , the Steering Committees and Data Safety Monitoring Committees ( DSMC ) of ongoing clinical trials to take into account information generated from studies that arise in the course of their trial . They must assess the quality of the new evidence and determine how this information influences the balance of risks to benefits of the ongoing trials . In the case of the Canadian trial , both the DSMC and the hospital Ethics Committee have review ed the information and made their recommendations to the trial Steering Committee . The following is our evaluation of the quality of the evidence of the meta- analysis by Miller et al. , and its implication s for ongoing clinical trials of antioxidants in the prevention of pre-eclampsia |
11,962 | 20,504,053 | Variation in reduced hospitalization was found to be mainly due to variation in control service practice but model fidelity to team organization principles was also associated with reduced hospitalization .
Low caseloads and specified ACT staffing , however , had no effect at all on outcome . '
Ordinary CMHTs ' share most of the organizational aspects of ACT and appear to deliver equal outcomes with much reduced re sources . | Assertive community treatment is one of the most research ed and clinical ly replicated of all community mental health teams .
It is clearly defined with established scales to measure its model fidelity .
In the last decade its earlier cl aims to substantially reduce hospitalization have not been replicated in research studies .
This inconsistency has generated considerable controversy . | The only r and omised controlled trial to test high-fidelity assertive community treatment ( ACT ) in the UK ( the R and omised Evaluation of Assertive Community Treatment ( REACT ) study ) found no advantage over usual care from community mental health teams in reducing the need for in-patient care and in other clinical outcomes , but participants found ACT more acceptable and engaged better with it . One possible reason for the lack of efficacy of ACT might be the short period of follow-up ( 18 months in the REACT study ) . This paper reports on participants ' service contact , in-patient service use and adverse events 36 months after r and omisation Integrated mental health and substance abuse treatment within an assertive community treatment ( ACT ) approach was compared to that within a st and ard case management approach for 223 patients with dual disorders over three years . ACT patients showed greater improvements on some measures of substance abuse and quality of life , but the groups were equivalent on most measures , including stable community days , hospital days , psychiatric symptoms , and remission of substance use disorder BACKGROUND The significant reductions in hospital admission demonstrated in US assertive community treatment ( ACT ) studies have not been replicated in the UK . Explanations cite poor UK ' model fidelity ' and /or better UK st and ard care . No international model-fidelity comparisons exist . AIMS To compare high-fidelity US ACT teams with a UK team . METHOD The UK 700 's ACT team ( n=97 ) was compared with high-fidelity US ACT teams ( n=73 ) by using two measures : a forerunner of the Dartmouth Assertive Community Treatment schedule ( to assess adherence to ACT principles ) and 2-year prospect i ve activity data . RESULTS The UK and US teams had similar high-fidelity scores . Although significant differences were found in the amount and type of activity , practice differences in areas central to ACT were not great . CONCLUSIONS The failure of UK ACT studies to demonstrate the outcome differences of early US studies can not be attributed entirely to the lack of ACT fidelity Abstract Objective To compare outcomes of care from assertive community treatment teams with care by community mental health teams for people with serious mental illnesses . Design Non-blind r and omised controlled trial . Setting Two inner London boroughs . Participants 251 men and women under the care of adult secondary mental health services with recent high use of inpatient care and difficulties engaging with community services . Interventions Treatment from assertive community treatment team ( 127 participants ) or continuation of care from community mental health team ( 124 participants ) . Main outcome measures Primary outcome was inpatient bed use 18 months after r and omisation . Secondary outcomes included symptoms , social function , client satisfaction , and engagement with services . Results No significant differences were found in inpatient bed use ( median difference 1 , 95 % confidence interval −16 to 38 ) or in clinical or social outcomes for the two treatment groups . Clients who received care from the assertive community treatment team seemed better engaged ( adapted homeless engagement acceptance schedule : difference in means 1.1 , 1.0 to 1.9 ) , and those who agreed to be interviewed were more satisfied with services ( adapted client satisfaction question naire : difference in means 7.14 , 0.9 to 13.4 ) . Conclusions Community mental health teams are able to support people with serious mental illnesses as effectively as assertive community treatment teams , but assertive community treatment may be better at engaging clients and may lead to greater satisfaction with services BACKGROUND The aim was to compare the efficacy of intensive clinical case management ( ICM ) with st and ard community care in the management of ' hard to treat ' patients with a severe mental illness . METHOD A r and omised controlled trial was carried out in East Lambeth , a deprived area of inner London . Seventy people with psychosis design ated as ' hard to treat ' by referring teams were included ; 35 were r and omised to ICM ( case load eight patients per worker ) , and 35 to st and ard care , which offered follow-up by a community psychiatric nursing service ( 30 patients per worker ) . Outcome measures were admissions and hospital bed utilisation ; contact with services ; symptomatology ; social behaviour ; social functioning ; quality of life ; patients ' satisfaction with care at 9 and 18 months . RESULTS There were no differences in patients ' symptoms , social behaviour or social functioning . Quality of life was significantly improved in patients receiving ICM at 9 months . Satisfaction with care was significantly greater among case-managed patients . All ICM patients remained in contact with services throughout the study , while six control patients were refusing all contact with services at 18 months . CONCLUSIONS ICM failed to improve the clinical outcome of ' hard to treat ' patients . The service was successful in maintaining contact with patients , was greatly appreciated and had a positive effect on their perceived quality of life BACKGROUND The PRiSM Psychosis Study investigated the outcomes of community mental health services for epidemiologically representative cases of psychosis in London . METHOD The results presented in the preceding nine papers are interpreted . RESULTS ( a ) The health and social gains reported in experimental studies of community health services are replicable in ordinary clinical setting s , and are more effective than hospital-oriented services which they replace . ( b ) Dilution does occur -- these gains are less pronounced than in experimental ( efficacy ) studies . ( c ) Both models of community services produced a range of improved outcomes . ( d ) Some limited extra advantages ( in terms of met needs , improved quality of life , and social networks ) were found in the intensive sector . ( e ) There is no consistent evidence that community-oriented services ( which include in-patient beds ) fail service users , their families or the wider public . On balance the results weigh slightly in favour of the two-team model ( for acute and continuing care ) in terms of clinical effectiveness , but the general model is almost as effective and is less expensive . CONCLUSIONS The evidence supports a community-oriented rather than a hospital-oriented approach and there is little difference between the community mental health team models OBJECTIVE The study examined the association between fidelity of programs to the assertive community treatment model and client outcomes in dual disorders programs . METHODS Assertive community treatment programs in the New Hampshire dual disorders study were classified as low-fidelity programs ( three programs ) or high-fidelity programs ( four programs ) based on extensive longitudinal process data . The study included 87 clients with a dual diagnosis of severe mental illness and a comorbid substance use disorder . Sixty-one clients were in the high-fidelity programs , and 26 were in the low-fidelity programs . Client outcomes were examined in the domains of substance abuse , housing , psychiatric symptoms , functional status , and quality of life , based on interviews conducted every six months for three years . RESULTS Clients in the high-fidelity assertive community treatment programs showed greater reductions in alcohol and drug use and attained higher rates of remission from substance use disorders than clients in the low-fidelity programs . Clients in high-fidelity programs had higher rates of retention in treatment and fewer hospital admissions than those in low-fidelity programs . No differences between groups were found in length of hospital stays and other residential measures , psychiatric symptoms , family and social relations , satisfaction with services , and overall life satisfaction . CONCLUSIONS Faithful implementation of , and adherence to , the assertive community treatment model for persons with dual disorders was associated with superior outcomes in the substance use domain . The findings underscore the value of measures of model fidelity , and they suggest that local modifications of the assertive community treatment model or failure to comply with it may jeopardize program success A 2-year experimental cost study of 10 Intensive Psychiatric Community Care ( IPCC ) programs was conducted at Department of Veterans Affairs ( VA ) medical centers in the Northeast . High hospital users were r and omly assigned to either IPCC ( n = 454 ) or st and ard VA care ( n = 419 ) at four neuropsychiatric ( NP ) and six general medical and surgical ( GMS ) hospitals . National computerized data were used to track all VA health care service usage and costs for 2 years following program entry . At 9 of the 10 sites , IPCC treatment result ed in reduced inpatient service usage . Overall , for IPCC patients compared with control patients , average inpatient usage was 89 days ( 33 % ) less while average cost per patient ( for IPCC inpatient , and outpatient services ) was $ 15,556 ( 20 % ) less . Additionally , costs for IPCC patients compared with control patients were $ 33,295 ( 29 % ) less at NP sites but were $ 6,273 ( 15 % ) greater at GMS sites . At both NP and GMS sites , costs were lower for IPCC patients in two subgroups : veterans over age 45 and veterans with high levels of inpatient service use before program entry . No interaction was noted between the impact of IPCC on costs and other clinical or sociodemographic characteristics . Similarly , no linear relationship was observed between the intensity of IPCC services and the impact of IPCC on VA costs , although the two sites that did not fully implement the IPCC program had the poorest results . With these sites excluded , the total cost of care for IPCC patients at GMS sites was $ 579 ( 3 % ) more per year than that for the control patients One hundred and twenty patients presenting for admission to a state psychiatric hospital were r and omly allocated into two groups . Control patients received st and ard hospital care and after-care . Experimental patients were not admitted if this could be avoided ; instead they and their relatives were provided with comprehensive community treatment and a 24-hour crisis service . Patients with a primary diagnosis of alcohol or drug dependence , organic brain disorder or mental retardation were excluded . Most patients were suffering from psychotic disorders -- more than half specifically from schizophrenia . During the 12 months study period 96 % of the control patients were admitted--51 % more than once . Of the experimental patients 60 % were not admitted at all and only 8 % were admitted more than once . Control patients spent an average of 53.5 days in psychiatric hospital , experimental patients spent an average of 8.4 days . Community treatment did not increase the burden upon the community , was considered to be significantly more satisfactory and helpful by patients and their relatives , achieved a clinical ly superior outcome , and cost less than st and ard care and after-care . The ingredients differentiating comprehensive community-based care from prevailing methods of psychiatric care are discussed BACKGROUND The costs and the effectiveness of mental health services need to be evaluated if provision is to be efficient . Service use and costs are described for two geographical areas in south London . METHOD Service use was measured comprehensively for clients in both sectors for two six-month time periods using the Client Service Receipt Interview . This information was combined with unit costs to calculate service costs . The ' hidden ' costs of informal care and unsupported accommodation were also calculated . RESULTS At baseline significantly more intensive sector clients had in-patient stays but by the follow-up this difference had disappeared . There was significantly more use of supported accommodation in the intensive sector during both time periods . Baseline and follow-up total service costs were significantly higher for the intensive sector . Costs were spread disproportionately and a small number of services accounted for a large proportion of cost . CONCLUSIONS While the cost at Time 2 was significantly greater in the intensive sector , this was largely due to the high use of supported accommodation . There was some convergence in cost between the sectors over time BACKGROUND Case management has increasingly been the recommended approach to care for severely mentally ill patients since the number of psychiatric beds has decreased . Despite equivocal results , in the UK and Europe , this approach is becoming accepted policy . We assessed the effect of smaller case loads . METHODS We r and omly assigned 708 psychotic patients in four centres st and ard case management ( 355 patients , case load 30 - 35 per case manager ) or intensive case management ( 353 patients , case load 10 - 15 per case manager ) . We measured clinical symptoms and social functioning at baseline , 1 year , and 2 years . The impact of treatment on hospital use was assessed at 2 years by subgroup analyses for Afro-Caribbean and for severely socially disabled patients . Analysis was by intention to treat . FINDINGS There was no significant decline in overall hospital use among intensive-case-management patients ( mean 73.5 vs 73.1 days in those who received st and ard care [ SD 0.4 , 95 % CI -17.4 to 18.1 ] ) , nor were there any significant gains in clinical or social functioning . There was no evidence of differential effect in Afro-Caribbean patients or the most socially disabled patients . INTERPRETATION In well-coordinated mental-health services , a decline in case load alone does not improve outcome for these patients . Mental-health planners may need to pay more attention to the content of treatment rather than changes in service organisation |
11,963 | 23,357,663 | Natriuretic peptides , including B-type natriuretic peptide ( BNP ) and N-terminal-proBNP ( NT-proBNP ) , have emerged as powerful markers of cardiovascular risk in patients with heart failure.1 Circulating natriuretic peptide ( NP ) levels add incremental prognostic value to st and ard clinical risk stratification algorithms for both ambulatory and hospitalized heart failure patients , with a steady increase in the risk of mortality and recurrent heart failure hospitalization as NT-proBNP levels rise above 1000 pg/mL.2–5 A systematic review of 19 studies of patients with heart failure demonstrated that for every 100-pg/mL rise in BNP concentration , there was a corresponding 35 % increase in the relative risk of death.6 Response by Januzzi and Troughton on p 516 Beyond the prognostic value of a single NP measurement , changes in NP concentrations over time may help to further stratify risk.2,7 Reductions in NP levels , whether achieved spontaneously or through application of appropriate medical therapy , appear to be associated with improvement in clinical outcomes .8,9 In the Valsartan Heart Failure Trial , subjects with the largest proportional reductions in BNP levels at 4 months after r and omization experienced the best outcomes , whereas those with the greatest increase in BNP levels experienced the highest event rates.7 Among patients hospitalized with decompensated heart failure , both predischarge NP levels and the relative change in NP levels during hospital treatment are strong predictors of the risk for death or hospital readmission at 6 months.8,10,11 In addition to their association with risk for adverse cardiovascular outcomes , circulating levels of NP appear to vary in relationship to the biology of heart failure progression .
NP levels tend to rise during acute heart failure decompensation and to fall with successful treatment in a pattern that mirrors reductions in filling pressure , improvements in left ventricular structure and function , | null | null |
11,964 | 27,649,908 | A meta- analysis found no evidence of increased HIV VL associated with HCV co-infection or between HIV VL and HCV treatment with pegylated interferon-alpha-2a/b and ribavirin .
CONCLUSIONS This finding is in contrast to the substantial increases in HIV VL observed with several other systemic infections . | INTRODUCTION Hepatitis C virus ( HCV ) and HIV infection frequently co-occur due to shared transmission routes .
Co-infection is associated with higher HCV viral load ( VL ) , but less is known about the effect of HCV infection on HIV VL and risk of onward transmission . | BACKGROUND The short- and long-term effects of anti-hepatitis C treatment on mortality in the HIV-HCV-coinfected population have not been evaluated in observational cohorts . Such evaluations must use methods that allow for time-varying prognostic factors that both predict treatment and are affected by prior treatment . We aim ed to study immunological changes in HIV-HCV-coinfected individuals during HCV treatment and to estimate the effect of HCV-treatment on mortality . METHODS Patients were included if they were aged ≥16 years , were HIV-HCV-coinfected and were enrolled in the COHERE cohort . Data were pooled within COHERE in December 2009 in EuroCoord . R and om-effects models were used to model immunological changes during HCV treatment . Marginal structural models were used to estimate the effect of HCV treatment on mortality , allowing for time-dependent confounders affected by prior treatment . RESULTS In total , 780/6,433 ( 12 % ) HIV-HCV-coinfected patients initiated HCV treatment ( interferon [ IFN ] and ribavirin n=692 , IFN alone n=88 ) . CD4(+ ) T-cell counts decreased during the first 12 weeks of treatment ( P<0.0001 ) and stabilized from week 24 onwards . The estimated mortality hazard ratio for comparing HCV-treated with -untreated individuals was 0.72 ( 95 % CI 0.43 , 1.21 ) . The estimated hazard ratio for liver-related death was 0.57 ( 95 % CI 0.21 , 1.55 ) . CONCLUSIONS Despite its effect in reducing CD4(+ ) T-cell counts , the effect of HCV treatment on mortality was in the direction of benefit and our results excluded a substantial increase in mortality . Such benefit may be related to a lower risk of liver-related death . New HCV treatment strategies might contribute to a further reduction in mortality Background Hepatitis C virus ( HCV ) is an RNA virus which has been known to cause acute and chronic necro-inflammatory disease of the liver . It is the leading cause of end-stage liver disease and hepatocellular carcinoma . HIV is known to have a negative impact on the natural disease outcome and immune response of HCV infection , whereas the reverse remains unclear . We evaluated the impact of HCV co-infection on recovery of CD4 + and CD8 + T-cells and liver enzyme levels before and after initiation of highly active antiretroviral therapy ( HAART ) in HIV/HCV co-infected patients . Methods A hospital-based , observational , prospect i ve cohort study design was used for this study . Pre-antiretroviral treatment ( Pre-ART ) and under HAART HIV mono-infected and HCV/HIV co-infected individuals who are under regular follow-up were recruited for this study . 387 blood sample s were collected from volunteer , known HIV positive Ethiopian patients and screened for HCV . Twenty five HCV/HIV co-infected patients were prospect ively followed for four years . CD4 + and CD8 + T-cells and liver enzyme levels were determined annually for each of the participant . Results The prevalence of HCV/HIV co-infection in this study was 6.5 % . Both HCV/HIV co-infected and HIV mono-infected under HAART groups showed CD4 + recovery ( 343 Vs 426 ; P < 0.004 , OR = 4.97 , 95 % CI = 2.41 to 10.27 ) respectively ; but , the recovery rate was higher in mono-infected ( 80 Vs 426 ) than co-infected group ( 148 Vs 343 ) . The recovery and /or decline pattern of CD8 + T-cells was the same with that of CD4 + . In 75 % of co-infected groups , the mean alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) levels were above the upper limit of normal reference range . Analyses restricted to individuals who initiated HAART and pre-ART showed similar results . Conclusion We found that CD4 + T-cell recovery was negatively affected by the presence of ongoing HCV replication in under HAART co-infected individuals and fast decline of CD4 + T-cells in pre-ART patients . It was also associated with increased ALT and AST enzyme levels in both HAART initiated and treatment naïve co-infected patients Background The purpose of this study was to evaluate the efficacy and safety of three nevirapine-based antiretroviral treatments for adult antiretroviral-naïve Chinese patients with HIV-1 infection . Methodology This was a prospect i ve , multicenter study . 198 antiretroviral-naïve HIV-1 positive subjects with CD4 lymphocyte counts between 100/ul and 350/ul and plasma HIV-1 RNA levels more than 500 copies/ml were r and omized to start three NVP-based antiretroviral treatments : group A , NVP+AZT+ddI ; group B , NVP+3TC+d4 T ; group C , NVP+AZT+3TC . Viral responses , immunologic responses , adverse events and drug resistence were monitored at baseline and the end of week 4 , 12 , 24 , 36 , 52 . Viralogical response and immunological response were also comparaed in different strata of baseline CD4 T lymphocyte counts and plasma HIV-1 RNA concentrations . At baseline , the plasma HIV-1 RNA was 4.44±0.68 , 4.52±0.71 and 4.41±0.63 lg copies/ml in group A , B and C respectively ( p = 0.628 ) . At the end of the study , the plasma viral load reached 2.54±1.11 , 1.89±0.46 and 1.92±0.58 lg copies/ml in group A , B and C respectively ( p<0.001 ) . At week 52 , suppression of plasma HIV-1 RNA to less than 50 copies/ml was achieved in more patients in group B and C than in group A ( 68.2 % , 69 % vs. 39.7 % ; p<0.001 ) . In planned subgroup analyses , the decrease of viral response rate was seen in group A when CD4 cell count > 200/ul ( subgroup H ) . But in subgroup L , viral response rate of three groups has no significant statistic difference . There were no statistically significant differences among three groups in immunological response wthin any of the CD4 or pVL strata . 3 out of 193 patients with available genotype at baseline showed primary drug resistant . Of 26 patients with virologic failure , 17 patients showed secondary drug resistant , 16 subjects in group A and 1 subject in group B. Logistic regression analysis indicated that presence of hepatotoxicity was associated with HCV-Ab positive ( OR = 2.096 , 95%CI : 1.106–3.973 , P = 0.023 ) and higher CD4 baseline ( CD4 count > 250/ul)(OR = 2.096 , 95%CI : 1.07–4.107 , P = 0.031 ) . Conclusion Our findings strongly support the use of 3TC+d4 T and 3TC+AZT as the nucleoside analogue combination in NVP-based antiretroviral therapy . The regimen of AZT+ddI+NVP produced poor virological response especially in the stratum of CD4 count more than 200/ul . More patients showed secondary drug resistant in this arm too . Patients with HCV-Ab+ and CD4 count > 250/ul appear to have significantly high risk of hepatoxicity . Trial Registration Clinical Trials.gov IMPORTANCE Patients co-infected with human immunodeficiency virus ( HIV ) and hepatitis C virus ( HCV ) are at high risk for liver disease progression . However , interferon-based treatments for HCV infection have significant toxicities , limiting treatment uptake . OBJECTIVE To assess the all-oral 3 direct-acting antiviral ( 3D ) regimen of ombitasvir , paritaprevir ( co-dosed with ritonavir [ paritaprevir/r ] ) , dasabuvir , and ribavirin in HCV genotype 1-infected adults with HIV-1 co-infection , including patients with cirrhosis . DESIGN , SETTING , AND PARTICIPANTS TURQUOISE-I is a r and omized , open-label study . Part 1a of this pilot study was conducted at 17 sites in the United States and Puerto Rico between September 2013 and August 2014 and included 63 patients with HCV genotype 1 and HIV-1 co-infection who were HCV treatment-naive or had history of prior treatment failure with peginterferon plus ribavirin therapy . The study allowed enrollment of patients , including those with cirrhosis , with a CD4 + count of 200/mm3 or greater or CD4 + percentage of 14 % or more and plasma HIV-1 RNA suppressed while taking a stable atazanavir- or raltegravir-inclusive antiretroviral regimen . INTERVENTIONS Ombitasvir/paritaprevir/r , dasabuvir , and ribavirin for 12 or 24 weeks of treatment as r and omized . MAIN OUTCOMES AND MEASURES The primary assessment was the proportion of patients with sustained virologic response ( HCV RNA < 25 IU/mL ) at posttreatment week 12 ( SVR12 ) . RESULTS Among patients receiving 12 or 24 weeks of 3D and ribavirin , SVR12 was achieved by 29 of 31 ( 94 % ; 95 % CI , 79%-98 % ) and 29 of 32 patients ( 91 % ; 95 % CI , 76%-97 % ) , respectively . Of the 5 patients who did not achieve SVR , 1 withdrew consent , 2 had confirmed virologic relapse or breakthrough , and 2 patients had clinical history and phylogenetic evidence consistent with HCV reinfection . The most common treatment-emergent adverse events were fatigue ( 48 % ) , insomnia ( 19 % ) , nausea ( 18 % ) , and headache ( 16 % ) . Adverse events were generally mild , with none reported as serious or leading to discontinuation . No patient had a confirmed HIV-1 breakthrough of 200 copies/mL or greater during treatment . CONCLUSIONS AND RELEVANCE In this open-label , r and omized uncontrolled study , treatment with the all-oral , interferon-free 3D-plus-ribavirin regimen result ed in high SVR rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks . Further phase 3 studies of this regimen are warranted in patients with co-infection . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01939197 BACKGROUND Hepatitis C virus ( HCV ) infection is highly prevalent among HIV-1-infected individuals , but its contribution to the morbidity and mortality of coinfected patients who receive potent antiretroviral therapy is controversial . We used data from the ongoing Swiss HIV Cohort Study to analyse clinical progression of HIV-1 , and the virological and immunological response to potent antiretroviral therapy in HIV-1-infected patients with or without concurrent HCV infection . METHODS We analysed prospect i ve data on survival , clinical disease progression , suppression of HIV-1 replication , CD4-cell recovery , and frequency of changes in antiretroviral therapy according to HCV status in 3111 patients starting potent antiretroviral therapy . RESULTS 1157 patients ( 37.2 % ) were coinfected with HCV , 1015 of whom ( 87.7 % ) had a history of intravenous drug use . In multivariate Cox 's regression , the probability of progression to a new AIDS-defining clinical event or to death was independently associated with HCV seropositivity ( hazard ratio 1.7 [ 95 % CI 1.26 - 2.30 ] ) , and with active intravenous drug use ( 1.38 [ 1.02 - 1.88 ] ) . Virological response to antiretroviral therapy and the probability of treatment change were not associated with HCV serostatus . In contrast , HCV seropositivity was associated with a smaller CD4-cell recovery ( hazard ratio for a CD4-cell count increase of at least 50 cells/microL=0.79 [ 0.72 - 0.87 ] ) . INTERPRETATION HCV and active intravenous drug use could be important factors in the morbidity and mortality among HIV-1-infected patients , possibly through impaired CD4-cell recovery in HCV seropositive patients receiving potent antiretroviral therapy . These findings are relevant for decisions about optimum timing for HCV treatment in the setting of HIV infection IMPORTANCE There is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus ( HCV ) infection in patients co-infected with human immunodeficiency virus ( HIV ) . OBJECTIVE To evaluate the rates of sustained virologic response ( SVR ) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir . DESIGN , SETTING , AND PARTICIPANTS Open-label , single-center , phase 2b pilot study of previously untreated , noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health , Bethesda , Maryl and , from June 2013 to September 2014 . Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater . Serial measurements of safety parameters , virologic and host immune correlates , and adherence were performed . INTERVENTIONS Fifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir ( 90 mg ) and sofosbuvir ( 400 mg ) once daily for 12 weeks . MAIN OUTCOMES AND MEASURES The primary study outcome was the proportion of patients with sustained viral response ( plasma HCV RNA level < 12 IU/mL ) 12 weeks after end of treatment . RESULTS Forty-nine of 50 participants ( 98 % [ 95 % CI , 89 % to 100 % ] ) achieved SVR 12 weeks after end of treatment , whereas 1 patient experienced relapse at week 4 following treatment . In the patient with relapse , deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors , such as ledipasvir . The most common adverse events were nasal congestion ( 16 % of patients ) and myalgia ( 14 % ) . There were no discontinuations or serious adverse events attributable to study drug . CONCLUSIONS AND RELEVANCE In this open-label , uncontrolled , pilot study enrolling patients co-infected with HCV genotype 1 and HIV , administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion . Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to underst and if the results of this study generalize to all patients co-infected with HCV and HIV . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01878799 BACKGROUND High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission . Initiation of antiretroviral therapy ( ART ) reduces plasma HIV-1 concentrations . We aim ed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners . METHODS Participants in our prospect i ve cohort analysis were from a r and omised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2 , and their HIV-1 seronegative partners . At enrolment , HIV-1 infected participants had CD4 counts of 250 cells per microL or greater and did not meet national guidelines for ART initiation ; during 24 months of follow-up , CD4 counts were measured every 6 months and ART was initiated in accordance with national guidelines . Uninfected partners were tested for HIV-1 every 3 months . The primary outcome was genetically-linked HIV-1 transmission within the study partnership . We assessed rates of HIV-1 transmission by ART status of infected participants . FINDINGS 3381 couples were eligible for analysis . 349 ( 10 % ) participants with HIV-1 initiated ART during the study , at a median CD4 cell count of 198 ( IQR 161 - 265 ) cells per microL. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started ART , corresponding to transmission rates of 0.37 ( 95 % CI 0.09 - 2.04 ) per 100 person-years in those who had initiated treatment and 2.24 ( 1.84 - 2.72 ) per 100 person-years in those who had not-a 92 % reduction ( adjusted incidence rate ratio 0.08 , 95 % CI 0.00 - 0.57 , p=0.004 ) . In participants not on ART , the highest HIV-1 transmission rate ( 8.79 per 100 person-years ) was from those with CD4 cell counts lower than 200 cells per microL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per microL , 66 ( 70 % ) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL. INTERPRETATION Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of ART to achieve an HIV-1 prevention benefit . Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population -level reductions in HIV-1 transmission . FUNDING Bill & Melinda Gates Foundation ; US National Institutes of Health BACKGROUND The roles of hepatitis C virus ( HCV ) viremia and HCV genotype in the immune response to highly active antiretroviral therapy ( HAART ) are poorly understood . Our aim was to assess the CD4 + cell count recovery after HAART in human immunodeficiency virus (HIV)-infected patients with HCV viremia and HIV-infected patients who tested negative for HCV antibody ( HCV-Ab ) . We also aim ed to assess whether the response to HAART in these patients varied according to HCV genotype . METHODS The analysis focused on 1219 HCV-Ab-negative patients and 284 HCV-viremic patients from a cohort of HIV-infected subjects that includes persons who were antiretroviral naive before initiating HAART after cohort enrollment . HCV RNA load and HCV genotype were determined in plasma specimens obtained and stored during the 6-month period preceding the initiation of HAART . RESULTS The chance of achieving a CD4 + cell count increase of > or = 100 cells/microL from the pre-HAART level tended to be poorer in HCV-viremic patients than in patients who tested negative for HCV-Ab ( adjusted relative hazard [ RH ] , 0.82 ; 95 % confidence interval [ CI ] , 0.66 - 1.01 ; P = .06 ) . In contrast , a comparison of patients who had a HCV RNA load > 1 x 10(6 ) IU/mL with patients who had a HCV RNA load of 5 - 1 x 10(6 ) IU/mL revealed no significant association between HCV RNA load and achievement of an increased CD4 + cell count ( adjusted RH , 0.97 ; 95 % CI , 0.75 - 1.27 ; P = .83 ) . There was no clear association between HCV genotype and the probability of achieving a CD4 + cell count increase . CONCLUSIONS An association between the presence of HCV-Ab and immune reconstitution after HAART has been shown elsewhere . Results of our large , prospect i ve study support a direct role of HCV viremia in the CD4 + cell count response to HAART . Moreover , our results underline the fact that , in individuals coinfected with HIV and HCV , the goal of treating HCV infection is to eradicate HCV , to both slow the rate of HCV progression and limit potential interference with the response to HAART BACKGROUND The combination of daclatasvir , a hepatitis C virus ( HCV ) NS5A inhibitor , and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection . Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 ( HIV-1 ) . METHODS This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients , all of whom were coinfected with HIV-1 . Previously untreated patients were r and omly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a st and ard dose of 60 mg daily ( with dose adjustment for concomitant antiretroviral medications ) plus 400 mg of sofosbuvir daily . Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses . The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks . RESULTS Patients had HCV genotypes 1 through 4 ( 83 % with genotype 1 ) , and 14 % had compensated cirrhosis ; 98 % were receiving antiretroviral therapy . Among patients with genotype 1 , a sustained virologic response was reported in 96.4 % ( 95 % confidence interval [ CI ] , 89.8 to 99.2 ) who were treated for 12 weeks and in 75.6 % ( 95 % CI , 59.7 to 87.6 ) who were treated for 8 weeks among previously untreated patients and in 97.7 % ( 95 % CI , 88.0 to 99.9 ) who were treated for 12 weeks among previously treated patients . Rates of sustained virologic response across all genotypes were 97.0 % ( 95 % CI , 91.6 to 99.4 ) , 76.0 % ( 95 % CI , 61.8 to 86.9 ) , and 98.1 % ( 95 % CI , 89.7 to 100 ) , respectively . The most common adverse events were fatigue , nausea , and headache . There were no study -drug discontinuations because of adverse events . HIV-1 suppression was not compromised . CONCLUSIONS Among previously untreated HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection , the rate of sustained virologic response across all genotypes was 97.0 % after 12 weeks of treatment and 76.0 % after 8 weeks . ( Funded by Bristol-Myers Squibb ; ALLY-2 Clinical Trials.gov number , NCT02032888 . ) Objective : HIV is known to have a negative impact on the progression of hepatitis C virus ( HCV ) infection , whereas the reverse remains unclear . We examined the impact of spontaneous clearance of HCV on CD4 + T-lymphocyte count progression before and after initiation of antiretroviral therapy ( ART ) in HIV – HCV coinfected adults . Methods : Data were analysed from participants in a Canadian , multisite prospect i ve cohort of HIV-infected adults with serologic evidence of HCV infection . The rate of CD4 + T-lymphocyte change was determined using multivariate mixed linear regression comparing chronically HCV RNA+ with spontaneous clearers ( persistently HCV RNA– without HCV therapy ) . Results : Baseline characteristics of the 271 participants analysed did not differ between individuals whose HCV RNA cleared ( n = 35 ) and those whose HCV RNA persisted ( n = 236 ) except with respect to markers of liver disease . HCV RNA+ individuals had on average seven-times slower recovery of CD4 + T-cells on chronic ART compared with HCV RNA− : ( adjusted change in absolute CD4 cell T-lymphocyte count per year : 4 ( 95 % confidence interval , −0.6 to 8) cells/μl vs. 26 ( 95 % confidence interval , 12 to 41 ) cells/μl ; P < 0.001 . Analyses restricted to individuals initiating ART showed similar results . There was also a trend to greater CD4 decline prior to ART initiation among those HCV RNA+ , although this did not reach statistical significance . Conclusion : We found that CD4 cell progression is negatively affected by the presence of ongoing HCV replication in coinfected individuals initiating ART which persisted throughout stable ART suggesting active HCV infection affects immune restoration even after years of ART exposure BACKGROUND Effective treatment for hepatitis C virus ( HCV ) in patients coinfected with human immunodeficiency virus type 1 ( HIV-1 ) remains an unmet medical need . METHODS We conducted a multicenter , single-group , open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz , rilpivirine , or raltegravir . All patients received ledipasvir , an NS5A inhibitor , and sofosbuvir , a nucleotide polymerase inhibitor , as a single fixed-dose combination for 12 weeks . The primary end point was a sustained virologic response at 12 weeks after the end of therapy . RESULTS Of the 335 patients enrolled , 34 % were black , 55 % had been previously treated for HCV , and 20 % had cirrhosis . Overall , 322 patients ( 96 % ) had a sustained virologic response at 12 weeks after the end of therapy ( 95 % confidence interval [ CI ] , 93 to 98 ) , including rates of 96 % ( 95 % CI , 93 to 98 ) in patients with HCV genotype 1a , 96 % ( 95 % CI , 89 to 99 ) in those with HCV genotype 1b , and 100 % ( 95 % CI , 63 to 100 ) in those with HCV genotype 4 . Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis . Of the 13 patients who did not have a sustained virologic response , 10 had a relapse after the end of treatment . No patient had confirmed HIV-1 virologic rebound . The most common adverse events were headache ( 25 % ) , fatigue ( 21 % ) , and diarrhea ( 11 % ) . No patient discontinued treatment because of adverse events . CONCLUSIONS Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4 . ( Funded by Gilead Sciences ; ION-4 Clinical Trials.gov number , NCT02073656 . ) |
11,965 | 20,478,951 | Conclusion : This systematic review could neither confirm nor rule out a causal link between emboli from CPB and postoperative cognitive decline | Background : The use of cardiopulmonary bypass ( CPB ) is associated with cerebral microemboli .
Cognitive decline after cardiac surgery has therefore always been attributed to the use of CPB .
However , r and omized studies comparing coronary bypass surgery with and without CPB failed to establish a clear cognitive benefit of avoiding CPB .
The aim of this analysis was to systematic ally review the studies that directly assessed the association between cerebral microemboli and cognitive decline after cardiac surgery . | BACKGROUND Coronary artery bypass surgery with cardiopulmonary bypass carries a significant risk of perioperative brain injury . At least 1 % to 5 % will suffer a stroke , and at 3-months postoperatively approximately 30 % are reported to have cognitive impairment assessed by neuropsychologic testing . In off-pump surgery cardiopulmonary bypass is not used and instrumentation on the ascending aorta is reduced . The main aim of this study was to assess if off-pump surgery reduces intraoperative cerebral embolization . METHODS This was a prospect i ve and r and omized study of two comparable groups with regard to age , sex , years of education , preoperative cognitive functioning , and surgical characteristics . Fifty-two patients ( 29 off-pump ) were monitored by the use of transcranial Doppler ultrasound for cerebral microembolization during surgery . Preoperative and postoperative clinical , cerebral magnetic resonance imaging , and neuropsychologic examinations were also carried out . RESULTS There was a significant reduction in the number of cerebral microemboli during off-pump compared with on-pump surgery ( 16.3 [ range 0 to 131 ] versus 90.0 [ range 15 to 274 ] , p < 0.0001 ) . No significant difference with regard to the incidence of neuropsychologic performance ( decline in 29 % off-pump , 35 % on-pump ) or neuroradiologic findings at 3 months was found , and there was no association between the number of cerebral microemboli and cognitive outcome . CONCLUSIONS This study clearly demonstrates that off-pump surgery leads to a reduction in intraoperative cerebral microembolization . A significant reduction in the number of off-pump patients with cognitive decline or ischemic brain lesions on cerebral magnetic resonance imaging could not be demonstrated in this relatively small patient population Background and Purpose — The aim of this study was to assess the first multifrequency transcranial Doppler system that was specially developed to automatically detect and discriminate between solid and gaseous cerebral microemboli . Methods — The multifrequency transcranial Doppler instrumentation insonates simultaneously with 2.5 and 2.0 MHz . Differentiation between solid and gaseous microemboli is based on the principle that solid microemboli reflect more ultrasound at the higher than at the lower frequency , whereas the opposite is the case for gaseous microemboli . In the in vitro studies , 159 plastic spheres ( 50 or 80 & mgr;m in diameter ) and 105 gas bubbles ( 8 to 25 & mgr;m ) were studied in a pulsatile closed-loop system containing irodinium or pig blood . In vivo studies were carried out for 1 hour in 15 patients with mechanical heart valves and in 45 patients with carotid stenosis . This gave a total of 60 hours of online automatic monitoring in patients . Results — In the in vitro studies , 152 of the 159 ( 95.6 % ) plastic spheres were classified as solid , and 7 ( 4.4 % ) were classified as uncertain solid . Of the 105 gas bubbles , 99 ( 94.3 % ) were classified as gaseous and 6 ( 5.7 % ) as uncertain gaseous . Thus , correct classification was made for 251 ( 95.1 % ) of the 264 embolic events studied . A comparison between the automatic multifrequency discrimination and the known embolic classification gave a & kgr ; value of 0.897 ( P < 0.0001 ) . The multifrequency Doppler classified 433 ( 84.2 % ) of the 514 emboli detected in the mechanical heart valve patients as gaseous , 74 ( 14.4 % ) as solid , and 7 ( 1.4 % ) as uncertain ( 3 uncertain solid , 4 uncertain gas ) . Thirty-two emboli were detected in 17 ( 38 % ) of the 45 carotid stenosis patients ; 30 ( 93.7 % ) were classified as solid and 2 ( 6.3 % ) as uncertain solid . Conclusions — This study has shown that multifrequency transcranial Doppler can be used to automatically differentiate between solid and gaseous microemboli online . Most detected microemboli in this initial study of mechanical heart valves were classified as gaseous , whereas most were classified as solid in the patients with carotid stenosis OBJECTIVE To analyze the frequency and severity of sub clinical cerebral complications associated with coronary artery bypass grafting ( CABG ) . DESIGN A prospect i ve controlled study using preoperative and postoperative magnetic resonance imaging ( MRI ) of the brain , quantitative electroencephalography ( QEEG ) , and detailed neuropsychological and neurologic examinations as potentially sensitive indicators of sub clinical cerebral injury associated with CABG . SETTING Multimodality evaluation in a tertiary care unit ( Kuopio University Hospital , Kuopio , Finl and ) . PATIENTS Thirty-eight patients undergoing elective CABG and 20 control patients undergoing other major vascular surgery , mostly operations on the abdominal aorta . MAIN OUTCOME MEASURES Coronary artery bypass grafting-associated cerebral complications assessed preoperatively and postoperatively by brain MRI , QEEG , detailed neurologic examination , and a neuropsychological test battery that evaluates cognitive functions in major areas known to be vulnerable to organic impairment ( learning and memory , attention , flexible mental processing , and psychomotor speed ) . RESULTS There were no major neurologic complications . A mild hemisyndrome developed in 1 patient who underwent CABG and in 1 control patient . Overall , there was no decline in mean cognitive performance 3 months after surgery . Electroencephalographic slowing of 0.5 Hz or more in at least 2 channels occurred in 11 patients who underwent CABG and in 1 control patient ( P=.03 ) . The postoperative brain MRI scan revealed new small ischemic lesions in 8 patients ( 21 % ) in the CABG group but in none of the control group ( P=.03 ) . These new cerebral MRI lesions did not explain deterioration in neuropsychological test performance or the QEEG slowing . CONCLUSIONS Coronary artery bypass grafting causes more QEEG alterations and small ischemic cerebral lesions that are detectable by MRI than does other major vascular surgery . The effect is mainly sub clinical , because no statistically significant deterioration in mean neuropsychological test performance was detected Background and Purpose Microemboli have been implicated in the etiology of neuropsychological deficits after cardiopulmonary bypass . This study examined the incidence of high‐intensity transcranial signals ( microemboli ) and their relation to changes in neuropsychological performance after surgery . Methods Transcranial Doppler ultrasonography was used to measure middle cerebral artery blood flow velocity and detect microemboli . The number of high‐intensity transcranial signals was determined and related to a neurological examination and absolute changes in neuropsychological performance as well as the number of patients considered to exhibit a neuropsychological deficit . Data were available on 100 consenting patients undergoing routine cardiopulmonary bypass . Fifty of the patients were r and omly assigned to a procedure that included a 40‐&mgr;m arterial line filter , and 50 had the procedure without any arterial line filter . Results Significantly more patients were found to have neuropsychological deficits in the group without the arterial line filter at both 8 days ( P<.05 ) and 8 weeks ( P<.03 ) after surgery . In addition , more “ soft ” neurological signs were found in the nonfiltered group 24 hours after surgery ( P<.05 ) . More high‐intensity transcranial signals were found in the nonfiltered group , and the number of high‐intensity transcranial signals was found to be related to the likelihood of a patient having a neuropsychological deficit at 8 weeks . Conclusions These data suggest that neuropsychological deficits after routine cardiopulmonary bypass are related to the number of microemboli delivered during surgery . Furthermore , the numbers of microemboli may be reduced by including a 40‐&mgr;m filter on the arterial line . ( Stroke . 1994;25:1393‐1399 . BACKGROUND Neurologic and clinical morbidity after coronary artery bypass grafting ( CABG ) can be significant . By avoiding cardiopulmonary bypass , off-pump CABG ( OPCAB ) may reduce morbidity . METHODS Sixty patients ( 30 CABG and 30 OPCAB ) were prospect ively r and omized . Neurocognitive testing was performed before the operation and 2 weeks and 1 year after the operation . Neurologic testing to detect stroke and (99m)Tc-HMPAO whole-brain single photon emission computed tomography scanning to assess cerebral perfusion were performed before the operation and 3 days afterward . Bilateral middle cerebral artery transcranial Doppler scanning was performed intraoperatively to detect cerebral microemboli . All examiners were blinded to treatment group . Clinical morbidity and costs were compared . RESULTS Coronary artery bypass grafting was associated with more cerebral microemboli ( 575 + /- 278.5 CABG versus 16.0 + /- 19.5 OPCAB ( median + /- semiinterquartile range ) and significantly reduced cerebral perfusion after the operation to the bilateral occipital , cerebellar , precunei , thalami , and left temporal lobes ( p < or = 0.01 ) . Cerebral perfusion with OPCAB was unchanged . Compared with base line , OPCAB patients performed better on the Rey Auditory Verbal Learning Test ( total and recognition scores ) at both 2 weeks and at 1 year ( p < or = 0.05 ) , whereas CABG performance was statistically unchanged for all cognitive measures . Patients who underwent CABG had more chest tube drainage ( 1389 + /- 1256 mL CABG versus 789 + /- 586 mL OPCAB , p = 0.02 ) and required more blood ( 3.9 + /- 5.8 U CABG versus 1.2 + /- 2.2 U OPCAB , p = 0.02 ) , fresh frozen plasma ( 3.0 + /- 6.0 U CABG versus 0.5 + /- 2.2 U OPCAB , p = 0.03 ) , and hours of postoperative use of dopamine ( 16.3 + /- 21.2 hours CABG versus 7.3 + /- 9.7 hours OPCAB , p = 0.04 ) . These differences culminated in higher costs for CABG ( $ 23,053 + /- $ 5,320 CABG versus $ 17,780 + /- $ 4,390 OPCAB , p < 0.0001 ) . One stroke occurred with CABG , compared with none with OPCAB ( p = NS ) . One OPCAB patient died because of a pulmonary embolus ( p = NS ) . CONCLUSIONS Compared with CABG , OPCAB may reduce neurologic and clinical morbidity as well as cost Background and Purpose — Improvements in cardiac surgery mortality and morbidity have focused interest on the neurological injury such as stroke and cognitive decline that may accompany an otherwise successful operation . We aim ed to investigate ( 1 ) the rate of stroke , new ischemic change on MRI , and cognitive impairment after cardiac valve surgery ; and ( 2 ) the controversial relationship between perioperative cerebral ischemia and cognitive decline . Methods — Forty patients ( 26 men ; mean [ SD ] age 62.1 [ 13.7 ] years ) undergoing intracardiac surgery ( 7 also with coronary artery bypass grafting ) were studied . Neurological , neuropsychological , and MRI examinations were performed 24 hours before surgery and 5 days ( MRI and neurology ) and 6 weeks ( neuropsychology and neurology ) after surgery . Cognitive decline from baseline was determined using the Reliable Change Index . Results — Two of 40 ( 5 % ) patients had perioperative strokes and 22 of 35 ( 63 % ) tested had cognitive decline in at least one measure ( range , 1 to 4 ) . Sixteen of 37 participants ( 43 % ) with postoperative imaging had new ischemic lesions ( range , 1 to 17 lesions ) with appearances consistent with cerebral embolization . Cognitive decline was seen in all patients with , and 35 % of those without , postoperative ischemic lesions ( P<0.001 ) , and there was an association between the number of abnormal cognitive tests and ischemic burden ( P<0.001 ) . Conclusion — We have provided a reliable estimate of the rate of stroke , postoperative ischemia , and cognitive impairment at 6 weeks after cardiac valve surgery . Cognitive impairment is associated with perioperative ischemia and is more severe with greater ischemic load Background — Reinfusion of unprocessed cardiotomy blood during cardiac surgery can introduce particulate material into the cardiopulmonary bypass circuit , which may contribute to postoperative cognitive dysfunction . On the other h and , processing of this blood by centrifugation and filtration removes coagulation factors and may potentially contribute to coagulopathy . We sought to evaluate the effects of cardiotomy blood processing on blood product use and neurocognitive functioning after cardiac surgery . Methods and Results — Patients undergoing coronary and /or aortic valve surgery using cardiopulmonary bypass were r and omized to receive unprocessed blood ( control , n=134 ) or cardiotomy blood that had been processed by centrifugal washing and lipid filtration ( treatment , n=132 ) . Patients and treating physicians were blinded to treatment assignment . A strict transfusion protocol was followed . Blood transfusion data were analyzed using Poisson regression models . The treatment group received more intraoperative red blood cell transfusions ( 0.23±0.69 U versus 0.08±0.34 U , P=0.004 ) . Both red blood cell and nonred blood cell blood product use was greater in the treatment group and postoperative bleeding was greater in the treatment group . Patients were monitored intraoperatively by transcranial Doppler and they underwent neuropsychometric testing before surgery and at 5 days and 3 months after surgery . There was no difference in the incidence of postoperative cognitive dysfunction in the 2 groups ( relative risk : 1.16 , 95 % CI : 0.86 to 1.57 at 5 days postoperatively ; relative risk : 1.05 , 95 % CI : 0.58 to 1.90 at 3 months ) . There was no difference in the quality of life nor was there a difference in the number of emboli detected in the 2 groups . Conclusions — Contrary to expectations , processing of cardiotomy blood before reinfusion results in greater blood product use with greater postoperative bleeding in patients undergoing cardiac surgery . There is no clinical evidence of any neurologic benefit with this approach in terms of postoperative cognitive function Background — It has been suggested that the risk of cerebral dysfunction is less with off-pump coronary artery bypass grafting ( OPCAB ) than with conventional coronary artery bypass grafting ( CCAB ) . However , evidence for this statement is preliminary , and additional insight is needed . Methods and Results — The study was a sub study of the r and omized Best Bypass Surgery trial that compared OPCAB with CCAB treatment with respect to intraoperative and postoperative mortality and morbidity in patients with a moderate to high level of predicted preoperative risk . The outcome was cognitive function . A total of 120 elderly patients ( mean age 76 years , SD 4.5 years ) underwent psychometric testing before surgery and at a mean of 103 ( SD 15 ) days postoperatively with a neuropsychological test battery that included 7 parameters from 4 tests . Cognitive dysfunction was defined as the occurrence of at least 2 of the 7 possible deficits . Secondary analysis was performed on the basis of the definition of a 20 % decline in cognitive scores compared with baseline , and with z score analysis . Cognitive dysfunction was identified in 4 of the 54 patients ( 7.4 % , 95 % confidence interval [ CI ] 2.1 % to 17.9 % ) in the OPCAB group and 5 of the 51 patients ( 9.8 % , 95 % CI 3.3 % to 21.4 % ) in the CCAB group . We found no difference in incidence of cognitive dysfunction between the groups regardless of the definition applied . Conclusions — In elderly high-risk patients , no significant difference was found in the incidence of cognitive dysfunction 3 months after either OPCAB or CCAB CONTEXT Conventional coronary artery bypass graft surgery with use of cardiopulmonary bypass ( on-pump CABG ) is associated with excellent long-term cardiac outcomes but also with a high incidence of cognitive decline . The effect of avoiding cardiopulmonary bypass ( off-pump CABG ) on long-term cognitive and cardiac outcomes is unknown . OBJECTIVE To compare the effect of off-pump CABG and on-pump CABG surgery on long-term cognitive and cardiac outcomes . DESIGN , SETTING , AND PARTICIPANTS The Octopus Study , a multicenter r and omized controlled trial conducted in the Netherl and s , which enrolled 281 low-risk CABG patients between 1998 and 2000 . Five years after their surgery , surviving patients were invited for a follow-up assessment . INTERVENTION Patients were r and omly assigned to receive either off-pump ( n = 142 ) or on-pump ( n = 139 ) CABG surgery . MAIN OUTCOME MEASURE The primary measure was cognitive status 5 years after surgery , which was determined by a psychologist blinded to treatment allocation who administered 10 st and ardized vali date d neuropsychological tests . Secondary measures were occurrence of cardiovascular events ( all-cause mortality , stroke , myocardial infa rct ion , and coronary reintervention ) , anginal status , and quality of life . RESULTS After 5 years , 130 patients were alive in each group . Cognitive outcomes could be determined in 123 and 117 patients in the off-pump and on-pump groups , respectively . When using a st and ard definition of cognitive decline ( 20 % decline in performance in 20 % of the neuropsychological test variables ) , 62 ( 50.4 % ) of 123 in the off-pump group and 59 ( 50.4 % ) of 117 in the on-pump group had cognitive decline ( absolute difference , 0 % ; 95 % confidence interval [ CI ] , -12.7 % to 12.6 % ; P>.99 ) . When a more conservative definition of cognitive decline was used , 41 ( 33.3 % ) in the off-pump group and 41 ( 35.0 % ) in the on-pump group had cognitive decline ( absolute difference , -1.7 % ; 95 % CI , -13.7 % to 10.3 % ; P = .79 ) . Thirty off-pump patients ( 21.1 % ) and 25 on-pump patients ( 18.0 % ) experienced a cardiovascular event ( absolute difference , 3.1 % ; 95 % CI , -6.1 % to 12.4 % ; P = .55 ) . No differences were observed in anginal status or quality of life . CONCLUSION In low-risk patients undergoing CABG surgery , avoiding the use of cardiopulmonary bypass had no effect on 5-year cognitive or cardiac outcomes . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N69438133 Background — Cerebral microembolization during cardiopulmonary bypass may lead to cognitive decline after cardiac surgery . Transfusion of the unprocessed shed blood ( major source of lipid microparticulates ) into the patient during cardiopulmonary bypass is common practice to reduce blood loss and blood transfusion . Processing of shed blood with cell saver before transfusion may limit cerebral microembolization and reduce cognitive decline after surgery . Methods and Results — A total of 226 elderly patients were r and omly allocated to either cell saver or control groups . Anesthesia and surgical management were st and ardized . Epiaortic scanning of the proximal thoracic aorta was performed in all patients . Transcranial Doppler was used to measure cerebral embolic rates . St and ardized neuropsychological testing was conducted 1 week before and 6 weeks after surgery . The raw scores for each test were converted to Z scores , and then a combined Z score of 10 main variables was calculated for both study groups . The primary analysis was based on dichotomous composite cognitive outcome with a 1-SD rule . Cognitive dysfunction was present in 6 % ( 95 % confidence interval , 1.3 % to 10.7 % ) of patients in the cell saver group and 15 % ( 95 % confidence interval , 8 % to 22 % ) of patients in the control group 6 weeks after surgery ( P=0.038 ) . The severity of aortic atheroma and cerebral embolic count were similar between the 2 groups . Conclusions — The present report demonstrates that processing of shed blood with cell saver results in clinical ly significant reduction in postoperative cognitive dysfunction after cardiac surgery . These findings emphasize the clinical importance of lipid embolization in contributing to postoperative cognitive decline in patients exposed to cardiopulmonary bypass BACKGROUND Neurocognitive impairment can be a debilitating complication after coronary artery bypass graft surgery ( CABG ) . Cardiopulmonary bypass , in particular , cerebral emboli , has been implicated . We compared neurocognitive function and cerebral emboli in patients undergoing on-pump and off-pump CABG . METHODS 212 patients admitted for CABG were r and omly assigned to on-pump ( n = 104 ) or off-pump ( n = 108 ) surgery . Embolic signals were detected with bilateral transcranial Doppler ultrasonography of the middle cerebral artery . Neurocognitive tests were administered preoperatively , on discharge from hospital , at 6 weeks , and at 6 months after surgery . Composite neurocognitive scores were derived using principal component analysis and were compared between the two groups , using analysis of covariance to adjust for baseline values . RESULTS At discharge from hospital , the adjusted composite neurocognitive score was 0.25 st and ard deviations greater in the off-pump group compared with the on-pump group ( 95 % confidence interval : 0.05 to 0.45 ; p = 0.01 ) . There was no significant difference at 6 weeks ( 0.09 st and ard deviations , 95 % confidence interval : -0.11 to + 0.30 ; p = 0.4 ) and 6 months ( -0.002 st and ard deviations , 95 % confidence interval : -0.23 to + 0.23 ; p = 1.0 ) . Median number of embolic signals was 1,605 ( 751 to 2,473 ) during on-pump and 9 ( 4 to 27 ) in off-pump CABG ( p < 0.001 ) . Age , length of education , and on-pump status were independent predictors of the predischarge neurocognitive score ( p = 0.02 , 0.03 , and 0.006 , respectively ) . CONCLUSIONS Cerebral emboli are more prevalent during on-pump CABG . At discharge from hospital , neurocognitive function is better after off-pump surgery , possibly as a result of the lower embolic load . However , the difference in neurocognitive function does not persist at 6 weeks and 6 months BACKGROUND : Postoperative cognitive dysfunction ( POCD ) can be a debilitating complication after coronary artery bypass graft ( CABG ) surgery . Cerebral microemboli during cardiopulmonary bypass ( CPB ) are believed to be an important etiologic factor of POCD . In this study , we examined whether avoidance of CPB with “ off-pump ” surgery reduces the number of cerebral microemboli and the incidence of POCD after CABG surgery in Chinese population . METHODS : Two hundred twenty-seven patients were enrolled in this prospect i ve cohort study . Fifty-nine patients underwent CABG surgery with CPB and 168 underwent off-pump surgery . Cerebral microemboli were measured continuously with bilateral transcranial Doppler ultrasonography of the middle cerebral arteries . A neuropsychological test battery that included seven tests with nine subscales was administered at baseline , as well as at 1 wk and 3 mo after surgery . POCD was defined using the international study of POCD1 definition . RESULTS : The median total number of cerebral microemboli for the case was 430 ( range : 155–2088 ) in patients undergoing surgery with CPB and 2 ( 0–66 ) in the off-pump patients ( P < 0.001 ) . There were no differences in the incidence of POCD between the patients having surgery with or without CPB either at 1 wk ( 55.2 % or 32 of 58 patients [ 95 % confidence interval : 41.5%–68.3 % ] vs 47.0 % or 78 of 166 patients [ 39.2%–54.9 % ] , P = 0.283 ) or 3 mo ( 6.4 % or 3 of 47 patients [ 1.3%–17.5 % ] vs 13.1 % or 16 of 122 of patients [ 7.7%–20.4 % ] , P = 0.214 ) after surgery . Increasing age and shorter duration of postoperative hospital stay were independently associated with cognitive dysfunction at 1 wk after surgery . Increasing age and a history of diabetes mellitus were independently associated with cognitive dysfunction 3 mo after surgery . CPB or cerebral microemboli were not significantly related to the occurrence of POCD . CONCLUSIONS : In Chinese population , avoidance of CPB during CABG surgery significantly decreased the number of cerebral microemboli , but it did not decrease the incidence of POCD at either 1 wk or 3 mo after CABG . Neither CPB nor cerebral microemboli was independently associated with the risk of POCD The choice of coronary artery bypass grafting ( CABG ) as an intervention for coronary artery disease has been clouded by concerns about postoperative cognitive decline . Long‐term cognitive decline after CABG has been reported , but without appropriate control subjects , it is not known whether this decline is specific to CABG or related to other factors such as cerebrovascular disease OBJECTIVE Neuropsychologic impairment remains a problem after coronary artery bypass grafting . Relatively few studies have examined the potential role of the perioperative inflammatory response . This study aim ed to determine whether there was any association between perioperative white cell count , microemboli , and cognitive performance after surgical intervention . METHODS White cell count and differential were prospect ively measured perioperatively in 161 patients undergoing coronary artery bypass grafting . A neuropsychologic test battery ( 9 tests ) was administered preoperatively and 6 to 8 weeks postoperatively in all 161 patients . Cerebral microemboli during cardiopulmonary bypass were also recorded by means of a transcranial Doppler scan of the right middle cerebral artery . RESULTS There was no correlation between microemboli and white cell counts at any time point . There were weak but significant inverse correlations between both preoperative ( r = -0.19 , P = .02 ) and postoperative ( r = -0.21 , P < .01 ) white cell count and a measure of overall neuropsychologic test performance ( total z change score ) . There was a weak but significant positive correlation between the neutrophil count 10 minutes after bypass and the intraoperative microemboli count ( r = 0.23 , P = .01 ) . CONCLUSIONS The correlation between white cell count and neuropsychologic outcome suggests that an inflammatory response might have a role in determining cognitive outcome after coronary artery surgery with cardiopulmonary bypass . The positive correlation between the microemboli during cardiopulmonary bypass and the neutrophil count 10 minutes after bypass is compatible with microemboli contributing to the inflammatory response . The patients ' preoperative inflammatory status might also be predictive of the response to surgical intervention OBJECTIVE Neurocognitive dysfunction is a common complication after cardiac surgery with cardiopulmonary bypass ( CPB ) . Studies using magnetic resonance imaging ( MRI ) have demonstrated that new focal brain lesions can occur after coronary artery bypass grafting ( CABG ) , even in patients without apparent neurological deficits . Diffusion-weighted MRI is superior to conventional MRI and allows for sensitive and early detection of ischemic brain lesions . We prospect ively investigated cerebral injury early and 3 months after CABG using diffusion-weighted MRI and related the findings to clinical data and neurocognitive functions . METHODS Twenty-nine patients [ 67.6+/-8.6 ( 52 - 85 ) years , 5 females ] undergoing elective CABG with CPB were examined before surgery , at discharge and 3 months after surgery . A battery of st and ardized neuropsychological tests and question naires on depression and mood were administered . Conventional and diffusion-weighted MRI of the brain was performed and new lesions were analyzed . Clinical characteristics , neuropsychological test performance and radiographic data were collected and compared . RESULTS There was no major neurological complication after CABG . Thirteen patients ( 45 % ) exhibited 32 new ischemic lesions on postoperative diffusion-weighted MRI . The lesions were small , rounded and equally dispersed in both hemispheres . Eight patients had at least two lesions . At discharge , significant deterioration of neuropsychological performance was observed in 6 of the 13 tests compared to baseline assessment . By 3 months postoperatively , 5 of the 6 tests returned to preoperative levels . Verbal learning ability , however , remained impaired . The presence of new focal brain lesions was not associated with impaired neuropsychological performance . There was also no correlation between clinical variables , intraoperative parameters and postoperative complications and MRI findings . CONCLUSIONS Although neurocognitive decline after CABG is mostly transient , memory impairment can persist for months . New ischemic brain lesions on postoperative diffusion-weighted MRI do not appear to account for the persistent neurocognitive decline A longitudinal study of cognitive function after coronary artery bypass surgery examined 107 participants using 11 tests , preoperatively and at 6 days , 8 weeks , and 5 years after surgery . The overall neuropsychological ( NP ) change score declined at 6 days , showed some recovery at 8 weeks , and declined again at 5 years . The number of microemboli recorded during surgery , postoperative short-term cognitive change , and degree of recovery at 8 weeks were identified as predictors of change in NP score to 5 years . This suggests that even over a 5-year period , operative damage is detectable . Patients ' vulnerability to short-term deterioration and resilience or ability to recover over a few weeks from operative cerebral insult are important processes of unknown mechanisms OBJECTIVE Following coronary artery bypass graft surgery , some studies using magnetic resonance imaging ( MRI ) have demonstrated new small ischemic brain lesions in patients without apparent neurological deficits . We aim ed to prospect ively evaluate brain injury after cardiac valve replacement using MRI and to determine the relationship to neurocognitive function . METHODS Thirty patients with a mean age of 64.9+/-9.8 years ( range , 32 - 82 , 12 female ) receiving cardiac valve replacement ( aortic valve replacement [ AVR ] , n = 24 ; mitral valve replacement [ MVR ] , n = 2 ; AVR and MVR , n = 2 ; AVR and mitral valve repair , n = 2 ) were investigated . Study protocol included neurological examination , comprehensive neuropsychological assessment and diffusion-weighted ( DW ) MRI . The investigations were performed before surgery and 5 days and 4 months after surgery . RESULTS Postoperative DW MRI detected new focal brain lesions in 14 patients ( 47 % ) . No patient revealed a focal neurological deficit . Six patients ( 43 % ) had multiple ( > or = 3 ) lesions ( range , 1 - 7 ) . Lesion volume ranged from 50 - 500 mm3 except 1 territorial infa rct of 1900 mm3 . Of a total of 41 lesions , 27 ( 66 % ) were located in the right hemisphere and 32 in a subcortical location . By 5 days postoperatively , significant neurocognitive decline was observed in 5 of 13 tests affecting memory , attention and rate of information processing . By 4 months , dysfunction had recovered in all cognitive areas . The presence of new ischemic lesions was not associated with neurocognitive decline at discharge . There was also no significant correlation between clinical and operative variables and the presence of new DW lesions or neuropsychological outcome . CONCLUSIONS Following cardiac valve replacement , new small ischemic brain lesions were detected by diffusion-weighted MRI . Neurocognitive decline was present early after operation , but resolved within 4 months . A correlation of new ischemic lesions to postoperative cognitive dysfunction or clinical variables was not found OBJECTIVES Cognitive deficits occur in up to 80 % of patients after cardiac surgery . We investigated the influence of cerebral perfusion and embolization during cardiopulmonary bypass on cognitive function and recovery . METHODS Cerebrovascular reactivity was measured in 70 patients before coronary operations in which nonpulsatile bypass was used . Throughout the operations , middle cerebral artery flow velocity and embolization were recorded by transcranial Doppler and regional oxygen saturation was recorded by near-infrared spectroscopy . Cognitive function was measured by a computerized battery of tests before the operation and 1 week , 2 months , and 6 months after surgery . Elderly patients undergoing urologic surgery served as controls . RESULTS Cerebrovascular reactivity was impaired preoperatively in 49 patients . Median ( interquartile range ) regional cerebral oxygen saturation fell during bypass by 10 % ( 6%-15 % ) , indicating increased oxygen extraction , whereas mean middle cerebral flow velocity increased significantly by a median of 6 cm/s ( both P < .0001 , Wilcoxon ) , suggesting increased arterial tone . More than 200 emboli were detected in 40 patients , mainly on aortic clamping and release , when bypass was initiated , and during defibrillation . Cognitive function deteriorated more in patients having cardiopulmonary bypass than in control patients having urologic operations but recovered in most tests by 2 months . Measures of cerebral perfusion ( poor cerebrovascular reactivity , low arterial pressures , and flow velocity in the middle cerebral artery ) predicted poor attention at 1 week ( r = 0.3 , P < .01 , Spearman ) . Emboli were associated with memory loss ( r = 0.3 , P < .02 , Spearman ) . CONCLUSIONS Cognitive deficits were common after cardiopulmonary bypass . Occult cerebrovascular disease was more severe than expected and predisposed to attention difficulties , whereas emboli caused memory deficits . We believe this to be the first report of differing cognitive effects from emboli and hypoperfusion which originally used the 20 % decline on 20 % of the tests criterion in the analysis of cognitive change after conventional and off-pump CABG [ 4 ] . Because this was a r and omized trial , nonsurgical controls were not included . In their original analysis , 31 % of the CABG patients were classified as having decline at 3 months . In a follow-up to this study , they recruited healthy controls not undergoing surgery and applied the same criteria for decline , and it was found that an unexpected 28 % of these normal controls also met this criterion for decline [ 6 ] . Using a more conservative definition to define decline , they then compared their original CABG group with this control group and found at 3 months that 7.7 % of the CABG and 4.6 % of the controls were classified as having decline . These authors conclude that their previous use of the 20 % decline of 20 % of test criteria had thus greatly overestimated the incidence of cognitive decline after CABG . We exp and on the findings just mentioned by illustrating the effects of applying the arbitrary criterion of 20 % decline on one or more tests to previously published data from our prospect i ve study of cognitive outcomes comparing CABG and nonsurgical controls with coronary artery disease and heart-healthy controls ( without risk factors for coronary artery disease ) [ 7 ] . The results clearly demonstrate that there is considerable variability ( both improvement and decline ) in the follow-up test performance even for the control subjects without surgery . Therefore , in the absence of a control group , this normal variability associated with follow-up cognitive testing might have been BACKGROUND Off-pump coronary artery bypass grafting surgery reduces the intraoperative cerebral embolic load and may therefore cause less brain injury . The main aim of this study was to compare off-pump and on-pump surgery with regard to the frequency of new postoperative cerebral ischemic lesions and the prevalence of postoperative cognitive impairment . We also assessed whether preoperative cerebral ischemic injury predicts the risk for cognitive dysfunction after surgery . METHODS One hundred twenty patients with ischemic coronary artery disease were prospect ively r and omized to undergo off-pump or on-pump surgery . A detailed neuropsychological assessment and a cerebral magnetic resonance imaging examination were performed on the day before and at 3 months postoperatively . The neuropsychological assessment was repeated at 12 months . RESULTS There was no significant ( p = 0.17 ) difference between off-pump ( 8.2 % ) and on-pump ( 17.3 % ) surgery with regard to new postoperative cerebral lesions . The prevalence of cognitive impairment after surgery was also similar in the two groups ( 3 months : off-pump 20.4 % , on-pump 23.1 % , p = 0.74 ; 12 months : off-pump 24.1 % , on-pump 23.1 % , p = 0.90 ) . The degree of preoperative cerebral ischemic injury was significantly associated with cognitive dysfunction after on-pump ( p = 0.02 ) but not after off-pump ( p = 0.22 ) surgery . None of the patients with normal preoperative radiologic findings were found to have cognitive impairment at 3 months postoperatively ( p = 0.04 ) . CONCLUSIONS Long-term cognitive function and magnetic resonance imaging evidence of brain injury were similar after off-pump and on-pump coronary artery bypass grafting surgery . Preoperative cerebral magnetic resonance imaging can be used to predict the risk for cognitive dysfunction after coronary artery bypass grafting surgery BACKGROUND Cognitive decline is well recognized early after coronary artery bypass graft surgery ( CABG ) , but controversy exists regarding the degree and duration of these changes . We investigated the course of cognitive performance during 3 years after surgery and determined whether ischemic brain injury detected by diffusion-weighted magnetic resonance imaging was related to cognitive decline . METHODS Thirty-nine patients undergoing on-pump CABG completed preoperative neuropsychologic examination and were followed up prospect ively at discharge , 3 months , and 3 years after surgery . Cognitive performance was assessed with a battery of 11 st and ardized psychometric tests assessing 7 cognitive domains . Cognitive outcome was analyzed by determining ( 1 ) mean changes in within-patient scores over time ( identifying cognitive functions with decline ) , and ( 2 ) the incidence of cognitive deficit for each individual ( identifying patients with decline ) . Objective evidence of acute cerebral ischemia was obtained by diffusion-weighted magnetic resonance imaging . Prospect ively collected data were used to identify predictors of cognitive deficits . RESULTS From baseline to discharge , cognitive test scores significantly declined in 7 measures . Most tests improved by 3 months . Between 3 months and 3 years , late decline was observed in 2 measures with persistent deterioration in 1 measure ( verbal memory ) relative to baseline . Postoperative cognitive deficits ( drop of > or = 1 SD in scores on > or = 3 tests ) were observed in 56 % of patients at discharge , 23 % at 3 months and 31 % at 3 years . On postoperative diffusion-weighted magnetic resonance imaging , there were new ischemic cerebral lesions in 51 % of patients . The presence of cognitive deficit at discharge was a significant univariate predictor of late cognitive decline ( p = 0.025 ) . A relation between the presence of new diffusion-weighted magnetic resonance imaging detected lesions and cognitive decline , however , was not found . CONCLUSIONS Longitudinal cognitive performance of patients with CABG showed a two-stage course with early improvement followed by later decline . Long-term cognitive deficit was predicted by early cognitive decline , but not by ischemic brain lesions on magnetic resonance imaging |
11,966 | 26,908,524 | Pharmacist-led medication reconciliation programmes are effective at improving post-hospital healthcare utilisation .
This review supports the implementation of pharmacist-led medication reconciliation programmes that include some component aim ed at improving medication safety | OBJECTIVES Pharmacists play a role in providing medication reconciliation .
However , data on effectiveness on patients ' clinical outcomes appear inconclusive .
Thus , the aim of this study was to systematic ally investigate the effect of pharmacist-led medication reconciliation programmes on clinical outcomes at hospital transitions . | OBJECTIVES To study the feasibility and effectiveness of a discharge planning intervention . DESIGN Quasi-experimental pre-post study design . SETTING General medicine wards at three hospitals : an academic medical center , a community teaching hospital , and a community-based nonteaching hospital . PARTICIPANTS All patients aged 65 and older admitted to the hospitalist services . INTERVENTION The intervention toolkit had five core elements : admission form with geriatric cues , facsimile to the primary care provider , interdisciplinary worksheet to identify barriers to discharge , pharmacist-physician collaborative medication reconciliation , and predischarge planning appointments . MEASUREMENTS Thirty-day readmission and return to emergency department rates and patient satisfaction with discharge . Odds ratios were determined , and site effects were examined accordig to interaction terms and Breslow Day statistics . RESULTS Two hundred thirty-seven patients were followed during the preintervention period , and 185 were exposed to the intervention . Patients characteristics were similar across the two time periods . The proportion of patients with high- quality transitions home , measured according to Coleman 's Care Transition Measures , increased from 68 % to 89 % ( odds ratio (OR)=3.49 , 95 % confidence interval (CI)=2.06 - 5.92 ) . Return to the emergency department within 3 days of discharge was lower in the intervention period ( 10 % vs 3 % , OR=0.25 , 95 % CI=0.10 - 0.62 ) . At 30 days , there was a lower rate of readmission ( 22 % vs 14 % , OR=0.59 , 95 % CI=0.34 - 0.97 ) and fewer visits to the emergency department ( 21 % vs 14 % , OR=0.61 , 95 % CI=0.36 - 1.03 ) ( P=.06 ) . CONCLUSION When hospitalized elderly patients are treated with consideration of their specific needs , healthcare outcomes can be improved Background : Hospital discharge is an interlace of care when patients are at a high risk of medication discrepancies as they transition from hospital to home . These discrepancies are important , as they may contribute to drug-related problems , medication errors , and adverse drug events . Objective : To Identify , characterize , and assess the clinical impact of unintentional medication discrepancies at hospital discharge . Methods : All consecutive general internal medicine patients admitted for at least 72 hours to a tertiary care teaching hospital were prospect ively assessed . Patients were excluded if they were discharged with verbal prescriptions ; died during hospitalization ; or transferred from or to a nursing home , another institution , or another unit within the same hospital . The primary endpoint was to determine the number of patients with at least one unintended medication discrepancy on hospital discharge . Medication discrepancies were assessed through comparison of a best possible medication discharge list with the actual discharge prescriptions . Secondary objectives were to characterize and assess the potential clinical impact of the unintentional discrepancies . Results : From March 14,2006 , to June 2,2006,430 patients were screened for eligibility ; 150 patients were included in the study . Overall , 106 ( 70.7 % ) patients had at least one actual or potential unintentional discrepancy . Sixty-two patients ( 41.3 % ) had at least one actual unintentional medication discrepancy al hospital discharge and 83 patients ( 55.3 % ) had at least one potential unintentional discrepancy . The most common unintentional discrepancies were an incomplete prescription requiring clarification , which could result in a patient delay in obtaining medications ( 49.5 % ) , and the omission of medications ( 22.9 % ) . Of the 105 unintentional discrepancies , 31 ( 29.5 % ) had the potential to cause possible or probable patient discomfort and /or clinical deterioration . Conclusions : Medication discrepancies occur commonly on hospital discharge . Underst and ing the type and frequency of discrepancies can help clinicians better underst and ways to prevent them . Structured medication reconciliation may help to prevent discharge medication discrepancies Objective Heart failure patients are regularly admitted to hospital and frequently use multiple medication . Besides intentional changes in pharmacotherapy , unintentional changes may occur during hospitalisation . The aim of this study was to investigate the effect of a clinical pharmacist discharge service on medication discrepancies and prescription errors in patients with heart failure . Setting A general teaching hospital in Tilburg , the Netherl and s. Method An open r and omized intervention study was performed comparing an intervention group , with a control group receiving regular care by doctors and nurses . The clinical pharmacist discharge service consisted of review of discharge medication , communicating prescribing errors with the cardiologist , giving patients information , preparation of a written overview of the discharge medication and communication to both the community pharmacist and the general practitioner about this medication . Within 6 weeks after discharge all patients were routinely scheduled to visit the outpatient clinic and medication discrepancies were measured . Main outcome measure The primary endpoint was the frequency of prescription errors in the discharge medication and medication discrepancies after discharge combined . Results Forty-four patients were included in the control group and 41 in the intervention group . Sixty-eight percent of patients in the control group had at least one discrepancy or prescription error against 39 % in the intervention group ( RR 0.57 ( 95 % CI 0.37–0.88 ) ) . The percentage of medications with a discrepancy or prescription error in the control group was 14.6 % and in the intervention group it was 6.1 % ( RR 0.42 ( 95 % CI 0.27–0.66 ) ) . Conclusion This clinical pharmacist discharge service significantly reduces the risk of discrepancies and prescription errors in medication of patients with heart failure in the 1st month after discharge BACKGROUND Prior studies suggest that unintended medication discrepancies that represent errors are common at the time of hospital admission . These errors are particularly worthy of attention because they are not likely to be detected by computerized physician order entry systems . METHODS We prospect ively studied patients reporting the use of at least 4 regular prescription medications who were admitted to general internal medicine clinical teaching units . The primary outcome was unintended discrepancies ( errors ) between the physicians ' admission medication orders and a comprehensive medication history obtained through interview . We also evaluated the potential seriousness of these discrepancies . All discrepancies were review ed with the medical team to determine if they were intentional or unintentional . All unintended discrepancies were rated for their potential to cause patient harm . RESULTS After screening 523 admissions , 151 patients were enrolled based on the inclusion criteria . Eighty-one patients ( 53.6 % ; 95 % confidence interval , 45.7%-61.6 % ) had at least 1 unintended discrepancy . The most common error ( 46.4 % ) was omission of a regularly used medication . Most ( 61.4 % ) of the discrepancies were judged to have no potential to cause serious harm . However , 38.6 % of the discrepancies had the potential to cause moderate to severe discomfort or clinical deterioration . CONCLUSIONS Medication errors at the time of hospital admission are common , and some have the potential to cause harm . Better methods of ensuring an accurate medication history at the time of hospital admission are needed BACKGROUND Hospitalization and subsequent discharge home often involve discontinuity of care , multiple changes in medication regimens , and inadequate patient education , which can lead to adverse drug events ( ADEs ) and avoidable health care utilization . Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs . METHODS We conducted a r and omized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital . Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later . Interventions focused on clarifying medication regimens ; review ing indications , directions , and potential side effects of medications ; screening for barriers to adherence and early side effects ; and providing patient counseling and /or physician feedback when appropriate . The primary outcome was rate of preventable ADEs . RESULTS Pharmacists observed the following drug-related problems in the intervention group : unexplained discrepancies between patients ' preadmission medication regimens and discharge medication orders in 49 % of patients , unexplained discrepancies between discharge medication lists and postdischarge regimens in 29 % of patients , and medication nonadherence in 23 % . Comparing trial outcomes 30 days after discharge , preventable ADEs were detected in 11 % of patients in the control group and 1 % of patients in the intervention group ( P = .01 ) . No differences were found between groups in total ADEs or total health care utilization . CONCLUSIONS Pharmacist medication review , patient counseling , and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge . Medication discrepancies before and after discharge were common targets of intervention Purpose To examine the impact of systematic medication reconciliations upon hospital admission and of a medication review while in hospital on the number of inappropriate medications and unscheduled drug-related hospital revisits in elderly patients . Methods This was a prospect i ve , controlled study in 210 patients , aged 65 years or older , who were admitted to one of three internal medicine wards at a University Hospital in Sweden . Intervention patients received the complete Lund Integrated Medicines Management model ( medication reconciliation upon admission and discharge , and medication review and monitoring ) provided by a multi-professional team , including a clinical pharmacist . Control patients received st and ard care and medication reconciliation upon discharge . Blinded review ers evaluated the appropriateness of the prescribing ( using the Medication Appropriateness Index ) on admission and discharge , and assessed the probability that a drug-related problem was the reason for any patient readmitted to hospital or visiting the emergency department within 3 months of discharge ( using World Health Organisation causality criteria ) . Results There was a greater decrease in the number of inappropriate drugs in the intervention group than in the control group for both the intention-to-treat population { 51 % [ 95 % confidence interval ( CI ) 43–58 % ] vs. 39 % ( 95 % CI 30–48 % ) ; p = 0.0446 } and the per- protocol population [ 60 % ( 95 % CI 51–67 % ) vs. 44 % ( 95 % CI 34–52 % ) ; p = 0.0106 ) ] . There were six revisits to hospital in the intervention group which were judged as ‘ possibly , probably or certainly drug-related ’ , compared with 12 in the control group ( p = 0.0469 ) . Conclusions In this study , medication reconciliation and review provided by a clinical pharmacist in a multi-professional team significantly reduced the number of inappropriate drugs and unscheduled drug-related hospital revisits among elderly patients OBJECTIVE To quantify admission medication discrepancies in a tertiary-care , general pediatric population , to describe their clinical importance and associated factors , and to assess a screening approach to pharmacist involvement . METHODS A total of 272 patients were studied prospect ively at hospital admission . The study pharmacist performed a medication history and compared it to physicians ' admission medication orders . Discrepancies between the 2 were coded as intentional but undocumented or unintentional . Unintentional discrepancies were rated for potential to cause harm by 3 physicians . Additional data collected included patients ' reason for admission and presence of chronic conditions , whether physicians used a medication reconciliation form , the characteristics of patients ' home medication regimen , and the time required to perform a pharmacist history and reconciliation . Interrater reliability and associations between baseline characteristics and discrepancy rates were explored . RESULTS Eighty patients ( 30 % ) had at least one undocumented intentional discrepancy ( range , 0 - 7 ) . At least one unintentional discrepancy ( range , 0 - 9 ) was found in 59 patients ( 22 % ) . Of the unintentional discrepancies , 23 % had moderate and 6 % had severe potential to cause discomfort or deterioration . Ratings were similar among the 3 physicians . Characteristics associated with higher risk of clinical ly important discrepancies were : use of the medication reconciliation form , > or = 4 prescription medications , and antiepileptic drug use . Logistic regression revealed that only the variable > or = 4 medications was independently associated with clinical ly important discrepancies . CONCLUSIONS Admission medication errors are common in this tertiary-care , general pediatric population , and nearly a third represent potential adverse events . The use of a medication reconciliation form by physicians without pharmacist involvement does not appear to reduce errors . A cutoff of > or = 4 prescription medications is highly sensitive for identifying patients at risk of clinical ly important discrepancies Background Medication reconciliation has been m and ated by the Irish government at transfer of care . Research is needed to determine the contribution of clinical pharmacists to the process . Objective To describe the contribution of emergency department based clinical pharmacists to admission medication reconciliation in Irel and . Main Outcome Measure Frequency of clinical pharmacist ’s activities . Setting Two public university teaching hospitals . Methodology Adults admitted via the accident and emergency department , from a non-acute setting , reporting the use of at least three regular prescription medications , were eligible for inclusion . Medication reconciliation was provided by clinical pharmacists to r and omly-selected patients within 24-hours of admission . This process includes collecting a gold-st and ard pre-admission medication list , checking this against the admission prescription and communicating any changes . A discrepancy was defined as any difference between the gold-st and ard pre-admission medication list and the admission prescription . Discrepancies were communicated to the clinician in the patient ’s healthcare record . Potentially harmful discrepancies were also communicated verbally . Pharmacist activities and unintentional discrepancies , both resolved and unresolved at 48-hours were measured . Unresolved discrepancies were confirmed verbally by the team as intentional or unintentional . A reliable and vali date d tool was used to assess clinical significance by medical consultants , clinical pharmacists , community pharmacists and general practitioners . Results In total , 134 patients , involving 1,556 medications , were included in the survey . Over 97 % of patients ( involving 59 % of medications ) experienced a medication change on admission . Over 90 % of patients ( involving 29 % of medications ) warranted clinical pharmacy input to determine whether such changes were intentional or unintentional . There were 447 interventions by the clinical pharmacist regarding apparently unintentional discrepancies , a mean of 3.3 per patient . In total , 227 ( 50 % ) interventions were accepted and discrepancies resolved . At 48-hours under half ( 46 % ) of patients remained affected by an unintentional unresolved discrepancy ( 60 % related to omissions ) . Verbally communicated discrepancies were more likely to be resolved than those not communicated verbally ( Chi-square ( 1 ) = 30.029 p < 0.05 ) . Under half of unintentional unresolved discrepancies ( 46 % ) had the potential to cause minor harm compared to 70 % of the resolved unintentional discrepancies . None had the potential to result in severe harm . Conclusion Clinical pharmacists contribute positively to admission medication reconciliation and should be engaged to deliver this service in Irel and BACKGROUND Patients 80 years or older are underrepresented in scientific studies . The objective of this study was to investigate the effectiveness of interventions performed by ward-based pharmacists in reducing morbidity and use of hospital care among older patients . METHODS A r and omized controlled study of patients 80 years or older was conducted at the University Hospital of Uppsala , Uppsala , Sweden . Four hundred patients were recruited consecutively between October 1 , 2005 , and June 30 , 2006 , and were r and omized to control ( n = 201 ) and intervention ( n = 199 ) groups . The interventions were performed by ward-based pharmacists . The control group received st and ard care without direct involvement of pharmacists at the ward level . The primary outcome measure was the frequency of hospital visits ( emergency department and readmissions [ total and drug-related ] ) during the 12-month follow-up period . RESULTS Three hundred sixty-eight patients ( 182 in the intervention group and 186 in the control group ) were analyzed . For the intervention group , there was a 16 % reduction in all visits to the hospital ( quotient , 1.88 vs 2.24 ; estimate , 0.84 ; 95 % confidence interval [ CI ] , 0.72 - 0.99 ) and a 47 % reduction in visits to the emergency department ( quotient , 0.35 vs 0.66 ; estimate , 0.53 ; 95 % CI , 0.37 - 0.75 ) . Drug-related readmissions were reduced by 80 % ( quotient , 0.06 vs 0.32 ; estimate , 0.20 ; 95 % CI , 0.10 - 0.41 ) . After inclusion of the intervention costs , the total cost per patient in the intervention group was $ 230 lower than that in the control group . CONCLUSION If implemented on a population basis , the addition of pharmacists to health care teams would lead to major reductions in morbidity and health care costs Background Pharmacists may improve medication-related outcomes during transitions of care . The aim of the Iowa Continuity of Care Study was to determine if a pharmacist case manager ( PCM ) providing a faxed discharge medication care plan from a tertiary care institution to primary care could improve medication appropriateness and reduce adverse events , rehospitalization and emergency department visits . Methods Design . R and omized , controlled trial of 945 participants assigned to enhanced , minimal and usual care groups conducted 2007 to 2012 . Subjects . Participants with cardiovascular-related conditions and /or asthma or chronic obstructive pulmonary disease were recruited from the University of Iowa Hospital and Clinics following admission to general medicine , family medicine , cardiology or orthopedics . Intervention . The minimal group received admission history , medication reconciliation , patient education , discharge medication list and medication recommendations to inpatient team . The enhanced group also received a faxed medication care plan to their community physician and pharmacy and telephone call 3–5 days post-discharge . Participants were followed for 90 days post-discharge . Main Outcomes and Measures . Medication appropriateness index ( MAI ) , adverse events , adverse drug events and post-discharge healthcare utilization were compared by study group using linear and logistic regression , as models accommodating r and om effects due to pharmacists indicated little clustering . Results Study groups were similar at baseline and the intervention fidelity was high . There were no statistically significant differences by study group in medication appropriateness , adverse events or adverse drug events at discharge , 30-day and 90-day post-discharge . The average MAI per medication as 0.53 at discharge and increased to 0.75 at 90 days , and this was true across all study groups . Post-discharge , about 16 % of all participants experienced an adverse event , and this did not differ by study group ( p > 0.05 ) . Almost one-third of all participants had any type of healthcare utilization within 30 days post-discharge , where 15 % of all participants had a 30-day readmission . Healthcare utilization post-discharge was not statistically significant different at 30 or 90 days by study group . Conclusion The pharmacist case manager did not affect medication use outcomes post-discharge perhaps because quality of care measures were high in all study groups . Trial registration Clinical trials.gov registration : NCT00513903 , August 7 , 2007 Objective : This study aim ed to evaluate the use of a shared electronic primary health care record ( EHR ) to assist with medicines reconciliation in the hospital from admission to discharge . Methods : This is a prospect i ve cross-sectional , comparison evaluation for 2 phases , in a short-term elderly admissions ward in the United Kingdom . In phase 1 , full reconciliation of the medication history was attempted , using conventional methods , before accessing the EHR , and then the EHR was used to verify the reconciliation . In phase 2 , the EHR was the initial method of retrieving the medication history-vali date d by conventional methods . Results : Where reconciliation was led by conventional methods , and before any access to the EHR was attempted , 28 ( 28 % ) of hospital prescriptions were found to contain errors . Of 99 prescriptions subsequently checked using the EHR , only 50 ( 50 % ) matched the EHR . Of the remainder , 25 % of prescriptions contained errors when verified by the EHR . However , 26 % of patients had an incorrect list of current medications on the EHR . Using the EHR as the primary method of reconciliation , 33 ( 32 % ) of 102 prescriptions matched the EHR . Of those that did not match , 39 ( 38 % ) of prescriptions were found to contain errors . Furthermore , 37 ( 36 % ) of patients had an incorrect list of current medications on the EHR . The most common error type on the discharge prescription was drug omission ; and on the EHR , wrong drug . Common potentially serious errors were related to unidentified allergies and adverse drug reactions . Conclusions : The EHR can reduce medication errors . However , the EHR should be seen as one of a range of information sources for reconciliation ; the primary source being the patient or their carer . Both primary care and hospital clinicians should have read- and -write access to the EHR to reduce errors at care transitions . We recommend further evaluation studies BACKGROUND Medication reconciliation at transitions in care is a national patient safety goal , but its effects on important patient outcomes require further evaluation . We sought to measure the impact of an information technology-based medication reconciliation intervention on medication discrepancies with potential for harm ( potential adverse drug events [ PADEs ] ) . METHODS We performed a controlled trial , r and omized by medical team , on general medical inpatient units at 2 academic hospitals from May to June 2006 . We enrolled 322 patients admitted to 14 medical teams , for whom a medication history could be obtained before discharge . The intervention was a computerized medication reconciliation tool and process re design involving physicians , nurses , and pharmacists . The main outcome was unintentional discrepancies between preadmission medications and admission or discharge medications that had potential for harm ( PADEs ) . RESULTS Among 160 control patients , there were 230 PADEs ( 1.44 per patient ) , while among 162 intervention patients there were 170 PADEs ( 1.05 per patient ) ( adjusted relative risk [ ARR ] , 0.72 ; 95 % confidence interval [ CI ] , 0.52 - 0.99 ) . A significant benefit was found at hospital 1 ( ARR , 0.60 ; 95 % CI , 0.38 - 0.97 ) but not at hospital 2 ( ARR , 0.87 ; 95 % CI , 0.57 - 1.32 ) ( P = .32 for test of effect modification ) . Hospitals differed in the extent of integration of the medication reconciliation tool into computerized provider order entry applications at discharge . CONCLUSIONS A computerized medication reconciliation tool and process re design were associated with a decrease in unintentional medication discrepancies with potential for patient harm . Software integration issues are likely important for successful implementation of computerized medication reconciliation tools OBJECTIVES The objective of this study was to evaluate the quality of medication information available in medical charts before and after the implementation of a medication reconciliation form . PATIENTS AND METHODS This study is a retrospective chart review of patients under 18 years who were taking two medications or more at home and were admitted to a paediatric hospital for more than 24 hours and discharged from a general paediatrics , infectious disease , gastroenterology or pneumology ward over two 20-week periods ( pre- and post-implementation ) . Each week , 10 medical records were r and omly chosen and review ed . The quality of the medication information was measured on admission ( dose , route of administration and frequency ) and on discharge ( dose , route of administration , frequency and duration of treatment ) . The proportion of medications that fully met these criteria was compared between the groups using the chi-squared test . RESULTS Information was analysed for a total of 3275 medications in the pre-implementation group , vs. 3240 medications in the post-implementation group . Baseline characteristics were similar in both groups . On admission , the quality of medication information was comparable between the pre- and post-implementation groups ( 29.1 vs. 29.3 % , respectively ; P = 0.86 ) . However , on discharge , an improvement in the quality of information was observed in the post-implementation group ( 51.7 vs. 65.2 % ; P < 0.001 ) . CONCLUSION Our study demonstrated that the forms used in the reconciliation process , in particular the discharge prescription , could increase the quality of the information related to drug use in medical charts . We believe that medication reconciliation forms should be widely used by all the health care professional teams involved in the drug history or prescription process Objective : To evaluate the impact of a hospital based community liaison pharmacy service on a range of outcomes in patients aged more than 55 years and taking more than 3 prescribed drugs , who had been admitted to the medical unit of a district general hospital in Northern Irel and . Methods : Having recruited 243 patients , a total of 162 patients completed the full protocol ( 81 r and omly assigned to intervention and 81 to control ; mean age of control patients 75 years ; mean age of intervention patients 73 years ) . The interventions by the community liaison pharmacist included : preparation of an accurate medication record following a full review of current medication use ; medication counselling ; provision of a medicines record sheet informing the patient how to take their drugs ; provision of a pharmaceutical discharge letter detailing changes made to drug therapy ( this was faxed to the patient 's GP and community pharmacist on the day of discharge ) ; provision of a Medicines Helpline . Results : The key findings were as follows : problems were identified in 80 % of the intervention patients ' prescription charts , 49 % of which related to drug omissions from the patients ' domiciliary prescriptions . The GP practice record was the most accurate ( mean error rate 12.6 % ) while the GP referral letter was the least accurate ( mean error rate 47.3 % ) source of medication information . Drugs patients brought to hospital were also an inaccurate source ( mean error rate 44.0 % ) . The intervention group patients , when compared with control patients , had a significant reduction ( P=0.005 ) in drug mismatch between drugs prescribed at discharge and taken at home , and had a greater knowledge of their drug regimen 10–14 days after discharge ( P |Ld 0.001 ) . The vast majority of patients ( 96 % ) felt that the provision of a medicine helpline was a useful service . Conclusions : The study indicated clear benefits from the involvement of a hospital based community liaison pharmacist in achieving seamless pharmaceutical care between the primary and secondary healthcare setting RATIONALE , AIMS AND OBJECTIVES To determine whether an increased input by clinical pharmacists at each stage of the patient 's hospital journey , from admission through discharge , result ed in an enhanced level of patient care as measured by a number of clinical and economic outcomes . METHODS This project was design ed to address medicines management issues in patients deemed at risk of drug-related problems . During the project , these latter patients at the time of admission were r and omly assigned to an integrated medicines management ( IMM ) service group ( n = 371 ) or regular hospital care group ( n = 391 ) . The IMM service involved comprehensive pharmaceutical care provided by a pharmacy team throughout each of three stages : patient admission , inpatient monitoring and counselling , and patient discharge . RESULTS Patients who received the IMM service benefited from a reduced length of hospital stay [ by 2 days ( P = 0.003 ; independent sample s t-test log(e ) ) ] . IMM patients also had a decreased rate of readmission over a 12-month follow-up period ( 40.8 % vs. 49.3 % ; p = 0.027 ; Fisher 's exact test ) and an increased time to readmission [ 20 days longer ( P = 0.0356 ; log rank test ) ] . A numbers-needed-to-treat calculation indicated that for approximately every 12 patients receiving the IMM service , one readmission to hospital , within 12 months of discharge , would be prevented . The new service was welcomed by cognate health care professionals . CONCLUSION The IMM service proved very effective and can be used as a template to support the implementation of comprehensive pharmaceutical care as a routine service across Northern Irel and and beyond BACKGROUND Medication histories acquired upon admission are often incomplete . Using a st and ardized approach warrants more complete medication reconciliation , however , this is too time consuming to be performed . Other strategies guaranteeing complete medication histories should be explored . We developed a limited list of st and ardized questions and assessed its impact on completeness of medication histories . METHODS This prospect i ve study enrolled adults presenting to a tertiary care emergency department . In the control group , medication histories were conducted by physicians of general internal medicine conform st and ard care . In the intervention group , the physicians were obliged to use , besides the st and ard care , the ' limited questions list ' for medication history acquisition . The clinical pharmacist re-obtained medication histories of the patients in both groups using a st and ardized approach . The primary outcome was the impact of the use of a ' limited questions list ' on the frequency of drug omissions in medication histories . RESULTS 260 consecutive patients were enrolled : 130 in the intervention group and 130 in the control group . There was a significant reduction of 49.3 % in drug omissions in the intervention group . The omission rate per medication history was 1.1 for the control group , which was significantly lower ( 0.6 ) in the intervention group . Antithrombotics were most frequently forgotten in the control care group as opposed to dietary supplements in the intervention group . CONCLUSION Drug omission rate in medication histories can be significantly reduced if a limited list of simple questions is used during anamnesis . Widespread use of this tool should be considered to be implemented RATIONALE Care coordination has shown inconsistent results as a mechanism to reduce hospital readmission and postdischarge emergency department ( ED ) visit rates . OBJECTIVE To assess the impact of a supplemental care bundle targeting high-risk elderly in patients implemented by hospital-based staff compared to usual care on a composite outcome of hospital readmission and /or ED visitation at 30 and 60 days following discharge . PATIENTS / METHODS R and omized controlled pilot study in 41 medical in patients predisposed to unplanned readmission or postdischarge ED visitation , conducted at Baylor University Medical Center . The intervention group care bundle consisted of medication counseling/reconciliation by a clinical pharmacist ( CP ) , condition specific education/enhanced discharge planning by a care coordinator ( CC ) , and phone follow-up . RESULTS Groups had similar baseline characteristics . Intervention group readmission/ED visit rates were reduced at 30 days compared to the control group ( 10.0 % versus 38.1 % , P = 0.04 ) , but not at 60 days ( 30.0 % versus 42.9 % , P = 0.52 ) . For those patients who had a readmission/postdischarge ED visit , the time interval to this event was longer in the intervention group compared to usual care ( 36.2 versus 15.7 days , P = 0.05 ) . Study power was insufficient to reliably compare the effects of the intervention on lengths of index hospital stay between groups . CONCLUSIONS A targeted care bundle delivered to high-risk elderly in patients decreased unplanned acute health care utilization up to 30 days following discharge . Dissipation of this effect by 60 days postdischarge defines reasonable expectations for analogous hospital-based educational interventions . Further research is needed regarding the impacts of similar care bundles in larger population s across a variety of inpatient setting Purpose : Medication errors related to hospital discharge result in rehospitalization and emergency department ( ED ) visits , yet no systematic approach has been implemented nationally to decrease these medication errors . Pharmacist involvement during postdischarge transitions of care may be an important strategy to prevent and correct medication discrepancies and reduce costly rehospitalization and ED visits . Methods : This prospect i ve , r and omized , open-label , pilot study evaluated the effect of a pharmacy clinic visit focused on medication reconciliation and patient education after hospital discharge on the incidence of rehospitalization and ED visits and the resolution of medication discrepancies . Results : Of the 61 subjects included in the study , 33 ( 54 % ) had medication discrepancies identified at discharge . Fifty percent of medication discrepancies were resolved in subjects r and omized to the pharmacist intervention arm compared with 9.5 % in the usual care arm ( P = .015 ) . Patients r and omized to the intervention arm had significantly lower rates of the primary composite outcome of 30-day rehospitalization and ED visits compared with the usual care arm ( 0 % vs 40.5 % , P < .001 ) . Conclusion : A pharmacist-driven intervention focused on patient education and medication reconciliation after discharge improved medication use and reduced health care re source utilization in this pilot study Background Failure to reconcile medications across transitions in care is an important source of potential harm to patients . Little is known about the predictors of unintentional medication discrepancies and how , when , and where they occur . Objective To determine the reasons , timing , and predictors of potentially harmful medication discrepancies . Design Prospect i ve observational study . Patients Admitted general medical patients . Measurements Study pharmacists took gold-st and ard medication histories and compared them with medical teams ’ medication histories , admission and discharge orders . Blinded teams of physicians adjudicated all unexplained discrepancies using a modification of an existing typology . The main outcome was the number of potentially harmful unintentional medication discrepancies per patient ( potential adverse drug events or PADEs ) . Results Among 180 patients , 2066 medication discrepancies were identified , and 257 ( 12 % ) were unintentional and had potential for harm ( 1.4 per patient ) . Of these , 186 ( 72 % ) were due to errors taking the preadmission medication history , while 68 ( 26 % ) were due to errors reconciling the medication history with discharge orders . Most PADEs occurred at discharge ( 75 % ) . In multivariable analyses , low patient underst and ing of preadmission medications , number of medication changes from preadmission to discharge , and medication history taken by an intern were associated with PADEs . Conclusions Unintentional medication discrepancies are common and more often due to errors taking an accurate medication history than errors reconciling this history with patient orders . Focusing on accurate medication histories , on potential medication errors at discharge , and on identifying high-risk patients for more intensive interventions may improve medication safety during and after hospitalization Background Recent literature revealed that medication histories obtained by physicians and nurses are often incomplete . However , the number of patients included was often low . Study objective In this study , the authors compare medication histories obtained in the Emergency Department ( ED ) by pharmacists versus physicians and identify characteristics contributing to discrepancies . Methods Medication histories were acquired by the pharmacist from patients admitted to the ED , planned to be hospitalised . A structured form was used to guide the pharmacist or technician to ensure a st and ardised approach . Discrepancies , defined as any difference between the pharmacist-acquired medication history and that obtained by the physician , were analysed . Results 3594 medication histories were acquired by pharmacy staff . 59 % ( 95 % CI 58.2 % to 59.8 % ) of medication histories recorded by physicians were different from those obtained by the pharmacy staff . Within these inaccurate medication histories , 5963 discrepancies were identified . The most common type of error was omission of a drug ( 61 % ; 95 % CI 60.4 % to 61.6 % ) , followed by omission of dose ( 18 % ; 95 % CI 17.6 % to 18.4 % ) . Drugs belonging to the class of psycholeptics , acid suppressors and beta blocking agents were related to the highest discrepancy rate . Acetylsalicylic acid , omeprazole and zolpidem were most commonly forgotten . Conclusion This large prospect i ve study demonstrates that medication history acquisition is very often incomplete in the ED . A structured form and a st and ardised method is necessary . Pharmacists are especially suited to acquire and supervise accurate medication histories , as they are educated and familiar with commonly used drugs Context Emergency department visits and rehospitalizations are common after hospital discharge . Contribution This trial demonstrated that a nurse discharge advocate and clinical pharmacist working together to coordinate hospital discharge , educate patients , and reconcile medications led to fewer follow-up emergency visits and rehospitalizations than usual care alone . Caution The trial was conducted at a single center , and not all eligible patients were enrolled . Implication A systematic approach to hospital discharges can reduce unnecessary health service use . The Editors One in 5 hospitalizations is complicated by postdischarge adverse events ( 1 , 2 ) , some of which may lead to preventable emergency department visits or readmissions . Despite this finding , hospital discharge procedures have not been st and ardized ( 3 ) . In addition , the declining presence of primary care providers ( PCPs ) in hospitals has not been adequately accompanied by systems to ensure that patient data are transferred to subsequent caregivers ( 4 , 5 ) . For example , discharge summaries frequently lack critical data and are not sent to the PCP in a timely fashion ( 6 , 7 ) , result ing in outpatient clinicians being unaware of test results that were pending at discharge ( 8) and evaluations that were scheduled to be done after discharge not being completed ( 9 ) . Similarly , patients are often left unprepared at discharge ; many do not underst and their discharge medications and can not recall their chief diagnoses ( 10 ) . With more than 32 million adult discharges in the United States each year ( 11 ) , these deficiencies in the transition of care increase illness , unnecessary hospital utilization , and cost . Some peridischarge interventions have shown a reduction in hospital readmission rates and cost ( 1214 ) , emergency department visits ( 15 ) , and postdischarge adverse events ( 16 ) , whereas some have shown little or no effect ( 1720 ) . Peridischarge interventions have also shown improved PCP follow-up and outpatient work-ups ( 21 ) and higher patient satisfaction ( 15 ) . Most of these studies have focused on specific diagnoses ( 14 , 22 , 23 ) or highly selected population s , such as geriatric adults ( 12 , 13 , 19 , 24 ) . Some have focused on specific aspects of the discharge , such as increasing access to primary care follow-up ( 25 ) , connecting with transitional nursing services ( 26 ) , or improving patients ' ability to advocate for themselves after discharge ( 12 ) . To date , no study has evaluated a st and ardized discharge intervention that includes patient education , comprehensive discharge planning , and postdischarge telephone reinforcement in a general medical population . In 2004 , we began an in-depth examination of hospital discharge , for which we design ed a package of services to minimize discharge failuresa process called reengineered discharge ( RED ) ( Table 1 ) ( 3 , 27 ) . We did a r and omized , controlled trial to evaluate the clinical effect of implementing RED among patients admitted to a general medical service . Table 1 . Components of Reengineered Hospital Discharge Methods Setting and Participants We conducted a 2-group , r and omized , controlled trial of English-speaking patients 18 years of age or older who were admitted to the medical teaching service of Boston Medical Center , Boston , Massachusettsa large , urban , safety-net hospital with an ethnically diverse patient population . Patients had to have a telephone , be able to comprehend study details and the consent process in English , and have plans to be discharged to a U.S. community . We did not enroll patients if they were admitted from a skilled nursing facility or other hospital , transferred to a different hospital service before enrollment , admitted for a planned hospitalization , were on hospital pre caution s or suicide watch , or were deaf or blind . Boston University 's institutional review board approved all study activities . R and omization Each morning , a list of admitted patients was review ed for initial eligibility ( hospital location , age , date and time of admission , and previous enrollment ) . Last names of potential participants were ranked by using a r and om-number sequence to determine the order in which to approach patients for enrollment . A trained research assistant then approached each patient and further determined eligibility according to inclusion and exclusion criteria ( Figure 1 ) . Figure 1 . Study flow diagram . * Patients did not meet inclusion criteria if they were admitted from or planned discharge to an institutional setting ( n= 74 ) , planned hospitalization ( n= 3 ) or discharge to a non-U.S. community ( n= 5 ) , were transferred to different hospital service ( n= 8) , did not speak English ( n= 371 ) or have a telephone ( n= 71 ) , were on hospital pre caution s ( n= 274 ) or suicide watch with a sitter ( n= 10 ) , were unable to consent ( n= 181 ) , had sickle cell disease as the admitting diagnosis ( n= 38 ) , had privacy status ( n= 8) , were deaf or blind ( n= 2 ) , or other ( n= 4 ) . Usual care participants did not meet eligibility criteria if they were discharged to a nursing facility ( n= 28 ) , were transferred to another hospital service ( n= 1 ) , were previously enrolled ( n= 1 ) , died during index admission ( n= 2 ) , requested to be removed ( n= 5 ) , or other ( n= 3 ) . Intervention participants did not meet eligibility criteria if they were discharged to a nursing facility ( n= 21 ) , were transferred to another hospital service ( n= 6 ) , died during index admission ( n= 1 ) , requested to be removed ( n= 2 ) , or other ( n= 8) . 107 intervention participants did not receive a reinforcement call because they could not be reached by telephone ( n= 93 ) , they were readmitted the same or next day ( n= 2 ) , there was no staffing coverage ( n= 8) , or other ( n= 4 ) . By using block r and omization ( 28 ) with varying block sizes of 6 and 8 , we r and omly arranged index cards indicating either the usual care or intervention group . We placed the cards in opaque envelopes labeled consecutively with study numbers . We assigned eligible participants who consented to enrollment to a study group by revealing the concealed index card . This process continued until 2 participants were enrolled each day of the week ( or 3 participants if the first 2 participants were r and omly assigned to the usual care group ) . This protocol ensured that research assistants could not selectively choose potential participants for enrollment or predict assignment . Participants r and omly assigned to usual care received no further intervention . There were 40 participants in the usual care group and 38 in the intervention group who were enrolled but no longer met inclusion criteria at discharge ( most commonly because they were discharged to a nursing facility ) . Because the primary analysis was by intention to treat , we included these participants in the analysis , with the exception of those who died before index discharge , requested to be removed , or were previously enrolled ( Figure 1 ) . Interventions Nurse discharge advocates ( DAs ) carried out all aspects of the in-hospital intervention . We hired 6 part-time DAs to work with intervention participants to ensure coverage by 1 DA 7 days a week , 5 hours a day . We trained all DAs to deliver the RED intervention by using a manual containing detailed scripts , observation of relevant clinical interactions , and simulated practice sessions . The primary goals of the DA were to coordinate the discharge plan with the hospital team and educate and prepare the participant for discharge . At admission , the DA completed the RED intervention components outlined in Table 1 . Additional information about the DA training manual is published elsewhere ( 3 ) and can be found on our Web site ( www.bu.edu/fammed/projectred/index.html ) . With information collected from the hospital team and the participant , the DA created the after-hospital care plan ( AHCP ) , which contained medical provider contact information , date s for appointments and tests , an appointment calendar , a color-coded medication schedule , a list of tests with pending results at discharge , an illustrated description of the discharge diagnosis , and information about what to do if a problem arises . Information for the AHCP was manually entered into a Microsoft Word ( Microsoft , Redmond , Washington ) template , printed , and spiral-bound to produce an individualized , color booklet design ed to be accessible to individuals with limited health literacy . By using scripts from the training manual , the DA used a teach-back methodology ( 29 ) to review the contents of the AHCP with the participant . On the day of discharge , the AHCP and discharge summary were faxed to the PCP . A clinical pharmacist telephoned the participants 2 to 4 days after the index discharge to reinforce the discharge plan by using a scripted interview . The pharmacist had access to the AHCP and hospital discharge summary and , over several days , made at least 3 attempts to reach each participant . The pharmacist asked participants to bring their medications to the telephone to review them and address medication-related problems ; the pharmacist communicated these issues to the PCP or DA . Outcomes Measures and Follow-up At the time of recruitment , research assistants collected baseline data , including sociodemographic characteristics ; the Short Form-12 Health Survey , Version 2 ( 30 ) ; the depression subscale from the Patient Health Question naire-9 ( 31 ) ; and the Rapid Estimate of Adult Literacy in Medicine ( 32 ) . We calculated the Charlson Comorbidity Index score by using primary and secondary diagnoses recorded on the index admission discharge summary ( 33 ) . We determined the number of hospital admissions and emergency department visits in the 6 months before index admission through medical record review ( Boston Medical Center hospital utilization ) and participant report ( all other hospital utilization ) . The primary end point was the rate of hospital utilizationthe total number of emergency department visits and readmissions per participant within 30 days of the index discharge . WHAT IS KNOWN AND OBJECTIVE Interventions involving medication reconciliation and review by clinical pharmacists can reduce drug-related problems and improve therapeutic outcomes . The objective of this study was to examine the impact of routine admission medication reconciliation and inpatient medication review on emergency department ( ED ) revisits after discharge . Secondary outcomes included the combined rate of post-discharge hospital revisits or death . METHODS This prospect i ve , controlled study included all patients hospitalized in three internal medicine wards in a university hospital , between 1 January 2006 and 31 May 2008 . Medication reconciliation on admission and inpatient medication review , conducted by clinical pharmacists in a multiprofessional team , were implemented in these wards at different times during 2007 and 2008 ( intervention periods ) . A discharge medication reconciliation was undertaken in all the study wards , during both control and intervention periods . Patients were included in the intervention group ( n = 1216 ) if they attended a ward with medication reconciliation and review , whether they had received the intervention or not . Control patients ( n = 2758 ) attended the wards before implementation of the intervention . RESULTS AND DISCUSSION No impact of medication reconciliation and review s on ED revisits [ hazard ratio ( HR ) , 0.95 ; 95 % confidence interval ( CI ) , 0.86 - 1.04]or event-free survival ( HR , 0.96 ; 95 % CI , 0.88 - 1.04 ) was demonstrated . In the intervention group , 594 patients ( 48.8 % ) visited the ED , compared with 1416 ( 51.3 % ) control patients . In total , 716 intervention ( 58.9 % ) and 1688 ( 61.2 % ) control patients experienced any event ( ED visit , hospitalization or death ) . Because the time to a subsequent ED visit was longer for the control as well as the intervention groups in 2007 than in 2006 ( P < 0.05 ) , we re-examined this cohort of patients ; the proportion of patients revisiting the ED was similar in both groups in 2007 ( P = 0.608 ) . WHAT IS NEW AND CONCLUSION Routine implementation of medication reconciliation and review s on admission and during the hospital stay did not appear to have any impact on ED revisits , re-hospitalizations or mortality over 6-month follow-up BACKGROUND Medication reconciliation can prevent some adverse drug events ( ADEs ) . Our prospect i ve study explored whether an easily replicable nurse-pharmacist led medication reconciliation process could efficiently and inexpensively prevent potential ADEs . METHODS Nurses at a 1000 bed urban , tertiary care hospital developed the home medication list ( HML ) through patient interview . If a patient was not able to provide a written HML or recall medications , the nurses review ed the electronic record along with other sources . The nurses then compared the HML to the patient 's active inpatient medications and judged whether the discrepancies were intentional or potentially unintentional . This was repeated at discharge as well . If the prescriber changed the order when contacted about a potential unintentional discrepancy , it was categorized as unintentional and rated on a 1 - 3 potential harm scale . RESULTS The study included 563 patients . HML information gathering averaged 29 minutes . Two hundred twenty-five patients ( 40 % ; 95 % confidence interval [ CI ] , 36%-44 % ) had at least 1 unintended discrepancy on admission or discharge . One hundred sixty-two of the 225 patients had an unintended discrepancy ranked 2 or 3 on the harm scale . It cost $ 113.64 to find 1 potentially harmful discrepancy . Based on the 2008 cost of an ADE , preventing 1 discrepancy in every 290 patient encounters would offset the intervention costs . We potentially averted 81 ADEs for every 290 patients . CONCLUSION Potentially harmful medication discrepancies occurred frequently at both admission and discharge . A nurse-pharmacist collaboration allowed many discrepancies to be reconciled before causing harm . The collaboration was efficient and cost-effective , and the process potentially improves patient safety Background The prevalence and cost of hospital readmissions have gained attention . The ability to identify patients at high risk for hospital readmission has implication s for quality and costs of care . Medication errors have been shown to increase the risk for readmission . Objective To study the impact of a pharmacist-based predischarge medication reconciliation and counseling program on 30-day readmission rates and determine whether polypharmacy and problem medications are important screening criteria . Methods A prospect i ve , nonr and omized cohort study performed at a single medical-surgical unit with telemetry capability at a single academic medical center . The participants were 729 patients , aged 18 years and older , who were discharged between July 1 and October 29 , 2010 . The intervention was pharmacist medication reconciliation and counseling based on a screening tool . The primary outcome was 30-day readmission rate . Secondary outcomes were the presence of polypharmacy and problem medications and their relationship with observed 30-day readmission rate , including calculation of a problem med/polypharmacy score . Results The pharmacy review group ( n = 537 ) had a lower 30-day readmission rate than the group receiving usual care ( n = 192 ) ( 16.8 % vs 26.0 % ; odds ratio [ OR ] 0.572 ; 95 % CI , 0.387 - 0.852 ; P = .006 ) . Polypharmacy , defined as either 5 or more or 10 or more scheduled medications , alone and in combination with at least one problem medication had higher 30-day readmission rates . A score of no factors present exhibited good negative predictive value . Conclusions Medication reconciliation and counseling by a pharmacist reduced the 30-day readmission rate . Polypharmacy and problem medications appear to have value individually and together . A pharmacist , guided by a screening tool in predischarge medication reconciliation , is one option to effectively reduce 30-day readmissions BACKGROUND Medication discrepancies may occur during transitions from community to acute care hospitals . The elderly are at risk for such discrepancies due to multiple comorbidities and complex medication regimens . Medication reconciliation involves verifying medication use and identifying and rectifying discrepancies . OBJECTIVE The aim of this study was to describe the prevalences and types of medication discrepancies in acutely ill older patients . METHODS Patients who were ≥ 70 years and were admitted to any of 3 acute care for elders ( ACE ) units over a period of 2 nonconsecutive months in 2008 were prospect ively enrolled . Medication discrepancies were classified as intentional , undocumented intentional , and unintentional . Unintentional medication discrepancies were classified by a blinded rater for potential to harm . This study was primarily qualitative , and descriptive ( univariate ) statistics are presented . RESULTS Sixty-seven patients ( 42 women ; mean [ SD ] age , 84.0 [ 6.5 ] years ) were enrolled . There were 37 unintentional prescription-medication discrepancies in 27 patients ( 40.3 % ) and 43 unintentional over-the-counter ( OTC ) medication discrepancies in 19 patients ( 28.4 % ) , which translates to Medication Reconciliation Success Index ( MRSI ) of 89 % for prescription medications and 59 % for OTC medications . The overall MRSI was 83 % . More than half of the prescription-medication discrepancies ( 56.8 % ) were classified as potentially causing moderate/severe discomfort or clinical deterioration . CONCLUSION Despite a fairly high overall MRSI in these patients admitted to ACE units , a substantial proportion of the prescription-medication discrepancies were associated with potential harm BACKGROUND Medication reconciliation ( MR ) has proven to be a problematic task for many hospitals to accomplish . It is important to know the clinical impact of physician- versus pharmacist-initiated MR in the re source -limited hospital environment . METHODS This quasi-experimental study took place from December 2005 to February 2006 at an urban US Veterans Affairs hospital . MR was implemented on 2 similar general medical units : one received physician-initiated MR and the other received pharmacist-initiated MR . Adverse drug events ( ADEs ) and a 72-hour medication-prescribing risk score were ascertained by research pharmacists for all admitted patients by structured record review . Multivariable models were tested for intervention effect , accounting for quasi-experimental design and clustered observations , and were adjusted for patient and encounter covariates . RESULTS Pharmacists completed the MR process in 102 admissions and physicians completed the process in 116 admissions . In completing the MR process , pharmacists documented statistically more admission medication changes than physicians ( 3.6 vs 0.8 ; P < 0.001 ) . The adjusted odds of an ADE caused by an admission prescribing change with pharmacist-initiated MR compared with a physician-initiated MR were 1.04 with a 95 % CI of 0.53 to 2.0 . The adjusted odds of an ADE caused by an admission prescribing change that was a prescribing error with pharmacist-initiated MR compared with a physician-initiated MR were 0.38 with a confidence interval of 0.14 to 1.05 . No difference was observed in 72-hour prescribing risk score ( coefficient = 0.10 ; 95 % CI , -0.54 to 0.75 ) . CONCLUSION MR performed by pharmacists versus physicians was more comprehensive and was followed by lower odds of ADEs from admission prescribing errors but with similar odds of all types of ADEs . Further research is warranted to examine how MR tasks may be optimally divided among clinicians and the mechanisms by which MR affects the likelihood of subsequent ADEs Background : As patients move across transition points of care , medication discrepancies are likely to occur . In the emergency department ( ED ) , patients are vulnerable to medication discrepancies because they are in an environment in which rapid decisions need to be made under high levels of stress . Objective : To identify the patient- , environment- , and medication-related factors involving unexplained medication discrepancies across transition points after ED presentation . Methods : Using a retrospective chart review design , a stratified , r and om sampling of data was undertaken over a 12-month period . Information was obtained from an electronic administrative data base and medical records as patients moved from the ED to another transition point of care . Medication discrepancies were classified into 2 outcome groups : ( 1 ) no discrepancies and situations in which discrepancies were adequately explained and ( 2 ) discrepancies that had no adequate explanation . Results : For the 12-month period , 210 r and omly selected patients were included ; 73 ( 34.8 % ) had at least one unexplained medication discrepancy . Binary logistic regression modeling showed 4 factors that were statistically significant in determining the incidence of at least one unexplained medication discrepancy . Benefit card holders ( individuals who receive benefits from government insurance programs comparable to the US-based Medicare and Medicaid initiatives , which include the elderly , the disabled , low income earners , and unemployed persons ) had 3.73 greater odds of experiencing an unexplained medication discrepancy ( 95 % CI 1.72 to 8.07 ; p = 0.001 ) . Patients prescribed 5 or more drugs at discharge from the ED had 12.22 greater odds of having at least one unexplained medication discrepancy ( 95 % CI 5.52 to 27.08 ; p < 0.001 ) . Patients who were first seen by a physician within 1 hour of a change in working shift had 3.70 greater odds of having an unexplained medication discrepancy ( 95 % CI 1.67 to 8.18 ; p = 0.001 ) . For each additional minute of wait time for a physician , the odds of having an unexplained medication discrepancy increased by a factor of 1.01 ( 95 % CI 1.00 to 1.01 ; p = 0.042 ) . Conclusions : Patient- , environment- , and drug-related factors contribute to the risk of medication discrepancies across transition points from the ED Background Medication discrepancies at the time of hospital discharge are common and can result in error , patient/carer inconvenience or patient harm . Providing accurate medication information to the next care provider is necessary to prevent adverse events . Aims To investigate the quality and consistency of medication details generated for such transfer from an Irish teaching hospital . Methods This was an observational study of 139 cardiology patients admitted over a 3 month period during which a pharmacist prospect ively recorded details of medication inconsistencies . Results A discrepancy in medication documentation at discharge occurred in 10.8 % of medication orders , affecting 65.5 % of patients . While patient harm was assessed , it was only felt necessary to contact three ( 2 % ) patients . The most common inconsistency was drug omission ( 20.9 % ) . Conclusions Inaccuracy of medication information at hospital discharge is common and compromises quality of care |
11,967 | 25,240,384 | One pilot study found balance board training reduced falls and most studies reported training improved physical ( e.g. balance and strength ) and cognitive ( e.g. attention , executive function ) measures .
Inconsistent results were found for psychological measures related to falls-efficacy .
Very few between-group differences were evident when interactive cognitive-motor interventions were compared to traditional training programs .
Conclusions The review findings provide preliminary evidence that interactive cognitive-motor interventions can improve physical and cognitive fall risk factors in older people , but that the effect of such interventions on falls has not been definitively demonstrated .
Interactive cognitive-motor interventions appear to be of equivalent efficacy in ameliorating fall risk as traditional training programs . | Background It is well-known physical exercise programs can reduce falls in older people .
Recently , several studies have evaluated interactive cognitive-motor training that combines cognitive and gross motor physical exercise components .
The aim of this systematic review was to determine the effects of these interactive cognitive-motor interventions on fall risk in older people . | Declined balance functions have adverse effects on elderly population . Lower limbs muscle power training is currently an emerging concept in rehabilitation on individuals with decreased balance and mobility . In this prospect i ve , controlled study , we used a human-computer interactive video-game-based rehabilitation device ( LLPR ) for training of lower limb muscle power in the elderly . Forty ( aged > 65 years ) individuals were recruited from the community . Twenty participants in the exercise group received 30-min training , twice a week , using the LLPR system . The LLPR system allows participants to perform fast speed sit-to-st and ( STS ) movements . Twenty age-matched participants in the control group performed slow speed STS movements , as well as strengthening and balance exercises , with the same frequency and duration . The results were compared after 12 sessions ( 6 weeks ) of training . The mechanical and time parameters during STS movement were measured using the LLPR system . Modified falls efficacy scale ( MFES ) , Tinetti Performance-Oriented Mobility Assessment ( POMA ) , function reach test , five times sit to st and ( FTSS ) and Timed Up and Go ( TUG ) were administered to participants as clinical assessment s. Results showed that in the exercise group , all the mechanical and time parameters showed significant improvement . In control group , only the maximal vertical ground reaction force ( MVGRF ) improved significantly . For clinical assessment s ( balance , mobility , and self-confidence ) , exercise group showed significantly better scores . The STS movements in video-game-based training mimic real life situations which may help to transfer the training effects into daily activities . The effectiveness of lower limb muscle training is worthy of further investigation Background Stepping impairments are associated with physical and cognitive decline in older adults and increased fall risk . Exercise interventions can reduce fall risk , but adherence is often low . A new exergame involving step training may provide an enjoyable exercise alternative for preventing falls in older people . Purpose To assess the feasibility and safety of unsupervised , home-based step pad training and determine the effectiveness of this intervention on stepping performance and associated fall risk in older people . Design Single-blinded two-arm r and omized controlled trial comparing step pad training with control ( no-intervention ) . Setting / Participants Thirty-seven older adults residing in independent-living units of a retirement village in Sydney , Australia . Intervention Intervention group ( IG ) participants were provided with a computerized step pad system connected to their TVs and played a step game as often as they liked ( with a recommended dose of 2–3 sessions per week for 15–20 minutes each ) for eight weeks . In addition , IG participants were asked to complete a choice stepping reaction time ( CSRT ) task once each week . Main Outcome Measures CSRT , the Physiological Profile Assessment ( PPA ) , neuropsychological and functional mobility measures were assessed at baseline and eight week follow-up . Results Thirty-two participants completed the study ( 86.5 % ) . IG participants played a median 2.75 sessions/week and no adverse events were reported . Compared to the control group , the IG significantly improved their CSRT ( F31,1 = 18.203 , p<.001 ) , PPA composite scores ( F31,1 = 12.706 , p = 0.001 ) , as well as the postural sway ( F31,1 = 4.226 , p = 0.049 ) and contrast sensitivity ( F31,1 = 4.415 , p = 0.044 ) PPA sub-component scores . In addition , the IG improved significantly in their dual-task ability as assessed by a timed up and go test/verbal fluency task ( F31,1 = 4.226 , p = 0.049 ) . Conclusions Step pad training can be safely undertaken at home to improve physical and cognitive parameters of fall risk in older people without major cognitive and physical impairments . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12611001081909 BACKGROUND Dementia cases may reach 100 million by 2050 . Interventions are sought to curb or prevent cognitive decline . Exercise yields cognitive benefits , but few older adults exercise . Virtual reality-enhanced exercise or " exergames " may elicit greater participation . PURPOSE To test the following hypotheses : ( 1 ) stationary cycling with virtual reality tours ( " cybercycle " ) will enhance executive function and clinical status more than traditional exercise ; ( 2 ) exercise effort will explain improvement ; and ( 3 ) brain-derived neurotrophic growth factor ( BDNF ) will increase . DESIGN Multi-site cluster r and omized clinical trial ( RCT ) of the impact of 3 months of cybercycling versus traditional exercise , on cognitive function in older adults . Data were collected in 2008 - 2010 ; analyses were conducted in 2010 - 2011 . SETTING / PARTICIPANTS 102 older adults from eight retirement communities enrolled ; 79 were r and omized and 63 completed . INTERVENTIONS A recumbent stationary ergometer was utilized ; virtual reality tours and competitors were enabled on the cybercycle . MAIN OUTCOME MEASURES Executive function ( Color Trails Difference , Stroop C , Digits Backward ) ; clinical status ( mild cognitive impairment ; MCI ) ; exercise effort/fitness ; and plasma BDNF . RESULTS Intent-to-treat analyses , controlling for age , education , and cluster r and omization , revealed a significant group X time interaction for composite executive function ( p=0.002 ) . Cybercycling yielded a medium effect over traditional exercise ( d=0.50 ) . Cybercyclists had a 23 % relative risk reduction in clinical progression to MCI . Exercise effort and fitness were comparable , suggesting another underlying mechanism . A significant group X time interaction for BDNF ( p=0.05 ) indicated enhanced neuroplasticity among cybercyclists . CONCLUSIONS Cybercycling older adults achieved better cognitive function than traditional exercisers , for the same effort , suggesting that simultaneous cognitive and physical exercise has greater potential for preventing cognitive decline . TRIAL REGISTRATION This study is registered at Clinical trials.gov NCT01167400 BACKGROUND Gait and cognitive disturbances are common in Parkinson 's disease ( PD ) . These deficits exacerbate fall risk and difficulties with mobility , especially during complex or dual-task walking . Traditional gait training generally fails to fully address these complex gait activities . Virtual reality ( VR ) incorporates principles of motor learning while delivering engaging and challenging training in complex environments . We hypothesized that VR may be applied to address the multifaceted deficits associated with fall risk in PD . METHODS Twenty patients received 18 sessions ( 3 per week ) of progressive intensive treadmill training with virtual obstacles ( TT + VR ) . Outcome measures included gait under usual-walking and dual-task conditions and while negotiating physical obstacles . Cognitive function and functional performance were also assessed . RESULTS Patients were 67.1 ± 6.5 years and had a mean disease duration of 9.8 ± 5.6 years . Posttraining , gait speed significantly improved during usual walking , during dual task , and while negotiating overground obstacles . Dual-task gait variability decreased ( ie , improved ) and Trail Making Test times ( parts A and B ) improved . Gains in functional performance measures and retention effects , 1 month later , were also observed . CONCLUSIONS To our knowledge , this is the first time that TT + VR has been used for gait training in PD . The results indicate that TT + VR is viable in PD and may significantly improve physical performance , gait during complex challenging conditions , and even certain aspects of cognitive function . These findings have important implication s for underst and ing motor learning in the presence of PD and for treating fall risk in PD , aging , and others who share a heightened risk of falls The combination of active video gaming and exercise ( exergaming ) is suggested to improve elderly people 's balance , thereby decreasing fall risk . Exergaming has been shown to increase motivation during exercise therapy , due to the enjoyable and challenging nature , which could support long-term adherence for exercising balance . However , scarce evidence is available of the direct effects of exergaming on postural control . Therefore , the aim of the study was to assess the effect of a six-week videogame-based exercise program aim ed at improving balance in elderly people . Task performance and postural control were examined using an interrupted time series design . Results of multilevel analyses showed that performance on the dot task improved within the first two weeks of training . Postural control improved during the intervention . After the intervention period task performance and balance were better than before the intervention . Results of this study show that healthy elderly can benefit from a videogame-based exercise program to improve balance and that all subjects were highly motivated to exercise balance because they found gaming challenging and enjoyable Background While many studies confirm the positive effect of cognitive and physical training on cognitive performance of older adults , only little is known about the effects of simultaneously performed cognitive and physical training . In the current study , older adults simultaneously performed a verbal working memory and a cardiovascular training to improve cognitive and motor-cognitive dual task performance . Twenty training sessions of 30 minutes each were conducted over a period of ten weeks , with a test session before , in the middle , and after the training . Training gains were tested in measures of selective attention , paired-associates learning , executive control , reasoning , memory span , information processing speed , and motor-cognitive dual task performance in the form of walking and simultaneously performing a working memory task . Results Sixty-three participants with a mean age of 71.8 ± 4.9 years ( range 65 to 84 ) either performed the simultaneous training ( N = 21 ) , performed a single working memory training ( N = 16 ) , or attended no training at all ( N = 26 ) . The results indicate similar training progress and larger improvements in the executive control task for both training groups when compared to the passive control group . In addition , the simultaneous training result ed in larger improvements compared to the single cognitive training in the paired-associates task and was able to reduce the step-to-step variability during the motor-cognitive dual task when compared to the single cognitive training and the passive control group . Conclusions The simultaneous training of cognitive and physical abilities presents a promising training concept to improve cognitive and motor-cognitive dual task performance , offering greater potential on daily life functioning , which usually involves the recruitment of multiple abilities and re sources rather than a single one BACKGROUND there are few longitudinal studies of the prognosis of falling at home . OBJECTIVE to determine outcomes in older people who fall once and more than once . DESIGN longitudinal prospect i ve cohort study . SETTING primary care in the UK . SUBJECTS 1815 subjects over 75 who had a st and ardized and vali date d health check . METHOD annual interviews over 4 years . Practice records were used to establish death and admission to institutions . RESULTS risk of death was increased at 1 year [ odds ratio ( OR ) 2.6 , 95 % confidence interval ( CI ) 1.4 - 4.7 ] and 3 years ( OR 1.9 , 95 % CI 1.2 - 3.0 ) for recurrent fallers but not single fallers ( OR 0.9 , 95 % CI 0.5 - 1.6 at 1 year ; OR 0.97 , 95 % CI 0.7 - 1.4 at 3 years ) . Risk of admission to long-term care over 1 year was markedly increased both for single fallers ( OR 3.8 , 95 % CI 1.8 - 8.3 ) and recurrent fallers ( OR 4.5 , 95 % CI 1.7 - 12 ) . Functional decline was not related to faller status , the latter being very variable from one year to the next . CONCLUSIONS the stronger relationship between falling and admission to long-term care rather than mortality supports the hypothesis that the perceived risks for those who fall only once are exaggerated Background Computer-based interventions have demonstrated consistent positive effects on various physical abilities in older adults . This study aims to compare two training groups that achieve similar amounts of strength and balance exercise where one group receives an intervention that includes additional dance video gaming . The aim is to investigate the different effects of the training programs on physical and psychological parameters in older adults . Methods Thirty-one participants ( mean age ± SD : 86.2 ± 4.6 years ) , residents of two Swiss hostels for the aged , were r and omly assigned to either the dance group ( n = 15 ) or the control group ( n = 16 ) . The dance group absolved a twelve-week cognitive-motor exercise program twice weekly that comprised progressive strength and balance training supplemented with additional dance video gaming . The control group performed only the strength and balance exercises during this period . Outcome measures were foot placement accuracy , gait performance under single and dual task conditions , and falls efficacy . Results After the intervention between-group comparison revealed significant differences for gait velocity ( U = 26 , P = .041 , r = .45 ) and for single support time ( U = 24 , P = .029 , r = .48 ) during the fast walking dual task condition in favor of the dance group . No significant between-group differences were observed either in the foot placement accuracy test or in falls efficacy . Conclusions There was a significant interaction in favor of the dance video game group for improvements in step time . Significant improved fast walking performance under dual task conditions ( velocity , double support time , step length ) was observed for the dance video game group only . These findings suggest that in older adults a cognitive-motor intervention may result in more improved gait under dual task conditions in comparison to a traditional strength and balance exercise program . Trial registration This trial has been registered under IS RCT N05350123 ( http://www.controlled-trials.com OBJECTIVES To evaluate the learning , retention and transfer of performance improvements after Nintendo Wii Fit ™ training in patients with Parkinson 's disease and healthy elderly people . DESIGN Longitudinal , controlled clinical study . PARTICIPANTS Sixteen patients with early-stage Parkinson 's disease and 11 healthy elderly people . INTERVENTIONS Warm-up exercises and Wii Fit training that involved training motor ( shifts centre of gravity and step alternation ) and cognitive skills . A follow-up evaluative Wii Fit session was held 60 days after the end of training . Participants performed a functional reach test before and after training as a measure of learning transfer . MAIN OUTCOME MEASURES Learning and retention were determined based on the scores of 10 Wii Fit games over eight sessions . Transfer of learning was assessed after training using the functional reach test . RESULTS Patients with Parkinson 's disease showed no deficit in learning or retention on seven of the 10 games , despite showing poorer performance on five games compared with the healthy elderly group . Patients with Parkinson 's disease showed marked learning deficits on three other games , independent of poorer initial performance . This deficit appears to be associated with cognitive dem and s of the games which require decision-making , response inhibition , divided attention and working memory . Finally , patients with Parkinson 's disease were able to transfer motor ability trained on the games to a similar untrained task . CONCLUSIONS The ability of patients with Parkinson 's disease to learn , retain and transfer performance improvements after training on the Nintendo Wii Fit depends largely on the dem and s , particularly cognitive dem and s , of the games involved , reiterating the importance of game selection for rehabilitation purpose Background This r and omized controlled pilot study aim ed to explore whether a cognitive-motor exercise program that combines traditional physical exercise with dance video gaming can improve the voluntary stepping responses of older adults under attention dem and ing dual task conditions . Methods Elderly subjects received twice weekly cognitive-motor exercise that included progressive strength and balance training supplemented by dance video gaming for 12 weeks ( intervention group ) . The control group received no specific intervention . Voluntary step execution under single and dual task conditions was recorded at baseline and post intervention ( Week 12 ) . Results After intervention between-group comparison revealed significant differences for initiation time of forward steps under dual task conditions ( U = 9 , P = 0.034 , r = 0.55 ) and backward steps under dual task conditions ( U = 10 , P = 0.045 , r = 0.52 ) in favor of the intervention group , showing altered stepping levels in the intervention group compared to the control group . Conclusion A cognitive-motor intervention based on strength and balance exercises with additional dance video gaming is able to improve voluntary step execution under both single and dual task conditions in older adults Objectives . To determine the effects on balance and gait of a Wii-Fit program compared to a walking program in subjects with mild Alzheimer 's dementia ( AD ) . Methods . A prospect i ve r and omized ( 1 : 1 ) pilot study with two intervention arms was conducted in an assisted living facility with twenty-two mild AD subjects . In both groups the intervention occurred under supervision for 30 minutes daily , five times a week for eight weeks . Repeated measures ANOVA and paired t-tests were used to analyze changes . Results . Both groups showed improvement in Berg Balance Scale ( BBS ) , Tinetti Test ( TT ) and Timed Up and Go ( TUG ) over 8 weeks . However , there was no statistically significant difference between the groups over time . Intragroup analysis in the Wii-Fit group showed significant improvement on BBS ( P = 0.003 ) , and TT ( P = 0.013 ) . The walking group showed a trend towards improvement on BBS ( P = 0.06 ) and TUG ( P = 0.07 ) and significant improvement in TT ( P = 0.06 ) . Conclusion . This pilot study demonstrates the safety and efficacy of Wii-Fit in an assisted living facility in subjects with mild AD . Use of Wii-Fit result ed in significant improvements in balance and gait comparable to those in the robust monitored walking program . These results need to be confirmed in a larger , method ologically sound study Cardiovascular fitness is thought to offset declines in cognitive performance , but little is known about the cortical mechanisms that underlie these changes in humans . Research using animal models shows that aerobic training increases cortical capillary supplies , the number of synaptic connections , and the development of new neurons . The end result is a brain that is more efficient , plastic , and adaptive , which translates into better performance in aging animals . Here , in two separate experiments , we demonstrate for the first time to our knowledge , in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task . Specifically , highly fit ( Study 1 ) or aerobically trained ( Study 2 ) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning , when compared with low-fit ( Study 1 ) or nonaerobic control ( Study 2 ) participants . Additionally , in both studies there exist groupwise differences in activation of the anterior cingulate cortex , which is thought to monitor for conflict in the attentional system , and signal the need for adaptation in the attentional network . These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain , and may serve to reduce both biological and cognitive senescence in humans Poor balance is considered a challenging risk factor for falls in older adults . Therefore , innovative interventions for balance improvement in this population are greatly needed . The aim of this study was to evaluate the effect of a new virtual-reality system ( the Balance Rehabilitation Unit [ BRU ] ) on balance , falls , and fear of falling in a population of community-dwelling older subjects with a known history of falls . In this study , 60 community-dwelling older subjects were recruited after being diagnosed with poor balance at the Falls and Fractures Clinic , Nepean Hospital ( Penrith , NSW , Australia ) . Subjects were r and omly assigned to either the BRU-training or control groups . Both groups received the usual falls prevention care . The BRU-training group attended balance training ( two sessions/week for 6 weeks ) using an established protocol . Change in balance parameters was assessed in the BRU-training group at the end of their 6-week training program . Both groups were assessed 9 months after their initial assessment ( month 0 ) . Adherence to the BRU-training program was 97 % . Balance parameters were significantly improved in the BRU-training group ( P < 0.01 ) . This effect was also associated with a significant reduction in falls and lower levels of fear of falling ( P < 0.01 ) . Some components of balance that were improved by BRU training showed a decline after 9 months post-training . In conclusion , BRU training is an effective and well-accepted intervention to improve balance , increase confidence , and prevent falls in the elderly OBJECTIVES Cognitive processing plays an important role in balance and gait and is a contributing factor to falls in older adults . This relationship may be explained by the fact that higher order cognitive functions such as executive functions are called upon while walking . The purpose of this study was to examine whether a cognitive training intervention leads to significant improvements on measures of balance and gait . METHOD This r and omized trial tested whether cognitive training over 10 weeks improves balance and gait in older adults . Participants were r and omly assigned to a computer-based cognitive training intervention or measurement-only control . Outcomes included Timed Up and Go ( TUG ) , gait speed , and gait speed with a cognitive distraction . Data were analyzed using analysis of covariance models with change scores . RESULTS Participants ' ( N = 51 ) average age was 82.7 for those r and omized to intervention and 81.1 for those r and omized to control . After 10 weeks , intervention group participants performed significantly better than controls on the TUG . When the cohort was limited to those categorized as slow walkers ( baseline 10-m walk ≥ 9 s ) , intervention participants performed significantly better than controls on TUG and distracted walking . DISCUSSION Cognitive training slows degradation of balance and improves gait while distracted , rendering it a promising approach to falls prevention Background and purpose Numerous interventions have been proposed to improve balance in older adults with varying degrees of success . A novel approach may be to use an off-the-shelf video game system utilizing real-time force feedback to train older adults . The purpose of this study is to investigate the feasibility of using Nintendo ’s Wii Fit for training to improve clinical measures of balance in older adults and to retain the improvements after a period of time . Methods Twelve healthy older adults ( aged > 70 years ) were r and omly divided into two groups . The experimental group completed training using Nintendo ’s Wii Fit game three times a week for 3 weeks while the control group continued with normal activities . Four clinical measures of balance were assessed before training , 1 week after training , and 1 month after training : Berg Balance Scale ( BBS ) , Fullerton Advanced Balance ( FAB ) scale , Functional Reach ( FR ) , and Timed Up and Go ( TUG ) . Friedman two-way analysis of variance by ranks was conducted on the control and experimental group to determine if training using the Wii Balance Board with Wii Fit had an influence on clinical measures of balance . Results Nine older adults completed the study ( experimental group n = 4 , control group n = 5 ) . The experimental group significantly increased their BBS after training while the control group did not . There was no significant change for either group with FAB , FR , and TUG . Conclusion Balance training with Nintendo ’s Wii Fit may be a novel way for older adults to improve balance as measured by the BBS The prevention of injury associated with falls in older people is a public health target in many countries around the world . Although there is good evidence that interventions such as multifactorial fall prevention and individually prescribed exercise are effective in reducing falls , the effect on serious injury rates is unclear . Historically , trials have not been adequately powered to detect injury endpoints , and variations in case definition across trials have hindered meta- analysis . It is possible that fall-prevention strategies have limited effect on falls that result in injuries or are ineffective in population s who are at a higher risk of injury . Further research is required to determine whether fall-prevention interventions can reduce serious injuries . Prevention of Falls Network Europe ( ProFaNE ) is a collaborative project to reduce the burden of fall injury in older people through excellence in research and promotion of best practice ( www.profane.eu.org ) . The European Commission funds the network , which links clinicians , members of the public , and research ers worldwide . The aims are to identify major gaps in knowledge in fall injury prevention and to facilitate the collaboration necessary for large-scale clinical research activity , including clinical trials , comparative research , and prospect i ve meta- analysis . Work is being undertaken in a 4-year program . As a first step , the development of a common set of outcome definitions and measures for future trials or meta- analysis was considered OBJECTIVE We investigated whether providing participants in an exercise programme with regular feedback on their exercise progress affected their adherence to the programme regimen . METHOD We conducted a r and omized controlled trial . Adult men and women with borderline hypertension and a body mass index ≥ 25.0 were r and omized to two intervention groups ( groups A and B ) and one control group ( group C ) and were prescribed regular aerobic exercise . During the 12-week study period , group A was provided with both feedback information on their exercise progress and a health letter , while group B was provided with the health letter only . The main outcome measure was exercise performance , per cent achievement of target exercise level ( % ) defined as the number of weeks during which the exercise target was reached divided by the number of weeks in the programme . Results were compared using the Kruskal-Wallis test . RESULTS A total of 105 study subjects were r and omized into three groups ( A , n = 37 ; B , n = 37 and C , n = 31 ) . Per cent achievement of target exercise level during the 12-week period was highest in group A ( 26.5 % ) , followed by groups B ( 22.9 % ) and C ( 17.4 % ) ( P = 0.36 ) . Subjects who received regular feedback during the exercise programme tended to have higher exercise performance . CONCLUSIONS In improving adherence to exercise intervention , the provision of regular feedback to participants in an exercise programme may be an effective intervention OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity OBJECTIVE To compare the effect of 3 different approaches to balance training on dual-task balance performance in older adults with balance impairment . DESIGN A double-blind , r and omized controlled trial . SETTING University research laboratory . PARTICIPANTS Older adults ( N=23 ) with balance impairment ( mean age , 74.8y ) . They scored 52 or less on the Berg Balance Scale ( BBS ) and /or walked with a self-selected gait speed of 1.1 m/s or less . INTERVENTIONS Participants were r and omly assigned to 1 of 3 interventions : single-task training , dual-task training with fixed-priority instructions , and dual-task training with variable-priority instructions . Participants received 45-minute individualized training sessions , 3 times a week for 4 weeks . MAIN OUTCOME MEASURES Gait speed under single-task and dual-task conditions was obtained at baseline , the second week , the end of training , and the twelfth week after the end of training . Other measures , including the BBS and the Activities-specific Balance Confidence ( ABC ) Scale , were collected at baseline and after training . RESULTS Participants in all groups improved on the BBS ( P<.001 ; effect size [ES]=.72 ) , and walked significantly faster after training ( P=.02 ; ES=.27 ) . When a cognitive task was added , however , only participants who received dual-task training with fixed-priority instructions and dual-task training with variable-priority instructions exhibited significant improvements in gait speed ( P<.001 , ES=.57 ; and P<.001 , ES=.46 , respectively ) . In addition , only the dual-task training with variable-priority instructions group demonstrated a dual-task training effect at the second week of training and maintained the training effect at the 12-week follow-up . Only the single-task training group showed a significant increase on the ABC after training ( P<.001 ; ES=.61 ) . CONCLUSIONS Dual-task training is effective in improving gait speed under dual-task conditions in elderly participants with balance impairment . Training balance under single-task conditions may not generalize to balance control during dual-task context s. Explicit instruction regarding attentional focus is an important factor contributing to the rate of learning and the retention of the dual-task training effect Two behavioral techniques were assessed to determine their effects on subjects ' adherence to unsupervised exercise . The subjects were 35 moderately fit persons who had just completed an adult fitness program ( AF group ) and 42 sedentary individuals who were recruited through the campus newspaper ( NEWS group ) . Participants were r and omly assigned to one of three conditions : ( a ) self-monitoring , ( b ) reinforcement supplied by another person , or ( c ) control . All subjects were given instructions on how to exercise and asked to exercise on their own for 18 weeks . Self-monitoring subjects kept written records of their exercise behavior , while reinforcement subjects verbally reported their exercise behavior to another person who periodically administered rewards . Pre- and posttreatment tests on the NEWS group revealed no significant treatment or interaction effects . However , the reinforcement group had an 11 % improvement in predicted max VO2 and a 9 bpm improvement in exercise heart rate compared to 7.8 % , 5 bpm for the self-monitoring ( SM ) group and 5.3 % , 6 bpm for the control group . T-tests indicated that reward and SM groups improved significantly on these variables , whereas the control group did not . SM ( M = 2.07 ) and reinforcement ( M = 2.29 ) groups reported a significantly higher frequency of exercise per week than the control ( M = 1.36 ) group . The AF subjects were able to maintain their fitness level ( with the exception of a small increase in body fat ) over the 18-week period . The behavioral interventions had little differential effect on adherence by AF subjects who were already regular exercisers BACKGROUND Attention and executive functions show strong associations with slow gait and falls in seniors and have been shown to be amenable to cognitive remediation . However , cognitive remediation as a strategy to improve mobility has not been investigated . METHODS Using a r and omized single-blind control design , 24 sedentary older adults ( exercise less than or equal to once weekly and gait velocity < 1 m/s ) were r and omly assigned to an 8-week computerized cognitive remediation program or wait-list . Primary outcome was change in gait velocity during normal pace and " walking while talking " conditions . We also compared the proportion of improvers ( velocity change ≥4 cm/s ) in each group . RESULTS The 10 participants who completed cognitive remediation improved gait velocity from baseline during normal walking ( 68.2 ± 20.0 vs 76.5 ± 17.9 cm/s , p = .05 ) and walking while talking ( 36.7 ± 13.5 vs 56.7 ± 20.4 cm/s , p = .002 ) . The 10 intervention participants improved gait velocity over the 8-week intervention both during normal walking ( change : 8.2 ± 11.4 - 1.3 ± 6.8 cm/s , p = .10 ) and walking while talking ( change : 19.9 ± 14.9 - 2.5 ± 20.1 cm/s , p = .05 ) compared with the 10 control participants . Six intervention participants were improvers on normal pace walking compared with three controls ( odds ratio = 3.0 , 95 % confidence interval = 0.5 - 19.6 ) . All 10 intervention participants improved on walking while talking compared with 3 controls ( odds ratio = 3.5 , 95 % confidence interval = 1.5 - 8.0 ) . CONCLUSIONS The findings of this pilot trial are promising and suggest that cognitive remediation may improve mobility in sedentary seniors . This approach should be vali date d in larger scale trials The objective of the study was to examine the predictive effect of prospect ively registered falls on survival within a r and omly selected group of elderly women . A longitudinal study , with 9 years follows up after 1 year prospect i ve fall registration was design ed . Persons age 75 or more living in the community . A total of 300 Norwegian women ; mean age was 80.8 participated in the study . Base-line registration s of health , functioning and medication were made . Falls which occurred during a 1-year period after baseline were registered as well as the date of death within a 9-year period after the end of the fall registration period . Half of the women reported one or more falls ( 1–11 ) . Eighty-six women ( 28.7 % ) experienced only one fall and 65 ( 21.7 % ) had at least two . During the 9-year follow-up period , 41.7 % died . Cox regression analyzes demonstrated that frequent falling , old age and a self-reported worsening of health were significantly associated with mortality during the follow-up period . Their relative risks of death when experiencing at least two falls was 1.6 ( 95 % CI 1.1–2.4 ) , P = 0.04 , when compared with no falls . Older fallers appear to have markedly increased mortality . Since falls are common among elderly people , this is a relevant fact for public health policy . Increasing age , poor self-rated health and high frequency of falls predict independently mortality in our 9 years follow up study . Because women represent the largest proportion of the elderly and falls are amendable , fall preventive may have the potential for significant impact on increasing year of life OBJECTIVE To study the long-term outcome of a physical training regimen of ambulant postward rehabilitation in community-dwelling geriatric patients with a history of injurious falls . DESIGN Prospect i ve 2-year follow-up of a r and omized placebo-controlled intervention trial . SETTING Postward rehabilitation in a geriatric hospital in Germany . PARTICIPANTS Fifty-seven geriatric patients ( mean age , 84.3+/-4.4 y ) with a history of severe falls . INTERVENTION Ambulatory training of strength , functional performance , and balance 3 times a week for 3 months for 31 patients versus placebo activities for 26 patients . MAIN OUTCOME MEASURES Strength , functional performance , fall-related psychologic parameters , and physical activity assessed by st and ardized protocol s 2 years after the training intervention , compared with baseline results . RESULTS Motor performance decreased substantially in both groups . As patients in the intervention group declined from significantly improved motor performance levels achieved in the initial training intervention , differences between the groups were still significant in most functional performances 2 years later . Functional decline was greater in persons who were institutionalized or being cared for by family members . Physical activity , which increased during the exercise intervention , returned to low baseline levels . CONCLUSIONS Improved functional performance in the training group did not lead to an increased level of physical activity after training , which might have preserved the functional improvements . In mobility-restricted , frail , geriatric patients such as our study population , training programs should continue to keep patients active and to prevent the decline in strength and functional performance that precedes loss of autonomy The aims of this r and omized , single-blind crossover trial were to investigate the effect of adding a simulated bowling video game via the Nintendo Wii ® gaming system to the st and ard exercise regimen of cognitively intact residents of long-term care ( LTC ) with upper extremity dysfunction and to identify individual characteristics that might predict improvement . Residents ( n=34 ) were recruited through two LTC facilities in southwestern Ontario and were r and omized into a st and ard exercise ( SG ) or st and ard exercise plus Wii bowling ( Wii ) arm . After 4 weeks of intervention , the groups were crossed over to the opposite arm . Outcomes included measures of pain intensity and bothersomeness , physical activity enjoyment , and a six-item measure of functional capacity design ed specifically for residents of LTC . Results suggest that subjects improved on all outcomes from pre- to postintervention but that only enjoyment of activity showed a significant difference between the SG and Wii groups . Effect sizes ( Cohen 's d ) ranged from small ( 0.30 for bothersomeness ) to large ( 1.77 for functional capacity ) . Responders , defined as those subjects who reported any degree of improvement following the Wii intervention , were less likely to complain of stiffness or shoulder symptoms and were more likely to complain of h and symptoms than non-responders . Limitations in interpretation and recommendations for future research are presented BACKGROUND Diabetes in elderly adults is associated with an increased risk of fall . The aim of study was to determine whether a virtual reality exercise ( VRE ) program would improve balance , strength , gait , and falls efficacy in elderly adults with diabetes . SUBJECTS AND METHODS Fifty-five subjects with diabetes mellitus over 65 years of age were r and omly assigned to a VRE group ( VREG ) ( n=27 ) and a control group ( CG ) ( n=28 ) . The VREG received the VRE program and diabetes education , whereas the CG received only the diabetes education . The VRE program used video gaming ( PlayStation ( ® ) 2 ; Sony , Tokyo , Japan ) and was conducted for 50 min twice a week for 10 weeks . Balance , muscle strength , gait , and falls efficacy were measured at baseline and after intervention . Measurements were taken using a clinical tests ( the one-leg-st and ing test , the Berg Balance Scale , the functional reach test , the timed up- and -go test , and the sit-to-st and test ) , and gait analysis . A self-administered question naire was used to measure falls efficacy . RESULTS After training , the VREG showed significantly improved balance , decreased sit-to-st and times , and increased gait speed , cadence , and falls efficacy . CONCLUSIONS The VRE program was to maximize the effects of exercise by triggering players was to be fully immersed into the games and enhanced major influential factors on the falls of subject . This study suggests VRE programs are feasible and effective for reduced the risk of falls in elderly adults with type 2 diabetes Background Physical activity promotes health in older adults but participation rates are low . Interactive video dance games can increase activity in young persons but have not been design ed for use with older adults . The purpose of this research was to evaluate healthy older adults ’ interest and participation in a dance game adapted for an older user . Methods Healthy older adults were recruited from 3 senior living setting s and offered three months of training and supervision using a video dance game design ed for older people . Before and after the program , data was collected on vital signs , physical function and self reported quality of life . Feedback was obtained during and after training . Results Of 36 persons who entered ( mean age 80.1 + 5.4 years , 83 % female ) , 25 completed the study . Completers were healthier than noncompleters . Completers showed gains in narrow walk time , self-reported balance confidence and mental health . While there were no serious adverse events , 4 of 11 noncompleters withdrew due to musculoskeletal complaints . Conclusions Adapted Interactive video dance is feasible for some healthy older adults and may help achieve physical activity goals OBJECTIVES To determine whether Nintendo Wii Fit ™ is an acceptable adjunct to physiotherapy treatment in the rehabilitation of balance , lower extremity movement , strength and function in out patients following total knee replacement . DESIGN Preliminary r and omised controlled trial . SETTING Outpatient department of a rehabilitation hospital . PARTICIPANTS Adult out patients following total knee replacement . INTERVENTIONS The study group received a physiotherapy session followed by 15minutes of Wii Fit gaming activities . The games encouraged lateral and multidirectional weight shifting , and provided visual feedback regarding postural balance . The control group received a physiotherapy session followed by 15minutes of lower extremity strengthening and balance training exercises . MAIN OUTCOME MEASURES Length of outpatient rehabilitation , 2-minute walk test , knee range of motion , timed st and ing , Activity-specific Balance Confidence Scale , Lower Extremity Functional Scale and Numeric Pain Rating Scale , all measured on admission and every 2 weeks until discharge . A patient satisfaction survey was completed at discharge . RESULTS Seventeen males ( 34 % ) and 33 females ( 66 % ) with a mean age of 68 ( st and ard deviation 11 ) years participated in the study . No significant differences in age , gender , days since surgery or length of outpatient rehabilitation were found between the groups . In addition , there were no significant differences in pain ( P=0.220 ) , knee flexion ( P=0.951 ) , knee extension ( P=0.492 ) , walking speed ( P=0.855 ) , timed st and ing tasks ( P=0.289 ) , Lower Extremity Functional Scale ( P=0.079 ) , Activity-specific Balance Confidence Scale ( P=0.523 ) or patient satisfaction with therapy services ( P=0.201 ) between the groups . CONCLUSIONS Wii Fit is potentially acceptable as an adjunct to physiotherapy intervention for out patients following total knee replacement , provided the games chosen challenge balance and postural control , and use the lower extremities . Further research is needed to establish whether video games as a therapy adjunct increase patient motivation and compliance with rehabilitation goals . Clinical Trials.gov ID : NCT01548664 OBJECTIVE To compare the impacts of Tai Chi , a st and ard balance exercise program , and a video game balance board program on postural control and perceived falls risk . DESIGN R and omized controlled trial . SETTING Research laboratory . PARTICIPANTS Independent seniors ( N=40 ; 72.5±8.40 ) began the training , 27 completed . INTERVENTIONS Tai Chi , a st and ard balance exercise program , and a video game balance board program . MAIN OUTCOME MEASURES The following were used as measures : Timed Up & Go , One-Leg Stance , functional reach , Tinetti Performance Oriented Mobility Assessment , force plate center of pressure ( COP ) and time to boundary , dynamic posturography ( DP ) , Falls Risk for Older People-Community Setting , and Falls Efficacy Scale . RESULTS No significant differences were seen between groups for any outcome measures at baseline , nor were significant time or group × time differences for any field test or question naire . No group × time differences were seen for any COP measures ; however , significant time differences were seen for total COP , 3 of 4 anterior/posterior displacement and both velocity , and 1 displacement and 1 velocity medial/lateral measure across time for the entire sample . For DP , significant improvements in the overall score ( dynamic movement analysis score ) , and in 2 of the 3 linear and angular measures were seen for the sample . CONCLUSIONS The video game balance board program , which can be performed at home , was as effective as Tai Chi and the st and ard balance exercise program in improving postural control and balance dictated by the force plate postural sway and DP measures . This finding may have implication s for exercise adherence because the at-home nature of the intervention eliminates many obstacles to exercise training BACKGROUND physical therapy interventions that increase functional strength and balance have been shown to reduce falls in older adults . AIM this study compared a virtual reality group ( VRG ) and a control group ( CG ) . DESIGN r and omised controlled 6-week intervention with pre- and post-test evaluations . SETTING outpatient geriatric orthopaedic and balance physical therapy clinic . POPULATION forty participants were r and omised into two groups . METHOD the VRG received three different Nintendo ® Wii FIT balance interventions three times per week for 6 weeks and the CG received no intervention . RESULTS compared with the CG , post-intervention measurements showed significant improvements for the VRG in the 8-foot Up & Go test [ median decrease of 1.0 versus -0.2 s , ( P=0.038 ) and the Activities-specific Balance Confidence Scale ( 6.9 versus 1.3 % ) ( P=0.038 ) ] . CONCLUSION virtual reality gaming provides clinicians with a useful tool for improving dynamic balance and balance confidence in older adults Objective The purpose of this study was to investigate the effectiveness of the virtual walking training program using a real-world video recording on walking balance and spatiotemporal gait parameters in patients with chronic stroke . Design Fourteen patients with chronic stroke were r and omly assigned to either the experimental group ( n = 7 ) or the control group ( n = 7 ) . The subjects in both groups underwent a st and ard rehabilitation program ; in addition , the experimental group participated in the virtual walking training program using a real-world video recording for 30 mins a day , three times a week , for 6 wks , and the control group participated in treadmill gait training for 30 mins a day , three times a week , for 6 wks . Walking balance was measured using the Berg Balance Scale ( BBS ) and the Timed Up and Go test . Gait performance was measured using an electrical walkway system . Results In walking balance , greater improvement on the Berg Balance Scale ( experimental group : 4.14 vs. control group : 1.85 ) and the Timed Up and Go test ( −2.25 vs. −0.94 ) was observed in the experimental group compared with the control group ( P < ; 0.05 ) . In the spatiotemporal gait parameters , greater improvement on velocity ( 25.40 vs. 9.74 ) and cadence ( 26.71 vs. 11.11 ) was observed in the experimental group compared with the control group ( P < ; 0.05 ) . Conclusions This study demonstrated the positive effects of the virtual walking training program using a real-world video recording on gait performance . These findings suggest that the virtual walking training program using a real-world video recording may be a valid approach to enhance gait performance in patients with chronic stroke Purpose : To assess the feasibility of a physiotherapy intervention using an interactive gaming program compared with conventional physiotherapy for hospitalised older people . Methods : R and omised controlled pilot study in a geriatric rehabilitation unit within an acute public hospital . Participants were r and omly allocated to physiotherapy using an interactive gaming program ( n = 22 ) or conventional physiotherapy in a ward-based gym ( n = 22 ) . Feasibility was assessed by comparing the effects of the intervention on clinical outcome measures ( primary outcome : mobility as assessed by the Timed Up and Go test , secondary outcomes : safety , adherence levels , eligibility and consent rates ) . Results : Participants ( n = 44 ) had a mean age of 85 years ( SD 4.5 ) and the majority ( 80 % ) were women . Univariable analyses showed no significant difference between groups following intervention . However , multivariable analyses suggested that participants using the interactive gaming program improved more on the Timed Up and Go test ( p = 0.048 ) than participants receiving conventional physiotherapy . There were no serious adverse events and high levels of adherence to therapy were evident in both groups . Only a small proportion of patients screened were recruited to the study . Conclusions : In this feasibility study , the use of a commercially available interactive gaming program by physiotherapists with older people in a hospital setting was safe and adherence levels were comparable with conventional therapy . Preliminary results suggest that further exploration of approaches using games as therapy for older people could include commonly used measures of balance and function . Implication s for Rehabilitation The use of an interactive gaming program by physiotherapists with hospitalised older people appeared to be safe and result ed in improvements in balance and mobility . Use of these programs may be limited to a relatively small proportion of older people , only those able to use and interested in this technological approach to therapy A goal - setting protocol , based on research in goal setting and performance and personal construct theory , was tested for its effect on adherence to a new exercise program . The Goal - setting group ( n = 50 ) had significantly less dropout ( 30 % ) than the control group ( n = 50 ) ( 74 % ) . The Goal - setting group also had significantly better attendance ( p<.0001 ) . Suggestions for increasing confidence in findings through further research and practical implication s of using the protocol to improve exercise maintenance across setting s were discussed Background Due to the many problems associated with reduced balance and mobility , providing an effective and engaging rehabilitation regimen is essential to progress recovery from impairments and to help prevent further degradation of motor skills . Objectives The purpose of this study was to examine the feasibility and benefits of physical therapy based on a task-oriented approach delivered via an engaging , interactive video game paradigm . The intervention focused on performing targeted dynamic tasks , which included reactive balance controls and environmental interaction . Design This study was a r and omized controlled trial . Setting The study was conducted in a geriatric day hospital . Participants Thirty community-dwelling and ambulatory older adults attending the day hospital for treatment of balance and mobility limitations participated in the study . Interventions Participants were r and omly assigned to either a control group or an experimental group . The control group received the typical rehabilitation program consisting of strengthening and balance exercises provided at the day hospital . The experimental group received a program of dynamic balance exercises coupled with video game play , using a center-of-pressure position signal as the computer mouse . The tasks were performed while st and ing on a fixed floor surface , with progression to a compliant sponge pad . Each group received 16 sessions , scheduled 2 per week , with each session lasting 45 minutes . Measurements Data for the following measures were obtained before and after treatment : Berg Balance Scale , Timed “ Up & Go ” Test , Activities-specific Balance Confidence Scale , modified Clinical Test of Sensory Interaction and Balance , and spatiotemporal gait variables assessed in an instrumented carpet system test . Results Findings demonstrated significant improvements in posttreatment balance performance scores for both groups , and change scores were significantly greater in the experimental group compared with the control group . No significant treatment effect was observed in either group for the Timed “ Up & Go ” Test or spatiotemporal gait variables . Limitations The sample size was small , and there were group differences at baseline in some performance measures . Conclusion Dynamic balance exercises on fixed and compliant sponge surfaces were feasibly coupled to interactive game-based exercise . This coupling , in turn , result ed in a greater improvement in dynamic st and ing balance control compared with the typical exercise program . However , there was no transfer of effect to gait function OBJECTIVES Subsyndromal depression ( SSD ) is several times more common than major depression in older adults and is associated with significant negative health outcomes . Physical activity can improve depression , but adherence is often poor . The authors assessed the feasibility , acceptability , and short-term efficacy and safety of a novel intervention using exergames ( entertaining video games that combine game play with exercise ) for SSD in older adults . METHODS Community-dwelling older adults ( N = 19 , aged 63 - 94 years ) with SSD participated in a 12-week pilot study ( with follow-up at 20 - 24 weeks ) of Nintendo 's Wii sports , with three 35-minute sessions a week . RESULTS Eight-six percent of enrolled participants completed the 12-week intervention . There was a significant improvement in depressive symptoms , mental health-related quality of life ( QoL ) , and cognitive performance but not physical health-related QoL. There were no major adverse events , and improvement in depression was maintained at follow-up . CONCLUSIONS The findings provide preliminary indication of the benefits of exergames in seniors with SSD . R and omized controlled trials of exergames for late-life SSD are warranted |
11,968 | 20,462,635 | INTERPRETATION Fibrates can reduce the risk of major cardiovascular events predominantly by prevention of coronary events , and might have a role in individuals at high risk of cardiovascular events and in those with combined dyslipidaemia . | BACKGROUND Several clinical trials have reported inconsistent findings for the effect of fibrates on cardiovascular risk .
We undertook a systematic review and meta- analysis to investigate the effects of fibrates on major clinical outcomes . | BACKGROUND Studies have shown that treatment of hyperlipidemia , especially lowering of plasma LDL levels , retards the progression of coronary atherosclerosis and prevents clinical cardiovascular events . No such studies have focused on subjects with low levels of HDL cholesterol . METHODS AND RESULTS We r and omly assigned 395 post-coronary bypass men , who had an HDL cholesterol concentration < or = 1.1 mmol/L and LDL cholesterol < or = 4.5 mmol/L , to receive gemfibrozil 1200 mg/d or placebo . Coronary angiography was performed at baseline and after , on average , 32 months of therapy . Changes in coronary dimensions were assessed by computer-assisted analysis . Average on-trial serum triglyceride concentrations were 1.69+/-0.68 and 1.02+/-0.37 , total cholesterol 5.48+/-0.68 and 4.83+/-0.63 , LDL cholesterol 3.84+/-0.59 and 3.39+/-0.56 , and HDL cholesterol 0.88+/-0.15 and 0.98+/-0.17 mmol/L in the placebo and gemfibrozil groups , respectively ( mean+/-SD , each P<.001 ) . The change in per-patient means of average diameters of native coronary segments was -0.04+/-0.11 mm in the placebo group and -0.01+/-0.10 mm in the gemfibrozil group ( P=.009 ) . The equivalent changes in minimum luminal diameters of stenoses were -0.09+/-0.18 and -0.04+/-0.15 mm , respectively ( P=.002 ) . A similar , albeit nonsignificant , trend toward treatment benefit was found in the predefined primary study end point , segments unaffected by grafts and those distal to graft insertions . In aortocoronary bypass grafts , 23 subjects ( 14 % ) assigned to placebo had new lesions in the follow-up angiogram , compared with 4 subjects ( 2 % ) assigned to gemfibrozil ( P<.001 ) . CONCLUSIONS Gemfibrozil therapy retarded the progression of coronary atherosclerosis and the formation of bypass-graft lesions after coronary bypass surgery in men with low HDL cholesterol as their main lipid abnormality In a double-blind clinical trial of clofibrate versus identical quantity of corn oil 497 patients with ischaemic heart disease were observed over a period of five years . The death rate and the rate of non-fatal infa rcts were significantly less among the clofibrate group , and the difference was greatest in respect of sudden deaths and among patients who had previously suffered from angina rather than infa rct ion . The cholesterol- and triglyceride-reducing properties of clofibrate were maintained throughout the period of the trial and side effects were very few . But the protective action of the drug against new infa rcts and death bore no apparent relation to these properties Objective : To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease . Design : Double blind placebo controlled r and omised trial . Setting : 85 general practice s and nine hospital vascular clinics . Participants : 1568 men , mean age 68.2 years ( range 35 to 92 ) at recruitment . Interventions : Bezafibrate 400 mg daily ( 783 men ) or placebo ( 785 men ) . Main outcome measures : Combination of coronary heart disease and of stroke . All coronary events , fatal and non-fatal coronary events separately , and strokes alone ( secondary end points ) . Results : Bezafibrate did not reduce the incidence of coronary heart disease and stroke . There were 150 and 160 events in the active and placebo groups respectively ( relative risk 0.96 , 95 % confidence interval 0.76 to 1.21 ) . There were 90 and 111 major coronary events in the active and placebo groups respectively ( 0.81 , 0.60 to 1.08 ) , of which 64 and 65 were fatal ( 0.95 , 0.66 to 1.37 ) and 26 and 46 non-fatal ( 0.60 , 0.36 to 0.99 ) . Beneficial effects on non-fatal events were greatest in men aged < 65 years at entry , in whom benefit was also seen for all coronary events ( 0.38 , 0.20 to 0.72 ) . There were no significant effects in older men . There were 60 strokes in those on active treatment and 49 in those on placebo ( 1.34 , 0.80 to 2.01 ) . There were 204 and 195 deaths from all causes in the two groups respectively ( 1.03 , 0.83 to 1.26 ) . Bezafibrate reduced the severity of intermittent claudication for up to three years . Conclusions : Bezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events , particularly in those aged < 65 years at entry , in whom all coronary events may also be reduced Background We studied the joint effect of baseline triglyceride and lipoprotein cholesterol levels on the incidence of cardiac end points in the trial group ( n = 4,081 ) of the Helsinki Heart Study , a 5-year r and omized coronary primary prevention trial among dyslipidemic middle-aged men . The relative risks ( RR ) were calculated using Cox proportional hazards models with a dummy variable technique that allows simultaneous study of subgroup combinations from the placebo and treatment groups . Methods and Results In the placebo group ( n = 2,045 ) , the low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol ( HDL-C ) ratio was the best single predictor of cardiac events . This ratio in combination with the serum triglyceride level revealed a high-risk subgroup : subjects with LDL-C/HDL-C ratio > 5 and triglycerides > 2.3 mmol/1 had a RR of 3.8 ( 95 % CI , 2.2 - 6.6 ) compared with those with LDL-C/HI)L-C ratio ≤5 and triglyceride concentration ≤2.3 mmol/1 . In subjects with triglyceride concentration > 2.3 mmol/l and LDL-C/H1)L-C ratio ≤5 , RR was close to unity ( 1.1 ) , whereas in those with triglyceride level ≤2.3 mmoVIl and LDL-C/HDL-C ratio > 5 , RR was 1.2 . The high-risk group with LDL-C/HDL-C ratio > 5 and triglyceride level > 2.3 mmol/1 profited most from treatment with gemfibrozil , with a 71 % lower incidence of coronary heart disease events than the corresponding placebo subgroup . In all other subgroups , the reduction in CHD incidence was substantially smaller Conclusions Serum triglyceride concentration has prognostic value , both for assessing coronary heart disease risk and in predicting the effect of gemfibrozil treatment , especially when used in combination with HDL-C and OBJECTIVE To determine whether serum lipid intervention , in addition to conventional diabetes treatment , could alter cardiovascular outcomes in type 2 diabetes . RESEARCH DESIGN AND METHODS There were 164 type 2 diabetic subjects ( 117 men , 47 women ) without a history of clinical cardiovascular disease r and omized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospect ively for a minimum of 3 years . Serial biochemical and noninvasive vascular assessment s , carotid and femoral artery B-mode ultrasound measurements , and those pertaining to coronary heart disease (CHD)— clinical history , the World Health Organization ( WHO ) cardiovascular question naire , and resting and exercise electrocardiogram (ECG)—were recorded . RESULTS Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride ( −32 vs. 4 % , P = 0.001 ) , total cholesterol ( −7 vs. −0.3 % , P = 0.004 ) , and total−to-HDL cholesterol ratio ( −12 vs. −0.0 % , P = 0.001 ) , and an increase in HDL cholesterol ( 6 vs. −2 % , P = 0.02 ) as compared with placebo . There was a trend toward a greater reduction of fibrinogen ( −18 vs. −6 % , P = 0.08 ) at 3 years . No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease . In those treated with bezafibrate , there was a significant reduction ( P = 0.01 , log-rank test ) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infa rct ion . CONCLUSIONS Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease , although the lower rate of “ definite CHD events ” in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease BACKGROUND We investigated whether combination therapy with a statin plus a fibrate , as compared with statin monotherapy , would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease . METHODS We r and omly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo . The primary outcome was the first occurrence of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The mean follow-up was 4.7 years . RESULTS The annual rate of the primary outcome was 2.2 % in the fenofibrate group and 2.4 % in the placebo group ( hazard ratio in the fenofibrate group , 0.92 ; 95 % confidence interval [ CI ] , 0.79 to 1.08 ; P=0.32 ) . There were also no significant differences between the two study groups with respect to any secondary outcome . Annual rates of death were 1.5 % in the fenofibrate group and 1.6 % in the placebo group ( hazard ratio , 0.91 ; 95 % CI , 0.75 to 1.10 ; P=0.33 ) . Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex , with a benefit for men and possible harm for women ( P=0.01 for interaction ) , and a possible interaction according to lipid subgroup , with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol ( P=0.057 for interaction ) . CONCLUSIONS The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events , nonfatal myocardial infa rct ion , or nonfatal stroke , as compared with simvastatin alone . These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 . Objective In a r and omized 5-yr multi-intervention trial , we tested the efficacy of intensified health education ( IHE ) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease ( IHD ) . Research Design and Methods Within the intervention group , the benefit of clofibric acid was evaluated in a double-blind study . One thous and one hundred thirty-nine newly diagnosed middle-aged ( 30- to 55-yr-old ) patients with non-insulindependent diabetes mellitus ( NIDDM ) entered the study . They were classified as diet controlled after a 6- wk screening phase with conventional dietary treatment . During the follow-up , the control group ( n = 378 ) was cared for at different diabetes outpatient clinics with a st and ardized surveillance . The intervention group ( n = 761 ) had a structured IHE that included dietary advice , antismoking and antialcohol education , and ways to enhance physical activity . Results R and omly , 379 of the IHE patients received 1.6 g clofibric acid/day , and the others received placebo . IHE result ed in improved glucose control ( adjusted fasting blood glucose ) levels after 5 yr ( control subjects 9.27 mM , IHE group 8.71 mM , and IHE plus clofibric acid group 8.60 mM , P < 0.01 ) . The better glycemic control was achieved with fewer antidiabetic drugs . After 5 yr , antidiabetic drugs were prescribed to 47 % of the control subjects , 28 % of the IHE group , and 34 % of the IHE plus clofibric acid group ( cutoff limit for drug application was postpr and ial blood glucose of ≥13.87 mM ) . The ratio of polyunsaturated to saturated fatty acids ( 0.26 vs. 0.40 , P < 0.01 ) and physical activity ( 174 vs. 327 scores , P < 0.01 ) were increased , and blood pressure , tobacco , and alcohol consumption were significantly reduced by IHE . However , IHE had no effect on calorie intake , percentage of fat in the diet ( 45 % ) , and body weight . The most important finding was the significant increase of blood cholesterol in all three groups ( + 0.47 , + 0.36 , and + 0.34 mM , respectively ) . Clofibric acid only prevented the increase of triglyceride levels ( + 0.56 , + 0.24 , and + 0.05 mM , respectively ) . The incidence rate per 1000 for myocardial infa rct ion was 30.3 for control subjects , 53.6 for the IHE group , and 55.6 for the IHE plus clofibric acid group . The corresponding rates for IHD incidence were 90.9 , 97.8 , and 98.8 , respectively . Men suffered more frequently from myocardial infa rct ion , whereas women developed ECG criteria for IHD more frequently . Among the 35 cases of death , besides cardiovascular diseases , liver cirrhosis and neoplasia were the predominant causes . The death rate per 1000 in control subjects was 46.2 , 30.6 in the IHE group , and 27 among patients with IHE plus clofibric acid . Conclusions IHE was of substantial benefit for the control of glycemia , significantly diminished the need for antidiabetic drugs , and reduced a cluster of risk factors but had no effect on the control of blood lipids . This could be one major reason for the failure of IHE , effective lowering of blood pressure , and clofibric acid to prevent cardiovascular complications . Clofibric acid was only effective in reducing triglycerides BACKGROUND Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk . However , a benefit of statins in such patients who are undergoing hemodialysis has not been proved . METHODS We conducted an international , multicenter , r and omized , double-blind , prospect i ve trial involving 2776 patients , 50 to 80 years of age , who were undergoing maintenance hemodialysis . We r and omly assigned patients to receive rosuvastatin , 10 mg daily , or placebo . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . Secondary end points included death from all causes and individual cardiac and vascular events . RESULTS After 3 months , the mean reduction in low-density lipoprotein ( LDL ) cholesterol levels was 43 % in patients receiving rosuvastatin , from a mean baseline level of 100 mg per deciliter ( 2.6 mmol per liter ) . During a median follow-up period of 3.8 years , 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point ( 9.2 and 9.5 events per 100 patient-years , respectively ; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group , 0.96 ; 95 % confidence interval [ CI ] , 0.84 to 1.11 ; P=0.59 ) . Rosuvastatin had no effect on individual components of the primary end point . There was also no significant effect on all-cause mortality ( 13.5 vs. 14.0 events per 100 patient-years ; hazard ratio , 0.96 ; 95 % CI , 0.86 to 1.07 ; P=0.51 ) . CONCLUSIONS In patients undergoing hemodialysis , the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . ( Clinical Trials.gov number , NCT00240331 . INTRODUCTION Diabetic retinopathy is the leading cause of vision loss or blindeness in working-age adults in the developed and developing countries . No curative treatments are available for diabetic retinopathy and the most common symptomatic treatment , laser photocoagulation , provides only partial and temporary relief from the progressive vascular damage caused by this disease . Etofibrate ( Lipo-Merz ) is an orally-administered treatment for lipid disorders that combines fibrate and nicotinic acid in a slow-release formulation . PATIENTS AND METHODS This report describes the results of a double-blind , r and omised , placebo-controlled study , performed to evaluate the efficacy and safety of etofibrat in patients with type 2 diabetes mellitus and concomitant diabetic retinopathy . They received either placebo or 1000 mg/day etofibrate for up to 12 months . Efficacy analyses were based on visual acuity assessment and blinded expert ratings of ocular fundus pathology , as well as laboratory analyses of serum lipid parameters . RESULTS The evaluable population comprised 296 patients , 148 in each treatment group , of whom 89 % completed the study and 73 % completed according to protocol . After 12 months of treatment , a significantly larger population of etofibrate-treated patients than placebo-treated patients showed improvements in ocular pathology ( 46 % versus 32 % , respectively , p < 0.001 ) ; similar findings were already apparent after 6 months of treatment ( 43 % versus 31 % , respectively p < 0.001 ) . Etofibrate treatment also produced significant improvements in total cholesterol , LDL-cholesterol and HDL-cholesterol in comparison to the placebo treatment group . Safety evaluations ( adverse events , laboratory parameters ) did not reveal any clinical ly significant adverse effects of etofibrate in comparison to placebo . CONCLUSION Etofibrate provides a safe and effective treatment for ocular pathology result ing from type 2 diabetes mellitus A double-blind intervention trial was started in 1965 to test the hypothesis that the incidence of ischaemic heart disease in middle-aged men can be reduced by lowering raised serum cholesterol levels . It was carried out in 3 European centres-Edinburgh , Budapest , and Prague . Serum cholesterol was to be lowered by the drug clofibrate ( ethyl chlorophenoxyisobutyrate ) which was considered to be free from serious side effects . Studies were carried out on 15 745 males , aged 30 to 59 at entry , for an average of 5 - 3 years , accumulating 83 534 years of experience . The treatment group , of about 5000 , Group I , was a r and omly chosen half of the men in the upper third of the serum cholesterol distribution in some 30 000 volunteers . The comparable control group , Group II , comprised the other 5000 men of the upper third of the cholesterol distribution , and these were given a placebo . A further control group , Group III , of 5000 men , was selected r and omly from the lower third of the cholesterol distribution . These numbers were chosen in order to be 90 per cent certain of detecting a 30 per cent reduction in the incidence of ischaemic heart disease should this occur . Subjects with manifest heart or other major disease were excluded from the trial . No attempt was made to correct other ' risk factors ' for IHD , but their presence was monitored and considered in the analysis . Investigators and participants in the trial were unaware of the groups to which individual men belonged . A mean reduction of approximately 9 per cent of the initial serum cholesterol levels was achieved in the treatment group ( ranging from 7 to 11 % in the 3 centres ) ; this was less than the 15 per cent fall expected . In Edinburgh , during treatment , serum triglyceride concentrations in Group I resembled those naturally occurring in Group III . The incidence ofIHO was lower by 20 per cent in the clofibrate group compared with the high cholesterol controls ( P < 0.05 ) ; this fall was confined to non-fatal myocardial infa rcts which were reduced by 25 per cent . The incidence offatal heart attacks was similar in the 2 high cholesterol groups and there was no significant difference in the incidence of angina . Group III showed substantially lower rates of ischaemic heart disease . The reduction of myocardial infa rct ion in the clofibrate-treated group was greatest in men with the highest levels , and greatest reduction in serum cholesterol . Men with a substantial reduction of cholesterol concentration , who smoked , and also had above average blood pressure levels showed the most benefit . The numbers of deaths , and crude mortality rates from all causes in the clofibrate-treated group significantly exceeded those in the high cholesterol control group ( P < 0.05 ) , though the age-st and ardised mortality rates did not differ significantly between the 3 groups . The numbers of deaths from ' BACKGROUND Laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects . Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment in patients with type 2 diabetes mellitus . METHODS The Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study was a multinational r and omised trial of 9795 patients aged 50 - 75 years with type 2 diabetes mellitus . Eligible patients were r and omly assigned to receive fenofibrate 200 mg/day ( n=4895 ) or matching placebo ( n=4900 ) . At each clinic visit , information concerning laser treatment for diabetic retinopathy-a prespecified tertiary endpoint of the main study -was gathered . Adjudication by ophthalmologists masked to treatment allocation defined instances of laser treatment for macular oedema , proliferative retinopathy , or other eye conditions . In a sub study of 1012 patients , st and ardised retinal photography was done and photographs grade d with Early Treatment Diabetic Retinopathy Study ( ETDRS ) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions . Analyses were by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N64783481 . FINDINGS Laser treatment was needed more frequently in participants with poorer glycaemic or blood pressure control than in those with good control of these factors , and in those with a greater burden of clinical microvascular disease , but the need for such treatment was not affected by plasma lipid concentrations . The requirement for first laser treatment for all retinopathy was significantly lower in the fenofibrate group than in the placebo group ( 164 [ 3.4 % ] patients on fenofibrate vs 238 [ 4.9 % ] on placebo ; hazard ratio [ HR ] 0.69 , 95 % CI 0.56 - 0.84 ; p=0.0002 ; absolute risk reduction 1.5 % [ 0.7 - 2.3 ] ) . In the ophthalmology sub study , the primary endpoint of 2-step progression of retinopathy grade did not differ significantly between the two groups overall ( 46 [ 9.6 % ] patients on fenofibrate vs 57 [ 12.3 % ] on placebo ; p=0.19 ) or in the subset of patients without pre-existing retinopathy ( 43 [ 11.4 % ] vs 43 [ 11.7 % ] ; p=0.87 ) . By contrast , in patients with pre-existing retinopathy , significantly fewer patients on fenofibrate had a 2-step progression than did those on placebo ( three [ 3.1 % ] patients vs 14 [ 14.6 % ] ; p=0.004 ) . An exploratory composite endpoint of 2-step progression of retinopathy grade , macular oedema , or laser treatments was significantly lower in the fenofibrate group than in the placebo group ( HR 0.66 , 95 % CI 0.47 - 0.94 ; p=0.022 ) . INTERPRETATION Treatment with fenofibrate in individuals with type 2 diabetes mellitus reduces the need for laser treatment for diabetic retinopathy , although the mechanism of this effect does not seem to be related to plasma concentrations of lipids In a r and omized , double-blind five-year trial , we tested the efficacy of simultaneously elevating serum levels of high-density lipoprotein ( HDL ) cholesterol and lowering levels of non-HDL cholesterol with gemfibrozil in reducing the risk of coronary heart disease in 4081 asymptomatic middle-aged men ( 40 to 55 years of age ) with primary dyslipidemia ( non-HDL cholesterol greater than or equal to 200 mg per deciliter [ 5.2 mmol per liter ] in two consecutive pretreatment measurements ) . One group ( 2051 men ) received 600 mg of gemfibrozil twice daily , and the other ( 2030 men ) received placebo . Gemfibrozil caused a marked increase in HDL cholesterol and persistent reductions in serum levels of total , low-density lipoprotein ( LDL ) , and non-HDL cholesterol and triglycerides . There were minimal changes in serum lipid levels in the placebo group . The cumulative rate of cardiac end points at five years was 27.3 per 1,000 in the gemfibrozil group and 41.4 per 1,000 in the placebo group -- a reduction of 34.0 percent in the incidence of coronary heart disease ( 95 percent confidence interval , 8.2 to 52.6 ; P less than 0.02 ; two-tailed test ) . The decline in incidence in the gemfibrozil group became evident in the second year and continued throughout the study . There was no difference between the groups in the total death rate , nor did the treatment influence the cancer rates . The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed BACKGROUND Microalbuminuria is an early marker of diabetic nephropathy and an independent risk factor for cardiovascular disease . In the Diabetes Atherosclerosis Intervention Study ( DAIS ) , treatment of people with type 2 diabetes with micronized fenofibrate for an average of 38 months reduced the progression of angiographically evaluated coronary artery disease and improved lipoprotein level abnormalities compared with placebo . The aim of this analysis is to study the influence of the treatment on changes in urinary albumin excretion . METHODS Microalbuminuria was measured on 2 to 3 occasions by using timed overnight sample s at baseline and yearly thereafter in 314 DAIS participants ( 77 women , 237 men ; average age , 56 years ) ; all except 3 participants had either a normal albumin excretion rate ( < 20 microg/min ; n = 214 ) or microalbuminuria ( albumin , 20 to 200 microg/min ; n = 97 ) before r and omization . Tabulated shifts ( between normal , microalbuminuria , and macroalbuminuria ) from baseline to last observed values were compared between treatment groups by means of chi-square or Fisher 's exact test . RESULTS Fenofibrate significantly reduced the worsening of albumin excretion ( fenofibrate , 8 % versus placebo , 18 % ; P < 0.05 ) . This effect was caused mostly by reduced progression from normal albumin excretion to microalbuminuria : 3 of 101 participants in the fenofibrate group versus 20 of 113 participants in the placebo group ( P < 0.001 ) . Overall , changes in albumin excretion were independent of age or changes in lipid or creatinine levels , weight , or blood pressure . CONCLUSION Improvement in lipid profiles with fenofibrate in patients with type 2 diabetes was associated with reduced progression from normal albumin excretion to microalbuminuria Abstract A controlled trial of Clofibrate in 95 patients with established cerebral vascular disease is described . The level of serum cholesterol is significantly lowered in patients on treatment compared with control patients . There is no evidence to indicate that lowering the level of serum cholesterol in patients with established cerebral vascular disease has affected either the incidence of further episodes of cerebral ischaemia or the mortality rate BACKGROUND Although it is generally accepted that lowering elevated serum levels of low-density lipoprotein ( LDL ) cholesterol in patients with coronary heart disease is beneficial , there are few data to guide decisions about therapy for patients whose primary lipid abnormality is a low level of high-density lipoprotein ( HDL ) cholesterol . METHODS We conducted a double-blind trial comparing gemfibrozil ( 1200 mg per day ) with placebo in 2531 men with coronary heart disease , an HDL cholesterol level of 40 mg per deciliter ( 1.0 mmol per liter ) or less , and an LDL cholesterol level of 140 mg per deciliter ( 3.6 mmol per liter ) or less . The primary study outcome was nonfatal myocardial infa rct ion or death from coronary causes . RESULTS The median follow-up was 5.1 years . At one year , the mean HDL cholesterol level was 6 percent higher , the mean triglyceride level was 31 percent lower , and the mean total cholesterol level was 4 percent lower in the gemfibrozil group than in the placebo group . LDL cholesterol levels did not differ significantly between the groups . A primary event occurred in 275 of the 1267 patients assigned to placebo ( 21.7 percent ) and in 219 of the 1264 patients assigned to gemfibrozil ( 17.3 percent ) . The overall reduction in the risk of an event was 4.4 percentage points , and the reduction in relative risk was 22 percent ( 95 percent confidence interval , 7 to 35 percent ; P=0.006 ) . We observed a 24 percent reduction in the combined outcome of death from coronary heart disease , nonfatal myocardial infa rct ion , and stroke ( P < 0.001 ) . There were no significant differences in the rates of coronary revascularization , hospitalization for unstable angina , death from any cause , and cancer . CONCLUSIONS Gemfibrozil therapy result ed in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level . The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels |
11,969 | 19,189,909 | Results Key Question Does screening in asymptomatic persons with whole-body examination by a primary care clinician or by self-examination reduce morbidity and mortality from skin cancer ?
We found no new evidence on the effectiveness of skin examination by a physician in reducing the morbidity or mortality of skin cancer .
Context ual Question 1 Can screening with whole-body examination by primary care clinicians or by self-examination accurately detect skin cancers ? | Skin cancer is the most commonly diagnosed cancer in the United States ( 1 ) .
The majority of skin cancer is nonmelanoma cancer , either basal cell cancer or squamous cell cancer ( 2 ) .
In the United States , melanoma of the skin is the sixth most common type of cancer in white men and women ( 3 ) .
The incidence of both melanoma and nonmelanoma skin cancer has been increasing over the past 3 decades ( 4 ) .
Several preventive strategies , including routine screening , have been proposed by professional organizations .
The U.S. Preventive Services Task Force ( USPSTF ) last review ed screening for skin cancer in 2001 and concluded that evidence was insufficient to recommend for or against routine screening for skin cancer by using wholebody skin examination for the early detection of cutaneous melanoma , basal cell cancer , or squamous cell cancer ( 5 ) .
Can screening with whole-body examination by primary care clinicians or by self-examination accurately detect skin cancer ?
Context ual Question 2 .
Does screening with whole-body examination or by self-examination detect melanomas at an earlier stage ( thinner lesions ) ?
Methods Data Sources and Search es We search ed the English- language literature in MEDLINE to identify r and omized , controlled trials ( RCTs ) or casecontrol trials published from 1 June 1999 to 9 August 2005 to answer the following key question : Can screening reduce morbidity and mortality from skin cancer ? | BACKGROUND The efficacy of the skin self-examination ( SSE ) to detect artificial changes in the size of nevi has not been evaluated in a controlled setting . OBJECTIVE Our purpose was to determine the sensitivity and specificity of the SSE in detecting artificial changes in mole size in patients at high risk for melanoma . METHODS In a single-center , single-blinded cross-over study , patients who had been performing the SSE confidently for at least 1 year examined their backs after the diameter of an existing mole was increased artificially in r and om order by 0 , 2 , or 4 mm . RESULTS The specificity of the SSE was 62 % ( 95 % confidence interval [ CI ] , 53%-72 % ) ( N = 103 ) . The sensitivity of the 2 mm change was 58 % ( 95 % CI , 49%-68 % ) and that of the 4 mm change was 75 % ( 95 % CI , 66%-83 % ) . SSE performance was not related to perceived risk , number of moles , gender , age , or frequency of self-examination . CONCLUSION Even in our highly motivated and selected group of high-risk patients , 25 % could not detect an obvious increase in the diameter of an existing nevus , whereas 38 % incorrectly identified a change when none was made . The SSE is only a moderately effective tool for the detection of acute , large , changes in mole size . The usefulness of the SSE in detection of new lesions or changes in existing lesions is likely due to a combination of factors or due to factors other than size , such as color , border irregularity , and texture , among others OBJECTIVE To determine the sensitivity and specificity of skin self-examination ( SSE ) to detect new and changing moles with and without the aid of baseline digital photographs in patients with dysplastic nevi . DESIGN AND INTERVENTION Patients had baseline digital photography and mole counts of their back , chest , and abdomen and were instructed to perform a baseline SSE . Print copies of the images were provided to the patient . Following the baseline examination , the appearance of existing moles was altered and new moles were created using cosmetic eyeliner . The number of moles altered and /or created totaled approximately 10 % of each patients ' absolute mole count . SETTING AND PATIENTS Fifty patients with 5 or more dysplastic nevi from the outpatient clinic at Memorial Sloan-Kettering Cancer Center , New York , NY . MAIN OUTCOME MEASURE Skin self-examinations with and without access to the baseline photographs to identify the number of new and altered moles . RESULTS The sensitivity and specificity of SSE for detection of both altered and new moles without photography were 60.2 % and 96.2 % , respectively . Skin self-examination with photography yielded a sensitivity and specificity of 72.4 % and 98.4 % , respectively . The findings were similar when stratified by site ( back vs chest or abdomen ) . The sensitivity and specificity for new moles were higher compared with altered moles . CONCLUSIONS Access to baseline photography improved the diagnostic accuracy of SSE on the back and chest or abdomen and improved detection of changing and new moles . Our results suggest that baseline digital photography in t and em with SSE may be effective in improving the diagnostic accuracy of patients performing SSE Objectives : Melanoma is a significant cause of morbidity and mortality worldwide and incidence is increasing . Survival after treatment is inversely related to the thickness of the tumour at diagnosis . Population screening has the potential to reduce mortality but there is no conclusive evidence of benefit . Such evidence can come best from a r and omised trial . Here we describe the design of a community based r and omised trial of a population screening programme for melanoma in Queensl and , Australia and early results of the first phase of the trial . Methods : A total of 44 communities ( aggregate population 560 000 adults aged 30 years or more ) will be r and omised to receive either a community based screening programme for 3 years or normal practice . The screening programme promotes thorough skin self examination and whole body skin examination by a doctor and provides open access skin cancer screening clinics . In its first phase , the trial is underway in nine intervention and nine control communities . The primary outcome measure is mortality from melanoma during 15 years of follow up . Results : The first phase of the trial has shown the feasibility of implementing a population skin screening programme including regular skin cancer screening clinics , and has shown the strong support of communities and doctors for the programme . There has been a significant 2.5-fold increase in participation in screening in the intervention communities in this first phase after the first 12 months of the trial and no significant increase in participation in screening in control communities during this period . Conclusions : The design of a community based r and omised trial of screening for melanoma has been successfully peer review ed and the intervention has been shown to be feasible in practice . This r and omised trial may be one of the last opportunities to develop the evidence required for public health recommendations for population screening for melanoma Background : Malignant melanoma is rising quickly in incidence and mortality rates . Family physicians ( FPs ) have been reported to lack confidence in diagnosing skin cancers . Objective : The aim of this study was to determine whether an educational intervention can improve FPs ’ abilities to diagnose skin cancers . Methods : The design was a prospect i ve , r and omized trial which included a skin cancer question naire , a video intervention , and a skin biopsy review . Results : Pre-intervention , FPs answered 57 % of the questions correctly on the skin cancer question naire . Post-intervention , the video intervention group scored higher than did the control group . The video intervention group removed 10 % fewer benign lesions and almost 3 times more malignant lesions compared with their pre-intervention biopsy rate . No findings were statistically significant . Conclusion : An educational intervention may improve FPs ’ knowledge and diagnosis of skin cancer . Our results may guide future studies with larger sample sizes in developing a skin cancer continuing medical education ( CME ) course for FPs . Antécédents : L’incidence des mélanomes et le taux de mortalité qui y est associé augmentent rapidement , ce qui laisse suggérer que les médecins de famille n’ont pas la confiance nécessaire pour diagnostiquer le cancer de la peau . Objectif : Déterminer si une campagne d’éducation peut améliorer la capacité des médecins de famille à diagnostiquer les cancers de la peau . Méthodes : Une étude prospect i ve r and omisée a été menée , comprenant un question naire sur le cancer de la peau , une séance éducative sur vidéo et un aperçu d’une biopsie de la peau . Résultats : Avant la séance , les médecins de famille ont obtenu de bonnes réponses à 57 % des questions figurant sur le question naire du cancer de la peau . Le groupe qui a assisté à la séance vidéo a eu un meilleur résultat que le groupe précédent . Le groupe a enlevé 10 % de moins de tumeurs bénignes et 3 fois plus de tumeurs malignes après l’aperçu de la biopsie . Toutefois , ces résultats ne représentent pas des statistiques significatives . Conclusion : Des mesures éducatives pourront améliorer les connaissances des médecins de famille et leurs capacités de diagnostiquer les mélanomes . Nos résultats pourront orienter de futures études , avec un plus large nombre de participants , dans la mise au point d’une stratégie d’éducation médicale continue ( EMC ) sur le cancer de la peau , destinée aux médecins de famille |
11,970 | 25,316,244 | RESULTS Based on several studies , Mediterranean diet is inversely related to type 2 diabetes and plays important roles in the management of type 2 diabetes .
Based on the evidence gathered and evaluated from various studies , we concluded combination and interaction of Mediterranean diet components , such as fruits , vegetables , nuts , legumes , whole grains , fish and moderate intakes of red wine , which contain essential nutrients and health promoting properties , including high fibers , high magnesium , high anti-oxidant and high monounsaturatal fatty acids ( MUFA ) .
Interaction and combination of these essential nutrients and health promoting properties found to lower body weight , hemoglobin A1C ( HbA1c ) , low density lipoprotein ( LDL ) , oxidative-stress and improve high density lipoprotein ( HDL ) level ; which are beneficial for prevention and prognosis improvement of type 2 diabetes .
In the modern society , poor dietary habits accompanied by inadequate physical activity are associated with the risk of having obesity and type 2 diabetes . | OBJECTIVE To summarize the importance of Mediterranean diet in the prevention and management of type 2 diabetes .
Promoting healthy lifestyle and diet are not only beneficial in the prevention and treatment of various diseases but also important in maintaining the overall health .
Switching from unhealthy diet to health-friendly diet such as Mediterranean diet represents healthy lifestyle choice | BACKGROUND The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus ( DM2 ) is unclear . Trials comparing the effectiveness of diets are frequently limited by short follow-up times and high dropout rates . AIM The effects of a low carbohydrate Mediterranean ( LCM ) , a traditional Mediterranean ( TM ) , and the 2003 American Diabetic Association ( ADA ) diet were compared , on health parameters during a 12-month period . METHODS In this 12-month trial , 259 overweight diabetic patients ( mean age 55 years , mean body mass index 31.4 kg/m(2 ) ) were r and omly assigned to one of the three diets . The primary end-points were reduction of fasting plasma glucose , HbA1c and triglyceride ( TG ) levels . RESULTS 194 patients out of 259 ( 74.9 % ) completed follow-up . After 12 months , the mean weight loss for all patients was 8.3 kg : 7.7 kg for ADA , 7.4 kg for TM and 10.1 kg for LCM diets . The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet ( -2.0 and -1.6 % , respectively , p < 0.022 ) . HDL cholesterol increased ( 0.1 mmol/l + /- 0.02 ) only on the LCM ( p < 0.002 ) . The reduction in serum TG was greater in the LCM ( -1.3 mmol/l ) and TM ( -1.5 mmol/l ) than in the ADA ( -0.7 mmol/l ) , p = 0.001 . CONCLUSIONS An intensive 12-month dietary intervention in a community-based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups . Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control OBJECTIVE To test the effects of two Mediterranean diet ( MedDiet ) interventions versus a low-fat diet on incidence of diabetes . RESEARCH DESIGN AND METHODS This was a three-arm r and omized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center ( PREDIMED-Reus , northeastern Spain ) of the Prevención con Dieta Mediterránea [ PREDIMED ] study , a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk . Participants were r and omly assigned to education on a low-fat diet ( control group ) or to one of two MedDiets , supplemented with either free virgin olive oil ( 1 liter/week ) or nuts ( 30 g/day ) . Diets were ad libitum , and no advice on physical activity was given . The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria . RESULTS After a median follow-up of 4.0 years , diabetes incidence was 10.1 % ( 95 % CI 5.1–15.1 ) , 11.0 % ( 5.9–16.1 ) , and 17.9 % ( 11.4–24.4 ) in the MedDiet with olive oil group , the MedDiet with nuts group , and the control group , respectively . Multivariable adjusted hazard ratios of diabetes were 0.49 ( 0.25–0.97 ) and 0.48 ( 0.24–0.96 ) in the MedDiet supplemented with olive oil and nuts groups , respectively , compared with the control group . When the two MedDiet groups were pooled and compared with the control group , diabetes incidence was reduced by 52 % ( 27–86 ) . In all study arms , increased adherence to the MedDiet was inversely associated with diabetes incidence . Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity . CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk 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 Objective To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants . Design Prospect i ve cohort study with estimates of relative risk adjusted for sex , age , years of university education , total energy intake , body mass index , physical activity , sedentary habits , smoking , family history of diabetes , and personal history of hypertension . Setting Spanish university department . Participants 13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years . Main outcome measures Dietary habits assessed at baseline with a vali date d 136 item food frequency question naire and scored on a nine point index . New cases of diabetes confirmed through medical reports and an additional detailed question naire posted to those who self reported a new diagnosis of diabetes by a doctor during follow-up . Confirmed cases of type 2 diabetes . Results Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes . The incidence rate ratios adjusted for sex and age were 0.41 ( 95 % confidence interval 0.19 to 0.87 ) for those with moderate adherence ( score 3 - 6 ) and 0.17 ( 0.04 to 0.75 ) for those with the highest adherence ( score 7 - 9 ) compared with those with low adherence ( score < 3 ) . In the fully adjusted analyses the results were similar . A two point increase in the score was associated with a 35 % relative reduction in the risk of diabetes ( incidence rate ratio 0.65 , 0.44 to 0.95 ) , with a significant inverse linear trend ( P=0.04 ) in the multivariate analysis . Conclusion Adherence to a Mediterranean diet is associated with a reduced risk of diabetes Background The effects of fish consumption and n-3 fatty acids on type 2 diabetes mellitus ( T2DM ) have recently been debated . Objective We explored the risk of T2DM in relation to consumption of lean fish , fatty fish , fish products and total fish as well as cod liver oil supplements in a representative sample of Norwegian women . Design This was a prospect i ve population based cohort study in 33740 women free of T2DM , stroke , angina or heart attack and with detailed information on important co-variates and dietary intake at baseline . Risk ratios and corresponding 95 % CI were estimated using Poisson regression with log-person time as offset . Results Lean fish consumption was inversely associated with T2DM compared to zero intake . Risk ratios and 95 % CI for intake of 75 and 100 g lean fish per day were 0.71 ( 0.51 , 0.98 ) and 0.67 ( 0.46 , 0.98 ) , respectively . There was no effect of intake of fatty fish , fish products , total fish or use of cod liver oil supplements on the risk of T2DM . Conclusion Lean fish consumption of 75–100 g/d had a beneficial effect on T2DM . It remains unclear whether lean fish in itself has a protective effect on T2DM or that lean fish consumers have a protective life-style that we were not able to take into account in this study . Unfavorable effects of fatty fish consumption or use of cod liver oil supplements on T2DM were not observed BACKGROUND Obesity is a strong risk factor for type 2 diabetes . However , few studies have compared the predictive power of overall obesity with that of central obesity . The cutoffs for waist circumference ( WC ) and waist-to-hip ratio ( WHR ) as measures of abdominal adiposity remain controversial . OBJECTIVE The objective was to compare body mass index ( BMI ) , WC , and WHR in predicting type 2 diabetes . DESIGN A prospect i ve cohort study ( Health Professionals Follow-Up Study ) of 27 270 men was conducted . WC , WHR , and BMI were assessed at baseline . Covariates and potential confounders were assessed repeatedly during the follow-up . RESULTS During 13 y of follow-up , we documented 884 incident type 2 diabetes cases . Age-adjusted relative risks ( RRs ) across quintiles of WC were 1.0 , 2.0 , 2.7 , 5.0 , and 12.0 ; those of WHR were 1.0 , 2.1 , 2.7 , 3.6 , and 6.9 ; and those of BMI were 1.0 , 1.1 , 1.8 , 2.9 , and 7.9 ( P for trend < 0.0001 for all ) . Multivariate adjustment for diabetes risk factors only slightly attenuated these RRs . Adjustment for BMI substantially attenuated RRs for both WC and WHR . The receiver operator characteristic curve analysis indicated that WC and BMI were similar and were better than WHR in predicting type 2 diabetes . The cumulative proportions of type 2 diabetes cases identified according to medians of BMI ( > /=24.8 ) , WC ( > /=94 cm ) , and WHR ( > /=0.94 ) were 82.5 % , 83.6 % , and 74.1 % , respectively . The corresponding proportions were 78.9 % , 50.5 % , and 65.7 % according to the recommended cutoffs . CONCLUSIONS Both overall and abdominal adiposity strongly and independently predict risk of type 2 diabetes . WC is a better predictor than is WHR . The currently recommended cutoff for WC of 102 cm for men may need to be reevaluated ; a lower cutoff may be more appropriate 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 OBJECTIVE To assess the long-term effects of dietary interventions on glycemic control , need for diabetes medications , and remission of type 2 diabetes . RESEARCH DESIGN AND METHODS Originally , in a two-arm trial design , overweight , middle-aged men and women with newly diagnosed type 2 diabetes were r and omized to a low-carbohydrate Mediterranean diet ( LCMD ; n = 108 ) or a low-fat diet ( n = 107 ) . After 4 years , participants who were still free of diabetes medications were further followed up until the primary end point ( need of a diabetic drug ) ; remission of diabetes ( partial or complete ) and changes in weight , glycemic control , and cardiovascular risk factors were also evaluated . RESULTS The primary end point was reached in all participants after a total follow-up of 6.1 years in the low-fat group and 8.1 years in the LCMD group ; median survival time was 2.8 years ( 95 % CI 2.4–3.2 ) and 4.8 years ( 4.3–5.2 ) , respectively . The unadjusted hazard ratio for the overall follow-up was 0.68 ( 0.50–0.89 ; P < 0.001 ) . LCMD participants were more likely to experience any remission ( partial or complete ) , with a prevalence of 14.7 % ( 13.0–16.5 % ) during the first year and 5.0 % ( 4.4–5.6 % ) during year 6 compared with 4.1 % ( 3.1–5.0 % ) at year 1 and 0 % at year 6 in the low-fat diet group . CONCLUSIONS In patients with newly diagnosed type 2 diabetes , an LCMD result ed in a greater reduction of HbA1c levels , higher rate of diabetes remission , and delayed need for diabetes medication compared with a low-fat diet CONTEXT Nuts are high in unsaturated ( polyunsaturated and monounsaturated ) fat and other nutrients that may improve glucose and insulin homeostasis . OBJECTIVE To examine prospect ively the relationship between nut consumption and risk of type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 83 818 women from 11 states in the Nurses ' Health Study . The women were aged 34 to 59 years , had no history of diabetes , cardiovascular disease , or cancer , completed a vali date d dietary question naire at baseline in 1980 , and were followed up for 16 years . MAIN OUTCOME MEASURE Incident cases of type 2 diabetes . RESULTS We documented 3206 new cases of type 2 diabetes . Nut consumption was inversely associated with risk of type 2 diabetes after adjustment for age , body mass index ( BMI ) , family history of diabetes , physical activity , smoking , alcohol use , and total energy intake . The multivariate relative risks ( RRs ) across categories of nut consumption ( never/almost never , or = 5 times/week ) for a 28-g ( 1 oz ) serving size were 1.0 , 0.92 ( 95 % confidence interval [ CI ] , 0.85 - 1.00 ) , 0.84 ( 0.95 % CI , 0.76 - 0.93 ) , and 0.73 ( 95 % CI , 0.60 - 0.89 ) ( P for trend < .001 ) . Further adjustment for intakes of dietary fats , cereal fiber , and other dietary factors did not appreciably change the results . The inverse association persisted within strata defined by levels of BMI , smoking , alcohol use , and other diabetes risk factors . Consumption of peanut butter was also inversely associated with type 2 diabetes . The multivariate RR was 0.79 ( 95 % CI , 0.68 - 0.91 ; P for trend < .001 ) in women consuming peanut butter 5 times or more a week ( equivalent to > or = 140 g [ 5 oz ] of peanuts/week ) compared with those who never/almost never ate peanut butter . CONCLUSIONS Our findings suggest potential benefits of higher nut and peanut butter consumption in lowering risk of type 2 diabetes in women . To avoid increasing caloric intake , regular nut consumption can be recommended as a replacement for consumption of refined grain products or red or processed meats Context Some experts attribute a low incidence of heart disease in Mediterranean countries to dietary habits . Contribution In this multicenter , 3-group trial , investigators r and omly assigned 772 adults at high risk for cardiovascular disease to a low-fat diet or to a Mediterranean diet supplemented with either virgin olive oil ( 1 L per week ) or nuts ( 30 g per day ) . After 3 months , the Mediterranean diet groups had lower mean plasma glucose level , systolic blood pressure , and total cholesterolhigh-density lipoprotein cholesterol ratio than the low-fat diet group . Caution s The Mediterranean diet groups received more nutritional education than the low-fat diet group . Implication s Mediterranean diets supplemented with olive oil or nuts may improve cardiovascular risk factors . The Editors Cardiovascular disease is the main cause of death in industrialized countries , but incidence rates have marked geographic differences . The low incidence of coronary heart disease ( CHD ) in Mediterranean countries has been partly ascribed to dietary habits ( 1 - 3 ) . Recent findings from large European cohort studies ( 4 - 6 ) suggest that a high degree of adherence to the Mediterranean diet is associated with a reduction in mortality . In small clinical studies , the Mediterranean diet or some of its components have reduced blood pressure ( 7 ) and have improved lipid profiles ( 8 , 9 ) and endothelial function ( 10 ) . Moreover , a recent cross-sectional study ( 11 ) and a 2-year feeding trial ( 12 ) have shown that adherence to the Mediterranean diet is associated with reduced markers of vascular inflammation . These beneficial effects on surrogate markers of cardiovascular risk add biological plausibility to the epidemiologic evidence that supports a protective effect of the Mediterranean diet . Olive oil , a rich source of monounsaturated fatty acids , is a main component of the Mediterranean diet . Virgin olive oil retains all the lipophilic components of the fruit , -tocopherol , and phenolic compounds with strong antioxidant and anti-inflammatory properties ( 13 , 14 ) . Tree nuts , which are also typical in the Mediterranean diet , have a favorable fatty acid profile and are a rich source of nutrients and other bioactive compounds that may beneficially influence the risk for CHD , such as fiber , phytosterols , folic acid , and antioxidants ( 15 ) . Frequent nut intake has been associated with decreased CHD rates in prospect i ve studies ( 15 ) . Walnuts differ from all other nuts through their high content of polyunsaturated fatty acids , particularly -linolenic acid , a plant n-3 fatty acid ( 16 ) , which may confer additional antiatherogenic properties ( 17 ) . Therefore , we design ed a large-scale feeding trial in high-risk participants to assess the effects of 2 Mediterranean diets , one supplemented with virgin olive oil and the other supplemented with mixed nuts , compared with a low-fat diet on cardiovascular outcomes . We report the results of a 3-month intervention on intermediate markers of cardiovascular risk in the first 772 participants who were recruited into the trial . Supplement . Original Version ( PDF ) Methods Study Design The Prevencin con Dieta Mediterrnea ( PREDIMED ) Study is a large , parallel-group , multicenter , r and omized , controlled , 4-year clinical trial that aims to assess the effects of the Mediterranean diet on the primary prevention of cardiovascular disease ( www.predimed.org ) . An estimated 9000 high-risk participants ( > 5000 participants are already recruited ) will be assigned to 3 interventions : Mediterranean diet with virgin olive oil , Mediterranean diet with mixed nuts , or low-fat diet . The main outcome is an aggregate of cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke ) . The anticipated completion date of the trial is December 2010 . We design ed our present study to assess the 3-month effects of the dietary interventions on surrogate markers of cardiovascular risk in participants entering the study during the first 6 months of recruitment . The institutional review boards of the 10 participating centers approved the study protocol . Participants and Recruitment From October 2003 to March 2004 , we selected 930 potential participants in primary care centers affiliated with 10 teaching hospitals across Spain . Eligible participants were community-dwelling men , 55 to 80 years of age , and women , 60 to 80 years of age , who fulfilled at least 1 of 2 criteria : type 2 diabetes or 3 or more CHD risk factors ( current smoking , hypertension [ blood pressure > 140/90 mm Hg or treatment with antihypertensive drugs ] , low-density lipoprotein [ LDL ] cholesterol level 4.14 mmol/L [ 160 mg/dL ] [ or treatment with hypolipidemic drugs ] , high-density lipoprotein [ HDL ] cholesterol level 1.04 mmol/L [ 40 mg/dL ] , body mass index [ BMI ] 25 kg/m2 , or a family history of premature CHD ) . Exclusion criteria were history of cardiovascular disease , any severe chronic illness , drug or alcohol addiction , history of allergy or intolerance to olive oil or nuts , or low predicted likelihood of changing dietary habits according to the stages-of-change model ( 18 ) . The primary care physicians based participants ' eligibility on review of clinical records and a screening visit . They obtained a list of c and i date s from computer-based records of patients who attended each participating center and review ed their clinical records to exclude those who did not meet eligibility criteria . They then invited suitable c and i date s by telephone to attend a screening visit . The visit included an interview with administration of a 26-item question naire to inquire about medical conditions and risk factors related to eligibility . Of the eligible c and i date s who met entry requirements , 95 % agreed to participate and provided informed consent . R and omization and Intervention After the screening visit , each center r and omly assigned eligible participants to 1 of 3 diet groups by using a computer-generated r and om-number sequence . The coordinating center constructed the r and omization table , and participants were r and omly assigned into blocks of 50 participants balanced by center , sex , and age group ( < 70 years and 70 years ) . We concealed allocation into the intervention groups by using closed envelopes with correlative numbers by prespecified subgroups of sex and age . The baseline examination included the administration of a 14-item question naire , an extension of a previously vali date d question naire ( 19 ) , that assessed the degree of adherence to the traditional Mediterranean diet . We assigned values of 0 or 1 to each item ( Appendix Table 1 ) . We also administered a 137-item vali date d food frequency question naire ( 20 ) ; the vali date d Spanish version ( 21 ) of the Minnesota Leisure Time Physical Activity Question naire ; and a 47-item question naire about education , lifestyle , history of illnesses , and medication use . We performed anthropometric and blood pressure measurements and obtained sample s of fasting blood and spot urine . We repeated all examinations at 3 months . The same dietitian delivered the interventions to the 3 r and omized groups in each center . On the basis of the assessment of individual Mediterranean diet scores , the dietitian gave personalized dietary advice during a 30-minute session to each participant , with recommendations on the desired frequency of intake of specific foods . We advised participants who were allocated to the low-fat diet to reduce intake of all types of fat , and we gave them a leaflet with written recommendations according to the American Heart Association guidelines ( 22 ) . For total fat intake , these recommendations were opposite to those given to participants in the 2 Mediterranean diet groups , who received instructions intended to increase the 14-item Mediterranean diet score , including increased consumption of vegetable fats and oils . We did not suggest any energy restriction . While the participants who were allocated to the low-fat diet did not receive further intervention , those assigned the 2 Mediterranean diet groups had access to more intense intervention in 2 ways . First , they were given a free provision of typical Mediterranean fatty foods ( olive oil or nuts ) . Depending on group assignment , participants were given either free virgin olive oil ( 15 L [ 1 L/wk ] for 3 months ) or free sachets of walnuts , hazelnuts , and almonds ( 1350 g of walnuts [ 15 g/d ] , 675 g of hazelnuts [ 7.5 g/d ] , and 675 g of almonds [ 7.5 g/d ] for 3 months ) . To improve adherence and account for family needs , participants in the corresponding Mediterranean diet groups were given excess olive oil or additional 1000-g packets of nuts . We analyzed the nutrient composition of the olive oil and nuts used in the study by st and ard methods in a reference laboratory ( Appendix Table 2 ) ) . Second , 1 week after inclusion , the dietitian delivered a 1-hour group session with up to 20 participants , with separate sessions for each Mediterranean diet group . Each group session consisted of informative talks and provision of written material s with elaborate descriptions of typical Mediterranean foods and seasonal shopping lists , meal plans , and cooking recipes . Throughout the study , all participants had free and continuous access to their center dietitian for advice and consultation . Measurements Trained personnel measured weight and height by using calibrated scales and a wall-mounted stadiometer , respectively ; waist circumference midway between the lowest rib and the iliac crest by using an anthropometric tape ; and blood pressure in triplicate with a vali date d semiautomatic oscillometer ( Omron HEM-705CP , Hoofddorp , the Netherl and s ) . We calculated energy and nutrient intake from Spanish food composition tables ( 23 ) . At the 3-month visit and when consulted by participants , dietitians assessed any adverse effects from the interventions by administering a checklist of symptoms and gave advice on how to remedy them . The checklist included mouth symptoms ; bloating , fullness , or indigestion ; altered bowel BACKGROUND Epidemiologic studies suggest that greater consumption of fruit and vegetables may decrease the risk of diabetes mellitus , but the evidence is limited and inconclusive . Plasma vitamin C level is a good biomarker of fruit and vegetable intake , but , to our knowledge , no prospect i ve studies have examined its association with diabetes risk . This study aims to examine whether fruit and vegetable intake and plasma vitamin C level are associated with the risk of incident type 2 diabetes . METHODS We administered a semiquantitative food frequency question naire to men and women from a population -based prospect i ve cohort ( European Prospect i ve Investigation of Cancer-Norfolk ) study who were aged 40 to 75 years at baseline ( 1993 - 1997 ) when plasma vitamin C level was determined and habitual intake of fruit and vegetables was assessed . During 12 years of follow-up between February 1993 and the end of December 2005 , 735 clinical ly incident cases of diabetes were identified among 21 831 healthy individuals . We report the odds ratios of diabetes associated with sex-specific quintiles of fruit and vegetable intake and of plasma vitamin C levels . RESULTS A strong inverse association was found between plasma vitamin C level and diabetes risk . The odds ratio of diabetes in the top quintile of plasma vitamin C was 0.38 ( 95 % confidence interval , 0.28 - 0.52 ) in a model adjusted for demographic , lifestyle , and anthropometric variables . In a similarly adjusted model , the odds ratio of diabetes in the top quintile of fruit and vegetable consumption was 0.78 ( 95 % confidence interval , 0.60 - 1.00 ) . CONCLUSIONS Higher plasma vitamin C level and , to a lesser degree , fruit and vegetable intake were associated with a substantially decreased risk of diabetes . Our findings highlight a potentially important public health message on the benefits of a diet rich in fruit and vegetables for the prevention of diabetes OBJECTIVE Epidemiological studies suggest that moderate alcohol consumers have enhanced insulin sensitivity and a reduced risk of type 2 diabetes . Adiponectin , an adipocyte-derived plasma protein , has been found to be negatively associated with adiposity and positively associated with insulin sensitivity . Moderate alcohol consumption may increase adiponectin , which in turn causes a decrease of tumor necrosis factor (TNF)-alpha . A decreased TNF-alpha level may consequently increase insulin sensitivity . RESEARCH DESIGN AND METHODS To test this hypothesis , we performed a r and omized crossover partially diet-controlled study . A total of 23 healthy middle-aged male subjects consumed daily four glasses of whisky ( 40 g ethanol ) or tap water with dinner during two successive periods of 17 days . RESULTS Moderate alcohol consumption increased plasma adiponectin level ( 11 % ; P = 0.0002 ) but did not affect plasma TNF-alpha level . An increase in insulin sensitivity index was observed in an insulin-resistant subgroup ( 21 % ; P = 0.11 ) , which positively correlated with the relative alcohol-induced increase in plasma adiponectin level ( r = 0.73 , P = 0.02 ) . CONCLUSIONS The experimental results are in agreement with observational data . Moderate alcohol consumption improved insulin sensitivity in relatively insulin-resistant middle-aged men , an effect that may be mediated through alcohol-induced increases in adiponectin BACKGROUND Plasma phospholipid concentrations of trans-palmitoleic acid ( trans-16:1n-7 ) , a biomarker of dairy fat intake , are inversely associated with incident type 2 diabetes in 2 US cohorts . OBJECTIVE The objective was to investigate whether the intake of trans-16:1n-7 in particular , or dairy fat in general , is associated with glucose tolerance and key factors determining glucose tolerance . DESIGN A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index ( BMI ) - and age-matched controls . The concentrations of trans-16:1n-7 and 2 other biomarkers of dairy fat intake , 15:0 and 17:0 , were measured in plasma phospholipids and free fatty acids ( FFAs ) . Liver fat was estimated by computed tomography-derived liver-spleen ratio . Intravenous-glucose-tolerance tests and oral-glucose-tolerance test ( OGTT ) and hyperinsulinemic-euglycemic clamps were performed to assess β-cell function and hepatic and systemic insulin sensitivity . RESULTS In multivariate analyses adjusted for age , sex , and BMI , phospholipid 17:0 , phospholipid trans-16:1n-7 , FFA 15:0 , and FFA 17:0 were inversely associated with fasting plasma glucose , the area under the curve for glucose during an OGTT , and liver fat . Phospholipid trans-16:1n-7 was also positively associated with hepatic and systemic insulin sensitivity . None of the biomarkers were associated with β-cell function . The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat , but strengthened by adjusting for β-cell function . CONCLUSION Although we can not rule out reverse causation , these data support the hypothesis that dairy fat improves glucose tolerance , possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat Abstract Objective : To investigate whether low vitamin E status is a risk factor for incident non-insulin dependent diabetes mellitus . Design : Population based follow up study with diabetes assessed at baseline and at four years . Setting : Eastern Finl and . Subjects : R and om sample of 944 men aged 42 - 60 who had no diabetes at the baseline examination . Intervention : Oral glucose tolerance test at four year follow up . Main outcome measures : A man was defined diabetic if he had either ( a ) a fasting blood glucose concentration > /=6.7 mmol/l , or ( b ) a blood glucose concentration > /=10.0 mmol/l two hours after a glucose load , or ( c ) a clinical diagnosis of diabetes with either dietary , oral , or insulin treatment . Results : 45 men developed diabetes during the follow up period . In a multivariate logistic regression model including the strongest predictors of diabetes , a low lipid st and ardised plasma vitamin E ( below median ) concentration was associated with a 3.9-fold ( 95 % confidence interval 1.8-fold to 8.6-fold ) risk of incident diabetes . A decrement of 1 µmol/l of uncategorised unst and ardised vitamin E concentration was associated with an increment of 22 % in the risk of diabetes when allowing for the strongest other risk factors as well as serum low density lipoprotein cholesterol and triglyceride concentrations . Conclusions : There was a strong independent association between low vitamin E status before follow up and an excess risk of diabetes at four years . This supports the theory that free radical stress has a role in the causation of non-insulin dependent diabetes mellitus AIMS Individuals with Type 2 diabetes are at high risk for coronary heart disease , and may benefit from aggressive lifestyle modification . We evaluated the prevalence of Type 2 diabetes , in a Greek adult population , in relation to physical activity and dietary habits . METHODS From May 2001 to December 2002 , we r and omly enrolled 1514 men and 1528 women , with no evidence of cardiovascular or any other chronic disease . The sampling was stratified by the age and gender distribution of the general population in the greater area of Athens ( census 2001 ) . Diabetes was defined according to the established American Diabetes Association criteria . Dietary habits were assessed through a vali date d food frequency question naire and a diet score was developed , in which higher values suggest greater adherence to the Mediterranean diet . Weekly energy expenditure was assessed by considering frequency , duration and intensity of sports-related physical activity during a usual week . RESULTS After age adjustment for the Greek adult population ( 2001 census ) , the projected prevalence of Type 2 diabetes was 7.6 % in men and 5.9 % in women . A significant proportion of diabetic subjects ( 24 % of men and 30 % of women ) were unaware of their condition . Moreover , a 10-unit increase in the diet score was associated with 21 % lower odds of diabetes ( P < 0.05 ) , while individuals taking light physical activity were at 35 % lower odds ratio of diabetes compared with sedentary individuals ( P < 0.05 ) . CONCLUSIONS Diabetes mellitus is common in our population , with approximately 1 in 5 individuals with Type 2 diabetes being unaware of their condition . The lifestyle approach described here may contribute significantly to the reduction in the prevalence of diabetes , at a population level The prevalence of type 2 diabetes mellitus is rapidly increasing in the United States ( 1 , 2 ) and worldwide ( 3 ) . Ecologic studies ( 4 ) , migration studies ( 4 , 5 ) , and analyses of secular trends ( 4 , 6 ) suggest that adoption of a western diet may be associated with increased incidence of type 2 diabetes . However , these studies could not separate the effects of diet from those of other risk factors , such as obesity and physical activity . Studies of the relation between diet and incidence of type 2 diabetes on an individual level have predominantly focused on intake of macronutrients and fiber ( 7 ) . However , these dietary factors alone probably explain only part of the effect of diet on glucose metabolism . Other nutrients , additives , contaminants , and unknown compounds and the physical properties of foods and interactions between nutrients ( for example , with respect to bioavailability ) may play a role in the deterioration of glucose metabolism . Hence , the examination of effects of food consumption may be an important complementary approach . Recently , the analysis of patterns of food consumption by using factor analysis has emerged as a useful tool for elucidating relationships between diet and health ( 8 - 11 ) . The overall dietary pattern may affect health more than individual foods and nutrients do . Furthermore , dietary patterns reflect the way foods are consumed in reality , which may provide insight into possibilities for dietary changes and may facilitate the translation of findings to public health recommendations . Recent dietary intervention studies have indicated that interventions focused on dietary patterns can decrease blood pressure ( 12 ) and reduce cardiovascular complications ( 13 ) . Data on dietary patterns and risk for type 2 diabetes are sparse . Although two cross-sectional studies of dietary patterns and diabetes have been conducted ( 11 , 14 ) , these studies incompletely controlled for confounding by other lifestyle factors . Therefore , we prospect ively examined the association between major dietary patterns and risk for type 2 diabetes in a large prospect i ve study of U.S. professional men with extensive , repeatedly obtained information on diet and other lifestyle factors . Methods Participants The Health Professionals Follow-up Study started in 1986 , when 51 529 male health professionals ( dentists , veterinarians , pharmacists , optometrists , osteopathic physicians , and podiatrists ) completed a detailed mailed question naire on medical history , diet , and other potential risk factors for major diseases . The participants lived in all 50 U.S. states , were predominantly white , and were 40 to 75 years of age in 1986 . We excluded from the current analysis 1595 men who did not satisfy the a priori criteria of reporting daily energy intake of 3.3 to 17.6 MJ ( 800 to 4200 kcal/24 h ) and leaving fewer than 70 responses blank of the 131 food items on the diet question naire ( < 5 % had > 11 blanks ) . We also excluded men who reported having diabetes , cardiovascular disease ( myocardial infa rct ion , angina pectoris , coronary artery surgery , or stroke ) , or cancer ( except nonmelanoma skin cancer ) at baseline because having these diagnoses may affect diet or reporting of diet . After exclusions , the study sample comprised 42 504 men , who were followed for incidence of type 2 diabetes and other diseases for 12 years ( 1986 to 1998 ) . Every 2 years , the participants received question naires by mail that asked for up date d information on exposures and newly diagnosed diseases . The follow-up rate for potential person-years was about 97 % for nonfatal events . We identified deaths by reports from family members , coworkers , or postal authorities or through systematic search es of the National Death Index . Assessment of Dietary Patterns To assess dietary intake , we used a 131-item semiquantitative food-frequency question naire in 1986 , 1990 , and 1994 . The question naire specified for each food a commonly used unit or portion size , and the participants were asked to indicate how often , on average , they had consumed a given amount of the specified food during the past year . Each such item provided nine possible responses , ranging from never or less than once a month to 6 or more times per day . To reduce within-respondent variation and to best represent long-term dietary habits , we averaged the dietary intakes from all available dietary question naires up to the start of each follow-up interval ( the average of the 1986 and 1990 dietary intakes was related to incidence of type 2 diabetes between 1990 and 1994 ) ( 15 ) . To identify dietary patterns , we applied factor analysis to data from the food-frequency question naire . First , we grouped the food items on the question naire into 37 predefined food groups . We combined food items that were similar in nutrient profile and culinary use ( for example , spinach , iceberg or head lettuce , and romaine or leaf lettuce were combined into green leafy vegetables ) . We classified a food item individually if its composition differed substantially from that of other foods ( for example , eggs or pizza ) or if we suspected that it represents a particular dietary habit ( for example , wine or French fries ) . Second , we applied the principal components program for factor analysis of SAS software ( 16 ) with varimax rotation to the 37 food groups . Factor analysis aggregates correlated variables . The obtained factors are linear combinations of the included variables , explaining as much of the variation in the original variables as possible . Our analysis retained two factors based on the eigenvalue of the factors , the Scree test , and the interpretability of the derived factors , and we labeled these diets as the prudent pattern and the western pattern ( 9 ) . Third , for each participant , we calculated a prudent pattern score and a western pattern score by summing the st and ardized intake of foods , weighted by the factor loadings of the foods ( 17 ) . We used these scores to rank participants according to the degree to which they conformed to each dietary pattern . We divided dietary pattern scores into quintiles ; thus , on this basis of his scores , each participant was grouped in a prudent-pattern quintile and a western-pattern quintile . To test the validity and reproducibility of the assessment of the dietary pattern scores by the food-frequency question naire , we examined a subgroup of 127 participants ( 9 ) . The Pearson correlation coefficient ( corrected for week-to-week variation in the diet records ) for a comparison between the responses to the food-frequency question naire and the diet records was 0.52 for the prudent dietary pattern and 0.74 for the western dietary pattern . Assessment of Nondietary Exposures The 1986 question naire and each biennial follow-up question naire assessed weight , smoking status , and physical activity . Participants provided information on age , diagnosis of hypertension and hypercholesterolemia , and height in 1986 and on family history of diabetes in 1987 . The criterion for family history of type 2 diabetes was having at least one first-degree relative with a diagnosis of diabetes after 30 years of age . For each participant , we determined a physical activity level , measured in weekly metabolic equivalent hours , on the basis of reported time spent on various activities , which we weighted according to intensity level ( 18 ) . The validity of self-reported weight ( 19 ) and physical activity ( 18 ) in this cohort has been reported previously . Ascertainment of Type 2 Diabetes Mellitus We mailed a supplementary question naire on symptoms , diagnostic tests , and medication use to participants who indicated on any biennial follow-up question naire that he had received a diagnosis of diabetes mellitus . Confirmation of diabetes required at least one of the following : 1 ) an elevated plasma glucose level ( fasting plasma glucose level 7.8 mmol/L [ 140 mg/dL ] ; r and om plasma glucose level 11.1 mmol/L [ 200 mg/dL ] ; or plasma glucose level after 2 hours or more during an oral glucose tolerance test 11.1 mmol/L [ 200 mg/dL ] ) plus at least one classic symptom [ excessive thirst , polyuria , weight loss , or hunger ] ; 2 ) at least two elevated plasma glucose levels measured on different occasions ; or 3 ) treatment with insulin or oral hypoglycemic medication . We excluded men who reported having type 1 diabetes on the supplementary question naire . These criteria for diabetes are consistent with those from the World Health Organization in 1985 ( 20 ) . We did not use the current diabetes classification of the American Diabetes Association ( 21 ) because among the men in our study , most cases of diabetes were diagnosed before these criteria were published . The validity of our assessment of type 2 diabetes was verified with medical records in a sub sample of 71 participants . A physician blinded to the information on the supplementary question naire review ed the records according to the diagnostic criteria . Of the 71 participants classified as having type 2 diabetes , 12 had incomplete medical recordsfor example , absent laboratory data ( n = 2 ) or only one set of laboratory data ( n = 9 ) . We confirmed the classification of type 2 diabetes in 57 ( 97 % ) of the other 59 other men in the sub sample . One participant denied having diabetes , and another participant lacked evidence of diabetes in his su bmi tted records . Statistical Analysis We used pooled logistic regression analyses with 2-year intervals to estimate the adjusted relative risk for each quintile compared with the lowest quintile of intake . With short time intervals and low rates of events , this approach gives results very similar to those of Cox proportional-hazards analyses ( 22 ) . Participants who died or received a diagnosis of diabetes during a 2-year cycle were censored at the end of that 2-year period and were not entered in any subsequent 2-year cycle . We used the cumulative average of available dietary assessment s up to the start of each 2-year follow-up interval ( 15 ) . We stopped updating a participant 's dietary Aims /hypothesisThe aim of this study was to identify a dietary pattern associated with diabetes-related biomarkers and to investigate whether this pattern is associated with the incidence of type 2 diabetes . Methods A nested case – control study of 192 cases of incident type 2 diabetes and 382 control subjects matched for sex and age was conducted . All subjects were participants in the population -based European Prospect i ve Investigation into Cancer and Nutrition (EPIC)—Potsdam Study . Dietary pattern score was derived using intake data on 48 food groups as exposure variables and the biomarkers HbA1c , HDL cholesterol , C-reactive protein and adiponectin as response variables in reduced rank regression . The association of the score with diabetes risk was estimated by conditional logistic regression analysis . Results A high score for the identified dietary pattern was characterised by a high intake of fresh fruit and a low intake of high-caloric soft drinks , beer , red meat , poultry , processed meat , legumes and bread ( excluding wholegrain bread ) . Subjects with high scores had high plasma concentrations of HDL cholesterol and adiponectin and low plasma concentrations of HbA1c and C-reactive protein . After multivariate adjustment , the odds ratios for type 2 diabetes across increasing quintiles of the dietary pattern score were 1.0 , 0.59 , 0.51 , 0.26 and 0.27 , respectively ( p=0.0006 for trend ) . Conclusions /interpretationA high score for the identified dietary pattern is associated with a more favourable biomarker profile and a substantially reduced incidence of type 2 diabetes BACKGROUND AND AIMS To investigate the impact of a diet modeled on the traditional Cretan Mediterranean diet on metabolic control and vascular risk in type 2 diabetes . METHODS AND RESULTS Twenty-seven subjects ( 47 - 77 yrs ) with type 2 diabetes were r and omly assigned to consume either the intervention diet ad libitum or their usual diet for 12 weeks and then cross over to the alternate diet . Most of the meals and staple foods for the intervention diet were provided . Lipids , glycemic variables , blood pressure , homocysteine , C-reactive protein , plasma carotenoids and body composition ( anthropometry and dual energy X-ray absorptiometry ) were assessed at baseline , and at the end of both diet periods . Dietary adherence was monitored using plasma carotenoid and fatty acid ( FA ) analysis , complemented by diet diaries . Compared with usual diet , on the ad libitum Mediterranean intervention diet glycosylated haemoglobin fell from 7.1 % ( 95 % CI : 6.5 - 7.7 ) to 6.8 % ( 95 % CI : 6.3 - 7.3 ) ( p=0.012 ) and diet quality improved significantly [ plant : animal ( g/day ) food ratio increased from 1.3 ( 95 % CI : 1.1 - 1.5 ) to 5.4 ( 95 % CI : 4.3 - 6.6 ) ( p<0.001 ) ] , plasma lycopene and lutein/zeaxanthin increased ( 36 % and 25 % , respectively ) , plasma saturated and trans FAs decreased , and monounsaturated FAs increased . CONCLUSION A traditional moderate-fat Mediterranean diet improves glycemic control and diet quality in men and women with well-controlled type 2 diabetes , without adverse effects on weight |
11,971 | 9,820,394 | Milk , wheat , and eggs were most frequently identified to cause symptom exacerbation ; of the foods identified the most common trait was a high salicylate content .
Foods high in amines were also identified .
Studies of diarrhea-predominant IBS identified a higher percentage of adverse food reactions .
Conclusion : Whether adverse reactions to foods are a key factor in exacerbating IBS symptoms or whether dietary manipulation is a valid treatment option is unclear . | Objective : We undertook to determine whether adverse food reactions play a role in irritable bowel syndrome ( IBS ) . | Thirteen out of 49 patients suspected of having specific food intolerance after withdrawal and re introduction of specific foods , were further subjected to double blind placebo controlled food challenges . Only three of these subjects were thus shown to have proven specific food intolerance . Of the remaining 10 , nine were strong ' placebo reactors ' . The study suggests that a small number of patients with gastrointestinal symptoms have verifiable specific food intolerance but that a greater number have symptoms attributable to psychogenic causes BACKGROUND Although previous studies have shown that psychological disturbances are frequently associated with the irritable bowel syndrome ( IBS ) , the relation was not necessarily cause and effect . The development of chronic bowel symptoms after an episode of acute gastroenteritis has allowed us to examine prospect ively the role of psychological factors . METHODS Seventy-five patients with acute gastroenteritis completed a series of psychometric tests soon after admission to hospital . Of these , 22 had persistent symptoms compatible with IBS after the acute illness , and in 20 of these the symptoms were still present at six months . FINDINGS At the time of their initial illness , patients who subsequently developed IBS had higher scores for anxiety , depression , somatization and neurotic trait than those who returned to normal bowel function . The psychometric scores had not changed when remeasured after the acute illness . Lactose malabsorption was not an important factor . INTERPRETATION These results support the hypothesis that psychological factors are important in IBS Food hypersensitivity as a cause of abdominal symptoms was investigated by means of exclusion diets and double-blind food provocation in patients with irritable bowel syndrome . Twenty-seven patients entered the study ; nineteen complied with dietary manipulation . Food hypersensitivity as a cause of their presenting symptoms was confirmed by double-blind food provocation in only three patients , who also had evidence of associated atopic disease and positive skin tests to common inhalant allergens . Evidence of minor psychiatric disorder was found in twelve of fourteen patients examined by an independent psychiatrist Specific foods were found to provoke symptoms of irritable bowel syndrome ( IBS ) in 14 of 21 patients . In 6 patients who were challenged double blind the food intolerance was confirmed . No difference was detected in changes in plasma glucose , histamine , immune complexes , haematocrit , eosinophil count , or breath hydrogen excretion produced after challenge or control foods . Rectal prostagl and in E2 ( PGE2 ) , however , increased significantly , and in a further 5 patients rectal PGE2 correlated with wet faecal weight . Food intolerance associated with prostagl and in production is an important factor in the pathogenesis of IBS |
11,972 | 24,353,906 | Results indicated that academic interest in using health videogames for childhood obesity prevention has increased during this time . | Childhood obesity is a global epidemic .
Health videogames are an emerging intervention strategy to combat childhood obesity .
This systematic review examined published research on the effect of health videogames on childhood obesity . | BACKGROUND Sedentary activities such as video gaming are independently associated with obesity . Active video games , in which players physically interact with images on screen , may help increase physical activity and improve body composition . OBJECTIVE The aim of this study was to evaluate the effect of active video games over a 6-mo period on weight , body composition , physical activity , and physical fitness . DESIGN We conducted a 2-arm , parallel , r and omized controlled trial in Auckl and , New Zeal and . A total of 322 overweight and obese children aged 10 - 14 y , who were current users of sedentary video games , were r and omly assigned at a 1:1 ratio to receive either an active video game up grade package ( intervention , n = 160 ) or to have no change ( control group , n = 162 ) . The primary outcome was the change from baseline in body mass index ( BMI ; in kg/m(2 ) ) . Secondary outcomes were changes in percentage body fat , physical activity , cardiorespiratory fitness , video game play , and food snacking . RESULTS At 24 wk , the treatment effect on BMI ( -0.24 ; 95 % CI : -0.44 , -0.05 ; P = 0.02 ) favored the intervention group . The change ( ±SE ) in BMI from baseline increased in the control group ( 0.34 ± 0.08 ) but remained the same in the intervention group ( 0.09 ± 0.08 ) . There was also evidence of a reduction in body fat in the intervention group ( -0.83 % ; 95 % CI : -1.54 % , -0.12 % ; P = 0.02 ) . The change in daily time spent playing active video games at 24 wk increased ( 10.03 min ; 95 % CI : 6.26 , 13.81 min ; P < 0.0001 ) with the intervention accompanied by a reduction in the change in daily time spent playing nonactive video games ( -9.39 min ; 95 % CI : -19.38 , 0.59 min ; P = 0.06 ) . CONCLUSION An active video game intervention has a small but definite effect on BMI and body composition in overweight and obese children . This trial was registered in the Australian New Zeal and Clinical Trials Registry at http://www.anzctr.org.au/ as ACTRN12607000632493 Physical inactivity among children is a serious public health problem . It has been suggested that high levels of screen time are contributory factors that encourage sedentary lifestyles in young people . As physical inactivity and obesity levels continue to rise in young people , it has been proposed that new-generation active computer- and video-console games ( otherwise known as “ exergaming ” ) may offer the opportunity to contribute to young people 's energy expenditure during their free time . Although studies have produced some encouraging results regarding the energy costs involved in playing active video-console games , the energy costs of playing the authentic versions of activity-based video games are substantially larger , highlighting that active gaming is no substitute for real sports and activities . A small number of exergaming activities engage children in moderate-intensity activity , but most do not . Only 3 very small trials have considered the effects of exergaming on physical activity levels and /or other health outcomes in children . Evidence from these trials has been mixed ; positive trends for improvements in some health outcomes in the intervention groups were noted in 2 trials . No adequately powered r and omized , controlled trial has been published to date , and no trial has assessed the long-term impact of exergaming on children 's health . We now need high- quality r and omized , controlled trials to evaluate the effectiveness and sustainability of exergaming , as well as its clinical relevance ; until such studies take place , we should remain cautious about its ability to positively affect children 's health BACKGROUND The rising prevalence of obesity in children has been linked in part to the consumption of sugar-sweetened drinks . Our aim was to examine this relation . METHODS We enrolled 548 ethnically diverse schoolchildren ( age 11.7 years , SD 0.8 ) from public schools in four Massachusetts communities , and studied them prospect ively for 19 months from October , 1995 , to May , 1997 . We examined the association between baseline and change in consumption of sugar-sweetened drinks ( the independent variables ) , and difference in measures of obesity , with linear and logistic regression analyses adjusted for potentially confounding variables and clustering of results within schools . FINDINGS For each additional serving of sugar-sweetened drink consumed , both body mass index ( BMI ) ( mean 0.24 kg/m2 ; 95 % CI 0.10 - 0.39 ; p=0.03 ) and frequency of obesity ( odds ratio 1.60 ; 95 % CI 1.14 - 2.24 ; p=0.02 ) increased after adjustment for anthropometric , demographic , dietary , and lifestyle variables . Baseline consumption of sugar-sweetened drinks was also independently associated with change in BMI ( mean 0.18 kg/m2 for each daily serving ; 95 % CI 0.09 - 0.27 ; p=0.02 ) . INTERPRETATION Consumption of sugar-sweetened drinks is associated with obesity in children The primary objective of this pilot study was to evaluate the effect of active video games on children 's physical activity levels . Twenty children ( mean ± SD age = 12 ± 1.5 years ; 40 % female ) were r and omised to receive either an active video game up grade package or to a control group ( no intervention ) . Effects on physical activity over the 12-week intervention period were measured using objective ( Actigraph accelerometer ) and subjective ( Physical Activity Question naire for Children [ PAQ-C ] ) measures . An activity log was used to estimate time spent playing active and non-active video games . Children in the intervention group spent less mean time over the total 12-week intervention period playing all video games compared to those in the control group ( 54 versus 98 minutes/day [ difference = -44 minutes/day , 95 % CI [ -92 , 2 ] ] , p = 0.06 ) . Average time spent in all physical activities measured with an accelerometer was higher in the active video game intervention group compared to the control group ( difference at 6 weeks = 194 counts/min , p = 0.04 , and at 12 weeks = 48 counts/min , p = 0.06).This preliminary study suggests that playing active video games on a regular basis may have positive effects on children 's overall physical activity levels . Further research is needed to confirm if playing these games over a longer period of time could also have positive effects on children 's body weight and body mass index . Trial Registration 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 Objective . To evaluate the efficacy and feasibility of a multifaceted , community-based weight intervention program for children using exergaming technology ( activity-promoting video gaming ) . Design and Methods . This is a prospect i ve observational pilot study . Forty-eight children , between the ages of 8 and 16 years , who are overweight or obese , enrolled in Exergaming for Health , a multidisciplinary weight management program , which used active video gaming . Primary outcome measures were change in body mass index ( BMI ) z scores . Results . Most children ( n = 40 , 83 % ) completed the program and participated in outcome evaluations . The average BMI change was −0.48 kg/m2 ( SD = 0.93 ) , P < .002 ( BMI z-score change was −0.072 , SD = 0.14 , P < .0001 ) . The average Global Self-Worth score improved , screen time and soda intake reduced , and exercise hours per week increased . Conclusions . The Exergaming for Health program may be an effective weight management intervention that is feasible with high participation rates . A larger r and omized controlled trial is needed to confirm these results OBJECTIVE We examined the feasibility of Dance Dance Revolution ( DDR ) , a dance video game , in participants ' homes , to increase physical activity ( PA ) and to decrease sedentary screen time ( SST ) . METHODS AND PROCEDURES Sixty children ( 7.5 + /- 0.5 years ) were r and omized in a 2:1 ratio to DDR or to wait-list control ( 10-week delay ) . DDR use was logged , PA was measured objective ly by accelerometry . SST was self-reported at weeks 0 and 10 . At week 28 , after both groups had access to DDR , accelerometry and SST were repeated . RESULTS Mean use of DDR was 89 + /- 82 ( range 0 - 660 min ) min per week ( mpw ) . The DDR group showed increased vigorous PA and a reduction in light PA ; the control group showed no increase in moderate and /or vigorous PA ( MVPA ) although they also had a reduction in light PA . Differences between the groups were not observed . The DDR group also reported a decrease in SST of -1.2 + /- 3.7 h per week ( hpw ) ( P < 0.05 ) , whereas the controls reported an increase of + 3.0 + /- 7.7 hpw ( nonsignificant ) . The difference in SST between the groups was significant , with less SST in the DDR group . Between weeks 10 and 28 , numeric reductions in SST were reported in both groups . In the DDR group , SST at week 28 ( 8.8 + /- 6.0 hpw ) was lower than baseline ( 10.5 + /- 5.5 hpw ; P < 0.03 ) . DISCUSSION This pilot study suggests that DDR reduces SST and may facilitate slight increases in vigorous PA . Further study is needed to better characterize children and context s in which DDR may promote a healthy lifestyle BACKGROUND There is a paucity of research investigating the effects of innovative physical activity programs on physical health and academic performance in the Latino population . PURPOSE To examine the impact of Dance Dance Revolution [DDR]-based exercise on Latino children 's physical fitness and academic achievement . DESIGN A repeated- measures crossover design was used . In Year 1 , Grade -4 students were assigned to the intervention group and offered 30 minutes of exercise ( DDR , aerobic dance ) three times per week . Grade -3 and Grade -5 students made up the comparison group and were offered no structured exercise at school . In Year 2 , the Grade -4 students were again assigned to the intervention , whereas Grade -5 and Grade -6 students were in the comparison group . SETTING / PARTICIPANTS Assessment s were conducted with 208 Latino school children . MAIN OUTCOME MEASURES The baseline measures included time to complete a 1-mile run , BMI , and reading and math scores . Data were collected again 9 months later . Overall , data were collected in 2009 - 2011 and analyzed in 2012 . RESULTS Data yielded significant differences between the intervention and comparison groups in differences in 1-mile run and math scores in Year 1 and Year 2 . The results also revealed net differences in the intervention versus comparison group scores on the 1-mile run for Grade 3 ( p<0.01 ) . Additionally , children 's yearly pre-test and post-test BMI group changes differed ( χ(2)((2 ) ) = 6.6 , p<0.05 ) only for the first year of intervention . CONCLUSIONS The DDR-based exercise intervention improved children 's cardiorespiratory endurance and math scores over time . Professionals should consider integrating exergaming at schools to achieve the goals of promoting a physically active lifestyle and enhancing academic success among Latino children OBJECTIVE We evaluated in a prospect i ve study microcomputer nutritional teaching games and their contribution to the children 's acquisition of nutritional knowledge and improvement of eating habits . MATERIAL AND METHODS One thous and eight hundred seventy-six children aged 7 - 12 years took part in this study at school . All 16 schools of the same school district were r and omized into two groups : games group and control group , both receiving conventional nutritional teaching by their teachers . The children in the games group played computer games during the conventional nutritional teaching period ( 2 hours a week for 5 weeks ) . At completion of the study , dietetic knowledge and dietary records were evaluated in both groups . RESULTS Dietary knowledge tests results were better in the games group ( p<0.001 ) . The children in the games group had a significantly better balanced diet for an energy intake of about 1900 kilocalories : more carbohydrate ( 46.4 + /- 0.2 % vs 45.7 + /- 0.2 % , p<0.05 ) , less fat ( 37.1 + /- 0.1 % vs 37.6 + /- 0.2 % , p<0.05 ) , less protein ( 16.5 + /- 0.1 % vs 16.7 + /- 0.1 % , p<0.05 ) , less saccharose ( 11.5 + /- 0.1 % vs 12.2 + /- 0.2 % , p<0.001 ) , more calcium ( p<0.001 ) and more fiber ( p<0.05 ) . The games group had a better snack at 10 a.m. , a less copious lunch and less nibbling ( p<0.001 ) . CONCLUSION The children in the games group had slightly but significantly better nutritional knowledge and dietary intake compared to children in the control group . Using our micro computer nutritional teaching games at school provides an additional and modern support to conventional teaching The need for successful nutrition interventions is critical as the prevalence of childhood obesity increases . Thus , this pilot project examines the effect of a nutrition education program , Color My Pyramid , on children ’s nutrition knowledge , self-care practice s , activity levels , and nutrition status . Using a pretest – posttest , quasiexperimental design , 126 fourth- and fifth- grade students from experimental and control schools are compared . The intervention program incorporates an online component www.MyPyramid.gov , Orem ’s Self-Care Deficit Nursing Theory , and consists of six classes taught over a 3-month period . Results indicated that the program increased nutrition knowledge in the control group . Furthermore , it increased activity time from pretest to posttest and decreased systolic blood pressure for children in both groups ; however , there were no significant differences in BMI percentiles . The findings indicate that Color My Pyramid can be successfully employed in school setting s and thus support school nursing practice BACKGROUND Fruit , juice , and vegetable ( FJV ) consumption among children is low . Innovative programs are needed to enable children to increase FJV intake . Psychoeducational multimedia permits the delivery of interventions as design ed and capitalizes on known behavior change principles . DESIGN Elementary school was the unit of recruitment , assignment , and analysis . Twenty-six elementary schools were pair matched on size and percentage of free or reduced-price lunch , and r and omly assigned to treatment or control groups . Data were collected just before and just after the program . SETTING / PARTICIPANTS All fourth- grade students in participating elementary schools were invited to participate . Data were collected on 1578 students . MAIN OUTCOME Servings of fruit , 100 % juice , and vegetables consumed . INTERVENTION Squire 's Quest ! is a ten-session , psychoeducational , multimedia game delivered over 5 weeks , with each session lasting about 25 minutes . Based on social cognitive theory , educational activities attempted to increase preferences for FJV through multiple exposures and associating fun with their consumption , increase asking behaviors for FJV at home and while eating out , and increase skills in FJV preparation through making virtual recipes . MEASURES Four days of dietary intake were assessed before and after the intervention . Assessment was made by the Food Intake Recording Software System ( FIRSSt ) , which conducts a multiple pass , 24-hour dietary intake interview directly with the children . RESULTS Children participating in Squire 's Quest ! increased their FJV consumption by 1.0 servings more than the children not receiving the program . CONCLUSIONS Psychoeducational multimedia games have the potential to substantially change dietary behavior . More research is warranted In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies OBJECTIVE To determine whether an exercise intervention using an active video game ( Dance Dance Revolution [ DDR ] ) is effective in improving endothelial dysfunction ( EDF ) and other risk factors in overweight children . DESIGN Thirty-five children ( Body mass index > or = 85(th ) percentile , mean age 10.21+/-1.67 years , 17 females ) with EDF were assessed for flow-mediated dilation ( FMD ) , lipids , insulin , glucose , NO(2)+NO(3 ) , asymmetric dimethylarginine , symmetric dimethylarginine , l-arginine , height , weight , aerobic fitness , and blood pressure . In a sub sample , tumor necrosis factor alpha , interleukin-6 , C-reactive protein , and adiponectin were also assessed . Subjects were r and omly assigned to 12-weeks of aerobic exercise ( EX ) using DDR or to a non-exercising delayed-treatment control group ( DTC ) . RESULTS EX had significant improvements in FMD ( 5.56+/-5.04 % compared with 0.263+/-4.54 % , p=0.008 ) , exercise time on the grade d exercise test ( 53.59+/-91.54 compared with -12.83+/-68.10 seconds , p=0.025 ) , mean arterial pressure ( MAP ) ( -5.62+/-7.03 compared with -1.44+/-2.16 mmHg , p=0.05 ) , weight ( 0.91+/-1.53 compared with 2.43+/-1.80 kg , p=0.017 ) and peak VO(2 ) ( 2.38+/-3.91 compared with -1.23+/-3.18 mg/kg/min , p=0.005 ) compared with the DTC . Thirteen EX subjects achieved normal EDF while ten did not . These groups differed at baseline with regard to total cholesterol ( TC ) and low-density lipoprotein ( LDL ) . CONCLUSION Twelve weeks of DDR-use improved FMD , aerobic fitness , and MAP in overweight children . Improvements occurred without changes in inflammatory markers or nitric oxide production . The results document the need to explore relationships between obesity , endothelial function , inflammation , lipids , exercise intensity , and gender in a larger sample of overweight children The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials |
11,973 | 29,935,574 | Proportions of IFT‐positive patients decreased significantly with increasing age and premedication use .
Conclusions St and ard general anaesthesia regimens might not prevent connected consciousness . | Background General anaesthesia should prevent patients from experiencing surgery , defined as connected consciousness .
The isolated forearm technique ( IFT ) is the current gold st and ard for connected consciousness monitoring .
We evaluated the efficacy of different anaesthesia regimens in preventing IFT responses . | Using the isolated arm technique , the frequency of awareness was evaluated in 50 full-term patients undergoing elective Caesarean section under general anaesthesia . In 20 patients , anaesthesia was induced with thiopentone 4 mg kg-1 , and in the other 30 patients , induction was with ketamine 1.5 mg kg-1 . Following suxamethonium 1.5 mg kg-1 and tracheal intubation , anaesthesia was supplemented during the induction-delivery period in the thiopentone group with 50 % nitrous oxide and 0.5 % halothane in oxygen in 10 patients , and with 1 % halothane in 100 % oxygen in the other 10 patients . In the ketamine group , the patients underwent ventilation with 50 % nitrous oxide and 0.5 % halothane in oxygen in 10 patients , with 1 % halothane in 100 % in 10 patients , and with 100 % oxygen only in the last 10 patients . Awareness was significantly greater after induction with thiopentone ( 14/20 ) than after ketamine ( 4/30 ) . There were no significant differences in Apgar scores or umbilical vein blood-gas values in the newborns Background : Intraoperative awareness with explicit recall occurs in approximately 0.15 % of all surgical cases . Efficacy trials based on the Bispectral Index ® ( BIS ) monitor ( Covidien , Boulder , CO ) and anesthetic concentrations have focused on high-risk patients , but there are no effectiveness data applicable to an unselected surgical population . Methods : We conducted a r and omized controlled trial of unselected surgical patients at three hospitals of a tertiary academic medical center . Surgical cases were r and omized to alerting algorithms based on either BIS values or anesthetic concentrations . The primary outcome was the incidence of definite intraoperative awareness ; prespecified secondary outcomes included postanesthetic recovery variables . Results : The study was terminated because of futility . At interim analysis the incidence of definite awareness was 0.12 % ( 11/9,376 ) ( 95 % CI : 0.07–0.21 % ) in the anesthetic concentration group and 0.08 % ( 8/9,460 ) ( 95 % CI : 0.04–0.16 % ) in the BIS group ( P = 0.48 ) . There was no significant difference between the two groups in terms of meeting criteria for recovery room discharge or incidence of nausea and vomiting . By post hoc secondary analysis , the BIS protocol was associated with a 4.7-fold reduction in definite or possible awareness events compared with a cohort receiving no intervention ( P = 0.001 ; 95 % CI : 1.7–13.1 ) . Conclusion : This negative trial could not detect a difference in the incidence of definite awareness or recovery variables between monitoring protocol s based on either BIS values or anesthetic concentration . By post hoc analysis , a protocol based on BIS monitoring reduced the incidence of definite or possible intraoperative awareness compared with routine care We examined the feasibility of administering nearly 100 % oxygen throughout the induction-delivery period of general anaesthesia for 113 Caesarean sections . Isoflurane 1.25 % was compared with 1.5 % enflurane for maintenance of anaesthesia . The level of anaesthesia was monitored by use of the isolated forearm technique . There was a greater amount of isolated forearm movement when enflurane was used . The three main criteria for a satisfactory general anaesthetic technique for Caesarean section were fulfilled , namely no maternal awareness , no undue depression of the fetus and no adverse effect on uterine contractility . Isoflurane and enflurane appear to be suitable anaesthetic agents for facilitating hyperoxygenation during Caesarean section 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 Patients who are given general anaesthesia are not guaranteed to remain unconscious during surgery . Knowledge about the effectiveness of current protective measures is scarce , as is our underst and ing of patients ' responses to this complication . We did a prospect i ve case study to assess conscious awareness during anaesthesia . METHODS 11785 patients who had undergone general anaesthesia were interviewed for awareness on three occasions : before they left the post-anaesthesia care unit , and 1 - 3 days and 7 - 14 days after the operation . FINDINGS We identified 18 cases of awareness and one case of inadvertent muscle blockade that had occurred before unconsciousness . Incidence of awareness was 0.18 % in cases in which neuromuscular blocking drugs were used , and 0.10 % in the absence of such drugs . 17 cases of awareness were identified at the final interview , but no more than 11 would have been detected if an interview had been done only when the patients left the post-anaesthesia care unit . Four non-paralysed patients recalled intraoperative events , but none had anxiety during wakefulness or had delayed neurotic symptoms . This finding contrasts with anaesthesia with muscle relaxants , during which 11 of 14 patients had pain , anxiety , or delayed neurotic symptoms . After repeated discussion and information , the delayed neurotic symptoms resolved within 3 weeks in all patients . Analysis of individual cases suggests that a reduced incidence of recall of intraoperative events would not be achieved by monitoring of end-tidal anaesthetic gas concentration or by more frequent use of benzodiazepines . INTERPRETATION The inability to prevent awareness by conventional measures may advocate monitoring of cerebral activity by neurophysiological techniques . However , the sensitivity of such techniques is not known , and in the light of our findings , at least 861 patients would need to be monitored to avoid one patient from suffering due to awareness during relaxant anaesthesia Failure of general anesthesia to render a patient insensate , termed " awareness , " is estimated to affect between 40,000 and 140,000 patients in the US each year . This study investigated the occurrence of post-traumatic stress disorder ( PTSD ) in subjects who reported a past episode of intraoperative awareness . We inquired about intraoperative and postoperative experiences and studied the relationship between various surgical experiences and currently meeting the diagnosis of PTSD . Sixteen postawareness subjects and 10 postgeneral anesthesia controls completed the Clinician Administered PTSD Scale ( CAPS ) , a st and ardized clinical rating scale for PTSD , and a question naire about peri-operative experiences . Nine of 16 subjects ( 56.3 % ) , a mean of 17.9 postoperative years , and no controls met diagnostic criteria for current PTSD ( X(2)= 8.6 , df = 1 , P<.01 ) . Common intraoperative experiences included an inability to communicate , helplessness , terror , and pain . Postawareness patients had significant postoperative distress related to feeling unable to communicate , unsafe , terrified , ab and oned and betrayed . Perioperative dissociative experiences predicted having current PTSD . Being conscious during surgery is a traumatic event that may result in developing chronic PTSD . Further studies should include prospect i ve design s of prevalence and long-term psychological , social , and overall health effects , and ways of preventing and treating awareness-induced PTSD Using the isolated forearm technique ( IFT ) , we wished to determine if patients known to be unresponsive to comm and s during general anaesthesia with nitrous oxide , halothane and neuromuscular blocking agents had any evidence of explicit or implicit recall . Two groups of women , studied in a single-blind sequential block design , heard different tapes , either a comm and and information tape ( n = 34 ) or radio static ( n = 34 ) , throughout surgery . Four women ( two radio static , two comm and ) had unequivocal evidence of explicit recall for a period near the beginning or end of the procedure , at a time when the IFT was not being used . With or without hypnosis , category generation , serial position of category exemplars and word association tests did not reveal evidence of priming . We conclude that during light general anaesthesia with nitrous oxide , halothane and atracurium , patients had neither explicit nor implicit memory for information presented during a period when they are known to be unresponsive to comm and Background : The isolated forearm technique allows assessment of consciousness of the external world ( connected consciousness ) through a verbal comm and to move the h and ( of a tourniquet-isolated arm ) during intended general anesthesia . Previous isolated forearm technique data suggest that the incidence of connected consciousness may approach 37 % after a noxious stimulus . The authors conducted an international , multicenter , pragmatic study to establish the incidence of isolated forearm technique responsiveness after intubation in routine practice . Methods : Two hundred sixty adult patients were recruited at six sites into a prospect i ve cohort study of the isolated forearm technique after intubation . Demographic , anesthetic , and intubation data , plus postoperative question naires , were collected . Univariate statistics , followed by bivariate logistic regression models for age plus variable , were conducted . Results : The incidence of isolated forearm technique responsiveness after intubation was 4.6 % ( 12/260 ) ; 5 of 12 responders reported pain through a second h and squeeze . Responders were younger than nonresponders ( 39 ± 17 vs. 51 ± 16 yr old ; P = 0.01 ) with more frequent signs of sympathetic activation ( 50 % vs. 2.4 % ; P = 0.03 ) . No participant had explicit recall of intraoperative events when question ed after surgery ( n = 253 ) . Across groups , depth of anesthesia monitoring values showed a wide range ; however , values were higher for responders before ( 54 ± 20 vs. 42 ± 14 ; P = 0.02 ) and after ( 52 ± 16 vs. 43 ± 16 ; P = 0.02 ) intubation . In patients not receiving total intravenous anesthesia , exposure to volatile anesthetics before intubation reduced the odds of responding ( odds ratio , 0.2 [ 0.1 to 0.8 ] ; P = 0.02 ) after adjustment for age . Conclusions : Intraoperative connected consciousness occurred frequently , although the rate is up to 10-times lower than anticipated . This should be considered a conservative estimate of intraoperative connected consciousness BACKGROUND Awareness during anesthesia is foremost assessed with postoperative interviews , which may underestimate its incidence . On-line monitors such as the Bispectral Index and patient response to verbal comm and are not necessarily commonly used . This study investigated response to comm and during deep sedation ( Bispectral Index 60 - 70 ) and the ability of prevailing monitoring techniques to indicate awareness and predict recall . METHODS The authors systematic ally assessed the response to comm and using the isolated forearm technique while monitoring electroencephalographic and hemodynamic variables . Fifty-six elective surgical patients were repeatedly given verbal instructions to squeeze the observer 's h and during target-controlled infusion with propofol and alfentanil . After recovery , conscious recall was assessed with a short structured interview . RESULTS Overall , 1,082 comm and s were given . No response was observed to 887 ( 82 % ) comm and s , an equivocal response was observed to 56 ( 5 % ) comm and s , and an unequivocal response was observed to 139 ( 13 % ) comm and s. Of the 37 patients ( 66 % ) with an unequivocal response to comm and ( " awareness " ) , nine ( 25 % ) reported conscious recall after recovery . Their reports provided valuable insights as to how awareness may be adequately addressed . Hemodynamic variables poorly predicted awareness , whereas parameters derived from the encephalogram , especially the Bispectral Index , were highly significant predictors ( P < 0.0001 ) . Electroencephalographic parameters did not discriminate between patients with or without conscious recall , whereas heart rate and responsiveness to comm and did . CONCLUSIONS The incidence of awareness is underestimated when conscious recall is taken as evidence . Awareness can be monitored on-line with behavioral and modern neurophysiologic measures . Providing feedback during intra-anesthetic awareness helps patients to cope with a potentially stressful situation Little is known about the effect of anesthetic management on long-term outcomes . We design ed a prospect i ve observational study of adult patients undergoing major noncardiac surgery with general anesthesia to determine if mortality in the first year after surgery is associated with demographic , preoperative clinical , surgical , or intraoperative variables . One-year mortality was 5.5 % in all patients ( n = 1064 ) and 10.3 % in patients ≥65 yr old ( n = 243 ) . Multivariate Cox Proportional Hazards modeling identified three variables as significant independent predictors of mortality : patient comorbidity ( relative risk , 16.116 ; P < 0.0001 ) , cumulative deep hypnotic time ( Bispectral Index ® < 45 ) ( relative risk = 1.244/h ; P = 0.0121 ) and intraoperative systolic hypotension ( relative risk = 1.036/min ; P = 0.0125 ) . Death during the first year after surgery is primarily associated with the natural history of preexisting conditions . However , cumulative deep hypnotic time and intraoperative hypotension were also significant , independent predictors of increased mortality . These associations suggest that intraoperative anesthetic management may affect outcomes over longer time periods than previously appreciated To assess the adequacy of the general anesthesia commonly employed for Cesarean section , we used isolated forearm technique to study 30 parturients ( physical status ASA I/II , aged 17 - 35 yr ) scheduled for nonemergent abdominal delivery . Anesthesia was induced with intravenous thiopental ( 3 mg/kg , 250 mg maximum ) and succinylcholine ( 1.5 mg/kg ) , and then proceeded with a mixture of 50 % N2O , 50 % O2 , and 0.5 % halothane at a flow of 5 L/min and end-tidal CO2 at 40 mm Hg . Paralysis was maintained with a 0.1 % succinylcholine infusion . When eyelash reflex disappeared , patients received taped instruction via headphones at 1-min intervals for 10 min . The tapes instructed patients to flex fingers if they were able to hear , to make a fist or squeeze the investigator 's h and if they felt pain , to remember six target words , and to respond with specific physical signals during later interviews . Three sets of tapes assigned at r and om were used in the study . For signs of inadequate anesthesia , other variables such as eye centering , pupil size , sweating , and lacrimation were concomitantly monitored at the time of induction , laryngoscopy/intubation , and skin incision , and then at 1-min intervals for 10 min . Brain activity was also monitored by means of computerized aperiodic analysis of electroencephalogram Lifescan ) . Patients were interviewed in the postanesthesia recovery room and again 24 h later . At the time of skin incision , 96.7 % of patients ( 29/30 ) signaled awareness by flexing fingers , 86.7 % ( 26/30 ) exhibited lacrimation , and 80 % ( 24/30 ) made a fist or squeezed the investigator 's h and , indicating pain perception . ( ABSTRACT TRUNCATED AT 250 WORDS The bispectral ( BIS ) index and 95 % spectral edge frequency ( SEF ) of the electroencephalograph ( EEG ) have been used to study the anesthetic and sedative effects of intravenously ( IV ) administered drugs . This prospect i ve study was design ed to evaluate the effectiveness of the BIS index and 95 % SEF for assessing the level of propofol-induced sedation and amnesia during regional anesthesia . Ten consenting adult patients undergoing surgery with regional anesthesia were administered propofol in increments of 10 - 20 mg IV , every 5 - 10 min until they became unresponsive to tactile stimulation ( i.e. , mild prodding or shaking ) . The BIS index and 95 % SEF were continuously recorded from a bifrontal montage ( Fp1-Cz and Fp2-Cz ) using the Aspect B500 monitor . The depth of sedation was assessed clinical ly at 5- to 10-min intervals using the observer 's assessment of alertness/sedation ( OAA/S ) scale , with 1 = no response to tactile stimulation to 5 = wide awake . Each patient was shown a picture of an animal ( cat ) prior to administration of an initial dose of propofol , 40 mg IV . Subsequently , patients were administered intermittent bolus doses of propofol , 10 - 20 mg IV , and shown different pictures upon achieving OAA/S scores of 4 , 3 , and 2 during the onset of and recovery from propofol-induced sedation . Picture recall was tested upon arrival of the patient in the postanesthesia care unit ( PACU ) . Of the two EEG variables studied , the BIS index exhibited a better correlation with the OAA/S scores during both the onset ( Spearman 's rho = 0.744 ) and recovery ( Spearman 's rho = 0.705 ) phases of propofol-induced sedation . With the increasing depth of sedation , there was a progressive decrease in the BIS index ( OAA/S score of 5 , BIS = 94.5 + /- 2.9 ; 4 , 93.3 + /- 3.3 ; 3 , 89 + /- 6.1 ; 2 , 80.1 + /- 8.7 ; 1 , 75.6 + /- 7.5 ; mean + /- SD ) . Conversely , there was a progressive increase in the BIS value during recovery from propofol sedation ( OAA/S score of 1 , BIS = 75.6 + /- 7.5 ; 2 , 82.4 + /- 10.5 ; 3 , 84.9 + /- 5.9 ; 4 , 93.8 + /- 0.8 ) . Although the changes in the 95 % SEF values were less consistent during the onset phase , this EEG variable increased from 16.4 + /- 5.0 to 19.3 + /- 5.6 as the OAA/S score increased from 1 to 4 during the recovery phase . Patient recall of the intraoperative pictures decreased with increasing depth of sedation and decreasing , BIS values ( OAA/S : BIS:% recall = 5:94.5 + /- 2.9:100 % ; 4:93.4 + /- 3:63 % ; 3:87.3 + /- 6.1:40 % ; 2:80.8 + /- 8.3:0 % ; 1:75.6 + /- 7.5:0 % ) . The BIS index appears to be a useful variable for assessing the depth of propofol-induced sedation . Increasing depth of sedation was associated with a significant decrease in intraoperative picture recall . ( Anesth Analg 1997;84:185 - 9 STUDY OBJECTIVE To measure the incidence of awareness during induction of anesthesia with etomi date and fentanyl , and to model its frequency as a function of dose of etomi date . DESIGN Prospect i ve cohort study . SETTING Anesthesia department of a university hospital . PATIENTS 30 ASA physical status I , II , and III patients undergoing elective general surgery . INTERVENTIONS Patients were assigned to one of three groups of etomi date ( 0.2 mg/kg , 0.3 mg/kg , 0.4 mg/kg ) and received fentanyl ( 2 microg/kg ) and 2 x ED(95 ) of cisatracurium ( 0.1 mg/kg ) . Neuromuscular block was monitored with a peripheral nerve stimulator . Intubation was performed after maximum T(1)-depression . To identify awareness , the isolated forearm technique ( IFT ) was used . The IFT was performed by prompting the patient every 20 seconds . Only a verified response was considered a positive IFT response . Anesthesia was maintained with isoflurane in oxygen/air and fentanyl . MEASUREMENTS AND MAIN RESULTS Maximum neuromuscular block occurred after 352 + /- 96 seconds and intubation was performed 424 + /- 86 seconds after loss of consciousness ( LOC ) . Awareness was dose dependent : 80 % of patients receiving 0.2 mg/kg etomi date , 70 % of patients receiving 0.3 mg/kg etomi date , and 20 % of patients receiving 0.4 mg/kg etomi date had a positive IFT response . Awareness occurred in one patient 3 minutes after LOC , in 65 % during laryngoscopy , and in 30 % within the following 120 seconds . One patient had explicit recall without finding awareness unpleasant . Hemodynamic parameters did not differ between patients with a positive or a negative IFT response . CONCLUSIONS The incidence of awareness during bolus induction can be modeled as dose dependent . However , when combining a short-acting induction drug and a delayed-onset neuromuscular blocker , the continuous infusion of the hypnotic drug may prevent awareness during induction Bispectral analysis ( BIS ) of the electroencephalogram ( EEG ) has been shown in retrospective studies to predict whether patients will move in response to skin incision . This prospect i ve multicenter study was design ed to evaluate the real-time utility of BIS in predicting movement response to skin incision using a variety of general anesthetic techniques . Three hundred patients from seven study sites received an anesthetic regimen expected to give an approximately 50 % movement response at skin incision . EEG was continuously recorded via an Aspect B-500 monitor and BIS was calculated in real time from bilateral fronto central channels displayed on the monitor . Half of the patients were r and omized to a treatment group in which anesthetic drug doses were increased to produce a lower BIS . In the control group , BIS was recorded , but no action taken on the data displayed . A determination of movement in response to skin incision was made in the 2 min succeeding incision . Retrospective pharmacodynamic modeling was performed using STANPUMP to estimate effect-site concentrations of intravenously administered anesthetics . BIS values were significantly higher in the control group ( 66 + /- 19 ) versus the BIS-guided group , in which additional anesthesia was administered to produce a lower BIS ( 51 + /- 19 ) . The movement response rate was significantly higher in the control group at 43 % compared with 13 % in the BIS-guided group , but response rates were low at sites which used larger doses of opioids . Logistic regression analysis showed that BIS , estimated opioid effect-site concentrations , and heart rate ( in that order ) were the best predictors of movement at skin incision . This study demonstrates that dosing anesthetic drugs to lower BIS values achieves a lower probability of movement in response to surgical stimulation . BIS is a significant predictor of patient response to incision , but the utility of the BIS depends on the anesthetic technique being used . When drugs such as propofol or isoflurane are used as the primary anesthetic , changes in BIS correlate with the probability of response to skin incision . When opioid analgesics are used , the correlation to patient movement becomes much less significant , so that patients with apparently " light " EEG profiles may not move or otherwise respond to incision . Therefore , the adjunctive use of opioid analgesics confounds the use of BIS as a measure of anesthetic adequacy when movement response to skin incision is used as the primary end point . ( Anesth Analg 1997;84:891 - 99 This study examined the relationship between the EEG ( spectral edge frequency 90-SEF90 ) and the occurrence of awareness defined for the purpose of this study as responsiveness to verbal comm and s. Fifty women undergoing general anaesthesia for elective Caesarean section were examined . Responsiveness to verbal comm and s was detected every minute in the period from the induction of anaesthesia to the delivery of the newborn using the Tunstall isolated forearm technique and correlated with the SEF90 value . The patients were assigned by a r and omized code to receive either thiopentone ( 4 mg.kg-1 ) or ketamine ( 1 mg.kg-1 ) for induction of anaesthesia . Before the administration of succinylcholine a tourniquet was applied to the free arm , and inflated to 200 mmHg , to maintain motor function to one arm . The EEG recordings started five minutes before induction and were recorded throughout anaesthesia . The incidence of responsiveness to verbal comm and s was lower in the ketamine group ( 24 % ) where the average SEF90 was 12.0 + /- 3 Hz , than in the thiopentone group ( 52 % ) , where the average SEF90 was 18.09 + /- 3 Hz ( P = 0.01 ) . The results suggest that SEF values of < or = 8.6 Hz were sufficient to avoid responsiveness to verbal comm and Wakefulness during general anaesthesia was assessed by the isolated forearm technique in two groups of patients for Caesarean section . The anaesthetic was based on the use of oxygen 66 % , nitrous oxide 33 % and halothane 0.4 % during the induction delivery interval . There was a highly significant reduction in wakefulness in the Group who received nitrous oxide at 66 % for the first 3 min only . The wakefulness was amnesic in all cases BACKGROUND : When anesthesia is titrated using bispectral index ( BIS ) monitoring , patients generally receive lower doses of hypnotic drugs . Intraoperative hypotension and organ toxicity might be avoided if lower doses of anesthetics are administered , but whether this translates into a reduction in serious morbidity or mortality remains controversial . The B-Aware Trial r and omly allocated 2463 patients at high risk of awareness to BIS-guided anesthesia or routine care . We tested the hypothesis that the risks of death , myocardial infa rct ion ( MI ) , and stroke would be lower in patients allocated to BIS-guided management than in those allocated to routine care . METHODS : The medical records of all patients who had not died within 30 days of surgery were review ed . The date and cause of death and occurrence of MI or stroke were recorded . A telephone interview was then conducted with all surviving patients . The primary end point of the study was survival . RESULTS : The median follow-up time was 4.1 ( range : 0–6.5 ) years . Five hundred forty-eight patients ( 22.2 % ) had died since the index surgery , 220 patients ( 8.9 % ) had an MI , and 115 patients ( 4.7 % ) had a stroke . The risk of death in BIS patients was not significantly different than in routine care patients ( hazard ratio = 0.86 [ 95 % confidence interval { CI } : 0.72–1.01 ] ; P = 0.07 ) . However , propensity score analysis indicated that the hazard ratio for death in patients who recorded BIS values < 40 for > 5 min compared with other BIS-monitored patients was 1.41 ( 95 % CI : 1.02–1.95 ; P = 0.039 ) . In addition , the odds ratios for MI in patients who recorded BIS values < 40 for > 5 min compared with other BIS-monitored patients was 1.94 ( 95 % CI : 1.12–3.35 ; P = 0.02 ) and the odds ratio for stroke was 3.23 ( 95 % CI : 1.29–8.07 ; P = 0.01 ) . CONCLUSIONS : Monitoring with BIS and absence of BIS values < 40 for > 5 min were associated with improved survival and reduced morbidity in patients enrolled in the B-Aware Trial |
11,974 | 30,077,988 | Findings from our study should be replicated in further research with larger sample s ; however , the results indicate that mindfulness-based interventions may be an effective treatment in reducing alexithymia | QUESTION Alexithymia has been found to be modifiable through treatment , with associated clinical benefits .
Recent studies have begun to test the potential of mindfulness-based interventions to reduce alexithymia , using skills-based , group training to improve non-judgemental , present-moment awareness .
The objective of this review therefore was to conduct a systematic synthesis to assess the current state of knowledge about the effect of mindfulness-based interventions on alexithymia to inform clinical practice . | Summary Background The rising number of young people going to university has led to concerns about an increasing dem and for student mental health services . We aim ed to assess whether provision of mindfulness courses to university students would improve their resilience to stress . Methods We did this pragmatic r and omised controlled trial at the University of Cambridge , UK . Students aged 18 years or older with no severe mental illness or crisis ( self-assessed ) were r and omly assigned ( 1:1 ) , via remote survey software using computer-generated r and om numbers , to receive either an 8 week mindfulness course adapted for university students ( Mindfulness Skills for Students [ MSS ] ) plus mental health support as usual , or mental health support as usual alone . Participants and the study management team were aware of group allocation , but allocation was concealed from the research ers , outcome assessors , and study statistician . The primary outcome was self-reported psychological distress during the examination period , as measured with the Clinical Outcomes in Routine Evaluation Outcome Measure ( CORE – OM ) , with higher scores indicating more distress . The primary analysis was by intention to treat . This trial is registered with the Australia and New Zeal and Clinical Trials Registry , number ACTRN12615001160527 . Findings Between Sept 28 , 2015 , and Jan 15 , 2016 , we r and omly assigned 616 students to the MSS group ( n=309 ) or the support as usual group ( n=307 ) . 453 ( 74 % ) participants completed the CORE – OM during the examination period and 182 ( 59 % ) MSS participants completed at least half of the course . MSS reduced distress scores during the examination period compared with support as usual , with mean CORE – OM scores of 0·87 ( SD 0·50 ) in 237 MSS participants versus 1·11 ( 0·57 ) in 216 support as usual participants ( adjusted mean difference −0·14 , 95 % CI −0·22 to −0·06 ; p=0·001 ) , showing a moderate effect size ( β −0·44 , 95 % CI −0·60 to −0·29 ; p<0·0001 ) . 123 ( 57 % ) of 214 participants in the support as usual group had distress scores above an accepted clinical threshold compared with 88 ( 37 % ) of 235 participants in the MSS group . On average , six students ( 95 % CI four to ten ) needed to be offered the MSS course to prevent one from experiencing clinical levels of distress . No participants had adverse reactions related to self-harm , suicidality , or harm to others . Interpretation Our findings show that provision of mindfulness training could be an effective component of a wider student mental health strategy . Further comparative effectiveness research with inclusion of controls for non-specific effects is needed to define a range of additional , effective interventions to increase resilience to stress in university students . Funding University of Cambridge and National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East of Engl and Objective : Both Mindfulness Based Cognitive Therapy ( MBCT ) and Cognitive Therapy ( CT ) enhance self-management of prodromal symptoms associated with depressive relapse , albeit through divergent therapeutic procedures . We evaluated rates of relapse in remitted depressed patients receiving MBCT and CT . Decentering and dysfunctional attitudes were assessed as treatment-specific process markers . Method : Participants in remission from Major Depressive Disorder ( MDD ; N = 166 ) were r and omized to 8 weeks of either MBCT ( N = 82 ) or CT ( N = 84 ) and were followed for 24 months , with process markers measured every 3 months . Attendance in both treatments was high ( 6.3/8 session ) and treatment fidelity and competence were evaluated . Relapse was defined as a return of symptoms meeting the criteria for major depression on Module A of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders ( SCID ) . Results : Intention-to-treat analyses indicated no differences between MBCT and CT in either rates of relapse to MDD or time to relapse across 24 months of follow up . Both groups experienced significant increases in decentering and participants in CT reported greater reductions in dysfunctional attitudes . Within both treatments , participants who relapsed evidence d lower decentering scores than those who stayed well over the follow up . Conclusions : This is the first study to directly compare relapse prophylaxis following MBCT and CT directly . The lack of group differences in time to relapse supports the view that both interventions are equally effective and that increases in decentering achieved via either treatment are associated with greater protection . These findings lend credence to Teasdale et al. ’s ( 2002 ) contention that , even though they may be taught through dissimilar methods , CT and MBCT help participants develop similar metacognitive skills for the regulation of distressing thoughts and emotions 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 OBJECTIVES Alexithymia is common among psychiatric out patients and can complicate treatment . There has been little research into whether alexithymia can be modified by psychological intervention , and whether change in alexithymia is related to other areas of improvement . The purpose of the present study was to examine whether participation in an integrated group therapy program could effect change in alexithymia , and whether such change is related to improvement in interpersonal functioning . DESIGN AND METHODS Sixty-eight consecutively admitted psychiatric out patients to a comprehensive group therapy program were evaluated at baseline , post-therapy , and 3-month follow-up using the Toronto Alexithymia Scale 20 , the Beck Depression Inventory , and the Inventory of Interpersonal Problems-28 . Associations among variables were evaluated with correlations and among group comparisons with t test , ANOVA , chi-square tests , and logistic regression . Change in alexithymia was examined using repeated measures ANOVA , controlling for change in depressive symptoms . RESULTS Alexithymia , particularly difficulty identifying feelings , decreased significantly during the treatment period . Post-therapy levels of alexithymia were maintained during the 3 months following treatment completion . Changes in alexithymia were significantly associated with changes in interpersonal problems , both during therapy and during the follow-up period . CONCLUSIONS The results of our study suggest that a comprehensive , integrated group therapy program can affect change in alexithymia , and that such change can be maintained once therapy is completed . Also , modifying alexithymia may contribute to improvement in interpersonal functioning Background : Although there is preliminary evidence that alexithymia may influence the course of coronary heart disease ( CHD ) , there are no studies exploring attempts to modify alexithymic characteristics in cardiac patients . Method : Twenty post-myocardial infa rct ion ( MI ) patients ( 19 men and 1 woman ) were placed in a treatment group , which received weekly group psychotherapy for 4 months . Seventeen post-MI patients ( 16 men and 1 woman ) were placed in a comparison group which received two educational sessions over a period of 1 month . All subjects completed the Toronto Alexithymia Scale ( TAS ) before the start of group therapy , at the end of the 4-month period , and in follow-up assessment after 6-month , 1-year , and 2-year intervals . Results : In the psychotherapy treatment group , there was a significant reduction in the mean TAS score following group therapy , which was maintained over the 2-year follow-up period . In the educational group , there were no significant changes in mean TAS scores between the initial testing and any of the follow-up intervals . On an individual basis , a decrease to a lower level of TAS scores occurred in a higher percentage of patients in the treatment group than in the educational group . Over the 2-year follow-up period , patients with decreased alexithymia following group therapy experienced fewer cardiac events ( reinfa rct ion , sudden cardiac death , or rehospitalization for rhythm disorder or severe angina ) than patients whose alexithymia remained unchanged . Conclusions : The results indicate that group psychotherapy is able to decrease alexithymia and that for many patients this change can be maintained for at least 2 years . A reduction in the degree of alexithymia seems to influence favorably the clinical course of CHD |
11,975 | 30,620,145 | Self-management interventions are effective for patients with chronic orofacial pain .
Packages of physical and psychosocial self-regulation and education appear beneficial .
SIGNIFICANCE This systematic review provides clear evidence for effectiveness of combined biomedical and psychological interventions ( incorporating self-management approaches ) on long-term outcomes in the management of chronic orofacial ( principally TMD ) pain . | BACKGROUND Psychosocial risk factors associated with chronic orofacial pain are amenable to self-management .
However , current management involves invasive therapies which lack an evidence base and has the potential to cause iatrogenic harm .
OBJECTIVES To determine : ( a ) whether self-management is more effective than usual care in improving pain intensity and psychosocial well-being and ( b ) optimal components of self-management interventions . | Objectives : Cognitive-behavioral treatment has proven efficacy for chronic temporom and ibular disorder ( TMD ) . However , most patients receive dental treatment that may not address psychological comorbidities often present in TMD . The aim of the present study was to evaluate the efficacy of biofeedback-based cognitive-behavioral treatment ( BFB-CBT ) versus dental treatment with occlusal splint ( OS ) . Moreover , changes in nocturnal masseter muscle activity ( NMMA ) were investigated . Methods : Fifty-eight patients with chronic TMD were r and omly assigned to receive either 8 weekly sessions of BFB-CBT or 8 weeks of OS treatment . Diagnoses were established using Research Diagnostic Criteria for TMD . Pain intensity and disability were defined as primary outcomes . Secondary outcomes included emotional functioning , pain coping , somatoform symptoms , treatment satisfaction , and adverse events . NMMA was assessed during 3 nights pretreatment and posttreatment with portable devices . Follow-up assessment took place 6 months after the treatment . Results : Both treatments result ed in significant reductions in pain intensity and disability , with similar amounts of clinical ly meaningful improvement ( 45 % for BFB-CBT and 48 % for OS ) . Patients receiving BFB-CBT showed significantly larger improvements in pain coping skills . Satisfaction with treatment and ratings of improvement were higher for BFB-CBT . Effects were stable over 6 months , and tended to be larger in the BFB-CBT group for all outcomes . No significant changes were observed in NMMA . Discussion : The fact that BFB-CBT result ed in larger improvements in pain coping skills , and was well accepted by the patients , underlines the importance and feasibility of psychological treatments in the clinical management of TMD Psychological characteristics potentially may be a cause or consequence of temporom and ibular disorder ( TMD ) . We hypothesized that psychological characteristics associated with pain sensitivity would influence risk of first-onset TMD , but the effect could be attributed to variation in the gene encoding catechol-O-methyltransferase ( COMT ) . We undertook a prospect i ve cohort study of healthy female volunteers aged 18–34 yrs . At baseline , participants were genotyped , they completed psychological question naires , and underwent quantitative sensory testing to determine pain sensitivity . We followed 171 participants for up to three years , and 8.8 % of them were diagnosed with first-onset TMD . Depression , perceived stress , and mood were associated with pain sensitivity and were predictive of 2- to 3-fold increases in risk of TMD ( P < 0.05 ) . However , the magnitude of increased TMD risk due to psychological factors remained unchanged after adjustment for the COMT haplotype . Psychological factors linked to pain sensitivity influenced TMD risk independently of the effects of the COMT haplotype on TMD risk Abstract Although cognitive – behavioral therapies ( CBT ) have been demonstrated to be effective for a variety of chronic pain problems , patients vary in their response and little is known about patient characteristics that predict or moderate treatment effects . Furthermore , although cognitive – behavioral theory posits that changes in patient beliefs and coping mediate the effects of CBT on patient outcomes , little research has systematic ally tested this . Therefore , we examined mediators , moderators , and predictors of treatment effects in a r and omized controlled trial of CBT for chronic temporom and ibular disorder ( TMD ) pain . Pre‐ to post‐treatment changes in pain beliefs ( control over pain , disability , and pain signals harm ) , catastrophizing , and self‐efficacy for managing pain mediated the effects of CBT on pain , activity interference , and jaw use limitations at one year . In individual mediator analyses , change in perceived pain control was the mediator that explained the greatest proportion of the total treatment effect on each outcome . Analyzing the mediators as a group , self‐efficacy had unique mediating effects beyond those of control and the other mediators . Patients who reported more pain sites , depressive symptoms , non‐specific physical problems , rumination , catastrophizing , and stress before treatment had higher activity interference at one year . The effects of CBT generally did not vary according to patient baseline characteristics , suggesting that all patients potentially may be helped by this therapy . The results provide further support for cognitive – behavioral models of chronic pain and point to the potential benefits of interventions to modify specific pain‐related beliefs in CBT and in other health care encounters ABSTRACT The purpose of this study was to determine whether cognitive – behavioral treatment ( CBT ) operates by effecting changes in cognitions , affects , and coping behaviors in the context of painful episodes . Patients were 54 men and women with temporom and ibular dysfunction‐related orofacial pain ( TMD ) enrolled in a study of brief ( 6 weeks ) st and ard conservative treatment ( STD ) or st and ard treatment plus CBT ( STD + CBT ) . Momentary affects , pain , and coping processes were recorded on a cell phone keypad four times per day for 7 days prior to treatment , and for 14 days after treatment had finished , in an experience sampling paradigm . Analyses indicated no treatment effects on general retrospective measures of pain , depression , or pain‐related interference with lifestyle at post‐treatment . However , mixed model analyses on momentary pain and coping recorded pre‐ and post‐treatment indicated that STD + CBT patients reported greater decreases in pain than did STD patients , significantly greater increases in the use of active cognitive and behavioral coping , and significantly decreased catastrophization . Analyses of experience sampling data indicated that post‐treatment momentary pain was negatively predicted by concurrent active coping , self‐efficacy , perceived control over pain , and positive‐high arousal affect . Concurrent catastrophization was strongly predictive of pain . Active behavioral coping and self‐efficacy reported at the prior time point ( about 3 h previously ) were also protective , while prior catastrophization and negative‐high arousal mood were predictive of momentary pain . The results suggest that CB treatment for TMD pain can help patients alter their coping behaviors , and that these changes translate into improved outcomes To assess the differential efficacy of two commonly used treatments for temporom and ibular disorders ( TMD ) , intraoral appliances ( IAs ) and biofeedback ( BF ) , separately and in combination , two studies were conducted . The first study directly compared IA treatment , a combination of biofeedback and stress management ( BF/SM ) , and a waiting list control group in a sample of 80 TMD patients . Both treatments were determined to be equally credible to patients , ruling out this potential threat to the validity of the results obtained . The results demonstrated that the IA treatment was more effective than the BF/SM treatment in reducing pain after treatment , but at a 6-month follow-up the IA group significantly relapsed , especially in depression , whereas the BF/SM maintained improvements on both pain and depression and continued to improve . The second study examined the combination of IA and BF/SM in a sample of 30 TMD patients . The results of this study demonstrated that the combined treatment approach was more effective than either of the single treatments alone , particularly in pain reduction , at the 6-month follow-up . These results support the importance of using both dental and psychologic treatments to successfully treat TMD patients if treatment gains are to be maintained AIMS To conduct a pilot trial to test the feasibility of a guided self-help intervention for chronic orofacial pain . METHODS A pilot r and omized controlled trial was conducted to compare the intervention with usual treatment . A total of 37 patients with chronic orofacial pain were r and omized into either the intervention group ( n = 19 ) or the usual treatment ( control ) group ( n = 18 ) . Vali date d outcome measures were used to measure the potential effectiveness of the intervention over a number of domains : physical and mental functioning ( Short Form 36 [ SF-36 ] ) ; anxiety and depression ( Hospital Anxiety and Depression Scale [ HADS ] ) ; pain intensity and interference with life ( Brief Pain Inventory [ BPI ] ) ; disability ( Manchester Orofacial Pain Disability Scale [ MOPDS ] ) ; and illness behavior ( Revised Illness Perceptions Question naire [ IPQr ] ) . Bootstrap confidence intervals were computed for the treatment effect ( ES ) posttreatment and at 3 months follow-up and adjusted for baseline values of the outcome measure by using analysis of covariance . RESULTS At posttreatment and the 3-month follow-up , 11 participants in the intervention group and 7 in the control group failed to complete outcome measures . The intervention was acceptable and could be feasibly delivered face to face or over the telephone . Although the pilot trial was not powered to draw conclusions about the effectiveness , it showed significant ( P < .05 ) effects of the intervention on physical and mental functioning and treatment control . CONCLUSION The self-help intervention was acceptable to patients and allowed them to better underst and and self-manage chronic orofacial pain . It showed potential effectiveness on outcome domains related to functioning and illness perception . Further research is needed to underst and the cost effectiveness of the intervention for chronic orofacial pain There are few robust , evidence -based data about what constitutes the diagnosis of atypical facial pain and how it is best treated . We therefore aim ed to find out the current opinion of those on specialist lists in the United Kingdom ( UK ) on whether they use the term atypical facial pain , how they reach their diagnosis , and what treatment they offer . We sent out question naires to 240 specialists r and omly selected from the UK lists of those most likely to deal with atypical facial pain ( oral and maxillofacial surgeons , oral medical specialists , ear nose and throat surgeons , anaesthetists , psychiatrists and neurologists ) . We divided the replies according to whether the specialists were medically or dentally based . Of the 209 valid question naires , 143 were returned ( a response rate of 68 % ) ; 127 of the 143 used the term atypical facial pain , the others used various other terms . The two groups used significantly different criteria , mainly to exclude other conditions to achieve a diagnosis . About half used haematological tests and most used radiographic investigations routinely , and there were no significant differences among the specialities . No unified pattern of referral between different units was found . Treatment was mainly by antidepressant and anticonvulsant drugs , and counselling OBJECTIVES ( i ) To examine the association between self-reported mechanical factors and chronic oro-facial pain . ( ii ) To test the hypothesis that this relationship could be explained by : ( a ) reporting of psychological factors , ( b ) common association of self-reported mechanical factors with other unexplained syndromes . METHODS A population based cross-sectional study of 4200 r and omly selected adults registered with a General Medical Practice in North West , Engl and . The study examined the association of chronic oro-facial pain with a variety of self-reported mechanical factors : teeth grinding , facial trauma , missing teeth and the feeling that the teeth did not fit together properly . Information was also collected on demographic factors , psychological factors and the reporting of other frequently unexplained syndromes . RESULTS An adjusted response rate of 72 % was achieved . Only two mechanical factors : teeth grinding ( odds ratio ( OR ) 2.0 , 95 % CI 1.3 - 3.0 ) and facial trauma ( OR 2.0 ; 95 % CI 1.3 - 2.9 ) were independently associated with chronic oro-facial pain after adjusting for psychological factors . However , these factors were also commonly associated with the reporting of other frequently unexplained syndromes : teeth grinding ( odds ratio ( OR ) 1.8 , 95 % CI 1.5 - 2.2 ) , facial trauma ( OR 2.1 ; 95 % CI 1.7 - 2.6 ) . CONCLUSIONS Self-reported mechanical factors associated with chronic oro-facial pain are confounded , in part , by psychological factors and are equally common across other frequently unexplained syndromes . They may represent another feature of somatisation . Therefore the use of extensive invasive therapy such as occlusal adjustments and surgery to change mechanical factors may not be justified in many cases Previous research has suggested that a habit reversal treatment might be used effectively in a home-based minimal therapist contact ( MTC ) protocol to facilitate flexibility and increase treatment completion rates . Recent review s of MTC interventions have found it to be generally efficacious , cost-effective , and generalizable . While MTC has been used for certain health-related disorders ( e.g. , headache ) , almost no research has evaluated the effectiveness of a MTC protocol with a population suffering from temporom and ibular disorder ( TMD ) . The current study utilized an oral habit reversal treatment in a MTC format in an attempt to reduce attrition and increase treatment flexibility . Twenty females suffering from TMD were r and omly assigned to either a treatment ( n = 10 ) or a wait-list control ( n = 10 ) condition . Six individuals in each group used telephone contact while 4 used e-mail for weekly communication with the therapist . Results demonstrated that a habit reversal treatment in a MTC format led to statistically and clinical ly significant improvements in mean weekly pain ratings , number of pain-free days per week , and highest weekly pain ratings . Also , a significant reduction in maladaptive oral habits occurred from pre- to post-treatment and significant reductions in life stress and pain interference were observed . Results were maintained at follow-up . The implication s for the use of MTC for treatment of facial pain are discussed , as are the implication s of these findings for the role of oral habits in the etiology of TMD & NA ; Temporom and ibular disorders ( TMD ) are currently viewed as an interrelated set of clinical conditions presenting with signs and symptoms in masticatory and related muscles of the head and neck , and the soft tissue and bony components of the temporom and ibular joint . Epidemiologie and clinical studies of TMD confirm its status as a chronic pain problem . In this report we present results from a r and omized clinical trial which compared , at 3‐ and 12‐month follow‐ups , the effects of usual TMD treatment on TMD pain and related physical and psychological variables with the effects of a cognitive‐behavioral ( CB ) intervention delivered to small groups of patients before usual TMD treatment began . The purpose of this study was to determine whether a minimal CB intervention followed by dental TMD treatment enhanced the effects of usual clinical dental treatment . A second purpose of the study was to determine whether patients classified as high in somatization and psychosocial dysfunction would respond less favorably to this minimal intervention than would those low in somatization and dysfunction . Patients who participated in the CB intervention followed by usual treatment showed greater long‐term decreases in reported pain level and pain interference in daily activities than did patients who received only usual treatment . The benefits of CB intervention were not seen when the CB and UT groups were compared at 3‐month follow‐up . During the 3–12‐month follow‐up interval , however , the UT group maintained essentially the same level of improvement in characteristic pain while the CB group continued to improve , as hypothesized . During this same follow‐up interval , the CB group also showed a strong trend toward continued improvement in pain interference . Such effects were not observed for depression , somatization , or clinical measures of jaw range of motion . Additionally , as hypothesized , dysfunctional chronic pain patients did not appear to benefit from the brief CB intervention . Intent to treat analyses were also performed to assess generalizability of the results Objective : This study examined the applicability of the cognitive-behavioral model for temporom and ibular disorders ( TMD ) by determining whether changes in TMD patient pain-related beliefs and coping over the course of treatment related to improvement in symptoms and disability and whether patients ' posttreatment beliefs and coping predicted future pain and functioning . Patients / Setting : We studied 139 TMD patients at a health maintenance organization or a university dental school who completed a clinical trial comparing usual treatment with or without a brief cognitive-behavioral intervention . Outcome Measures / Design : Pain , disability , depression , objective physical impairment , and pain beliefs and coping strategies were assessed pretreatment and at 3− and 12-month follow-ups . Results : Increased ability to control pain and decreased Disease Conviction and Passive Coping scores were associated with improved pain , jaw opening , and depression from pretreatment to 3-month follow-up . Patient beliefs and coping at 3-month follow-up did not contribute much to the prediction of pain or physical and psychological functioning at 12-month follow-up after controlling for 3-month pain and functioning scores . However , passive coping and low ability to control pain at 3 months predicted greater activity interference at 12 months . Conclusions : Pretreatment to 3-month follow-up changes in beliefs and coping are associated modestly with TMD patient improvement after conservative dental treatment with and without a brief cognitive-behavioral intervention . Research is needed to develop interventions that produce greater decreases in disease conviction , passive coping , and perceived inability to control pain and to determine whether these changes mediate symptom and disability improvement Summary Background Back pain remains a challenge for primary care internationally . One model that has not been tested is stratification of the management according to the patient 's prognosis ( low , medium , or high risk ) . We compared the clinical effectiveness and cost-effectiveness of stratified primary care ( intervention ) with non-stratified current best practice ( control ) . Methods 1573 adults ( aged ≥18 years ) with back pain ( with or without radiculopathy ) consultations at ten general practice s in Engl and responded to invitations to attend an assessment clinic . Eligible participants were r and omly assigned by use of computer-generated stratified blocks with a 2:1 ratio to intervention or control group . Primary outcome was the effect of treatment on the Rol and Morris Disability Question naire ( RMDQ ) score at 12 months . In the economic evaluation , we focused on estimating incremental quality -adjusted life years ( QALYs ) and health-care costs related to back pain . Analysis was by intention to treat . This study is registered , number IS RCT N37113406 . Findings 851 patients were assigned to the intervention ( n=568 ) and control groups ( n=283 ) . Overall , adjusted mean changes in RMDQ scores were significantly higher in the intervention group than in the control group at 4 months ( 4·7 [ SD 5·9 ] vs 3·0 [ 5·9 ] , between-group difference 1·81 [ 95 % CI 1·06–2·57 ] ) and at 12 months ( 4·3 [ 6·4 ] vs 3·3 [ 6·2 ] , 1·06 [ 0·25–1·86 ] ) , equating to effect sizes of 0·32 ( 0·19–0·45 ) and 0·19 ( 0·04–0·33 ) , respectively . At 12 months , stratified care was associated with a mean increase in generic health benefit ( 0·039 additional QALYs ) and cost savings ( £ 240·01 vs £ 274·40 ) compared with the control group . Interpretation The results show that a stratified approach , by use of prognostic screening with matched pathways , will have important implication s for the future management of back pain in primary care . Funding Arthritis Research UK A new r and omised controlled trial of intervention in low back pain has been described recently . In this trial , a screening and targeted approach was found to be more effective and cost-effective than current best practice . Nested within the intervention arm were three different interventions targeting patients identified as ' low ' , ' medium ' or ' high ' risk dependent on the presence of ( mainly ) psychosocial risk factors . In this paper , the development and content of the STarT Back trial 's ' high-risk ' intervention is described . It offers a systematic approach , termed ' psychologically informed practice ' , to the integration of physical and psychological approaches to treatment for the management of people with low back pain by physiotherapists . The term ' disability ' is used to refer to self-reported pain-associated functional limitations , and ' psychological ' is used to refer to the beliefs/expectations , emotional responses and behavioural responses associated with low back pain This study evaluated the relative long-term efficacy of biofeedback , cognitive – behavioral skills training ( CBST ) , combined biofeedback and CBST ( Combined ) , and no-treatment comparison groups in 108 patients suffering from chronic temporom and ibular disorder ( TMD ) . After an initial evaluation , patients were assigned to one of the four treatment conditions . The three biobehavioral treatment interventions consisted of 12 st and ardized sessions . Patients were reevaluated 1 year after completing treatment . Results demonstrated that patients who received the biobehavioral treatments reported significant improvement in subjective pain , pain-related disability , and m and ibular functioning 1 year after receiving treatment . The no-treatment comparison group did not demonstrate such improvements . The combined biofeedback and CBST treatment produced the most comprehensive improvements across all outcome measures . These results again demonstrate the heuristic value of adopting a biopsychosocial perspective to the assessment and treatment of chronic medical/dental disorders such as TMD AIMS To test the usefulness of tailoring cognitive-behavioral therapy ( CBT ) for patients with temporom and ibular disorders ( TMD ) who demonstrated poor psychosocial adaptation to their TMD condition , independent of physical diagnosis . METHODS A r and omized clinical trial compared a 6-session CBT intervention delivered in conjunction with the usual TMD treatment to the usual conservative treatment by TMD specialist dentists . For study inclusion , Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) , Axis II criteria , were used to target patients with elevated levels of TMD pain-related interference with daily activities , independent of physical diagnosis ( i.e. , Axis I ) . RESULTS At the post-treatment assessment , about 4 months after the baseline evaluations , the comprehensive care group , when compared to the usual treatment group , showed significantly lower levels of characteristic pain intensity , significantly higher self-reported ability to control their TMD pain , and a strong trend ( P = .07 ) toward lower pain-related interference in daily activities . From post-intervention to 1-year follow-up , all subjects showed improvement . At the 1-year follow-up , the comprehensive care group , while not losing any of its early gains , was not significantly different from the usual care group with regard to reported levels of pain , ability to control pain , and levels of interference in activities . For many of these psychosocially disabled TMD patients , pain and interference 1 year after treatment remained at the same or higher levels than those observed at baseline among a group of patients selected for a separate r and omized clinical trial on the basis of better psychosocial adaptation . CONCLUSION The 6-session CBT intervention for patients with heightened psychologic and psychosocial disability was effective in improving pain-related variables over the course of the CBT in conjunction with usual treatment , but was too brief an intervention to result in further improvement after the sessions ended . Patient ratings of treatment satisfaction and helfulness were high for both groups , but they were significantly higher for the comprehensive care group Objective To determine the effectiveness of an intervention to enhance self management support for patients with chronic conditions in UK primary care . Design Pragmatic , two arm , cluster r and omised controlled trial . Setting General practice s , serving a population in northwest Engl and with high levels of deprivation . Participants 5599 patients with a diagnosis of diabetes ( n=2546 ) , chronic obstructive pulmonary disease ( n=1634 ) , and irritable bowel syndrome ( n=1419 ) from 43 practice s ( 19 intervention and 22 control practice s ) . Intervention Practice level training in a whole systems approach to self management support . Practice s were trained to use a range of re sources : a tool to assess the support needs of patients , guidebooks on self management , and a web based directory of local self management re sources . Training facilitators were employed by the health management organisation . Main outcome measures Primary outcomes were shared decision making , self efficacy , and generic health related quality of life measured at 12 months . Secondary outcomes were general health , social or role limitations , energy and vitality , psychological wellbeing , self care activity , and enablement . Results We r and omised 44 practice s and recruited 5599 patients , representing 43 % of the eligible population on the practice lists . 4533 patients ( 81.0 % ) completed the six month follow-up and 4076 ( 72.8 % ) the 12 month follow-up . No statistically significant differences were found between patients attending trained practice s and those attending control practice s on any of the primary or secondary outcomes . All effect size estimates were well below the prespecified threshold of clinical ly important difference . Conclusions An intervention to enhance self management support in routine primary care did not add noticeable value to existing care for long term conditions . The active components required for effective self management support need to be better understood , both within primary care and in patients ’ everyday lives . Trial registration Current Controlled Trials IS RCT N90940049 & NA ; The purpose of this study was to determine whether a brief ( 6–8 sessions ) cognitive‐behavioral treatment for temporom and ibular dysfunction‐related pain could be efficacious in reducing pain , pain‐related interference with lifestyle and depressive symptoms . The patients were 101 men and women with pain in the area of the temporom and ibular joint of at least 3 months duration , r and omly assigned to either st and ard treatment ( STD ; n = 49 ) or st and ard treatment + cognitive‐behavioral skills training ( STD + CBT ; n = 52 ) . Patients were assessed at posttreatment ( 6 weeks ) , 12 weeks , 24 weeks , 36 weeks , and 52 weeks . Linear mixed model analyses of reported pain indicated that both treatments yielded significant decreases in pain , with the STD + CBT condition result ing in steeper decreases in pain over time compared to the STD condition . Somatization , self‐efficacy and readiness for treatment emerged as significant moderators of outcome , such that those low in somatization , or higher in self‐efficacy or readiness , and treated with STD + CBT reported of lower pain over time . Somatization was also a significant moderator of treatment effects on pain‐related interference with functioning , with those low on somatization reporting of less pain interference over time when treated in the STD + CBT condition . It was concluded that brief treatments can yield significant reductions in pain , life interference and depressive symptoms in TMD sufferers , and that the addition of cognitive‐behavioral coping skills will add to efficacy , especially for those low in somatization , or high in readiness or self‐efficacy AIMS To carry out a r and omized clinical trial ( RCT ) contrasting usual conservative treatment of TMD by clinical TMD specialists with a structured self-care intervention , targeted to clinic cases independent of TMD physical diagnosis , who were reporting minimal levels of psychosocial dysfunction ; the intervention was delivered by dental hygienists in lieu of usual treatment . METHODS The Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) was used to target subjects who exhibited minimal TMD-related psychosocial interference . Criteria for study inclusion were : ( 1 ) self-report of facial and /or masticatory muscle pain discomfort for which usual care was prescribed by the clinic TMD specialist ; ( 2 ) RDC/TMD Axis II grade d scale of chronic pain ( GCP ) score of 0 , I , or II-Low . ( 3 ) Age 18 to 70 years . RESULTS On 1-year follow-up , while both groups showed improvement in all clinical and self-report categories measured , patients in the tailored self-care treatment program compared to usual TMD treatment showed significantly ; ( a ) decreased TMD pain , ( b ) decreased pain-related interference in activity ; ( c ) reduced number of masticatory muscles painful ; ( d ) fewer additional visits for TMD treatment . Groups were comparable with regard to measures of vertical range of motion . The self-care program was associated with consistent , but non-statistically significant , trends towards lower levels of depression and somatization . Ability to cope with TMD , knowledge concerning TMD and patient satisfaction was significantly enhanced for the self-care group . No participating patients experienced physical or personal adverse effects during the 1-year post-treatment follow-up period . CONCLUSION Use of RDC/TMD psychosocial assessment criteria can contribute to successful clinical decision-making for the management of TMD AIMS To evaluate the long-term effectiveness of a brief skills training program for the management of chronic facial muscle pain . This program of physical self-regulation ( PSR ) involved primarily training in breathing , postural relaxation , and proprioceptive re-education . METHODS Physical self-regulation training was presented by a dentist during two 50-minute sessions spaced at 3-week intervals and was compared to a st and ard dental care ( SDC ) program that included a flat-plane intraoral appliance and self-care instructions provided by a dentist . Participants ( n = 44 ) were initially evaluated by a dentist experienced in the diagnosis and management of orofacial pain and were determined to have myofascial pain ( Type 1a and 1b diagnoses per the Research Diagnostic Criteria ) prior to r and om assignment to either the PSR or SDC conditions . Posttreatment evaluations 6 weeks and 26 weeks after treatment had begun were conducted by a dentist who was not aware of which treatment the participants received . RESULTS Initial results indicated that pain severity and life interference from pain were reduced in both groups ( P < 0.001 ) , while perception of control was increased ( P < 0.001 ) , as was incisal opening without pain ( P < 0.05 ) . At the 26-week follow-up , the PSR group reported less pain ( P < 0.04 ) and greater incisal opening , both with ( P < 0.04 ) and without ( P < 0.01 ) pain , than the SDC group . There were also significant decreases ( P < 0.05 ) in affective distress , somatization , obsessive-compulsive symptoms , tender point sensitivity , awareness of tooth contact , and sleep dysfunction for both groups over time . CONCLUSION The findings support the use of PSR for the short- and long-term management of muscle pain in the facial region . These results are discussed in terms of the potential mechanisms by which self-regulation treatment strategies are effective for the management of these pain disorders BACKGROUND The authors conducted a r and omized clinical trial to evaluate the efficacy of a biopsychosocial intervention for patients who were at high risk ( HR ) of progressing from acute to chronic temporom and ibular disorder (TMD)-related pain . METHODS The authors classified subjects ' risk using a predictive algorithm and r and omized them into an early-intervention ( EI ) or a nonintervention ( NI ) group . The EI included cognitive behavioral skills training and biofeedback . The authors assessed pain and psychosocial measures at intake and at a one-year follow-up . Subjects ' self-reported pain levels were measured on an analog scale and as a response to palpation . RESULTS At one year , EI-group subjects had significantly lower levels of self-reported pain and depression . At one year , more NI-group subjects than EI-group subjects had utilized health care for jaw-related pain . NI-group subjects were 12.5 times as likely to have a somatoform disorder , more than seven times as likely to have an anxiety disorder , and 2.7 times more likely to have an affective disorder at one year , compared with EI-group subjects . CONCLUSIONS EI-group subjects had reduced pain levels , improved coping abilities and reduced emotional distress at one year . CLINICAL IMPLICATION S The TMD-related pain experience is complex and requires early identification with a biopsychosocial EI to achieve maximal , sustainable results STUDY OBJECTIVE To determine the prevalence of oro-facial pain ( OFP ) in the population and within- population subgroups and to describe the associated disability . DESIGN Cross-sectional population study . SETTING General medical practice in South East Cheshire , United Kingdom . PARTICIPANTS A r and om sample of 4000 adults aged 18 - 65 years of whom 2504 responded ( adjusted participation rate 74 % ) . MAIN RESULTS The overall prevalence of OFP was 26 % ( 95 % Confidence Interval ( CI ) 24 % , 28 % ) . The prevalence of symptoms was higher in women ( 30 % ) than in men ( 21 % ) and in both sexes the highest ( 30 % ) prevalence was found in the 18 - 25 year age group and the lowest ( 22 % ) in the 56 - 65 age group . Of all the participants , 12 % had pain in or around the eyes , 10 % reported pain in and around the temples , 6 % pain in front of the ears and 6 % pain in the jaw joints . Only 46 % of the participants with OFP had sought professional advice from a dentist or general medical practitioner and 17 % had to take time off work or were unable to carry out normal activities because of pain . CONCLUSIONS OFP is a common symptom experienced by a quarter of the adult population , of whom only 46 % seek treatment . The prevalence is higher in women and younger age groups Forty-eight dysfunctional patients ( i.e. , high levels of pain , interference , and affective distress and low levels of perceived control ) with temporom and ibular disorders ( TMDs ) were r and omly assigned either to a treatment consisting of an intraoral appliance ( IA ) and stress management with biofeedback ( SM ) plus nondirective , supportive counseling ( SC ) -- IA + SM + SC -- or to a customized treatment that included cognitive therapy ( CT ) with the IA and SM -- IA + SM + CT . Both treatment groups reported statistically significant reductions on a set of physical , psychosocial , and behavioral measures posttreatment and at a 6-month follow-up . However , the intervention that included CT demonstrated significantly greater reductions in pain , depression , and medication use . Only the groups receiving the treatment that included the CT demonstrated continued improvements to the follow-up on pain associated with muscle palpation , self-reported pain severity , depression , and use of medications . These results support the efficacy of the tailored treatment for dysfunctional TMD This research compares different treatment regimes for the management of chronic facial pain associated with the masticatory musculature . Twenty-one females meeting specific criteria were r and omly assigned to one of three treatment conditions : a dental splint and physiotherapy program ; a relaxation program utilizing progressive muscle relaxation , biofeedback , and stress management techniques ; or a minimal treatment program involving transcutaneous electrical nerve stimulation . Improvement was assessed through a dental examination , self-monitoring of pain , and an assessment of EMG activity during resting and task conditions . Significant changes were obtained in response to all treatment programs . The treatment programs differed only in the relative pattern of treatment effects obtained from the self-report monitoring of pain . The data are consistent with the concept of MPD as a psychological response to stress which maintains chronic pain through increased muscle tension in the jaw Abstract We evaluated the short‐ and long‐term efficacy of a brief cognitive‐behavioral therapy ( CBT ) for chronic temporom and ibular disorder ( TMD ) pain in a r and omized controlled trial . TMD clinic patients were assigned r and omly to four sessions of either CBT ( n = 79 ) or an education/attention control condition ( n = 79 ) . Participants completed outcome ( pain , activity interference , jaw function , and depression ) and process ( pain beliefs , catastrophizing , and coping ) measures before r and omization , and 3 ( post‐treatment ) , 6 , and 12 months later . As compared with the control group , the CBT group showed significantly greater improvement across the follow‐ups on each outcome , belief , and catastrophizing measure ( intent‐to‐treat analyses ) . The CBT group also showed a greater increase in use of relaxation techniques to cope with pain , but not in use of other coping strategies assessed . On the primary outcome measure , activity interference , the proportion of patients who reported no interference at 12 months was nearly three times higher in the CBT group ( 35 % ) than in the control group ( 13 % ) ( P = 0.004 ) . In addition , more CBT than control group patients had clinical ly meaningful improvement in pain intensity ( 50 % versus 29 % showed ≥50 % decrease , P = 0.01 ) , masticatory jaw function ( P < 0.001 ) , and depression ( P = 0.016 ) at 12 months ( intent‐to‐treat analyses ) . The two groups improved equivalently on a measure of TMD knowledge . A brief CBT intervention improves one‐year clinical outcomes of TMD clinic patients and these effects appear to result from specific ingredients of the CBT The effect of cognitive therapy ( CT ) on resistant burning mouth syndrome ( BMS ) was studied . Thirty patients with resistant BMS after odontological and medical treatment were r and omly divided into two equal groups ; a therapy group ( TG ) was treated with CT and an attention/placebo group ( APG ) served as a control group . The intensity of BMS , which was estimated by the use of a visual analogue scale , was significantly reduced in the TG directly after CT was completed and was further reduced in a 6-month follow-up . The APG did not show any decrease in intensity of BMS . The results of this study indicate that , in some cases , resistant BMS probably is of psychological origin In this study , we applied cognitive behavioural intervention to subjects who had painful limited mouth opening , with or without posture correction in daily life . The efficacy of non-intervention control was then compared with it in order to study the effectiveness of posture correction as part of a biobehavioural therapy . The visual analogue scale ( VAS ) value of pain intensity at maximum mouth opening and disturbance in daily life sharply declined in the group which received only cognitive behavioural intervention and those who received it together with posture correction in daily life compared to the non-intervention control group although there was little difference between the intervention groups . Moreover , pain-free unassisted mouth opening was restored earlier in the group which had added posture correction . This suggests that posture correction in daily life has a positive effect in alleviating myofascial pain with limited mouth opening |
11,976 | 31,448,119 | Our meta-analyses may suggest a protective effect of voluntary medical male circumcision against HIV infection among men who have sex with men , especially in setting s like Asia/Africa | Background : With the rapidly-increased HIV epidemic among men who have sex with men worldwide , the effectiveness of voluntary medical male circumcision as the tool of HIV prevention still remains undetermined .
Purpose : In the current study , we conducted a systematic review and meta- analysis to assess the association between voluntary medical male circumcision and HIV risk among men who have sex with men . | Background : In the And ean Region , HIV and sexually transmitted infections ( STI ) are most prevalent among men who have sex with men ( MSM ) , but incidence estimates and associated factors have never been prospect ively assessed . Methods : A cohort of 1056 high-risk HIV-negative MSM in Lima , Peru , were recruited during 1998 - 2000 ( the ALASKA Cohort ) , and a nested case-control analysis was conducted between seroconverters and nonseroconverters , matched 1:3 by age and duration of follow-up for comparison of risk behaviors , acute retroviral symptoms , circumcision , and STI . Results : During average follow-up of 335 days , 34 men seroconverted , providing a HIV incidence estimate of 3.5 per 100 person-years [ 95 % confidence interval ( CI ) : 2.3 to 4.7 ] . High syphilis ( 8.4 per 100 person-years , 95 % CI : 6.7 to 10.1 ) and herpes simplex virus type 2 ( HSV-2 ) infection ( 10.4 per 100 person-years , 95 % CI : 8.6 to 11.9 ) incidence estimates were obtained . HIV seroconverters were more likely than men who remained seronegative to report fever ≥3 days ( 46 % vs. 7 % ) , to seek medical care ( 62 % vs. 27 % ) , and to have ≥1 casual partner ( 86.2 % vs. 74.1 % ) since their last visit . HIV seroconverters also were more likely to have acquired syphilis or HSV-2 infection ( 31 % vs. 8 % among initially HSV-2-seronegative men ) although they were less likely to be circumcised ( 4.2 % vs. 20.6 % , a nonsignificant difference ) . In multivariate analysis , incident syphilis or HSV-2 infection ( odds ratio [ OR ] : 5.9 , 95 % CI : 1.5 to 22.7 ) and sex with any casual partner ( OR : 4.8 , 95 % CI : 0.9 to 26.2 ) were associated with HIV seroconversion . Conclusions : STI that may cause anogenital ulcers are important risk factors for HIV acquisition among high-risk MSM in Lima , a population with a very high HIV incidence estimate . Synergistic interventions focusing in preventing both HIV and HSV-2 , like male circumcision , are warranted to be assessed , especially in MSM population s with low levels of circumcision and high incidence estimates of ulcerative STI BACKGROUND Observational data and non-human primate challenge studies suggest that cell-mediated immune responses might provide control of HIV replication . The Step Study directly assessed the efficacy of a cell-mediated immunity vaccine to protect against HIV-1 infection or change in early plasma HIV-1 levels . METHODS We undertook a double-blind , phase II , test-of-concept study at 34 sites in North America , the Caribbean , South America , and Australia . We r and omly assigned 3000 HIV-1-seronegative participants by computer-generated assignments to receive three injections of MRKAd5 HIV-1 gag/pol/nef vaccine ( n=1494 ) or placebo ( n=1506 ) . R and omisation was prestratified by sex , adenovirus type 5 ( Ad5 ) antibody titre at baseline , and study site . Primary objective was a reduction in HIV-1 acquisition rates ( tested every 6 months ) or a decrease in HIV-1 viral-load setpoint ( early plasma HIV-1 RNA measured 3 months after HIV-1 diagnosis ) . Analyses were per protocol and modified intention to treat . The study was stopped early because it unexpectedly met the prespecified futility boundaries at the first interim analysis . This study is registered with Clinical Trials.gov , number NCT00095576 . FINDINGS In a prespecified interim analysis in participants with baseline Ad5 antibody titre 200 or less , 24 ( 3 % ) of 741 vaccine recipients became HIV-1 infected versus 21 ( 3 % ) of 762 placebo recipients ( hazard ratio [ HR ] 1.2 [ 95 % CI 0.6 - 2.2 ] ) . All but one infection occurred in men . The corresponding geometric mean plasma HIV-1 RNA was comparable in infected male vaccine and placebo recipients ( 4.61 vs 4.41 log(10 ) copies per mL , one tailed p value for potential benefit 0.66 ) . The vaccine elicited interferon-gamma ELISPOT responses in 75 % ( 267 ) of the 25 % r and om sample of all vaccine recipients ( including both low and high Ad5 antibody titres ) on whose specimens this testing was done ( n=354 ) . In exploratory analyses of all study volunteers , irrespective of baseline Ad5 antibody titre , the HR of HIV-1 infection between vaccine and placebo recipients was higher in Ad5 seropositive men ( HR 2.3 [ 95 % CI 1.2 - 4.3 ] ) and uncircumcised men ( 3.8 [ 1.5 - 9.3 ] ) , but was not increased in Ad5 seronegative ( 1.0 [ 0.5 - 1.9 ] ) or circumcised ( 1.0 [ 0.6 - 1.7 ] ) men . INTERPRETATION This cell-mediated immunity vaccine did not prevent HIV-1 infection or reduce early viral level . Mechanisms for insufficient efficacy of the vaccine and the increased HIV-1 infection rates in subgroups of vaccine recipients are being explored 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 Background Black men who have sex with men ( MSM ) in the United States ( US ) are affected by HIV at disproportionate rates compared to MSM of other race/ethnicities . Current HIV incidence estimates in this group are needed to appropriately target prevention efforts . Methods From July 2009 to October 2010 , Black MSM reporting unprotected anal intercourse with a man in the past six months were enrolled and followed for one year in six US cities for a feasibility study of a multi-component intervention to reduce HIV infection . HIV incidence based on HIV seroconversion was calculated as number of events/100 person-years . Multivariate proportional hazards modeling with time-dependent covariates was used to identify correlates of HIV acquisition . Results Of 1,553 Black MSM enrolled , 1,164 were HIV-uninfected at baseline and included in follow-up . Overall annual HIV incidence was 3.0 % ( 95 % confidence interval ( CI ) : 2.0 , 4.4 % ) and 5.9 % among men ≤30 years old ( 95 % CI : 3.6 , 9.1 % ) . Men ≤30 years old reported significantly higher levels of sexual risk and were more likely to have a sexually transmitted infection diagnosed during follow-up . Younger men also were more likely to not have a usual place for health care , not have visited a health care provider recently , and to have unmet health care needs . In multivariate analysis , age ≤30 years ( hazard ratio ( HR ) : 3.4 ; 95 % CI : 1.4 , 8.3 ) and unprotected receptive anal intercourse with HIV-positive or unknown status partners ( HR : 4.1 ; 95 % CI : 1.9 , 9.1 ) were significantly associated with HIV acquisition . Conclusion In the largest cohort of prospect ively-followed Black MSM in the US , HIV incidence was high , particularly among young men . Targeted , tailored and culturally appropriate HIV prevention strategies incorporating behavioral , social and biomedical based interventions are urgently needed to lower these rates Background Observational studies suggest that male circumcision may provide protection against HIV-1 infection . A r and omized , controlled intervention trial was conducted in a general population of South Africa to test this hypothesis . Methods and Findings A total of 3,274 uncircumcised men , aged 18–24 y , were r and omized to a control or an intervention group with follow-up visits at months 3 , 12 , and 21 . Male circumcision was offered to the intervention group immediately after r and omization and to the control group at the end of the follow-up . The grouped censored data were analyzed in intention-to-treat , univariate and multivariate , analyses , using piecewise exponential , proportional hazards models . Rate ratios ( RR ) of HIV incidence were determined with 95 % CI . Protection against HIV infection was calculated as 1 − RR . The trial was stopped at the interim analysis , and the mean ( interquartile range ) follow-up was 18.1 mo ( 13.0–21.0 ) when the data were analyzed . There were 20 HIV infections ( incidence rate = 0.85 per 100 person-years ) in the intervention group and 49 ( 2.1 per 100 person-years ) in the control group , corresponding to an RR of 0.40 ( 95 % CI : 0.24%–0.68 % ; p < 0.001 ) . This RR corresponds to a protection of 60 % ( 95 % CI : 32%–76 % ) . When controlling for behavioural factors , including sexual behaviour that increased slightly in the intervention group , condom use , and health-seeking behaviour , the protection was of 61 % ( 95 % CI : 34%–77 % ) . Conclusion Male circumcision provides a degree of protection against acquiring HIV infection , equivalent to what a vaccine of high efficacy would have achieved . Male circumcision may provide an important way of reducing the spread of HIV infection in sub-Saharan Africa . ( Preliminary and partial results were presented at the International AIDS Society 2005 Conference , on 26 July 2005 , in Rio de Janeiro , Brazil . Background The Step Study found that men who had sex with men ( MSM ) who received an adenovirus type 5 ( Ad5 ) vector – based vaccine and were uncircumcised or had prior Ad5 immunity , had a higher HIV incidence than MSM who received placebo . We investigated whether differences in HIV exposure , measured by reported sexual risk behaviors , may explain the increased risk . Methods Among 1764 MSM in the trial , 726 were uncircumcised , 994 had prior Ad5 immunity , and 563 were both uncircumcised and had prior Ad5 immunity . Analyses compared sexual risk behaviors and perceived treatment assignment among vaccine and placebo recipients , determined risk factors for HIV acquisition , and examined the role of insertive anal intercourse in HIV risk among uncircumcised men . Results Few sexual risk behaviors were significantly higher in vaccine versus placebo recipients at baseline or during follow-up . Among uncircumcised men , vaccine recipients at baseline were more likely to report unprotected insertive anal intercourse with HIV-negative partners ( 24.9 % vs. 18.1 % ; P = 0.03 ) . Among uncircumcised men who had prior Ad5 immunity , vaccine recipients were more likely to report unprotected insertive anal intercourse with partners of unknown HIV status ( 46.0 % vs. 37.8 % ; P = 0.05 ) . Vaccine recipients remained at higher risk of HIV infection compared with placebo recipients ( hazard ratio = 2.8 ; 95 % confidence interval , 1.2–6.8 ) controlling for potential confounders . Conclusions These analyses do not support a behavioral explanation for the increased HIV infection rates observed among uncircumcised men in the Step Study . Identifying biologic mechanisms to explain the increased risk is a priority BACKGROUND Ecological and observational studies suggest that male circumcision reduces the risk of HIV acquisition in men . Our aim was to investigate the effect of male circumcision on HIV incidence in men . METHODS 4996 uncircumcised , HIV-negative men aged 15 - 49 years who agreed to HIV testing and counselling were enrolled in this r and omised trial in rural Rakai district , Ug and a. Men were r and omly assigned to receive immediate circumcision ( n=2474 ) or circumcision delayed for 24 months ( 2522 ) . HIV testing , physical examination , and interviews were repeated at 6 , 12 , and 24 month follow-up visits . The primary outcome was HIV incidence . Analyses were done on a modified intention-to-treat basis . This trial is registered with Clinical Trials.gov , with the number NCT00425984 . FINDINGS Baseline characteristics of the men in the intervention and control groups were much the same at enrollment . Retention rates were much the same in the two groups , with 90 - 92 % of participants retained at all time points . In the modified intention-to-treat analysis , HIV incidence over 24 months was 0.66 cases per 100 person-years in the intervention group and 1.33 cases per 100 person-years in the control group ( estimated efficacy of intervention 51 % , 95 % CI 16 - 72 ; p=0.006 ) . The as-treated efficacy was 55 % ( 95 % CI 22 - 75 ; p=0.002 ) ; efficacy from the Kaplan-Meier time-to-HIV-detection as-treated analysis was 60 % ( 30 - 77 ; p=0.003 ) . HIV incidence was lower in the intervention group than it was in the control group in all sociodemographic , behavioural , and sexually transmitted disease symptom subgroups . Moderate or severe adverse events occurred in 84 ( 3.6 % ) circumcisions ; all resolved with treatment . Behaviours were much the same in both groups during follow-up . INTERPRETATION Male circumcision reduced HIV incidence in men without behavioural disinhibition . Circumcision can be recommended for HIV prevention in men Objectives : To assess the association between male circumcision , insertive anal sex practice s , and HIV acquisition in a cohort of MSM . Methods : Data were from 1824 HSV-2-seropositive , HIV-seronegative MSM , 1362 ( 75 % ) from Peru and 462 ( 25 % ) from the US , who participated in a r and omized placebo-controlled trial of HSV-2 suppression for HIV prevention ( HPTN 039 ) . Circumcision status was determined by examination at enrollment . HIV testing was done every 3 months for up to 18 months . Partner-specific sexual behavior for up to the last three partners during the previous 3 months was analyzed . Results : There was no significant association between male circumcision and HIV acquisition in univariate analysis [ relative risk ( RR ) = 0.84 , 95 % confidence interval ( CI ) 0.50–1.42 ] . In a prespecified multivariate analysis that assumed a linear relationship between the proportion of insertive acts and effect of circumcision on HIV acquisition , the interaction between circumcision and proportion of insertive acts was not significant ( P = 0.11 ) . In an exploratory analysis that categorized behavior with recent partners by proportion of insertive acts ( < 60 or ≥60 % insertive acts ) , circumcision was associated with a nonstatistically significant 69 % reduction in the risk of HIV acquisition ( RR = 0.31 , 95 % CI 0.06–1.51 ) among men who reported at least 60 % of insertive acts with recent male partners . Conclusion : Circumcision does not have a significant protective effect against HIV acquisition among MSM from Peru and US , although there may be reduced risk for men who are primarily insertive with their male partners . This association needs to be investigated across diverse cohorts of MSM Background : The efficacy of male circumcision for HIV prevention over 2 years has been demonstrated in three r and omized trials , but the longer-term effectiveness of male circumcision is unknown . Methods : We conducted a r and omized trial of male circumcision in 4996 HIV-negative men aged 15–49 in Rakai , Ug and a. Following trial closure , we offered male circumcision to control participants and have maintained surveillance for up to 4.79 years . HIV incidence per 100 person-years was assessed in an as-treated analysis , and the effectiveness of male circumcision was estimated using Cox regression models , adjusted for sociodemographic and time-dependent sexual behaviors . For men uncircumcised at trial closure , sexual risk behaviors at the last trial and first posttrial visits were assessed by subsequent circumcision acceptance to detect behavioral risk compensation . Results : By 15 December 2010 , 78.4 % of uncircumcised trial participants accepted male circumcision following trial closure . During posttrial surveillance , overall HIV incidence was 0.50/100 person-years in circumcised men and 1.93/100 person-years in uncircumcised men { adjusted effectiveness 73 % [ 95 % confidence interval ( CI ) 55–84%]}. In control arm participants , posttrial HIV incidence was 0.54/100 person-years in circumcised and 1.71/100 person-years in uncircumcised men [ adjusted effectiveness 67 % ( 95 % CI 38–83 % ) ] . There were no significant differences in sociodemographic characteristics and sexual behaviors between controls accepting male circumcision and those remaining uncircumcised . Conclusion : High effectiveness of male circumcision for HIV prevention was maintained for almost 5 years following trial closure . There was no self- selection or evidence of behavioral risk compensation associated with posttrial male circumcision acceptance Objective : To assess circumcision status as a risk factor for HIV seroconversion in homosexual men . Design , setting and participants : The Health in Men ( HIM ) study was a prospect i ve cohort of homosexual men in Sydney , Australia . HIV-negative men ( n = 1426 ) were recruited primarily from community-based sources between 2001 and 2004 and followed to mid-2007 . Participants underwent annual HIV testing , and detailed information on sexual risk behaviour was collected every 6 months . Main outcome measure : HIV incidence in circumcised compared with uncircumcised participants , stratified by whether or not men predominantly practised the insertive role in anal intercourse . Results : There were 53 HIV seroconversions during follow-up ; an incidence of 0.78 per 100 person-years . On multivariate analysis controlling for behavioural risk factors , being circumcised was associated with a nonsignificant reduction in risk of HIV seroconversion [ hazard ratio 0.78 , 95 % confidence interval ( CI ) 0.42–1.45 , P = 0.424 ] . Among one-third of study participants who reported a preference for the insertive role in anal intercourse , being circumcised was associated with a significant reduction in HIV incidence after controlling for age and unprotected anal intercourse ( UAI ) ( hazard ratio 0.11 , 95 % CI 0.03–0.80 , P = 0.041 ) . Those who reported a preference for the insertive role overwhelmingly practised insertive rather than receptive UAI . Conclusions : Overall , circumcision did not significantly reduce the risk of HIV infection in the HIM cohort . However , it was associated with a significant reduction in HIV incidence among those participants who reported a preference for the insertive role in anal intercourse . Circumcision may have a role as an HIV prevention intervention in this subset of homosexual men Pre-exposure prophylaxis ( PrEP ) is effective in preventing HIV acquisition among men who have sex with men ( MSM ) . However , little is known about unhealthy substance use among MSM initiating PrEP in real-world setting s. Unhealthy substance use is a risk factor for HIV acquisition and non-adherence to treatment , and may also impact PrEP use . MSM who were prescribed PrEP from 2015 to 2017 at clinics in Providence , Rhode Isl and and New Haven , Connecticut were recruited to participate in a prospect i ve observational study . Structured clinical assessment s were used to assess demographics , HIV risk behaviors , and unhealthy alcohol ( alcohol use disorders identification test [AUDIT]-C scores ≥ 4 ) and drug use ( use of any drugs in the past 3 months ) . Bivariate and multivariate analyses were performed to determine demographics and behaviors associated with unhealthy alcohol and drug use . Among 172 MSM initiating PrEP , 64 % were white and 40 % were 25–34 years old . Participants reported a median of 3 ( IQR 2–7 ) sexual partners in the last 3 months ; 20 % reported an HIV positive partner . Unhealthy alcohol and any drug use were reported by 54 and 57 % , respectively , and 76 % reported at least one of the two . The majority of drug use reported was marijuana and poppers ( 41 and 26 % of participants , respectively ) . Relative to those without unhealthy alcohol use , unhealthy alcohol use was independently associated with any drug use ( adjusted odds ratio [ AOR ] = 2.57 , 95 % CI 1.32–5.01 ) . Frequent drug use was associated with younger age ( < 25 years , AOR 4.27 , 95 % CI 1.51–12.09 ) . Unhealthy alcohol use is common among MSM taking PrEP . Drug use other than marijuana and poppers was uncommon among our cohort . Further efforts may be needed to underst and the influence of unhealthy alcohol and other substance use on PrEP outcomes and to engage MSM who use drugs for PrEP |
11,977 | 31,941,489 | There was no consistent evidence of an effect on quality of life , medication adherence or knowledge .
Conclusion A systematic review of twelve RCTs assessing the impact of pharmacist home visits for individuals at risk of medication related problems found no evidence of effect on hospital admission or mortality rates , and limited evidence of effect on quality of life . | Background Medication mismanagement is a major cause of both hospital admission and nursing home placement of frail older adults .
Medication review s by community pharmacists aim to maximise therapeutic benefit but also minimise harm .
Pharmacist-led medication review s have been the focus of several systematic review s , but none have focussed on the home setting . | BACKGROUND AND OBJECTIVES CKD is characterized by remarkably high hospitalization and readmission rates . Our study aim was to test a medication therapy management intervention to reduce subsequent acute care utilization . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The CKD Medication Intervention Trial was a single-blind ( investigators ) , r and omized clinical trial conducted at Providence Health Care in Spokane , Washington . Patients with CKD stages 3 - 5 not treated by dialysis who were hospitalized for acute illness were recruited . The intervention was design ed to improve posthospitalization care by medication therapy management . A pharmacist delivered the intervention as a single home visit within 7 days of discharge . The intervention included these fundamental elements : comprehensive medication review , medication action plan , and a personal medication list . The primary outcome was a composite of acute care utilization ( hospital readmissions and emergency department and urgent care visits ) for 90 days after hospitalization . RESULTS Baseline characteristics of participants ( n=141 ) included the following : age , 69±11 ( mean±SD ) years old ; women , 48 % ( 67 of 141 ) ; diabetes , 56 % ( 79 of 141 ) ; hypertension , 83 % ( 117 of 141 ) ; eGFR , 41±14 ml/min per 1.73 m2 ( serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation ) ; and urine albumin-to-creatinine ratio median , 43 mg/g ( interquartile range , 8 - 528 ) creatinine . The most common primary diagnoses for hospitalization were the following : cardiovascular events , 36 % ( 51 of 141 ) ; infections , 18 % ( 26 of 141 ) ; and kidney diseases , 12 % ( 17 of 141 ) . The primary outcome occurred in 32 of 72 ( 44 % ) of the medication intervention group and 28 of 69 ( 41 % ) of those in usual care ( log rank P=0.72 ) . For only hospital readmission , the rate was 19 of 72 ( 26 % ) in the medication intervention group and 18 of 69 ( 26 % ) in the usual care group ( log rank P=0.95 ) . There was no between-group difference in achievement of guideline -based goals for use of renin-angiotensin system inhibition or for BP , hemoglobin , phosphorus , or parathyroid hormone . CONCLUSIONS Acute care utilization after hospitalization was not reduced by a pharmacist-led medication therapy management intervention at the transition from hospital to home Introduction Older people experience greater morbidity with a corresponding increase in medication use result ing in a potentially higher risk of adverse drug reactions ( ADRs ) . The aim of this study is to determine the prevalence and characteristics of ADR-related hospital admissions among older patients ( ≥65 years ) and their associated health and cost outcomes . Methods and analysis The proposed study will include a cross-sectional study of ADR prevalence in all patients aged ≥65 years admitted acutely to a large tertiary referral hospital in Irel and over a 9-month period ( 2016–2017 ) and a prospect i ve cohort study of patient-reported health outcomes and costs associated with ADR-related hospital admissions . All acute medical admissions will be screened for a suspected ADR-related hospital admission . A number of vali date d algorithms will be applied to assess the type , causative medications , preventability and severity of each ADR . ADRs will be determined , using a consensus method , by an expert panel . Patients who provide consent will be followed up 3 months post-discharge to establish patient-reported health outcomes ( health service use , health-related quality of life , adherence ) and costs associated with ADR-related hospital admissions . A r and om sample of patients admitted to hospital without a suspected ADR will be invited to take part in the study as a control group . Ethics and dissemination Ethical approval was obtained from Beaumont Hospital Ethics Committee . Findings will be disseminated through presentations and peer- review ed publications 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 Lack of information about medications coupled with high rates of utilization complicates compliance with medication regimens and increases the risk of adverse effects among older adults . We undertook a study of the efficacy of community-based interventions by pharmacists in a r and omly-allocated one-half of a sample of 284 older adults considered to be at high risk for medication-related problems . Information and attitudes towards prescription and over-the-counter medications did not differ significantly between the intervention and comparison groups , either before or after the pharmacist interventions . However , visits to physicians were significantly less in the intervention group , suggesting an important if unexpected impact on health-related behavior Objective To test whether a drug review and symptom self management and lifestyle advice intervention by community pharmacists could reduce hospital admissions or mortality in heart failure patients . Design R and omised controlled trial . Setting Home based intervention in heart failure patients . Participants 293 patients diagnosed with heart failure were included ( 149 intervention , 144 control ) after an emergency admission . Intervention Two home visits by one of 17 community pharmacists within two and eight weeks of discharge . Pharmacists review ed drugs and gave symptom self management and lifestyle advice . Controls received usual care . Main outcome measures The primary outcome was total hospital readmissions at six months . Secondary outcomes included mortality and quality of life ( Minnesota living with heart failure question naire and EQ-5D ) . Results Primary outcome data were available for 291 participants ( 99 % ) . 136 ( 91 % ) intervention patients received one or two visits . 134 admissions occurred in the intervention group compared with 112 in the control group ( rate ratio=1.15 , 95 % confidence interval 0.89 to 1.48 ; P=0.28 , Poisson model ) . 30 intervention patients died compared with 24 controls ( hazard ratio=1.18 , 0.69 to 2.03 ; P=0.54 ) . Although EQ-5D scores favoured the intervention group , Minnesota living with heart failure question naire scores favoured controls ; neither difference was statistically significant . Conclusion This community pharmacist intervention did not lead to reductions in hospital admissions in contrast to those found in trials of specialist nurse led interventions in heart failure . Given that heart failure accounts for 5 % of hospital admissions , these results present a problem for policy makers who are faced with a shortage of specialist provision and have hoped that skilled community pharmacists could produce the same benefits . Trial registration number IS RCT N59427925 PURPOSE The effect of pharmaceutical care services for home care patients with heart failure on death and rehospitalization rates was studied . METHODS Eligible patients had to be at least 21 years old and included those with a primary or secondary diagnosis of heart failure who were referred to receive skilled nursing services . Patients were then r and omized to receive usual care or pharmaceutical care . Patients assigned to the usual care group received the services typically provided by the visiting nurses association , while patients in the pharmaceutical care group received usual care plus st and ardized services from a clinical pharmacist . Pharmaceutical care services consisted of an initial comprehensive in home medication assessment and two follow-up visits . Throughout the three-week intervention period , the clinical pharmacist accessed and review ed all pertinent physician notes and laboratory test values and interacted with prescribers on behalf of the patients as necessary . RESULTS A total of 154 patients met all criteria and participated in the study . The pharmacist made 79 specific therapy recommendations , 47 ( 60 % ) of which were related directly to drug therapy for heart failure or cardiovascular disease . Overall , 14 therapy recommendations were fully implemented , and 10 heart failure-specific recommendations were fully implemented . Patients for whom the pharmacist had made recommendations that were followed by the prescriber had a reduced rate of the composite primary endpoint , but this difference did not reach statistical significance . CONCLUSION A home-based pharmaceutical care model for recently hospitalized patients with heart failure did not significantly improve the combined rate of death or rehospitalization OBJECTIVES A number of studies have reported that the risk of bleeding associated with warfarin is highest early in the course of therapy . This study examined the effect of a programme focused on the transition of newly anticoagulated patients from hospital to the community . DESIGN Open-label r and omized controlled trial . SETTING Home-based follow-up of patients discharged from acute care hospital in southern Tasmania , Australia . SUBJECTS A total of 128 patients initiated on warfarin in hospital and subsequently discharged to general practitioner ( GP ) care were enrolled in the study . Sixty were r and omized to home monitoring ( HM ) and 68 received usual care ( UC ) . INTERVENTIONS HM patients received a home-visit by the project pharmacist and point-of-care international normalized ratio ( INR ) testing on alternate days on 4 occasions , with the initial visit two days after discharge . The UC group was solely managed by the GP and only received a visit 8 days after discharge to determine anticoagulant control . RESULTS At discharge , 42 % of the HM group and 45 % of the UC group had a therapeutic INR . At day 8 , 67 % of the HM patients had a therapeutic INR , compared with 42 % of UC patients ( P < 0.002 ) . In addition , 26 % of UC patients had a high INR , compared with only 4 % of HM patients . Bleeding events were assessed 3 months after discharge and occurred in 15 % of HM patients , compared with 36 % of the UC group ( P < 0.01 ) . CONCLUSIONS This programme improved the initiation of warfarin therapy and result ed in a significant decrease in haemorrhagic complications in the first 3 months of therapy OBJECTIVE To assess whether home-based medication review by a pharmacist for at-risk older patients in a primary care setting can reduce hospital admissions . DESIGN R and omised controlled trial comparing home-based medication review with st and ard care . SETTING Home-based medication review of 136 patients registered with one general practice . METHOD Study participants were over 80 years of age , living at home , taking four or more medicines , and had at least one additional medicines-related risk factor . The intervention comprised two home visits by a community pharmacist who educated the patient/carer about their medicines , noted any pharmaceutical care issues , assessed need for an adherence aid , and subsequently met with the lead GP to agree on actions . MAIN OUTCOME MEASURE Total non-elective hospital admissions within 6 months . Secondary outcomes included number of deaths , care home admissions and quality of life ( EQ-5d ) . Impact on number of medicines prescribed was also assessed . RESULTS At 6 months , no difference in hospital admissions ( 21 intervention versus 20 control P = 0.80 ) , and no difference in care home admissions or deaths were detected between groups . There was a small ( non-significant ) decrease in quality of life in the intervention group . There was a statistically significant reduction in the mean number of medicines prescribed ( -0.87 items in favour of the intervention group , 95 % confidence interval -1.66 to -0.08 , P = 0.03 ) . CONCLUSIONS No positive impact on clinical outcomes or quality of life was demonstrated , however , this intervention did appear to reduce prescribing . This is in line with other evidence and suggests that this form of intervention may not have a clear health gain , but may lead to modest savings in terms of reduced prescribing . Future research should focus on whether such a prescribing effect would make this type of intervention cost effective Background Elderly polypharmacy patients may be more at risk of not adhering to medication . If so , the underlying reasons may be more readily disclosed during private discussion s with patients . Hence pharmaceutical care discussion s at home might improve treatment adherence . Objective The aim of this study was to investigate the impact of pharmaceutical care on medication adherence , hospitalisation and mortality in elderly patients prescribed polypharmacy . Setting Pharmaceutical care discussed at home . Methods A r and omised controlled trial with two arms ; pharmaceutical care ( n = 315 ) and controls ( n = 315 ) was design ed . It involved patients aged 65 + years living in Aarhus , Denmark who used five drugs or more without assistance . Pharmacists visited the pharmaceuticalcare patients at home , once only , and followed them during the subsequent year with three telephone calls . Non-adherence was measured by a pill-count . Patients were categorised as non-adherent if their mean adherence rate for all drugs consumed was < 80 % . The impact of pharmaceutical care on non-adherence and hospitalisation was analysed by 2 × 2 tables , and mortality by Cox regression . Main outcome measure Medication adherence , hospitalisation and mortality . Results The final analyses included 517 patients ( median age 74 years ; females 52 % ) . Dropouts were more frequent for the pharmaceutical-care group than for controls . Pharmacists encountered drug-related problems amongst 72 % of pharmaceutical-care patients . Pharmaceutical-care patients ( 11 % ) and control patients ( 10 % ) were similarly nonadherent ( Odds ratio 1.14 ; 95 % confidence interval 0.65–2.00 ) , and similar with respect to hospitalisation frequency ( 30 vs. 28 % ; Odds ratio 1.14 ; 95 % confidence interval 0.78–1.67 ) and mortality ( 7.5 vs. 5 % ; Hazard ratio 1.41 ; 95 % confidence interval 0.71–2.82 ) . Conclusions Pharmaceutical care given to our elderly polypharmacy patients made no significant impact on medication adherence , hospitalisation or mortality , when compared to comparable control patients BACKGROUND Medication review by pharmacists is increasingly being implemented in the primary care setting and has been incorporated into the new pharmacy contract in the UK . This study aims to determine the cost effectiveness of home-based medication review in older people . METHODS This economic evaluation was based on a r and omised controlled trial ( the HOMER [ HOME-based medication Review ] trial ) . Patients aged > 80 years ( n = 872 ) were recruited if admitted as an emergency to an acute or community hospital in Norfolk or Suffolk ( any cause ) , returning to their own home or warden-controlled accommodation , and taking two or more drugs daily on discharge . Patients r and omised to the intervention group received two home visits by a pharmacist within 2 and 8 weeks of discharge to educate patients and carers about their drugs , remove out-of- date drugs , inform GPs of drug reactions or interactions and inform the local pharmacist if an adherence aid was needed . The control arm received usual care . Economic evaluation was performed from the UK NHS perspective , with follow-up for 6 months and cost data from 2000 . Re source use data were collected from hospital episode statistics and from a sample of GP records of trial participants . Intervention , hospital , ambulance and general practice costs were considered to determine average costs and incremental cost-effectiveness ratios . Use of the EQ-5D question naire permitted outcomes to be expressed as QALYs . Probabilistic sensitivity analysis was employed to calculate cost-effectiveness acceptability curves . RESULTS Mortality and admission data were available for 829 of 855 patients included in the study ( 415 intervention and 414 control patients ) . Of those patients r and omised to the intervention group , 358 had a medication review at a total intervention cost of 51,622 pound ( or 124 pound per r and omised patient ) . The intervention did not reduce hospital admissions . The average cost per intervention group patient was 1695 pound compared with 1424 pound for control patients . The incremental cost per life year gained through the intervention was 33,541 pound . The incremental cost per QALY gained in the intervention was 54,454 pound . Sensitivity analysis suggested a 25 % probability that home-based medication review is cost effective using a threshold of 30,000 pound per QALY . CONCLUSION The current policy imperative for implementing medicines review needs to be reconsidered in the light of the findings of this study : a small , non significant gain in quality of life , no reduction in hospital admissions and a low probability of cost effectiveness OBJECTIVE To evaluate a pharmacist-conducted educational and monitoring programme , design ed to promote dietary and lifestyle modification and compliance with lipid-lowering drug therapy , for patients with dyslipidaemia . METHODS This was a prospect i ve , r and omized , controlled study . The participants were 94 adults , with 81 completing the study ( intervention group : 39 ; control group : 42 ) , with a cardiovascular-related diagnosis and discharged from hospital , between April and October 2001 , on lipid-lowering drug therapy . Patients in the intervention group were visited at home monthly by a pharmacist , who educated the patients on the goals of lipid-lowering treatment and the importance of lifestyle issues in dyslipidaemia and compliance with therapy , assessed patients for drug-related problems , and measured total blood cholesterol levels using point-of-care testing . Patients in the control group received st and ard medical care . The main outcome measure was total blood cholesterol levels after 6 months , and an evaluation of patient and general practitioner satisfaction with the programme . RESULTS There was no significant difference in baseline total blood cholesterol levels between the two groups . The reduction over the course of the study in cholesterol levels within the intervention group was statistically significant ( 4.9 + /- 0.7 to 4.4 + /- 0.6 , P<0.005 ) , whereas there was no change within the control group ( P=0.26 ) . At follow-up , 44 % of the intervention group patients and 24 % of the control group patients had cholesterol levels below 4.0 mmol/L ( P=0.06 ) . The reduction in total cholesterol in the intervention group should translate to an expected 21 % reduction in cardiovascular mortality risk and a 16 % reduction in total mortality risk -- more than twice the risk reduction achieved in the control group . In addition , the programme was very well received by the patients and their general practitioners , by satisfaction question naire . CONCLUSION A pharmacist-conducted educational and monitoring intervention improved the outcomes of lipid-lowering drug therapy OBJECTIVES To study the effect of caregiver-focused interventions to support medication safety in older adults with chronic disease . DESIGN Systematic review . SETTING Studies published before January 31 , 2017 , search ed using Ovid Medline , PubMed , EMBASE , Scopus , CINAHL , PsycINFO , and Google Scholar . PARTICIPANTS Caregivers with or without a care recipient . MEASUREMENTS Inclusion criteria : interventions focused on caregivers aim ing to improve medication safety . Studies not focusing on older adults , not evaluating medication safety , failing to include caregivers , or without a comparison group were excluded . RESULTS The initial search revealed 1,311 titles . Eight studies met inclusion criteria . The strategies used in r and omized trials were a home-based medication review and adherence assessment by a clinical pharmacist ( 2 home visits 6 - 8 weeks apart , with pharmacist and physician meeting independently ) that found no difference in nonelective hospital admissions ( p=.8 ) but fewer medications ( p=.03 ) ; a 19-minute educational DVD and an hour-long medication education and training that improved caregiver satisfaction ( p<.04 ) ; a medication education and adherence intervention ( 2 - 3 home visits per care recipient and caregiver dyad over 8 weeks ) that found no difference in knowledge , administration , or accessibility of medications ( p=.29 ) ; and a collaborative case management program ( 16-month program of assessment , meeting , and monthly follow-up telephone calls ) that reduced perceived caregiver burden ( p=.03 ) . Quasi-experimental trials included collaborative care transitional coaches , an outpatient collaborative care model , and education and training programs . Of these , educational interventions showed improvements in self-efficacy , confidence , and preparedness . The collaborative care intervention reduced rehospitalizations ( p=.04 ) and improved quality -of-care outcomes . CONCLUSION Although some interventions improved caregiver medication knowledge and self-efficacy , effects on clinical outcomes and healthcare use were insufficiently studied . Two studies implementing collaborative care models with medication management components showed potential for improvement in quality of clinical care and reductions in healthcare visits and warrant further study with respect to medication safety . J Am Geriatr Soc 66:2128 - 2135 , 2018 |
11,978 | 32,234,640 | The 5-HT transporter ( 5-HTT ) binding was increased or diminished in different specific cortical areas and in relation to Eating Disorder ( ED ) subtypes .
Some evidence s of blunted Dopamine ( DA ) release in the putamen in BN patients suggest that their DA function might be impaired as in addictive behaviours .
Studies estimating the regional Cerebral Blood Flow ( rCBF ) with SPECT demonstrated that temporal areas seem to play a key role in ED corroborating the hypothesis of a cingulate-temporal cortical dysfunction in AN .
In addition , alterations of both parietal and prefrontal cortex provide a possible common neural substrate in AN .
Studies included in this review are heterogeneous preventing robust conclusions , however , our findings add knowledge on some of the neurotransmitters involved in ED | null | null |
11,979 | 32,280,800 | Conclusion A combination of multiple cytokines had a better association with MACE than individual cytokines . | Background Inflammatory cytokines are involved in the pathophysiology of acute coronary syndromes ( ACS ) and have been associated with major adverse cardiovascular events ( MACE ) .
We systematic ally review ed studies investigating the ability of multiple cytokines to predict MACE in ACS patients with follow-up of at least one year . | AIM Interleukin (IL)-17 pathway is being clinical ly targeted in immune-mediated diseases , most of which are associated with a significant cardiovascular risk . We investigated the relationship between serum levels of IL-17 and the risk of cardiovascular events in patients with acute myocardial infa rct ion . METHODS AND RESULTS We used data from 981 patients enrolled in the prospect i ve , multicentre French registry of Acute ST elevation , or non-ST-elevation Myocardial Infa rct ion ( Fast-MI , NCT00673036 ) . Serum levels of IL-17 were associated with the risk of all-cause death and recurrent MI at 2 years , with levels of IL-17 below the median indicative of a worse outcome . The impact of IL-17 remained significant after adjustment for known cardiovascular risk factors , C-reactive protein , and treatments including statins : hazard ratio ( HR ) = 1.40 ( 1.03 - 1.91 ) ; P = 0.03 . IL-17 inhibited mononuclear cell adhesion to endothelium and reduced endothelial vascular cell adhesion molecule ( VCAM-1 ) expression . Patients with low ( below the median ) IL-17 levels and high ( above the median ) soluble VCAM-1 ( sVCAM-1 ) levels were at particularly increased risk of death and MI : adjusted HR = 2.22 ( 1.32 - 3.75 ) compared with the high IL-17/low sVCAM-1 group ( P = 0.002 ) . CONCLUSIONS Low serum levels of IL-17 are associated with a higher risk of major cardiovascular events in Caucasian patients with acute MI . Our results raise possible concern about the use of inhibitors of the IL-17 pathway in clinical setting s associated with a high cardiovascular risk . CLINICAL TRIALS REGISTRATION NCT00673036 BACKGROUND ACE inhibitors attenuate the detrimental effects of angiotensin II , and improve survival and reduce morbidity in patients with acute myocardial infa rct ion and evidence of heart failure or left-ventricular dysfunction . Selective antagonism of the angiotensin type 1 receptor represents an alternative approach to inhibition of the renin-angiotensin system . We did a multicentre , r and omised trial to test the hypothesis that the angiotensin II antagonist losartan would be superior or non-inferior to the ACE inhibitor captopril in decreasing all-cause mortality in high-risk patients after acute myocardial infa rct ion . METHODS 5477 patients 50 years of age or older ( mean age 67.4 years [ SD 9.8 ] ) , with confirmed acute myocardial infa rct ion and heart failure during the acute phase or a new Q-wave anterior infa rct ion or reinfa rct ion , were recruited from 329 centres in seven European countries . Patients were r and omly assigned and titrated to a target dose of losartan ( 50 mg once daily ) or captopril ( 50 mg three times daily ) as tolerated . The primary endpoint was all-cause mortality . Analysis was by intention to treat . FINDINGS There were 946 deaths during a mean follow-up of 2.7 ( 0.9 ) years : 499 ( 18 % ) in the losartan group and 447 ( 16 % ) in the captopril group ( relative risk 1.13 [ 95 % CI 0.99 - 1.28 ] , p=0.07 ) . The results for the secondary and tertiary endpoints were as follows : sudden cardiac death or resuscitated cardiac arrest 239 ( 9 % ) versus 203 ( 7 % ) , 1.19 ( 0.98 - 1.43 ) , p=0.07 , and fatal or non-fatal reinfa rct ion 384 ( 14 % ) versus 379 ( 14 % ) , 1.03 ( 0.89 - 1.18 ) , p=0.72 . The all-cause hospital admission rates were 1806 ( 66 % ) versus 1774 ( 65 % ) , 1.03 ( 0.97 - 1.10 ) , p=0.37 . Losartan was significantly better tolerated than captopril , with fewer patients discontinuing study medication ( 458 [ 17 % ] vs 624 [ 23 % ] , 0.70 [ 0.62 - 0.79 ] , p<0.0001 ) . INTERPRETATION Since we saw a non-significant difference in total mortality in favour of captopril , ACE inhibitors should remain first-choice treatment in patients after complicated acute myocardial infa rct ion . Losartan can not be generally recommended in this population . However , it was better tolerated than captopril , and was associated with significantly fewer discontinuations . Although the role of losartan in patients intolerant of ACE inhibition is not clearly defined , it can be considered in such patients BACKGROUND The aim of our study was to evaluate the clinical utility and prognostic significance of a cluster of 27 serum cytokines for risk stratification after myocardial infa rct ion . MATERIAL S AND METHODS We enrolled 33 consecutive patients admitted to our institution for acute myocardial infa rct ion and prospect ively followed . We evaluated traditional cardiovascular risk factors and assayed , during the acute phase , 27 serum cytokines ( IL-1 , IL-1ra , IL-2 , IL-4 , IL-5 , IL-6 , IL -7 , IL-8 , IL-9 , IL-10 , IL-12 , IL-13 , IL-15 , IL-17 , EOTAXIN , FGF , G-CSF , GM-CSF , IFN-γ , IP-10 , MCP-1 , MIP-1α , MIP-1β , PDGF , RANTES , TNF-α , VEGF ) potentially associated with cardiovascular risk . Patients were divided into two groups during follow-up according to the occurrence or absence of adverse cardiovascular events ( recurrence of angina , re-infa rct ion , death , need of new revascularization , occurrence of heart failure ) . We developed an additive risk score by assigning one point for each cytokine that had a value greater than the median value ( range 0 - 27 ) . Cytokines alone and the cytokines score were related to cardiovascular events . RESULTS Patients with and without major adverse cardiovascular events ( MACEs ) at follow up had a homogenous distribution of the main cardiovascular risk factors ; differences were detected only for sex and age . Patients who experienced MACE had a significantly different distribution of I troponin ( p=0.036 ) , IL-8 ( p=0.006 ) , IL-13 ( p=0.06 ) , IL-10 ( p=0.02 ) , IL-17 ( p=0.015 ) , IP-10 ( p=0.02 ) , MIP-1β ( p=0.05 ) . At univariate analysis , IL -8 ( p=0.046 OR 1.13 ) , IL-10 ( p=0.05 OR 1.14 ) and MIP-1β ( p=0.016 , OR 1.02 ) were significantly associated with the occurrence of MACE . This association was not confirmed at multivariate analysis . At the analysis of variance , a higher score was significantly associated with the occurrence of adverse events at follow up ( F=5.07 , p=0.03 ) . At ROC curve analysis , a score greater than 13 better predicted the occurrence of adverse events at follow-up ( AUC 0.72 , p=0.03 , sensibility 59.1 % , specificity 81.8 % ) . CONCLUSIONS In our study we did not identify a single inflammatory cytokine able to predict adverse events in a long term follow up , whereas the presence of more than 13 cytokines above the median value was useful for risk stratification Background The Proximity Extension Assay proteomics chip provides a large-scale analysis of 92 biomarkers linked to cardiovascular disease or inflammation . We aim ed to identify the biomarkers that best predicted long-term all-cause mortality in patients with acute myocardial infa rct ion . Methods In this prospect i ve cohort study , 92 biomarkers were analysed in 847 consecutive patients from the Västmanl and Myocardial Infa rct ion Study with a median follow-up of 6.9 years . Results The mean ( ± st and ard deviation ) age of the patients was 70 ( 11.8 ) years and 32.7 % were female . Two hundred and seven patients had died after follow-up . The biomarkers most strongly linked to all-cause mortality were growth differentiation factor 15 ( GDF-15 ) and tumour necrosis factor-related apoptosis-inducing lig and receptor 2 ( TRAIL-R2 ) . Cox regression analysis showed that GDF-15 ( hazard ratio 1.25 per unit change , 95 % confidence interval , 1.02–1.53 , p = 0.031 ) and TRAIL-R2 ( hazard ratio 1.37 per unit change , 95 % confidence interval 1.12–1.67 , p = 0.002 ) were independent predictors of long-term all-cause mortality after adjusting for age , gender , diabetes , previous myocardial infa rct ion , stroke , heart failure , hypertension , smoking , hypercholesterolaemia , body mass index , ST-elevation myocardial infa rct ion , left ventricular ejection fraction , troponin I , estimated glomerular filtration rate , N-terminal pro-brain natriuretic peptide and C-reactive protein . The combination of GDF-15 and TRAIL-R2 with established risk factors and biomarkers showed a discriminating accuracy of separating survivors from non-survivors with a cross-vali date d area under the receiving operating characteristics curve of 0.88 within five years . Conclusion GDF-15 and TRAIL-R2 were the most powerful Proximity Extension Assay chip biomarkers in predicting long-term all-cause mortality in patients with acute myocardial infa rct ion Objective : To investigate the relation between serum high sensitivity ( hs ) C reactive protein ( CRP ) , proinflammatory cytokine concentrations , proinflammatory to anti-inflammatory cytokine ratios and long-term prognosis in patients with non-ST elevation acute coronary syndrome ( NSTEACS ) . Design : Prospect i ve follow-up study for the first six months and then for the first year after admission to hospital . Setting : Tertiary referral centre . Patients : 80 patients ( 60 men , 20 women , mean age 60 ( SD 10 ) years ) with NSTEACS and moderate to high TIMI ( Thrombolysis In Myocardial Infa rct ion ) risk scores . Interventions : Blood sample s from patients with NSTEACS were obtained at the time of admission . Serum concentrations of hs-CRP , ( hs ) pro-inflammatory ( interleukin ( IL ) -1β , IL-6 , tumour necrosis factor α ) and ( hs ) anti-inflammatory ( IL-10 ) cytokines were analysed and proinflammatory to anti-inflammatory cytokine ratios were calculated by dividing proinflammatory cytokine concentrations by anti-inflammatory cytokine IL-10 . Main outcome measure : The primary end point of the study was new coronary events ( NCE ) defined as the combination of cardiac death , non-fatal myocardial infa rct ion and recurrent rest angina that required hospitalisation within 12 months of follow up . Results : During the one-year follow-up period , 23 patients ( 29 % ) met the NCE criteria . Concentrations of hs-CRP , IL-1β and IL-6 and ratios of IL-1β : IL-10 and IL-6:IL-10 were significantly higher in patients with NCE than in patients without NCE . In the logistic regression analysis , IL-6:IL-10 ratio was the most important predictor for NCE ( p = 0.006 ) with an odds ratio of 2.24 ( 95 % CI 1.26 to 3.97 ) . Conclusions : Cytokine concentrations and proinflammatory to anti-inflammatory cytokine ratios may be useful markers for predicting vascular risk in patients with NSTEACS BACKGROUND Inflammatory responses after intracoronary injection of autologous mononuclear bone marrow cells ( m BMC ) are not clarified . The aim of this study was to investigate the influence of intracoronary injection of m BMC on inflammatory mediators in patients with acute myocardial infa rct ion ( AMI ) . METHODS Patients with AMI in the ASTAMI trial ( N = 100 ) treated with percutaneous coronary intervention were r and omized to intracoronary injections of m BMC or control . Fasting blood sample s were drawn the day before stem cell transplantation ( baseline 4 - 5 days after AMI ) and 1 day , 3 days , 2 to 3 weeks , and 3 months after transplantation for determination of circulating levels of selected inflammatory markers and mRNA levels in whole blood sample s. RESULTS From baseline to day 1 , the levels of interleukin 6 and the expression of tumor necrosis factor alpha mRNA increased significantly in the m BMC group compared to the control group ( P < .05 for both ) . The decrease in interleukin 6 levels from baseline to 2 to 3 weeks in the m BMC group was less pronounced than in the controls ( P < .05 ) , as was also the decrease in C-reactive protein levels from baseline to day 1 and day 3 in the m BMC group ( P < .05 ) . However , from baseline to 3 months the levels of tumor necrosis factor alpha and monocyte chemoattractant protein 1 increased less in the m BMC group ( P < .05 for both ) . CONCLUSION Intracoronary injection of m BMC in patients with AMI induces a marked short-term inflammatory response , but a slightly reduced inflammation after 3 months which may have implication s for the timing of stem cell transplantation in AMI AIMS Interleukin-6 ( IL-6 ) contributes to atherosclerotic plaque destabilization and is involved in myocardial injury during ischaemia-reperfusion . Interleukin-6 is therefore a potential therapeutic target in myocardial infa rct ion ( MI ) . We hypothesized that the IL-6 receptor antagonist tocilizumab would attenuate inflammation , and secondarily reduce troponin T ( TnT ) release in non-ST-elevation MI ( NSTEMI ) . METHODS AND RESULTS In a two-centre , double-blind , placebo-controlled trial , 117 patients with NSTEMI were r and omized at a median of 2 days after symptom onset to receive placebo ( n = 59 ) or tocilizumab ( n = 58 ) , administered as a single dose prior to coronary angiography . High sensitivity ( hs ) C-reactive protein and hsTnT were measured at seven consecutive timepoints between Days 1 and 3 . The area under the curve ( AUC ) for high-sensitivity C-reactive protein was the primary endpoint . The median AUC for high-sensitivity C-reactive protein during hospitalization was 2.1 times higher in the placebo than in the tocilizumab group ( 4.2 vs. 2.0 mg/L/h , P < 0.001 ) . Also , the median AUC for hsTnT during hospitalization was 1.5 times higher in the placebo group compared with the tocilizumab group ( 234 vs. 159 ng/L/h , P = 0.007 ) . The differences between the two treatment groups were observed mainly in ( i ) patients included ≤2 days from symptom onset and ( ii ) patients treated with percutaneous coronary intervention ( PCI ) . No safety issues in the tocilizumab group were detected during 6 months of follow-up . CONCLUSION Tocilizumab attenuated the inflammatory response and primarily PCI-related TnT release in NSTEMI patients BACKGROUND Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease . Yet , the inflammatory hypothesis of atherothrombosis has remained unproved . METHODS We conducted a r and omized , double‐blind trial of canakinumab , a therapeutic monoclonal antibody targeting interleukin‐1β , involving 10,061 patients with previous myocardial infa rct ion and a high‐sensitivity C‐reactive protein level of 2 mg or more per liter . The trial compared three doses of canakinumab ( 50 mg , 150 mg , and 300 mg , administered subcutaneously every 3 months ) with placebo . The primary efficacy end point was nonfatal myocardial infa rct ion , nonfatal stroke , or cardiovascular death . RESULTS At 48 months , the median reduction from baseline in the high‐sensitivity C‐reactive protein level was 26 percentage points greater in the group that received the 50‐mg dose of canakinumab , 37 percentage points greater in the 150‐mg group , and 41 percentage points greater in the 300‐mg group than in the placebo group . Canakinumab did not reduce lipid levels from baseline . At a median follow‐up of 3.7 years , the incidence rate for the primary end point was 4.50 events per 100 person‐years in the placebo group , 4.11 events per 100 person‐years in the 50‐mg group , 3.86 events per 100 person‐years in the 150‐mg group , and 3.90 events per 100 person‐years in the 300‐mg group . The hazard ratios as compared with placebo were as follows : in the 50‐mg group , 0.93 ( 95 % confidence interval [ CI ] , 0.80 to 1.07 ; P=0.30 ) ; in the 150‐mg group , 0.85 ( 95 % CI , 0.74 to 0.98 ; P=0.021 ) ; and in the 300‐mg group , 0.86 ( 95 % CI , 0.75 to 0.99 ; P=0.031 ) . The 150‐mg dose , but not the other doses , met the prespecified multiplicity‐adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization ( hazard ratio vs. placebo , 0.83 ; 95 % CI , 0.73 to 0.95 ; P=0.005 ) . Canakinumab was associated with a higher incidence of fatal infection than was placebo . There was no significant difference in all‐cause mortality ( hazard ratio for all canakinumab doses vs. placebo , 0.94 ; 95 % CI , 0.83 to 1.06 ; P=0.31 ) . CONCLUSIONS Antiinflammatory therapy targeting the interleukin‐1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo , independent of lipid‐level lowering . ( Funded by Novartis ; CANTOS Clinical Trials.gov number , NCT01327846 . |
11,980 | 24,856,442 | OXA-based chemotherapy is effective in advanced HCC and represents a viable option in these patients . | Advanced hepatocellular carcinoma ( HCC ) , for which locoregional treatment is not an option , is a c and i date for palliative systemic therapy , but an accepted chemotherapy regimen does not exist .
We have conducted a systematic literature review and meta-analyses to quantify the benefits of oxaliplatin (OXA)-based chemotherapy in advanced HCC in patients not exposed to sorafenib . | PURPOSE Open-label , phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer . PATIENTS AND METHODS Patients were stratified and r and omly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day . Primary end point was overall survival ( OS ) . RESULTS Early trial termination occurred for futility and safety reasons . A total of 1,074 patients were r and omly assigned to the study ( sunitinib arm , n = 530 ; sorafenib arm , n = 544 ) . For sunitinib and sorafenib , respectively , median OS was 7.9 versus 10.2 months ( hazard ratio [ HR ] , 1.30 ; one-sided P = .9990 ; two-sided P = .0014 ) ; median progression-free survival ( PFS ; 3.6 v 3.0 months ; HR , 1.13 ; one-sided P = .8785 ; two-sided P = .2286 ) and time to progression ( TTP ; 4.1 v 3.8 months ; HR , 1.13 ; one-sided P = .8312 ; two-sided P = .3082 ) were comparable . Median OS was similar among Asian ( 7.7 v 8.8 months ; HR , 1.21 ; one-sided P = .9829 ) and hepatitis B-infected patients ( 7.6 v 8.0 months ; HR , 1.10 ; one-sided P = .8286 ) , but was shorter with sunitinib in hepatitis C-infected patients ( 9.2 v 17.6 months ; HR , 1.52 ; one-sided P = .9835 ) . Sunitinib was associated with more frequent and severe adverse events ( AEs ) than sorafenib . Common grade 3/4 AEs were thrombocytopenia ( 29.7 % ) and neutropenia ( 25.7 % ) for sunitinib ; h and -foot syndrome ( 21.2 % ) for sorafenib . Discontinuations owing to AEs were similar ( sunitinib , 13.3 % ; sorafenib , 12.7 % ) . CONCLUSION OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib . OS was comparable in Asian and hepatitis B-infected patients . OS was superior in hepatitis C-infected patients who received sorafenib . Sunitinib-treated patients reported more frequent and severe toxicity Objective : A phase II study was performed to evaluate the efficacy and tolerability of bevacizumab and erlotinib in advanced hepatocellular carcinoma ( HCC ) patients , and to investigate clinical and molecular predictors of outcome . Methods : 59 patients with advanced HCC received 10 mg/kg i.v . of bevacizumab every 14 days and 150 mg p.o . of erlotinib daily . The primary endpoint was progression-free survival ( PFS ) at 16 weeks . Clinical characteristics and plasma biomarkers expression levels were analyzed . Results : PFS at 16 weeks was 64 % ( 95 % CI 51–76 ) : 14 patients achieved partial response ( 24 % ) , 33 had stable disease ( 56 % ) , 6 progressed ( 10 % ) , and 6 were not evaluable ( 10 % ) . Median overall survival was 13.7 months ( 95 % CI 9.6–19.7 ) , and median PFS was 7.2 months ( 95 % CI 5.6–8.3 ) . Grade 3–4 adverse events included fatigue ( 30 % ) , diarrhea ( 17 % ) , hypertension ( 14 % ) , elevated transaminases ( 12 % ) , and gastrointestinal hemorrhage ( 10 % ) . High plasma angiopoietin-2 , epidermal growth factor receptor , and endothelin-1 , and lack of acneiform rash were associated with poor outcome . Conclusions : The combination of bevacizumab with erlotinib achieved encouraging results in patients with advanced HCC . Current correlatives may help to guide future HCC studies Summary Purpose The only drug that improves survival in hepatocellular carcinoma is sorafenib . FOLFOX-4 regimen is safe and widely used in patients with colorectal cancer , yielding interesting results with little toxicity . We conducted a retrospective study to evaluate the safety and the effectiveness of FOLFOX-4 in cirrhotic or liver transplanted patients with hepatocellular carcinoma ineligible for sorafenib . Methods Thirty seven patients were enrolled in the study . The medical record of either cirrhotic patients or liver transplanted patients with advanced hepatocellular carcinoma receiving FOLFOX-4 regimen between November 1999 and March 2006 were retrospectively analyzed . Patients received oxaliplatin 85 mg/m2 as a 2-hour infusion on day one , and leucovorin 200 mg/m2 as a 2-hour infusion followed by bolus 5-fluorouracil 400 mg/m2 and a 48-hours infusion of 5-fluorouracil 2400 mg/m2 . Treatment was repeated every 2 weeks until disease progression or unacceptable adverse effects occurred . Results Patients had a Child-Pugh class A ( n = 16 ) , class B cirrhosis ( n = 10 ) or a liver transplant ( n = 11 ) and received 2 to 37 cycles of chemotherapy ( total of 310 cycles ) . Two ( 5.4 % ) cirrhotic patients developed neutropenic sepsis and one ( 2.7 % ) toxic death occurred . At first assessment , five patients from Child-Pugh class A ( 33 % ) and two from Child-Pugh class B group ( 20 % ) achieved a radiological response and /or alpha foeto-protein decrease , and no patient achieved a complete response . Conclusions In conclusion , with a manageable toxicity profile in cirrhotic Child-Pugh class A-B or liver transplanted patients , the FOLFOX-4 regimen appears to be a feasible treatment option for patients with advanced hepatocellular carcinoma unfit for sorafenib . These data need to be confirmed in a prospect i ve study Purpose We design ed a phase II trial of the combination with oxaliplatin and doxorubicin for patients with unresectable HCC to evaluate the overall response rate ( ORR ) and the toxicity . Methods Forty patients with inoperable , systemic chemotherapy naive HCC were enrolled . Finally , 32 patients received oxaliplatin ( 130 mg/m2 ) and doxorubicin ( 60 mg/m2 ) every 3 weeks . Results Eighty-two treatment cycles were administered ( median 2 cycles , range 1–6 ) . There was no treatment-related mortality . The ORR was 15.6 % ( 95 % CI , 3.3–28.7 ) with five partial responses . The median overall survival and median overall progression free survival were 31 weeks ( 95 % CI , 22–40 weeks ) and 12 weeks ( 95 % CI , 5 - 19 weeks ) . Nausea and peripheral neuropathy were most frequent non-hematologic toxicities ( nausea , n = 15 ; peripheral neuropathy , n = 10 ) . The most frequent grade 3–4 hematologic adverse event was neutropenia ( 14 of 82 cycles ) including three cases of febrile neutropenia . Conclusions The combination of oxaliplatin and doxorubicin showed modest activity and a tolerable toxicity profile in advanced HCC patients Evaluation of new drug combinations is needed to improve patients ' prognosis in advanced hepatocellular carcinoma ( HCC ) . The purpose of this study was to evaluate the safety and efficacy of the capecitabine – oxaliplatine combination ( XELOX ) in HCC patients . First-line chemotherapy with XELOX regimen consisting of a 3-week cycle of intravenous oxaliplatin ( 130 mg m−2 ) on Day 1 , and oral capecitabine twice daily from Days 1–14 ( 1000 mg m−2 ) was administered in patients with measurable , unresectable HCC . Fifty patients ( male , 88 % ; median age , 68 years ) received a total of 295 cycles ( median , 6 ) of treatment . Disease control ( three partial responses , 29 stable diseases ) rate was 72 % ( 95 % CI 57–83 % ) . Median overall and median progression-free ( PFS ) survival was 9.3 months and 4.1 months , respectively . Progression-free survival rates at 6 and 12 months were 38 % ( 95 % CI 26–52 % ) and 14 % ( 95 % CI 7–26 % ) , respectively . Main grade 3–4 drug-related toxicities included diarrhoea ( 16 % ) , elevation of aminotransferases and /or bilirubin ( 16 % ) , thrombocytopenia ( 12 % ) , and neurotoxicity ( 6 % ) . Capecitabine plus oxaliplatin regimen showed modest anti-tumour activity with tolerable toxicities in patients with advanced HCC . However , the manageable toxicity profile and the encouraging disease control rate deserve further attention for this convenient , outpatient-based chemotherapy regimen PURPOSE Hepatocellular carcinoma ( HCC ) is a vascular tumor with poor prognosis . Given the reported activity of gemcitabine and oxaliplatin ( GEMOX ) in HCC and the potential benefits of targeting the vascular endothelial growth factor pathway with bevacizumab ( B ) , a phase II study of GEMOX-B was undertaken to define efficacy and toxicity profiles in HCC patients . PATIENTS AND METHODS Eligible patients had pathologically proven measurable unresectable or metastatic HCC . For cycle 1 ( 14 days ) , bevacizumab 10 mg/kg was administered alone intravenously on day 1 . For cycle 2 and beyond ( 28 days/cycle ) , bevacizumab 10 mg/kg was administered on days 1 and 15 , gemcitabine 1,000 mg/m2 was administered as a dose rate infusion at 10 mg/m2/min followed by oxaliplatin at 85 mg/m2 on days 2 and 16 . RESULTS Thirty-three patients were enrolled and 30 patients were assessable for efficacy . The objective response rate was 20 % , and 27 % of patients had stable disease . Median overall survival was 9.6 months ( 95 % CI , 8.0 months to not available ) and median progression-free survival ( PFS ) was 5.3 months ( 95 % CI , 3.7 to 8.7 months ) ; the PFS rate at 3 and 6 months was 70 % ( 95 % CI , 54 % to 85 % ) and 48 % ( 95 % CI , 31 % to 65 % ) , respectively . The most common treatment-related grade 3 to 4 toxicities included leukopenia/neutropenia , transient elevation of aminotransferases , hypertension , and fatigue . CONCLUSION GEMOX-B could be safely administered with close monitoring and had moderate antitumor activity for patients with advanced HCC . The high 6-month PFS rate is encouraging , and this regimen is worthy of further investigation BACKGROUND Sorafenib has shown survival benefits in patients with advanced hepatocellular carcinoma ( HCC ) and Child-Pugh ( CP ) class A liver function . There are few prospect i ve data on sorafenib in patients with HCC and CP class B. PATIENTS AND METHODS A consecutive prospect i ve series of 300 patients with CP class A or B HCC were enrolled in a dual-phase trial to determine survival and safety data according to liver function ( class A or B ) in patients receiving oral sorafenib 800 mg daily . [ Results of this study were presented in part at the ASCO 2012 Gastrointestinal Cancers Symposium , 19 - 21 January 2012 . J Clin Oncol 2012 ; 30 ( Suppl 4 ) : abstract 306 . ] RESULTS Overall progression-free survival ( PFS ) , time to progression ( TTP ) and overall survival ( OS ) were 3.9 , 4.1 and 9.1 months , respectively . For patients with CP class A versus B status , PFS was 4.3 versus 2.1 months , TTP was 4.2 versus 3.8 months and OS was 10.0 versus 3 . 8 months . Extrahepatic spread was associated with worse outcomes but taken together with CP class , liver function played a greater role in reducing survival . Adverse events for the two CP groups were similar . CONCLUSION Although patients with HCC and CP class B liver function have poorer outcomes than those with CP class A function , data suggest that patients with CP class B liver function can tolerate treatment and may still benefit from sorafenib New systemic therapies are needed to improve the prognosis of patients with advanced‐stage hepatocellular carcinoma ( HCC ) . In a Phase II trial involving previously untreated patients with advanced HCC , the more favorable schedule from a previous pilot study was evaluated Purpose : Sorafenib improves survival in advanced hepatocellular carcinoma ( HCC ) , but the demonstration of its efficacy and safety is limited to Child-Pugh A cirrhotic patients . The biweekly combination of gemcitabine and oxaliplatin ( GEMOX ) is safe and widely used in patients with advanced malignancies . We aim ed to evaluate the feasibility of GEMOX in HCC patients with Child-Pugh B cirrhosis ineligible for sorafenib . Methods : The medical records of cirrhotic patients with advanced HCC receiving the GEMOX regimen between July 2006 and November 2011 were retrospectively review ed . Treatment was repeated every 2 weeks until disease progression or unacceptable adverse effects occurred . The primary evaluation criterion was safety . Secondary evaluation criteria were the presence of muscle wasting ( sarcopenia ) , response rate , progression-free survival and overall survival ( OS ) . Results : Patients with Child-Pugh A ( group A , n = 17 ) or Child-Pugh B cirrhosis ( group B , n = 15 ) received a total of 169 cycles ( median 4 , range 1–16/patient ) . Eight patients in each group had sarcopenia . Common toxicities were thrombocytopenia ( 25 and 14 in groups A and B , respectively ; p = 0.65 ) and peripheral neuropathy ( 44 and 54 % in groups A and B , respectively ; p = 1 ) . Neither febrile neutropenia nor toxic death occurred . One patient in each group experienced grade 3 oesophageal varices bleeding . The response and disease control rates were 18 % ( 95 % CI 0–35.8 ) and 58.8 % ( 95 % CI 35.4–82.2 ) in group A , and 27 % ( 95 % CI 4.3–49.1 ) and 60.0 % ( 95 % CI 35.2–84.8 ) in group B. The median progression-free survival and OS did not differ between the two groups , but median OS was significantly shorter in sarcopenic patients . Conclusions : The GEMOX regimen appears feasible in HCC patients with Child-Pugh B cirrhosis and exerts anti-tumour activity . These data need to be confirmed in a prospect i ve study BACKGROUND Single-agent doxorubicin has been widely used to treat unresectable hepatocellular carcinoma ( HCC ) , but the response rate is low ( < 20 % ) and there is no convincing evidence for improved survival . Cisplatin , interferon , doxorubicin , and fluorouracil ( PIAF ) used in combination , by contrast , has shown promise in a phase II study . We compared doxorubicin to PIAF in patients with unresectable HCC in a phase III trial . METHODS Patients with histologically confirmed unresectable HCC were r and omly assigned to receive either doxorubicin or PIAF every 3 weeks , for up to six cycles . The primary endpoint was overall survival , and secondary endpoints were response rate and toxicity . Survival differences were calculated using the Kaplan-Meier method . Treatment groups were compared for differences in the incidence of adverse events using chi-square tests . All statistical tests were two-sided . RESULTS The median survival of the doxorubicin and PIAF groups was 6.83 months ( 95 % confidence [ CI ] = 4.80 to 9.56 ) and 8.67 months ( 95 % CI = 6.36 to 12.00 ) , respectively ( P = 0.83 ) . The hazard ratio for death from any cause in the PIAF compared with the doxorubicin groups was 0.97 ( 95 % CI = 0.71 to 1.32 ) . Eighty-six of the 94 patients receiving doxorubicin and 91 of the 94 receiving PIAF were assessable for response . The overall response rates in the doxorubicin and PIAF groups were 10.5 % ( 95 % CI = 3.9 % to 16.9 % ) and 20.9 % ( 95 % CI = 12.5 % to 29.2 % ) , respectively . Neutropenia , thrombocytopenia , and hypokalemia were statistically significantly more common in patients treated with PIAF than in patients treated with doxorubicin . CONCLUSION Although patients on PIAF had a higher overall response rate and better survival than patients on doxorubicin , the differences were not statistically significant . PIAF was also associated with increased treatment-related toxicity . The prognosis of patients with unresectable HCC remains poor Anti‐angiogenesis agents have shown effectiveness in treatment of hepatocellular carcinoma ( HCC ) . It is important to investigate more effective and safe systemic treatment options for patients with advanced HCC . This phase 2 study was design ed to determine the efficacy and toxicity of the combination of bevacizumab , capecitabine , and oxaliplatin in patients with advanced unresectable and untransplantable HCC PURPOSE Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma ( HCC ) . An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who can not tolerate it . This multicenter , double-blind , r and omized , placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib . PATIENTS AND METHODS In all , 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were r and omly assigned ( 2:1 ) to receive brivanib 800 mg orally once per day plus best supportive care ( BSC ) or placebo plus BSC . The primary end point was overall survival ( OS ) . Secondary end points included time to progression ( TTP ) , objective response rate ( ORR ) , and disease control rate based on modified Response Evaluation Criteria in Solid Tumors ( mRECIST ) and safety . RESULTS Median OS was 9.4 months for brivanib and 8.2 months for placebo ( hazard ratio [ HR ] , 0.89 ; 95.8 % CI , 0.69 to 1.15 ; P = .3307 ) . Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 ( 95 % CI , 0.63 to 1.04 ; P = .1044 ) . Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo ( HR , 0.56 ; 95 % CI , 0.42 to 0.76 ; P < .001 ) , and an mRECIST ORR of 10 % for brivanib and 2 % for placebo ( odds ratio , 5.72 ) . Study discontinuation due to treatment-related adverse events ( AEs ) occurred in 61 brivanib patients ( 23 % ) and nine placebo patients ( 7 % ) . The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension ( 17 % ) , fatigue ( 13 % ) , hyponatremia ( 11 % ) , and decreased appetite ( 10 % ) . CONCLUSION In patients with HCC who had been treated with sorafenib , brivanib did not significantly improve OS . The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation CONTEXT In a r and omized phase 3 trial , 400 mg of sorafenib twice daily prolonged overall survival of patients with advanced hepatocellular carcinoma ( HCC ) and Child-Pugh A disease . In a phase 1 study , sorafenib combined with doxorubicin , 60 mg/m(2 ) , was well tolerated by patients with refractory solid tumors . The combination of sorafenib and doxorubicin in patients with advanced HCC has not been evaluated in a phase 2 or 3 trial . OBJECTIVE To evaluate the efficacy and safety of doxorubicin plus sorafenib compared with doxorubicin alone in patients with advanced HCC and Child-Pugh A disease . DESIGN , SETTING , AND PATIENTS In a double-blind phase 2 multinational study , conducted from April 2005 to October 2006 , 96 patients ( 76 % male ; median age , 65 years [ range , 38 - 82 years ] ) with advanced HCC , Eastern Cooperative Oncology Group performance status 0 to 2 , Child-Pugh A status , and no prior systemic therapy were r and omly assigned to receive 60 mg/m(2 ) of doxorubicin intravenously every 21 days plus either 400 mg of sorafenib or placebo orally twice a day . The date of the last patient 's follow-up was April 2008 . MAIN OUTCOME MEASURE Time to progression as determined by independent review . RESULTS Following complete accrual , an unplanned early analysis for efficacy was performed by the independent data monitoring committee , so the trial was halted . The 2 patients remaining in the placebo group at that time were offered sorafenib . Based on 51 progressions , 63 deaths , and 70 events for progression-free survival , median time to progression was 6.4 months in the sorafenib-doxorubicin group ( 95 % confidence interval [ CI ] , 4.8 - 9.2 ) , and 2.8 months ( 95 % CI , 1.6 - 5 ) in the doxorubicin-placebo monotherapy group ( P = .02 ) . Median overall survival was 13.7 months ( 95 % CI , 8.9 - -not reached ) and 6.5 months ( 95 % CI , 4.5 - 9.9 ; P = .006 ) , and progression-free survival was 6.0 months ( 95 % CI , 4.6 - 8.6 ) and 2.7 months ( 95 % CI , 1.4 - 2.8 ) in these groups , respectively ( P = .006 ) . Toxicity profiles were similar to those for the single agents . CONCLUSIONS Among patients with advanced HCC , treatment with sorafenib plus doxorubicin compared with doxorubicin monotherapy result ed in greater median time to progression , overall survival , and progression-free survival . The degree to which this improvement may represent synergism between sorafenib and doxorubicin remains to be defined . The combination of sorafenib and doxorubicin is not yet indicated for routine clinical use . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00108953 The oncologic community is faced with a steady increase in the incidence of hepatocellular carcinoma ( HCC ) [ 1 ] . Liver cancer represents the sixth most common cancer in the world ( 749 000 new cases ) and the third cause of cancer-related death ( 692 000 cases ) . The incidence varies from 3 out of 100 000 in Western countries , to more than 15 out of 100 000 in certain areas of the world , mapping the geographical distribution of viral hepatitis B ( HBV ) and hepatitis C ( HCV ) , the most important causes of chronic liver disease and HCC [ 2 ] . Most cases arise in those regions with limited re sources . The incidence of HCC increases progressively with advancing age in all population s , with a strong male preponderance . The association of chronic liver disease and HCC represents the basis for preventive strategies , including universal vaccination at birth against hepatitis B , programs to stop transmission and early antiviral eradication of viral hepatitis B and C [ III , A ] . It is unclear whether HBV vaccination will result in a decline in HCC as was seen in Taiwan , given the importance of other risk factors in Europe , such as alcoholic and non-alcoholic fatty liver disease . The control of other risk factors for chronic liver disease and cancer is more difficult to implement , such as cutting down on the consumption of alcohol and programs aim ing at a healthier lifestyle in the light of the obesity p and emic [ 3 , 4 ] . In Africa , reduction of exposure to aflatoxin B1 , especially in HBV-infected individuals , may lower the risk of HCC . HCC may evolve from subclasses of adenomas , and in < 10 % of cases HCC occurs in a normal liver . Surveillance of HCC involves the repeated application of screening tools in patients at risk for HCC and aims for the reduction in mortality of this patient population . The success of surveillance is influenced by the incidence of HCC in the target population , the availability and acceptance of efficient diagnostic tests and the availability of effective treatment . Costeffectiveness studies suggest surveillance of HCC is warranted in cirrhotic patients irrespective of its etiology [ 5 ] . Surveillance of non-cirrhotic patients is also advocated , especially in HBV carriers with serum viral load > 10 000 copies/ml [ 6 ] or HCVinfected patients with bridging fibrosis ( F3 ) [ III , A ] . Patients with HCV infection and advanced fibrosis remain at risk for HCC even after achieving sustained virological response following antiviral treatment [ III , A ] . Japanese cohort studies have shown that surveillance by abdominal ultrasound result ed in an average size of the detected tumors of 1.6 ± 0.6 cm , with < 2 % of the cases exceeding 3 cm [ 7 ] . In the Western world and in less experienced centers , sensitivity of finding early-stage HCC by ultrasound is considerably less effective [ 8 ] . There are no data to support the use of contrast-enhanced computed tomography ( CT ) or magnetic resonance imaging ( MRI ) for surveillance . In many centers , ultrasound surveillance is complemented with the determination of serum alphafetoprotein ( AFP ) , which can lead to a 6%–8 % gain in the tumor detection rate but at the price of false-positive results . A r and omized , controlled trial ( RCT ) of Chinese patients with chronic hepatitis B infection compared surveillance ( ultrasound and serum AFP measurements every 6 months ) versus no surveillance [ 9 ] . Despite low compliance with the surveillance program ( 55 % ) , HCC-related mortality was reduced by 37 % in the surveillance arm . Considering the most appropriate surveillance interval , a r and omized study comparing a 3versus 6-month based schedule failed to detect any differences [ 10 ] . Therefore , surveillance of patients at risk for HCC should be carried out by abdominal ultrasound every 6 months [ I , A ] The authors conducted a phase 2 trial of the antiepidermal growth factor receptor ( EGFR ) monoclonal antibody cetuximab in combination with the gemcitabine plus oxaliplatin ( GEMOX ) regimen in patients with documented progressive hepatocellular carcinoma ( HCC ) BACKGROUND No effective systemic therapy exists for patients with advanced hepatocellular carcinoma . A preliminary study suggested that sorafenib , an oral multikinase inhibitor of the vascular endothelial growth factor receptor , the platelet-derived growth factor receptor , and Raf may be effective in hepatocellular carcinoma . METHODS In this multicenter , phase 3 , double-blind , placebo-controlled trial , we r and omly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or placebo . Primary outcomes were overall survival and the time to symptomatic progression . Secondary outcomes included the time to radiologic progression and safety . RESULTS At the second planned interim analysis , 321 deaths had occurred , and the study was stopped . Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group ( hazard ratio in the sorafenib group , 0.69 ; 95 % confidence interval , 0.55 to 0.87 ; P<0.001 ) . There was no significant difference between the two groups in the median time to symptomatic progression ( 4.1 months vs. 4.9 months , respectively , P=0.77 ) . The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( P<0.001 ) . Seven patients in the sorafenib group ( 2 % ) and two patients in the placebo group ( 1 % ) had a partial response ; no patients had a complete response . Diarrhea , weight loss , h and -foot skin reaction , and hypophosphatemia were more frequent in the sorafenib group . CONCLUSIONS In patients with advanced hepatocellular carcinoma , median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo . ( Clinical Trials.gov number , NCT00105443 . BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important . We did a multinational phase III , r and omised , double-blind , placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced ( unresectable or metastatic ) hepatocellular carcinoma . METHODS Between Sept 20 , 2005 , and Jan 31 , 2007 , patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A , were r and omly assigned to receive either oral sorafenib ( 400 mg ) or placebo twice daily in 6-week cycles , with efficacy measured at the end of each 6-week period . Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread ( or both ) , Eastern Cooperative Oncology Group performance status , and geographical region . R and omisation was done central ly and in a 2:1 ratio by means of an interactive voice-response system . There was no predefined primary endpoint ; overall survival , time to progression ( TTP ) , time to symptomatic progression ( TTSP ) , disease control rate ( DCR ) , and safety were assessed . Efficacy analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00492752 . FINDINGS 271 patients from 23 centres in China , South Korea , and Taiwan were enrolled in the study . Of these , 226 patients were r and omly assigned to the experimental group ( n=150 ) or to the placebo group ( n=76 ) . Median overall survival was 6.5 months ( 95 % CI 5.56 - 7.56 ) in patients treated with sorafenib , compared with 4.2 months ( 3.75 - 5.46 ) in those who received placebo ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.50 - 0.93 ] ; p=0.014 ) . Median TTP was 2.8 months ( 2.63 - 3.58 ) in the sorafenib group compared with 1.4 months ( 1.35 - 1.55 ) in the placebo group ( HR 0.57 [ 0.42 - 0.79 ] ; p=0.0005 ) . The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were h and -foot skin reaction ( HFSR ; 16 patients [ 10.7 % ] ) , diarrhoea ( nine patients [ 6.0 % ] ) , and fatigue ( five patients [ 3.4 % ] ) . The most common adverse events result ing in dose reductions were HFSR ( 17 patients [ 11.4 % ] ) and diarrhoea ( 11 patients [ 7.4 % ] ) ; these adverse events rarely led to discontinuation . INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region , and is well tolerated . Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment R and omised Protocol ( SHARP ) trial , sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma PURPOSE The study objective was to compare the overall survival ( OS ) of patients with unresectable or metastatic hepatocellular carcinoma ( HCC ) treated with nolatrexed ( NOL ) or doxorubicin ( DOX ) . PATIENTS AND METHODS Patients from North America , Europe , and South Africa ( N = 445 ) with HCC were r and omly assigned to receive NOL or DOX . Eligible patients had Karnofsky performance status ( KPS ) > or = 60 % , Cancer of the Liver Italian Program ( CLIP ) score < or = 3 , and adequate organ function . Primary end point was OS . Secondary end points included progression-free survival ( PFS ) , objective response rates , and safety . The treatment groups were well-balanced with regards to age , sex , ethnic origin , and underlying liver disease . R and omization was stratified according to KPS and CLIP score . RESULTS At the time of the final analysis , 377 patients had died . Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX ( P = .0068 ) . The hazard ratio was 0.753 in favor of DOX . Objective response rate ( complete response [ CR ] plus partial response [ PR ] ) was 1.4 % for NOL and 4.0 % for DOX . Median PFS was 12 weeks for NOL and 10 weeks for DOX ( P = .7091 ) . Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX ( P = .0969 ) . Grade 3 and 4 stomatitis , vomiting , diarrhea , and thrombocytopenia were more common in the NOL arm . Alopecia was more common in the DOX arm . More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm . CONCLUSION NOL showed minimal activity in this phase III trial . Further exploration at this dose and schedule in HCC is not warranted The primary objective of this study was to determine the response rates of a combination of gemcitabine and cisplatin in unresectable hepatocellular carcinoma ( HCC ) in Indian patients . The secondary objectives were to evaluate the toxicity , time to progressive disease and overall survival for this combination . Chemonaive patients with histopathologically proven , bidimensionally measurable , stage Ill or IV unresectable HCC were enrolled into this study . All the patients were required to have a Zubrod 's performance status not greater than 2 , should not have undergone prior radiotherapy and were required to have adequate major organ function . Patients received gemcitabine ( 1250 mg/m2 intravenously over 30 to 60 min ) on days 1 and 8 , and cisplatin ( 70 mg/m2 intravenously over 2 hours ) on day l and every 21 days . Response assessment was done by a Computed Tomography scan after every two cycles of chemotherapy . From May to December 1999 , 30 patients were enrolled in the study ; they were all eligible for efficacy and toxicity analysis . Six ( 20 % ) patients achieved a partial response and 13 ( 43 % ) patients demonstrated stable disease with 11 ( 37 % ) patients showing disease progression . The median time to progression was 18 weeks ( range 1 to 74 weeks ) and the median duration of response was 13 weeks ( range 4 to 68 weeks ) . The 1-year survival rate was 27 % and the median overall survival was 21 weeks ( 95 % CI : 17 to 43 weeks ) . WHO grade 3 and 4 anemia was seen in 11 ( 37 % ) and 2 ( 7 % ) patients , respectively . Four ( 13 % ) patients each experienced grade 3 and 4 neutropenia and grade 3 and 4 thrombocytopenia was seen in 2 ( 7 % ) patients each . Major , non-hematologic toxicities were grade 4 elevated bilirubin levels and grade 3 oral toxicity , in 1 patient ( 3 % ) each . This regimen was well tolerated and did show activity in Indian patients with advanced unresectable HCC . There is a need to further evaluate this combination in order to define its role in the treatment of HCC This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma ( HCC ) . Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospect i ve r and omized controlled trials ( RCT ) were investigated through uni‐ and multivariate analyses . None of them was suitable for radical therapies ( surgical resection , liver transplantation , or ethanol injection ) or presented end‐stage disease as reflected by an Okuda stage 3 or a Performance Status ≥3 . Sixty‐five patients were Child‐Pugh A , 34 were B , and 3 were C. Most of them exhibited a preserved Performance Status Test ( PST ) ( 0 = 56 ; 1 = 38 ; 2 = 8) . Tumor was solitary in 26 ( ≤5 cm in 16 ) and multinodular/massive in 76 . After a median follow‐up of 17 months , 79 patients died , the 1‐ , 2‐ , and 3‐year survival being 54 % , 40 % , and 28 % . The multivariate study identified PST ( P = .01 ) , constitutional syndrome ( P = .04 ) , vascular invasion ( P = .001 ) , and extrahepatic spread ( P = .04 ) as independent predictors for mortality . The 1‐ , 2‐ , and 3‐year survival for the 48 patients without adverse factors ( Stage 0 ) was 80 % , 65 % , and 50 % , respectively , and 29 % , 16 % , and 8 % in the 54 patients with at least one adverse parameter ( Stage I ) . Therefore , Stage 0 would correspond to an intermediate stage , while Stage I would represent an advanced status , before reaching an end‐stage phase . In conclusion , the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern . Therapeutic trials should be design ed and evaluated considering these characteristics To assess the efficacy and safety of Adriamycin ( Adria Laboratories , Columbus , OH ) in inoperable hepatocellular carcinoma ( HCC ) , 60 patients were r and omized to receive Adriamycin 60 to 75 mg/m2 at 3‐week intervals and 46 patients to receive no antitumor therapy . The median survival rate of the Adriamycin group was 10.6 weeks ; that of the group receiving no antitumor therapy was 7.5 weeks ( P = 0.036 ) . Adriamycin induced tumor regression of 25 % to 50 % in 5 % of patients and of over 50 % in only 3.3 % of patients . It caused fatal complications ( septicemia and cardiotoxicity ) in 25 % of patients . The severity of neutropenia leading to septicemia for a particular dose was unpredictable . Four of eight patients who developed cardiotoxicity received less than 500 mg/m2 of Adriamycin . We conclude that Adriamycin is not an ideal drug for the treatment of inoperable HCC PURPOSE To determine whether FOLFOX4 ( infusional fluorouracil , leucovorin , and oxaliplatin ) administered as palliative chemotherapy to patients with advanced hepatocellular carcinoma ( HCC ) provides a survival benefit and efficacy versus doxorubicin . PATIENTS AND METHODS This multicenter , open-label , r and omized , phase III study in mainl and China , Taiwan , Korea , and Thail and involved 371 patients age 18 to 75 years who had locally advanced or metastatic HCC and were ineligible for curative resection or local treatment . They were r and omly assigned at a ratio of one to one to receive either FOLFOX4 ( n = 184 ) or doxorubicin ( n = 187 ) . The primary end point was overall survival ( OS ) ; secondary end points included progression-free survival ( PFS ) , response rate ( RR ) by RECIST ( version 1.0 ) , and safety . RESULTS At the prespecified final analysis , median OS was 6.40 months with FOLFOX4 ( 95 % CI , 5.30 to 7.03 ) and 4.97 months with doxorubicin ( 95 % CI , 4.23 to 6.03 ; P = .07 ; hazard ratio [ HR ] , 0.80 ; 95 % CI , 0.63 to 1.02 ) . Median PFS was 2.93 months with FOLFOX4 ( 95 % CI , 2.43 to 3.53 ) , and 1.77 months with doxorubicin ( 95 % CI , 1.63 to 2.30 ; P < .001 ; HR , 0.62 ; 95 % CI , 0.49 to 0.79 ) . RR was 8.15 % with FOLFOX4 and 2.67 % with doxorubicin ( P = .02 ) . On continued follow-up , the trend toward increased OS with FOLFOX4 was maintained ( P = .04 ; HR , 0.79 ; 95 % CI , 0.63 to 0.99 ) . Toxicity was consistent with previous experiences with FOLFOX4 ; proportions of grade 3 to 4 adverse events were similar between treatments . CONCLUSION Although the study did not meet its primary end point , the trend toward improved OS with FOLFOX4 , along with increased PFS and RR , suggests that this regimen may confer some benefit to Asian patients , but an OS benefit can not be concluded from these data |
11,981 | 15,247,576 | Single or multiple ( 3 - 11 ) sessions of manipulation or mobilization showed no benefit in pain relief when assessed against placebo , control groups , or other treatments for acute/subacute/chronic mechanical neck disorders with or without headache .
Mobilization and /or manipulation when used with exercise are beneficial for persistent mechanical neck disorders with or without headache .
Done alone , manipulation and /or mobilization were not beneficial ; when compared to one another , neither was superior .
There was insufficient evidence available to draw conclusions for neck disorder with radicular findings .
Factorial design would help determine the active agent(s ) within a treatment mix | STUDY DESIGN AND OBJECTIVES Our systematic review of r and omized trials assessed whether manipulation and mobilization relieve pain or improve function/disability , patient satisfaction , and global perceived effect in adults with mechanical neck disorders .
SUMMARY OF BACKGROUND DATA Neck disorders are common , disabling , and costly . | OBJECTIVE --To assess the long term effect of early mobilisation exercises in patients with acute sprains of the neck after road accidents . DESIGN --Single blind r and omised prospect i ve study of patients receiving physiotherapy , advice on mobilisation , or on an initial period of rest followed up after two years by postal question naire . SETTING --Accident and emergency department in urban hospital . PATIENTS --247 Consecutive patients ( mean age at injury 30.6 years ) presenting within 48 hours after injury with no pre-existing disease of the neck or serious skeletal injury . Of these , 167 patients responded to the question naire ; 77 who responded but had not completed their treatment or review course were included in the analysis as a fourth group ( non-attenders ) . MAIN OUTCOME MEASURE -- Presence of symptoms after two years . RESULTS --Of the 167 patients ( 68 % ) responding , the percentage of patients still with symptoms was not significantly different in those receiving rest or physiotherapy ( 46 % , 12/26 v 44 % , 24/54 ) , but that in those receiving advice on early mobilisation was significantly lower ( 23 % , 11/48 , p = 0.02 ) . Of the 104 patients without symptoms , 94 ( 90 % ) recovered within six months and 62 ( 60 % ) within three months . Patients without symptoms who received advice or physiotherapy wore a collar for a significantly shorter time than those with persistent symptoms ( mean duration 1.4 ( SD 0.7 ) months v 2.8 ( 1.6 ) months , p = 0.005 and 1.6 ( 1.1 ) months v 1.8 ( 1.3 ) months , p = 0.006 respectively ) . CONCLUSIONS --Advice to mobilise in the early phase after neck injury reduces the number of patients with symptoms at two years and is superior to manipulative physiotherapy . Prolonged wearing of a collar is associated with persistence of symptoms Study Design . A question naire was mailed to 3000 r and omly selected 35‐45‐year‐old individuals in three communities in central Sweden . Objectives . To study the 1‐year prevalence of spinal pain and its ramifications in the form of pain , function , sick leave , and health care use . Summary of Background Data . Previous research ers have used a variety of definitions and population s , but primarily have investigated the occurrence of pain . Comprehensive data are needed concerning health care use , the degree of the pain problem , functional disturbances , and sick leave . Method . Participants in the study completed a question naire regarding spinal pain during the past year including the degree of their experienced pain , functional impairment , lost work days , and health care use . Results . A total of 2305 people ( 78.5 % ) responded to the question naire . Nonrespondents had similar characteristics but a slightly lower 1‐year prevalence rate than did respondents . For respondents , the prevalence of spinal pain during the past year was 66.3 % , with women having a slightly higher prevalence than men . Approximately 25 % of the respondents indicated that they had a substantial problem based on ratings of pain , functional impairment , and sick leave . Work absenteeism reported to the Public Social Insurance Office involved 19 % of those with pain , but an additional 15 % indicated unreported absenteeism . On average , those with pain visited health care providers three times during the past year , but a small number of those who experienced pain consumed large amounts of health care and illness benefits . An important gender difference was shown , such that when pain was at its worst , men took sick leave , whereas women sought health care . Conclusions . Taken together , these data indicate that spinal pain is common among 35‐45‐year‐old men and ‐ women , and that it is related to marked problems for approximately one fourth of those who experience pain . Gender differences exist in the pattern of sick leave and health care use , and a small proportion of those with pain consume very large amounts of the re sources . Consequently , there is a need for early , effective , preventive treatments Objectives The authors ' goals were to compare the effectiveness of manual therapy ( MT ; mainly spinal mobilization ) , physical therapy ( PT ; mainly exercise therapy ) , and continued care by the general practitioner ( GP ; analgesics , counseling and education ) over a period of 1 year . Methods One hundred eighty-three patients suffering for at least 2 weeks from nonspecific neck pain were r and omized to receive a 6-week treatment strategy of MT once a week , PT twice a week , or GP care once every 2 weeks . The primary outcome measures were perceived recovery , severity of physical dysfunctioning , pain intensity , and functional disability . Results The differences between groups considered over 1 year were statistically significant ( repeated measurements analyses P<0.001 to P=0.02 ) for all outcomes but borderline for the Neck Disability Index ( P=0.06 ) . Higher improvement scores were observed for MT for all outcomes , followed by PT and GP care . The success rate , based on perceived recovery after 13 weeks , was 72 % for MT , which was significantly higher than the success rate for continued GP care ( 42 % , P=0.001 ) but not significantly higher compared with PT treatment ( 59 % , P=0.16 ) . The difference between PT and GP approached statistical significance ( P=0.06 ) . After 1 year the success rates were 75 % , 63 % , and 56 % , respectively , and no longer significantly different . Conclusions Short-term results ( at 7 weeks ) have shown that MT speeded recovery compared with GP care and , to a lesser extent , also compared with PT . In the long-term , GP treatment and PT caught up with MT , and differences between the three treatment groups decreased and lost statistical significance at the 13-week and 52-week follow-up Abstract The inability to predict outcome in patients with low back/neck pain leads to inappropriate or unnecessary treatment . The aims of the study were to identify prognostic factors for disability at 1‐year follow‐up in patients with back pain visiting primary care , and to compare the effect of these in two treatment strategies – chiropractic and physiotherapy . Data were taken from a r and omised trial on patients with back/neck pain visiting the general practitioner , in which patients were allocated to chiropractic and physiotherapy as primary management . Three hundred and twenty‐three patients , aged 18–60 years , who had no contraindications to manipulation and who had not been treated within the previous month were included in the study . Multiple regression analysis was used to identify prognostic factors . Dependent variables were mean Oswestry score and mean change in Oswestry score at 12‐month follow‐up . The multiple regression analysis revealed five significant ( P<0.001–0.01 ) prognostic factors ; duration of current episode , Oswestry score at entry , expectations of treatment , number of localisations , and well‐being . Besides , the regression coefficients for the significant factors were compared between the two treatment strategies . No significant difference in effect or regression coefficients for the prognostic factors were seen between the two treatment strategies . Twelve per cent of the patients had poor prognostic factors ( duration ≥1 month , more than one localisation , low expectations of treatment and low well‐being ) at entry . These patients had a mean Oswestry score above 20 % at 1‐year follow‐up . Clinical decision models for the management of patients with back pain visiting primary care that consider prognostic factors need to be implemented and prospect ively evaluated PURPOSE To study whether the isolated intervention of high-speed , low-amplitude spinal manipulation in the cervical spine has any effect on cervicogenic headache . DESIGN Prospect i ve r and omized controlled trial with a blinded observer . SETTING Ambulatory outpatient facility in an independent research institution . PARTICIPANTS Fifty-three subjects suffering from frequent headaches who fulfilled the International Headache Society criteria for cervicogenic headache ( excluding radiological criteria ) . These subjects were recruited from 450 headache sufferers who responded to newspaper advertisements . INTERVENTION After r and omization , 28 of the group received high-velocity , low-amplitude cervical manipulation twice a week for 3 wk . The remaining 25 received low-level laser in the upper cervical region and deep friction massage ( including trigger points ) in the lower cervical/upper thoracic region , also twice a week for 3 wk . MAIN OUTCOME MEASURES The change from week 1 to week 5 in analgesic use per day , in headache intensity per episode and in number of headache hours per day , as registered in a headache diary . RESULTS The use of analgesics decreased by 36 % in the manipulation group , but was unchanged in the soft-tissue group ; this difference was statistically significant ( p = .04 , chi 2 for trend ) . The number of headache hours per day decreased by 69 % in the manipulation group , compared with 37 % in the soft-tissue group ; this was significant at p = .03 ( Mann-Whitney ) . Finally , headache intensity per episode decreased by 36 % in the manipulation group , compared with 17 % in the soft-tissue group ; this was significant at p = .04 ( Mann-Whitney ) . CONCLUSION Spinal manipulation has a significant positive effect in cases of cervicogenic headache OBJECTIVE To determine the relative effect of instrument-delivered thrust cervical manipulations in comparison with traditional manual-delivered thrust cervical manipulations in the treatment of cervical spine dysfunction . DESIGN Prospect i ve , r and omized , comparative clinical trial . SETTING Outpatient chiropractic clinic , Technikon Natal , South Africa . PATIENTS Thirty patients diagnosed with neck pain and restricted cervical spine range of motion without complicating pathosis for at least 1 month were included in the study . INTERVENTIONS The patients were r and omized into 2 groups . Those in one group received mechanical force , manually assisted ( MFMA ) manipulation to the cervical spine , delivered by means of a h and -held instrument ( Activator II Adjusting Instrument ) . Those in the other group received specific contact high-velocity , low-amplitude ( HVLA ) manipulation consisting of st and ard Diversified rotary/lateral break techniques to the cervical spine . Each group received only the specific therapeutic intervention , no other treatment modalities or interventions ( including medication ) being used , until asymptomatic status was achieved or a maximum of 8 treatments had been received . MAIN OUTCOME MEASURES Both treatment groups were assessed through use of subjective ( Numerical Pain Rating Scale 101 , McGill Short-Form Pain Question naire , and Neck Disability Index ) and objective ( goniometer cervical range of motion ) measurement parameters at specific intervals during the treatment period and at 1-month follow-up . The data were assessed through use of 2-tailed nonparametric paired and unpaired analysis , descriptive statistics , and power analysis of the data . RESULTS The results indicate that both treatment methods had a positive effect on the subjective and objective clinical outcome measures , no significant difference being observed between the 2 groups ( P < .025 ) . The subjective data from all 3 question naires showed statistically significant changes from initial to final consultations as well as from initial consultation to 1-month follow-up ( P < .025 ) . The objective range of motion measures showed statistically significant changes in the MFMA group for left and right rotation and left and right lateral flexion from initial consultation to final consultations and for right rotation and right lateral flexion from initial consultation to 1-month follow-up . The HVLA group showed only the change in left rotation from initial to final consultations and from initial consultation to 1-month follow-up to be statistically significant . CONCLUSIONS The results of this clinical trial indicate that both instrumental ( MFMA ) manipulation and manual ( HVLA ) manipulation have beneficial effects associated with reducing pain and disability and improving cervical range of motion in this patient population . A r and omized , controlled clinical trial in a similar patient base with a larger sample size is necessary to verify the clinical relevance of these findings Study Design . A multicenter , r and omized controlled trial with unblinded treatment and blinded outcome assessment was conducted . The treatment period was 6 weeks with follow-up assessment after treatment , then at 3 , 6 , and 12 months . Objectives . To determine the effectiveness of manipulative therapy and a low-load exercise program for cervicogenic headache when used alone and in combination , as compared with a control group . Summary of Background Data . Headaches arising from cervical musculoskeletal disorders are common . Conservative therapies are recommended as the first treatment of choice . Evidence for the effectiveness of manipulative therapy is inconclusive and available only for the short term . There is no evidence for exercise , and no study has investigated the effect of combined therapies for cervicogenic headache . Methods . In this study , 200 participants who met the diagnostic criteria for cervicogenic headache were r and omized into four groups : manipulative therapy group , exercise therapy group , combined therapy group , and a control group . The primary outcome was a change in headache frequency . Other outcomes included changes in headache intensity and duration , the Northwick Park Neck Pain Index , medication intake , and patient satisfaction . Physical outcomes included pain on neck movement , upper cervical joint tenderness , a craniocervical flexion muscle test , and a photographic measure of posture . Results . There were no differences in headache-related and demographic characteristics between the groups at baseline . The loss to follow-up evaluation was 3.5 % . At the 12-month follow-up assessment , both manipulative therapy and specific exercise had significantly reduced headache frequency and intensity , and the neck pain and effects were maintained ( P < 0.05 for all ) . The combined therapies was not significantly superior to either therapy alone , but 10 % more patients gained relief with the combination . Effect sizes were at least moderate and clinical ly relevant . Conclusion . Manipulative therapy and exercise can reduce the symptoms of cervicogenic headache , and the effects are maintained OBJECTIVE To assess postural performance in patients with dizziness of suspected cervical origin in whom extracervical causes had been excluded , and to assess the effects of physiotherapy on postural performance and subjective complaints of neck pain and dizziness . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Primary care centers and a tertiary referral center . PATIENTS AND SUBJECTS Of 65 referrals , 43 patients were excluded because extracervical etiology was suspected . Of the remaining 22 patients , 17 completed the study ( 15 women , 2 men , x age 37 yr , range 26 - 49 ) . The controls were 17 healthy subjects ( 15 women , 2 men , x age 36 yr , range 25 - 55 ) . INTERVENTION Physiotherapy based on analysis of symptoms and findings , and aim ed to reduce cervical discomfort . Patients were r and omized either to receive immediate physiotherapy ( n = 9 ) , or to wait 2 months , undergo repeat measurements , and then receive physiotherapy ( n = 8) . MAIN OUTCOME MEASURES Posturography , measuring velocity and variance of vibration-induced body sway and variance of galvanically induced body sway . Subjective intensity of neck pain ( Visual Analog Scale ratings , 0 - 100 ) , intensity and frequency of dizziness ( subjective score 0 - 4 ) . RESULTS The patients manifested significantly poorer postural performance than did healthy subjects ( .05 > p > .0001 ) . Physiotherapy significantly reduced neck pain and intensity and the frequency of dizziness ( p < .01 ) , and significantly improved postural performance ( .05 > p > .0007 ) . CONCLUSIONS Patients with dizziness of suspected cervical origin are characterized by impaired postural performance . Physiotherapy reduces neck pain and dizziness and improves postural performance . Neck disorders should be considered when assessing patients complaining of dizziness , but alternative diagnoses are common Thirty patients with acute cervical pain were r and omized into 3 groups and treated with neck collar , transcutaneous nerve stimulation , or manual therapy . The improvement was rapid in all groups , but the restoration of the cervical mobility was significantly more rapid in the transcutaneous nerve stimulation group . Some of the patients with manual therapy treatment had remarkably quick symptom reduction , although this was not significantly better than the collar alone . It is concluded that transcutaneous nerve stimulation is a valuable pain reducer and gives a more rapid restoration of cervical mobility in acute cervical pain Methods of sample size and power calculations are review ed for the most common study design s. The sample size and power equations for these design s are shown to be special cases of two generic formulae for sample size and power calculations . A computer program is available that can be used for studies with dichotomous , continuous , or survival response measures . The alternative hypotheses of interest may be specified either in terms of differing response rates , means , or survival times , or in terms of relative risks or odds ratios . Studies with dichotomous or continuous outcomes may involve either a matched or independent study design . The program can determine the sample size needed to detect a specified alternative hypothesis with the required power , the power with which a specific alternative hypothesis can be detected with a given sample size , or the specific alternative hypotheses that can be detected with a given power and sample size . The program can generate help messages on request that facilitate the use of this software . It writes a log file of all calculated estimates and can produce an output file for plotting power curves . It is written in FORTRAN-77 and is in the public domain Nine subjects with chronic mechanical neck pain syndromes were evaluated for pressure pain threshold ( PPT ) over st and ardized tender points in the paraspinal area surrounding a manipulable spinal lesion . The subjects were then allocated r and omly to an intervention consisting of either an oscillatory mobilization of the cervical spine ( n = 4 ) , which was design ated as the control procedure , or a rotational manipulation of the cervical spine ( n = 5 ) . An assessor-blinded re-evaluation of the pressure pain threshold levels was conducted after 5 min . In the group receiving a manipulation the mean increases in pressure pain threshold ranged from 40 - 56 % with an average of 45 % . In the control group no change in any of the pressure pain thresholds was found . These results were analyzed using ANOVA and were found to be statistically significant ( p less than 0.0001 ) . This study confirms that manipulation can increase local paraspinal pain threshold levels . The use of the pressure pain threshold meter allows for the determination of such a beneficial effect in the deeper tissues Study Design . Population ‐based , cross‐sectional mailed survey . Objective . To determine the lifetime , period , and point prevalence of neck pain and its related disability among Saskatchewan adults and investigate the presence and strength of nonresponse bias . Summary of Background Data . In Europe , the life‐time and point prevalence of neck pain is almost as high as the prevalence of low back pain . Similarly , chronic neck pain is highly prevalent and a common source of disability in the working‐age population . However , no studies specifically have documented the prevalence of neck pain and its related disability in North America . Methods . The Saskatchewan Health and Back Pain Survey was mailed to 2184 r and omly selected Saskatchewan adults aged 20‐69 years . Fifty‐five percent of the study population participated . The presence of nonresponse bias was investigated through logistic regression and wave analysis . The Chronic Pain Question naire was used to classify the severity of chronic neck pain . Results . The age‐st and ardized lifetime prevalence of neck pain is 66.7 % ( 95 % confidence interval , 63.8‐69.5 ) , and the point prevalence is 22.2 % ( 95 % confidence interval , 19.7‐24.7 ) . The age‐st and ardized 6‐month prevalence of low‐intensity and low‐disability neck pain is 39.7 % ( 95 % confidence interval , 36.7‐42.7 ) , whereas it is 10.1 % ( 95 % confidence interval , 8.2‐11.9 ) for high‐intensity and low‐disability neck pain and 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) for significantly disabling neck pain . The prevalence of low‐intensity and low‐disability neck pain decreases with age . More women experience high‐disability neck pain than men . Wave analysis suggests that the point prevalence and 6‐month prevalence of high‐intensity and low‐disability neck pain are overestimated in this survey . Conclusion . This cross‐sectional study shows that neck pain is highly prevalent in Saskatchewan and that it significantly disables 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) of the adult population Study Design . A r and omized , parallel-group , single-blinded clinical trial was performed . After a 1-week baseline period , patients were r and omized to 11 weeks of therapy , with posttreatment follow-up assessment 3 , 6 , and 12 months later . Objectives . To compare the relative efficacy of rehabilitative neck exercise and spinal manipulation for the management of patients with chronic neck pain . Summary of Background Data . Mechanical neck pain is a common condition associated with substantial morbidity and cost . Relatively little is known about the efficacy of spinal manipulation and exercise for chronic neck pain . Also , the combination of both therapies has yet to be explored . Methods . Altogether , 191 patients with chronic mechanical neck pain were r and omized to receive 20 sessions of spinal manipulation combined with rehabilitative neck exercise ( spinal manipulation with exercise ) , MedX rehabilitative neck exercise , or spinal manipulation alone . The main outcome measures were patient-rated neck pain , neck disability , functional health status ( as measured by Short Form-36 [ SF-36 ] ) , global improvement , satisfaction with care , and medication use . Range of motion , muscle strength , and muscle endurance were assessed by examiners blinded to patients ’ treatment assignment . Results . Clinical and demographic characteristics were similar among groups at baseline . A total of 93 % of the patients completed the intervention phase . The response rate for the 12-month follow-up period was 84 % . Except for patient satisfaction , where spinal manipulative therapy and exercise were superior to spinal manipulation with ( P = 0.03 ) , the group differences in patient-rated outcomes after 11 weeks of treatment were not statistically significant ( P = 0.13 ) . However , the spinal manipulative therapy and exercise group showed greater gains in all measures of strength , endurance , and range of motion than the spinal manipulation group ( P < 0.05 ) . The spinal manipulation with exercise group also demonstrated more improvement in flexion endurance and in flexion and rotation strength than the MedX group ( P < 0.03 ) . The MedX exercise group had larger gains in extension strength and flexion – extension range of motion than the spinal manipulation group ( P < 0.05 ) . During the follow-up year , a greater improvement in patient-rated outcomes were observed for spinal manipulation with exercise and for MedX exercise than for spinal manipulation alone ( P = 0.01 ) . Both exercise groups showed very similar levels of improvement in patient-rated outcomes , although the spinal manipulation and exercise group reported greater satisfaction with care ( P < 0.01 ) . Conclusions . For chronic neck pain , the use of strengthening exercise , whether in combination with spinal manipulation or in the form of a high-technology MedX program , appears to be more beneficial to patients with chronic neck pain than the use of spinal manipulation alone . The effect of low-technology exercise or spinal manipulative therapy alone , as compared with no treatment or placebo , and the optimal dose and relative cost effectiveness of these therapies , need to be evaluated in future studies One year after head trauma , 23 patients with post-traumatic headache entered a prospect i ve clinical controlled trial to find out if specific manual therapy on the neck could reduce the headache . The study was completed by 19 patients ( 83 % ) . Ten patients were treated twice with manual therapy and nine patients were treated twice with cold packs on the neck . The pain index was calculated blindly . Two weeks after the last treatment the mean pain index was significantly reduced to 43 % in the group treated with manual therapy compared with the pretreatment level . At follow-up five weeks later , the pain index was still lower in this group compared with the group treated with cold packs , but this difference was not statistically significant . The pain index for all 19 patients was significantly correlated to the use of analgesics as well as to the frequency of associated symptoms ( number of days per week with dizziness , visual disturbances and ear symptoms ) . It is concluded that the type of manual therapy used in this study seems to have a specific effect in reducing post-traumatic headache . The result supports the hypothesis of a cervical mechanism causing post-traumatic headache and suggests that post-traumatic dizziness , visual disturbances and ear symptoms could be part of a cervical syndrome Study Design . A r and omized , prospect i ve clinical study was conducted that included 119 patients with chronic neck pain of greater than 3 months ' duration . Objectives . To compare the relative effectiveness of intensive training of the cervical musculature , a physiotherapy treatment regimen , and chiropractic treatment on this patient group . Summary of Background Data . There are only a few studies involving chronic neck pain patients representative of those seeking care in primary health care centers . Mobilization techniques and intensive training have been shown to be useful , but cervical manipulation has not been assessed . Clinical results involving these commonly used therapies have not been compared . Methods . A total of 167 consecutive patients were screened . One hundred nineteen patients were admitted to the study and were r and omized according to Taves ' minimization principles . Primary outcome measures included self‐reported pain , disability , medication use , patients ' perceived effect , and physician 's global assessment . Patients were assessed at enrollment and at completion of the study . Postal question naires were used to carry out 4‐ and 12‐month follow‐up assessment s. Secondary outcome measures included active range of motion of the cervical spine as well as strength and endurance measurements of the cervical musculature . These measurements were carried out at enrollment and completion of the study . Results . A total of 88 % of the patients completed the study . Of these , 97 % completed the 4‐month question naire and 93 % the 12‐month question naire . Patients from all three groups demonstrated significant improvements regarding self‐reported pain and disability on completion of the study . Improvements were maintained throughout the follow‐up period . Medication use was also significantly reduced in all groups . There was , however , no significant difference between groups at any assessment period . Physician 's and patients ' assessment s were also positive , and again group scores were essentially equal . Patients who underwent intensive training demonstrated significantly greater endurance levels at the completion of treatment . Conclusions . There was no clinical difference between the three treatments . All three treatment interventions demonstrated meaningful improvement in all primary effect parameters . Improvements were maintained at 4‐ and 12‐month follow‐up . However , whether this was a result of the treatments or simply a result of time is unknown . Future studies will be necessary to delineate ideal treatment strategies PURPOSE To describe and explore the relationships between pain , emotional state and coping strategies in patients with chronic radicular neck pain before and after surgery or conservative treatments . METHODS We r and omize 81 conseutive patients with cervical radicular pain and nerve root compression , verified by MRI , to either surgical decompression with fusion or physiotherapy or neck collar . Emotional state was both measured with Mood Adjective Check List . Hospital Anxiety and Depression Scale and with a Coping Strategies Question naire . Pain was measured with VAS and function with Disability Index Rating . Measurements were made before treatment , and follow ups after 3 and 12 months post treatment . RESULTS We found generally a low emotional state with anxiety , depression and sleep-disturbances not only connected to pain . Pain improved faster in the surgery group but after one year no differences were seen . Surgery and physiotherapy improved function with heavy work compared to collar after 3 months . Many patients used active coping before treatment , but after treatment more passive coping strategies were found . CONCLUSION We recommend a multidisciplinary rehabilitation with cognitive behavioural therapy and psychological interventions STUDY DESIGN R and omized clinical trial . OBJECTIVES To analyze the immediate treatment effects of cervical mobilization and therapeutic ultrasound in patients with neurogenic cervicobrachial pain . BACKGROUND Different treatment modalities have been described for patients with neurogenic cervicobrachial pain . Although it has been suggested that a more specific approach , like cervical mobilization , would be more effective , effect studies are scarce . METHODS AND MEASURES Twenty patients with subacute peripheral neurogenic cervicobrachial pain were assessed . Besides other criteria , patients were included if a cervical segmental motion restriction was present which could be regarded as a possible cause of the neurogenic disorder . Patients were r and omly assigned to a mobilization or ultrasound group . Mobilization consisted of a contralateral lateral glide technique . The range of elbow extension , symptom distribution , and pain intensity during the neural tissue provocation test for the median nerve were used as outcome measures . Results were analyzed using a 2-way mixed- design ANOVA . RESULTS Significant differences in treatment effects between the 2 groups could be observed for all outcome measures ( P < or = .0306 ) . For the mobilization group , the increase in elbow extension from 137.3 degrees to 156.7 degrees , the 43.4 % decrease in area of symptom distribution , and the decreased pain intensity from 7.3 to 5.8 were significant ( P < or = .0003 ) . For the ultrasound group , there were no significant improvements ( P > or = .0521 ) . CONCLUSIONS When a cervical dysfunction can be regarded as a cause of the neurogenic disorder or as a contributing factor that impedes natural recovery , a cervical lateral glide mobilization has positive immediate effects in patients with subacute peripheral neurogenic cervicobrachial pain . This movement-based approach seems preferable to ultrasound Cervico-brachial pain syndrome is an upper quarter pain condition in which mechanosensitive neural tissue is considered a primary feature . A single-blind r and omized controlled trial was conducted to determine the clinical effect of two manual therapy interventions . Thirty subjects ( 20 females and 10 males ) were r and omly allocated to one of three groups - one of two manual therapy intervention groups or a control group . One manual therapy intervention group consisted of passive techniques aim ed at mobilizing neural tissue structures and the cervical spine . The other involved indirect manual therapy techniques with a focus on articular components of the gleno-humeral joint and thoracic spine . The treatment period lasted 8 weeks in total and was combined with a home exercise programme . Following the 8-week baseline period the control group were crossed over into the specific neural tissue manual therapy group . Pain visual analogue scale ( VAS ) , the short-form McGill pain and Northwick Park neck pain question naires were completed before , midway and after the treatment period . The findings suggest that both manual physiotherapy interventions combined with home exercises are effective in improving pain intensity , pain quality scores and functional disability levels . A group difference was observed for the VAS scores at 8 weeks with the neural manual therapy technique having a significantly lower score OBJECTIVES This study compared the relative effectiveness of cervical spine manipulation and mobilization for neck pain . METHODS Neck-pain patients were r and omized to the following conditions : manipulation with or without heat , manipulation with or without electrical muscle stimulation , mobilization with or without heat , and mobilization with or without electrical muscle stimulation . RESULTS Of 960 eligible patients , 336 enrolled in the study . Mean reductions in pain and disability were similar in the manipulation and mobilization groups through 6 months . CONCLUSIONS Cervical spine manipulation and mobilization yield comparable clinical outcomes This prospect i ve , r and omised study compares the efficacy of surgery , physiotherapy and cervical collar with respect to pain , motor weakness and sensory loss in 81 patients with long-lasting cervical radiculopathy corresponding to a nerve root that was significantly compressed by spondylotic encroachment , with or without an additional bulging disk , as verified by MRI or CT-myelography . Pain intensity was registered on a visual analogue scale ( VAS ) , muscle strength was measured by a h and -held dynamometer , Vigorometer and pinchometer . Sensory loss and paraesthesia were recorded . The measurements were performed before treatment ( control 1 ) , 4 months after the start of treatment ( control 2 ) and after a further 12 months ( control 3 ) . A healthy control group was used for comparison and to test the reliability of the muscle-strength measurements . The study found that before start of treatment the groups were uniform with respect to pain , motor weakness and sensory loss . At control 2 the surgery group reported less pain , less sensory loss and had better muscle strength , measured as the ratio of the affected side to the non-affected side , compared to the two conservative treatment groups . After a further year ( control 3 ) , there were no differences in pain intensity , sensory loss or paraesthesia between the groups . An improvement in muscle strengths , measured as the ratio of the affected to the non-affected side , was seen in the surgery group compared to the physiotherapy group in wrist extension , elbow extension , shoulder abduction and internal rotation , but there were no differences in the ratios between the collar group and the other treatment groups . With respect to absolute muscle strength of the affected sides , there were no differences at control 1 . At control 2 , the surgery group performed somewhat better than the two other groups but at control 3 there were no differences between the groups . We conclude that pain intensity , muscle weakness and sensory loss can be expected to improve within a few months after surgery , while slow improvement with conservative treatments and recurrent symptoms in the surgery group make the 1-year results about equal OBJECTIVE To compare needle acupuncture , medication ( tenoxicam with ranitidine ) , and spinal manipulation for managing chronic ( > 13 weeks duration ) spinal pain syndromes . DESIGN Prospect i ve , r and omized , independently assessed preintervention and postintervention clinical pilot trial . SETTING Specialized spinal pain syndrome out-patient unit at Townsville General Hospital , Queensl and , Australia . SUBJECTS Seventy-seven patients ( without contraindication to manipulation or medication ) were recruited . INTERVENTIONS One of three separate , clearly defined intervention protocol s : needle acupuncture , nonsteroidal anti-inflammatory medication , or chiropractic spinal manipulation . MAIN OUTCOME MEASURES Main outcome measures were changes ( 4 weeks vs. initial visit ) in the scores of the ( 1 ) Oswestry Back Pain Disability Index , ( 2 ) Neck Disability Index , and ( 3 ) three visual analogue scales of local pain intensity . RESULTS R and omization was successful . After a median intervention period of 30 days , spinal manipulation was the only intervention that achieved statistically significant improvements ( all expressed as percentages of the original scores ) with ( 1 ) a reduction of 30.7 % on the Oswestry scale , ( 2 ) an improvement of 25 % on the neck disability index , and ( 3 ) reductions on the visual analogue scale of 50 % for low back pain , 46 % for upper back pain , and 33 % for neck pain ( all P<.001 ) . Neither of the other interventions showed any significant improvement on any of the outcome measures . CONCLUSIONS The consistency of the results provides , in spite of several discussed shortcomings of this pilot study , evidence that in patients with chronic spinal pain syndromes spinal manipulation , if not contraindicated , results in greater improvement than acupuncture and medicine In acute whiplash injuries , early physiotherapy has been shown to reduce pain and increase cervical movement , but the cost-effectiveness of this treatment has been question ed . It is unclear whether the benefits result from manipulative physiotherapy or from the patient 's ability to perform the accompanying home exercise programme when instructed about its importance . In a single blind prospect i ve r and omized trial 71 patients who received out-patient physiotherapy were shown to have significant improvement in severity of neck pain ( P less than 0.01 ) and cervical movement ( P less than 0.01 ) at 1 and 2 months post-injury when compared with 33 patients who received analgesia and a cervical collar . Sixty-six patients who were offered comprehensive advice for home mobilization by a physiotherapist showed a similar improvement . There appears to be no difference in effectiveness between outpatient physiotherapy and home mobilization PURPOSE To study whether a 3-wk series of spinal manipulation has any lasting effect on passive cervical range of motion . DESIGN R and omized , controlled trial with a blind observer . SETTING Ambulatory outpatient facility in an independent National Health Service funded chiropractic research institution . PARTICIPANTS Thirty-nine headache sufferers who , on entering the study , displayed objective ly decreased passive cervical range of motion . These subjects were recruited from 400 headache sufferers who responded to newspaper advertisements . INTERVENTION Half of the group received high-velocity , low-amplitude cervical manipulation twice a week for 3 wk . The other half received low-level laser in the upper cervical region and deep friction massage in the lower cervical/upper thoracic region , also twice a week for 3 wk . MAIN OUTCOME MEASURE Goniometrically assessed passive range of motion of the cervical spine . RESULTS Although passive cervical range of motion increased in both groups during the trial period , there were no statistically significant differences between the two groups 1 wk after the last treatment . CONCLUSION It seems that any changes in passive range of motion after spinal manipulation are of a temporary nature Study Design . This prospect i ve , r and omized study compares the efficacy of surgical and conservative treatments in patients with long-lasting cervical radicular pain . Objectives . To compare the effects of surgery , physiotherapy , and a cervical collar . Summary of Background Data . There are no previous controlled outcome studies that have compared surgical treatment with nonsurgical treatment of patients with cervical radicular pain . Methods . The study group comprised 81 patients with cervicobrachial pain of at least 3 months ' duration , in whom the distribution of the arm pain corresponded to a nerve root that was significantly compressed by spondylotic encroachment with or without an additional bulging disc , as verified by magnetic resonance imaging or computed tomographic myelography . The patients were r and omly allocated to surgery ( Cloward technique ) , individually adapted physiotherapy , or a cervical collar . The therapeutic effects were evaluated with respect to pain intensity by the visual analogue scale , function by the Sickness Impact Profile , and mood by the Mood Adjective Check List . The measurements were performed before treatment ( control 1 ) , shortly after treatment ( control 2 ) , and after a further 12 months ( control 3 ) . Results . At control 1 , the groups were uniform . At control 2 , the surgery group reported less pain ( visual analogue scale ) and , like the physiotherapy group , better function ( Sickness Impact Profile ) than the collar group . At control 3 , there was no difference in visual analogue scale , Sickness Impact Profile , and Mood Adjective Check List measurements among the groups . Conclusions . In the treatment of patients with long-lasting cervical radicular pain , it appears that a cervical collar , physiotherapy , or surgery are equally effective in the long term The study was initiated to evaluate the effect of pain-reducing therapies on factors previously associated with work-related shoulder and neck pain , namely increased muscle activity in the upper trapezius and perceived general tension . Thirty-three women in three groups were assessed before and after an intervention period and by question naire 6 months later . The purpose of this study was primarily to investigate associations between upper trapezius muscle activity , perceived general tension and pain , and secondly , to compare effects of individually based physiotherapy and group exercise for workers with shoulder and neck myalgia . All three groups reported a significant alleviation of pain and perceived general tension , while the electromyographically ( EMG ) recorded upper trapezius muscle activity level remained unchanged or increased . Improvements were similar in all three treatment groups , but individual-based therapies were rated more beneficial on subjective measures . Significant correlation was found between pain and perceived general tension ( r = 0.66 , p < 0.01 ) , while there was no correlation between pain or perceived general tension and recorded muscle activity OBJECTIVE To evaluate the possible effect of the supine cervical rotary manipulation and the supine lateral break manipulation in the treatment of mechanical neck pain , according to subjective and objective clinical findings . BACKGROUND Delivering a supine lateral break manipulation to the ipsilateral side of an inflamed facet joint(s ) that exhibits a lateral flexion fixation may result in pain and /or discomfort to the patient . Thus the proposed alternative is a supine cervical rotary manipulation delivered on the ipsilateral side or a supine lateral break manipulation delivered on the contralateral side of the relevant joint(s ) . DESIGN R and omized , comparative clinical trial . SUBJECTS Two groups of 15 subjects diagnosed with mechanical neck pain . INTERVENTION The diagnosis of mechanical neck pain and the identification of lateral flexion fixations in the cervical spine were made with conventional clinical evaluation , including motion palpation . Group A received a cervical rotary manipulation(s ) on the ipsilateral side of the lateral flexion fixation(s ) , while group B received a supine lateral break manipulation(s ) on the contralateral side of the lateral flexion fixation(s ) . Subjects received a maximum of 10 treatments over a 4-week treatment period . OUTCOME MEASURES Both treatment groups were assessed with subjective ( Numerical Pain Rating Scale 101 , McGill Short-Form Pain Question naire and the Canadian Memorial Chiropractic College Neck Disability Index ) and objective ( cervical range of motion goniometer and algometer ) measurement parameters at the initial consultation ( before any treatment ) , the final consultation , and at a 1-month follow-up consultation . Statistical analysis was conducted at a 95 % confidence level ( alpha = .05 ) with the non-parametric 2-tailed Wilcoxon signed ranks test , the Mann-Whitney U test , and descriptive statistics . Two-tailed power analysis was conducted after the fact , where a confidence level of 80 % ( beta = .20 ) was considered satisfactory . RESULTS Intragroup analysis indicated a significant difference between the initial consultation data and the final consultation data for the subjective data , indicating an effect . Analysis of the objective data did not reveal any significant difference . Intergroup analysis did not reveal any significant difference between the 2 groups when comparing the data of the initial consultation and the final consultation , indicating that both treatments had a similar or equal effect . Power analysis was not satisfactory for most data , indicating the possibility of many Type II errors . CONCLUSION AND RECOMMENDATIONS Statistically , the results suggested that both treatments had an effect but that neither group showed a benefit over the other . However , because of the unsatisfactory power of the study , conclusions are to be drawn with caution . Clinical significance supported the statistical outcomes where it was suggested that both treatments had an effect and that neither treatment had a greater effect . A larger sample size and the inclusion of a placebo group is recommended to reveal true treatment outcomes and trends A r and omized controlled trial of manipulation of the cervial spine was carried out on 52 patients in general practice , and the results were assessed symptomatically and goniometrically for three weeks . Manipulation produced a significant immediate improvement in symptoms in those with pain or stiffness in the neck , and pain/paraesthesia in the shoulder , and a nearly significant improvement in those with pain/paraesthesia in the arm/h and . Manipulation also produced a significant increase in measured rotation that was maintained for three weeks and an immediate improvement in lateral flexion that was not maintained . This is to our knowledge the first published formal trial of such manipulation and should increase interest in this form of treatment by the medical profession OBJECTIVE The main objective of this study is to compare the immediate results of manipulation to mobilization in neck pain patients . DESIGN The patients were compared in a r and omized controlled trial without long-term follow-up . SETTING The study was conducted at an outpatient teaching clinic on primary and referred patients . PATIENTS One hundred consecutive out patients suffering from unilateral neck pain with referral into the trapezius muscle were studied . Fifty-two subjects were manipulated and 48 subjects were mobilized . The mean ( SD ) age was 34.5 ( 13.0 ) yr for the manipulated group and 37.7 ( 12.5 ) yr for the mobilized group . Sixteen subjects had neck pain for less than 1 wk , 34 subjects had pain for between 1 wk and 6 mo and 50 subjects had pain for more than 6 mo . Seventy-eight subjects had a past history of neck pain . Thirty-one subjects had been involved in an injurious motor vehicle accident and 28 subjects had other types of minor trauma to the neck . There were no significant differences between the two treatment groups with respect to history of neck pain or level of disability as measured by the Pain Disability Index . INTERVENTION The patients received either a single rotational manipulation ( high-velocity , low-amplitude thrust ) or mobilization in the form of muscle energy technique . MAIN OUTCOME MEASURES Prior to and immediately after the treatments , cervical spine range of motion was recorded in three planes , and pain intensity was rated on the 101-point numerical rating scale ( NRS-101 ) . Both pre- and post-test measurements were conducted in a blinded fashion . RESULTS The results show that both treatments increase range of motion , but manipulation has a significantly greater effect on pain intensity . Eighty-five percent of the manipulated patients and 69 % of the mobilized patients reported pain improvement immediately after treatment . However , the decrease in pain intensity was more than 1.5 times greater in the manipulated group ( p = .05 ) . CONCLUSION This study demonstrates that a single manipulation is more effective than mobilization in decreasing pain in patients with mechanical neck pain . Both treatments increase range of motion in the neck to a similar degree . Further studies are required to determine any long-term benefits of manipulation for mechanical neck pain OBJECTIVE To review the literature on outcome studies of chiropractic/manipulation for tension-type and migraine headaches . DESIGN Qualitative literature review . RESULTS Of nine studies of manipulation for tension-type headaches that reported quantitative outcomes , four were r and omized clinical trials and five were case series design s. These studies reported on 729 subjects , 613 of whom received manipulation . Outcomes ranged from good to excellent . Manipulation seems to be better than no treatment , some types of mobilization and ice , and it seems to be equivalent to amitriptyline but with greater durability of effect than this medication . Of three studies on migraine , only one was a r and omized clinical trial . These studies reported on 202 subjects , 156 of whom received manipulation . The outcomes ranged from fair to very good . CONCLUSION A modest body of clinical studies exists dealing with the effect of manipulation and headache . The overall results are encouraging , even if not quite supportive in the case of tension-type headache . Further studies in this area are definitely warranted , particularly well-controlled studies in migraine Twenty-one patients with symptomatic cervical spondylosis or nonspecific neck pain were given an amnesic dose of diazepam before manipulation of the cervical spine . Eighteen patients served as controls and also received diazepam but no manipulation . Results were obtained in a r and omized , double-blind fashion . Statements of outcome by patients and mean visual analog scales for pain and activity showed no significant differences between manipulation and control groups , though both tests favored manipulation . Control subjects subsequently treated by manipulation showed no consistent favorable response . Question naires dealing with personality , life events , social and medical histories , etc . , provided no correlations with outcome , nor did radiographic findings . Diffuse local tenderness correlated with high pain scores after treatment . The authors conclude that the value of a single manipulation of the cervical spine has not been established and that further exploration of indications is needed . The use of intravenous diazepam should be considered because it allows a double-blind experimental design OBJECTIVE To evaluate the effectiveness of acupuncture , as compared with physiotherapy , in the management of chronic neck pain . DESIGN Seventy adult patients with non-inflammatory neck pain of > 6 weeks duration and with no abnormal neurology were r and omly assigned to receive either of the treatments . Thirty-five patients were included in each group . OUTCOME MEASURES Pain by visual analogue scale and neck pain question naire , improvement in range of movement of neck relative to baseline , and well-being ( general health question naire ) . Measurements were recorded at the start of treatment , at 6 weeks and at 6 months . RESULTS Both treatment groups improved in all criteria . Acupuncture was slightly more effective in patients who had higher baseline pain scores . CONCLUSIONS Both acupuncture and physiotherapy are effective forms of treatment . Since an untreated control group was not part of the study design , the magnitude of this improvement can not be quantified In order to assess the long-term efficacy of a multi-modal rehabilitation approach on whiplash injury , 60 patients were recruited within two months after neck injury . They were r and omly allocated either to an experimental multimodal treatment ( A ) consisting of postural training , manual technique and psychological support or to a control treatment ( B ) , using physical agents only , such as electrical and sonic modalities . Pain level , range of movement , self-rating scale of treatment efficacy and return-to-work delay were evaluated before and at the end of treatment , and later , 30 and 180 days after r and omisation . The benefit obtained with treatment " A " was greater and longer lasting than that experienced using " B " , despite the fact that the same benefit was obtained in joint mobility in the two groups . Patients undergoing the experimental treatment returned to their usual occupations sooner than the controls . The results seem to confirm the hypothesis of a multifactorial involvement as a possible mechanism for the late whiplash syndrome BACKGROUND Observation of the occurrence of protective muscle activity is advocated in assessment of the peripheral nervous system by means of neural provocation tests . However , no studies have yet demonstrated abnormal force generation in a patient population . OBJECTIVES To analyze whether aberrations in shoulder girdle-elevation force during neural tissue provocation testing for the median nerve ( NTPT1 ) can be demonstrated , and whether possible aberrations can be normalized following cervical mobilization . STUDY DESIGN A single-blind r and omized comparative controlled study . SETTING Laboratory setting annex in a manual therapy teaching practice . PARTICIPANTS Twenty patients with unilateral or bilateral neurogenic cervicobrachial pain . METHODS During the NTPT1 , we used a load cell and electrogoniometer to record continuously the shoulder-girdle elevation force in relation to the available range of elbow extension . Following r and omization , we analyzed the immediate treatment effects of a cervical contralateral lateral glide mobilization technique ( experimental group ) and therapeutic ultrasound ( control group ) . RESULTS On the involved side , the shoulder-girdle elevation force occurred earlier , and the amount of force at the end of the test was substantially , though not significantly , greater than that on the uninvolved side at the corresponding range of motion . Together with a significant reduction in pain perception after cervical mobilization , a clear tendency toward normalization of the force curve could be observed , namely , a significant decrease in force generation and a delayed onset . The control group demonstrated no differences . CONCLUSIONS Aberrations in force generation during neural provocation testing are present in patients with neurogenic pain and can be normalized with appropriate treatment modalities PURPOSE To determine whether the isolated intervention of high-velocity , low-amplitude spinal manipulation in the cervical spine has any effect on cervicogenic headache . DESIGN R and omized controlled trial with a blind observer . SETTING Ambulatory outpatient facility in an independent NHS-funded chiropractic research institution . PARTICIPANTS Thirty-nine subjects suffering from frequent headaches who fulfilled the IHS criteria for cervicogenic headache ( excluding radiological criteria ) . These subjects were recruited from among some 400 headache sufferers who responded to newspaper advertisements . INTERVENTION Half of the group received high-velocity , low-amplitude cervical manipulation twice/wk for 3 wk . The other half received low-level laser in the upper cervical region and deep friction massage ( including trigger points ) in the lower cervical/upper thoracic region , also twice/wk for 3 wk . MAIN OUTCOME MEASURE The change from week 2 to week 6 in analgesics use per day , headache intensity per episode and number of headache hr per day . RESULTS Despite a significant reduction in the manipulation group on all three outcome measures , differences between the two treatment groups failed to reach statistical significance . CONCLUSION The results suggest a possible effect of manipulation on cervicogenic headache , but because of method ological problems , such an effect could not be unequivocally demonstrated Context Neck pain is common among primary care patients . Evidence on the effectiveness of therapies for neck pain is limited . A previous r and omized , controlled trial suggested benefits from manual therapy and physical therapy . Contribution This r and omized , controlled trial of manual therapy , physical therapy , and continued care by a doctor confirms the superiority of manual therapy and physical therapy over continued care . At 7 weeks , 68.3 % of patients in the manual therapy group reported resolved or much improved pain , compared with 50.8 % of patients in the physical therapy group and 35.9 % of patients in the continued care group . Clinical Implication s Primary care physicians should consider manual therapy when treating patients with neck pain . The Editors Neck pain is a common problem in the general population , with point prevalences between 10 % and 15 % ( 1 - 3 ) . It is most common at approximately 50 years of age and is more common in women than in men ( 1 , 2 , 4 - 6 ) . Neck pain can be severely disabling and costly , and little is known about its clinical course ( 7 - 9 ) . Limited range of motion and a subjective feeling of stiffness may accompany neck pain , which is often precipitated or aggravated by neck movements or sustained neck postures . Headache , brachialgia , dizziness , and other signs and symptoms may also be present in combination with neck pain ( 10 , 11 ) . Although history taking and diagnostic examination can suggest a potential cause , in most cases the pathologic basis for neck pain is unclear and the pain is labeled nonspecific . Conservative treatment methods that are frequently used in general practice include analgesics , rest , or referral to a physical therapist or manual therapist ( 12 , 13 ) . Physical therapy may include passive treatment , such as massage , interferential current , or heat applications , and active treatment , such as exercise therapies . Physical therapists can specialize in passive manual ( or h and s-on ) techniques , including mobilization or manipulation ( high-velocity thrust techniques ) , also referred to as manual therapy ( 14 - 19 ) . According to the International Federation of Orthopedic Manipulative Therapies , Orthopedic manipulative ( manual ) therapy is a specialization within physical therapy and provides comprehensive conservative management for pain and other symptoms of neuro-musculo-articular dysfunction in the spine and extremities ( unpublished data ) . Today , many different manual therapy approaches are applied by various health professionals , including medical doctors , physical therapists , massage therapists , manual therapists , chiropractors , and osteopathic doctors . Review s of trials involving manual therapy or physical therapy show that most interventions in these categories are characterized by a combination of passive and active components ( 20 - 23 ) . Although a combination of manual therapy or physical therapy that includes exercises appears to be effective for neck pain , these therapies have not been studied in sufficient detail to draw firm conclusions , and the method ologic quality of most trials on neck pain is rather low ( 20 - 23 ) . Koes and colleagues ( 24 , 25 ) performed a r and omized trial on back and neck pain and found promising results for manual therapy and physical therapy in subgroup analyses of patients with neck pain . In our r and omized , controlled trial , we compared the effectiveness of manual therapy , physical therapy , and continued care by a general practitioner in patients with nonspecific neck pain . Methods Patients Patients with nonspecific neck pain whose clinical presentation did not warrant referral for further diagnostic screening were referred to one of four research centers by 42 general practitioners for study selection . We excluded patients whose history , signs , and symptoms suggested a potential nonbenign cause ( including previous surgery of the neck ) or evidence of a specific pathologic condition , such as malignancy , neurologic disease , fracture , herniated disc , or systemic rheumatic disease . Two research assistants who were experienced physical therapists and were blinded to treatment allocation performed physical examinations at baseline and follow-up . They used st and ardized inclusion and exclusion criteria and performed a short neurologic examination ( Appendix Table 1 ) and range-of-motion assessment . The eligibility criteria were age between 18 and 70 years , pain or stiffness in the neck for at least 2 weeks , neck symptoms reproducible during physical examination , willingness to adhere to treatment and measurement regimens , no physical therapy or manual therapy for neck pain during the previous 6 months , no involvement in litigation , and written informed consent . Patients with concurrent headaches , nonradicular pain in the upper extremities , and low back pain were not excluded , but neck pain had to be the main symptom for all patients . R and om Assignment and Data Collection All patient data were collected before r and omization . Patients were assigned to a treatment group on the basis of block r and omization after prestratification for symptom severity ( severity scores < 7 points or 7 points on a scale of 0 to 10 ) ; age ( < 40 years or 40 years ) ; and , mainly for practical reasons , research center ( four local centers ) . R and omized permuted blocks of six patients were generated for each stratum by using a computer-generated r and om-sequence table . A research er who was not involved in the project prepared opaque , sequentially numbered sealed envelopes that contained folded cards indicating one of the three interventions . Interventions The intervention period lasted 6 weeks . Patients were allowed to perform exercises at home and to continue medication prescribed at baseline or use over-the-counter analgesics . Other co- interventions were discouraged but were registered if they occurred . Within the boundaries of the protocol , treatment could be reassessed and adapted to the patient 's condition . The specific treatment characteristics were registered at each visit . A maximum number of visits was set for each intervention group ; however , the patients did not have to complete this maximum number if symptoms had resolved . Manual Therapy Our approach to manual therapy was eclectic and incorporated several techniques used in western Europe , North America , and Australia , including those described by Cyriax , Kaltenborn , Maitl and , and Mennel ( 15 , 16 , 19 ) . In our trial , manual therapy ( defined as the use of passive movements to help restore normal spinal function ) included h and s-on muscular mobilization techniques ( aim ed at improving soft tissue function ) , specific articular mobilization techniques ( to improve overall joint function and decrease any restrictions in movement at single or multiple segmental levels in the cervical spine ) , and coordination or stabilization techniques ( to improve postural control , coordination , and movement patterns by using the stabilizing cervical musculature ) ( 26 ) . Joint mobilization is a form of manual therapy that involves low-velocity passive movements within or at the limit of joint range of motion ( 27 ) . Manual therapists must undergo extensive training to be able to skillfully perform mobilization techniques ( 15 , 19 ) . Spinal manipulations ( low-amplitude , high-velocity thrust techniques ) were not included in this protocol . Forty-five minute treatment sessions were scheduled once per week , for a maximum of six treatments . Six experienced manual therapists acknowledged by the Netherl and s Manual Therapy Association performed the treatment . Physical Therapy The physical therapists used a combination of several treatment options , but active exercise therapies were the cornerstone of their strategy . Active exercise therapy involves participation by the patient and includes active exercises ( to improve strength or range of motion ) , postural exercises , stretching , relaxation exercises , and functional exercises . Manual traction or stretching , massage , or physical therapy methods , such as interferential current or heat applications , could precede the exercise therapy . Specific manual mobilization techniques were not included in this protocol . Thirty-minute treatment sessions were scheduled twice per week for a maximum of 12 treatments . The treatment was performed by five experienced physical therapists . We prevented cross-contamination with manual therapy by choosing physical therapists who were not manual therapy specialists . Continued Care by a General Practitioner Each patient in this group received st and ardized care from his or her general practitioner , including advice on prognosis , advice on psychosocial issues , advice on self-care ( heat application , home exercises ) , advice on ergonomics ( for example , size of pillow , work position ) , and encouragement to await further recovery . The treatment protocol was similar to the practice guidelines for low back pain issued by the Dutch College of General Practitioners ( 28 ) . Patients received an educational booklet containing ergonomic advice and exercises ( 29 ) . Medication , including paracetamol or nonsteroidal anti-inflammatory drugs , was prescribed on a time-contingent basis if necessary . Ten-minute follow-up visits , scheduled every 2 weeks , were optional , and referral during the intervention period was discouraged . Outcome Measures Data were collected at the research center after 3 and 7 weeks . At 7 weeks , treatment results were expected to be maximal . The patients were repeatedly asked not to reveal any information about their treatment allocation to the research assistants . The success of blinding was evaluated at 7 weeks . Primary outcome measures focused on perceived recovery , pain , and functional disability . Patients rated perceived recovery on a 6-point ordinal transition scale , ranging from much worse to completely recovered . Success was defined a priori as completely recovered or much improved ( 30 ) . In addition , on the basis of the systematic assessment of spinal mobility , palpation , and pain reported by |
11,982 | 28,368,090 | The quality of the evidence for the most important outcomes of bypass surgery versus PTA was high except for clinical improvement and primary patency .
Our analysis has shown that PTA is associated with decreased peri-interventional complications in participants treated for CLI and shorter hospital stay compared with bypass surgery .
Surgical treatment seems to confer improved patency rates up to one year .
Endovascular treatment may be advisable in patients with significant comorbidity , rendering them high risk surgical c and i date s. No solid conclusions can be drawn regarding comparisons of bypass surgery with other treatments because of the paucity of available evidence . | BACKGROUND Bypass surgery is one of the mainstay treatments for patients with critical lower limb ischaemia ( CLI ) .
This is the second up date of the review first published in 2000 .
OBJECTIVES To assess the effects of bypass surgery in patients with chronic lower limb ischaemia . | Poor patency of synthetic grafts for infragenicular revascularization has led to use of distal vein patches or cuffs . The aim of this study was to compare the distally widened DistafloTM PTFE graft , which mimics a vein cuff , with a PTFE graft with distal vein modification . In this prospect i ve , r and omized , multicenter trial we compared use of a precuffed PTFE graft wit that of PTFE grafts with distal vein modification for infragenicular revascularization in patients with critical limb ischemia without saphenous vein . Study end points were primary and secondary patency and limb salvage rates at 2 years . From January 28,1999 to November 1 , 2000 , 104 patients were enrolled in 10 North American centers . Thirteen were excluded for protocol violation . Ninety-one bypasses were performed in 89 patients with a mean age of 73 years ( range 47 - 90 ) . By r and omization , 47 bypasses were done with the precuffed graft and 44 with PTFE graft with vein cuff . Both groups were comparable for comorbidities and operative variables , except for a higher incidence of acute ischemia in the precuffed group ( 19 % vs. 4.5 % , p = 0.03 ) . Bypass was a redo procedure in 53 % and was performed at the infrapopliteal vessels in 79 % . Operative mortality was 2.2 % ( 2/91 ) . Mean follow-up was 14 months ( range 1 - 30 ) . At 1 and 2 years , primary patency was 52 % and 49 % for the precuffed group and 62 % and 44 % for the vein cuffed group , respectively ( p = 0.53 ) . At 1 year and 2 years , the limb salvage rate was 72 % and 65 % for the precuffed group and 75 % and 62 % in the vein cuffed group ( p = 0.88 ) . Although numbers are small and follow-up short , this midterm analysis shows similar results for the Distaflo precuffed grafts and PTFE grafts with vein cuff . A precuffed graft is a reasonable alternative conduit for infragenicular reconstruction in the absence of saphenous vein and provides favorable limb salvage 1 . The activities of phosphofructokinase ( PFK ) , citrate synthetase ( CS ) , lactate dehydrogenase ( LDH ) , 3-hydroxyacyl-CoA dehydrogenase ( ACDH ) and cytochrome-c oxidase(Cyt-ox ) in the calf muscle tissue were compared in subjects with intermittent claudication ( n = 38 ) and controls ( n = 20 ) . The activities of CS , ACDH and Cyt-ox were increased and the activity of Cytox was positively correlated to the maximal walking distance ( MWD ) in the patients . 2 . Thirty-three patients with intermittent claudication were r and omized to three treatment groups : ( 1 ) operative surgery , ( 2 ) operative surgery supplemented with physical training and ( 3 ) physical training alone . Before and after 6 - 12 months of treatment , symptom-free walking distance ( SFWD ) , MWD , ankle-brachial blood pressure quotient ( ankle index ) , maximal plethysmographic calf blood flow ( MPBF ) and the activities of PFK , CS , LDH , ACDH and Cyt-ox were measured . 3 . SFWD and MWD increased in all three groups . Ankle index and MPBF increased in groups 1 and 2 , but were unchanged in group 3 . The activities of Cyt-ox and CS decreased with operation , but the activity of Cyt-ox was further augmented with training in group 3 . Overall , the change in ankle index explained 80 - 90 % of the variability in walking performance . In a separate analysis , the increased activity of Cyt-ox in group 3 was positively correlated to , and explained 31 % of the variability in , the improvement in SFWD . 4 . These findings indicate that both physical activity and a reduced calf blood flow are necessary conditions for the enzymatic adaptation to take place . A causal relationship between metabolic adaptation in the muscle tissue and walking performance is suggested . ( ABSTRACT TRUNCATED AT 250 WORDS Intermittent claudication is the primary symptom of peripheral arterial disease , affecting between 1 and 3 million Americans . Symptomatic improvement can be achieved by endovascular revascularization , but such procedures are invasive , expensive , and may be associated with procedural adverse events . Medical treatment options , including claudication medications and supervised exercise training , are also known to be effective , albeit also with associated limitations . The CLEVER ( Claudication : Exercise Vs . Endoluminal Revascularization ) study , funded by the Heart , Lung , and Blood Institute of the National Institutes of Health , is a prospect i ve , multicenter , r and omized , controlled clinical trial evaluating the relative efficacy , safety , and health economic impact of four treatment strategies for people with aortoiliac peripheral arterial disease and claudication . The treatment arms are : ( 1 ) optimal medical care ( claudication pharmacotherapy ) ; ( 2 ) primary stent placement ; ( 3 ) supervised exercise rehabilitation ; and ( 4 ) combined stenting with supervised exercise rehabilitation . The CLEVER study is a 5-year r and omized , controlled clinical trial to be conducted at approximately 25 centers in the United States that will monitor 252 patients and their responses to treatment during an 18-month follow-up period . The primary end point is change in maximum walking duration on a grade d treadmill test . Secondary end points include the change at 18 months in maximum walking duration from baseline , comparisons of free-living daily activity levels assessed by pedometer , health-related quality of life , and cost-effectiveness . Other analyses include the effect of these treatment strategies on anthropomorphic and physiologic variables , including body mass index , waist circumference , blood pressure , pulse pressure , and resting pulse as well as biochemical markers of cardiovascular health , including fasting lipids , fibrinogen , C-reactive protein , and hemoglobin A 1c values OBJECTIVE Despite many clinical studies , there is still uncertainty as to whether venous material is superior to prosthetic material s for femoropopliteal reconstruction proximal to the knee joint . A prospect ively r and omized clinical trial was design ed to evaluate the effectiveness of reversed saphenous vein in comparison with that of collagen impregnated woven polyester prosthesis in above-knee arterial reconstruction . METHODS In a 3-year period , 103 above-knee femoropopliteal bypass graft operations were performed and followed in 85 patients ( 52 male , 33 female ) . The indication for operation was severe claudication in 74 cases , rest pain in 7 cases , and ulceration in 4 cases . For the bypass graft , a reversed saphenous vein was used in each of 51 cases , and a collagen impregnated woven polyester prosthesis was used in each of 52 cases . Preoperative risk factors were diabetes ( 24 % ) , a history of myocardial infa rct ion ( 23 % ) , and current status with respect to smoking ( 74 % ) . There was no hospital mortality ; 5 % of patients had minor postoperative complications . RESULTS After 2 years of follow-up , the primary patency was 81 % for saphenous vein and 67 % for collagen impregnated woven polyester prosthesis ( P=0.065 ) ; the secondary patency was 81 % for saphenous vein and 77 % for collagen impregnated woven polyester prosthesis ( P=0.298 ) . During this follow-up period of 2 years , we found no statistically significant difference in primary and secondary patency between saphenous vein and collagen impregnated woven polyester prosthesis . We found no predictive factor for the occlusion of either bypass graft . CONCLUSION The use of collagen impregnated woven polyester prosthesis above the knee is a reasonable alternative in femoropopliteal bypass grafting that is associated with acceptable short-term patency rates OBJECTIVE To evaluate the feasibility and efficacy of simultaneous combined endovascular and open lower extremity arterial reconstruction . DESIGN Case series study with retrospective analysis of prospect ively collected non-r and omised data . METHODS Patients were divided into three groups : group 1 and group 2 included patients who underwent endovascular reconstruction proximal and distal to the site of open reconstruction , respectively , whereas group 3 included patients who underwent open surgery with both proximal and distal endoluminal procedures . Patency analyses were performed using Kaplan-Meier life tables . Univariate and multivariate analyses were used to assess the influence of various risk factors on primary patency . RESULTS Complete data were obtained from 60 patients who underwent 61 single-step hybrid procedures . Technical and haemodynamic success rates were 100 % and 95 % , respectively . The perioperative mortality rate was 3 % . The primary and assisted- primary patency rates at 12 months were 71 % and 98 % , respectively . Primary patency rates were lower in group 3 when compared with groups 1 and 2 ( log-rank test , p=0.006 ) . The presence of diabetes and dyslipidaemia were independent predictors of decreased primary patency ( p=0.003 and p=0.014 , respectively ) . CONCLUSIONS Hybrid procedures provide an effective treatment management of selected patients with multilevel lower extremity arterial disease . The extent of the disease , diabetes and dyslipidaemia are associated with worse outcome BACKGROUND An intention-to-treat analysis of r and omized Bypass versus Angioplasty in Severe Ischaemia of the Leg ( BASIL ) trial data showed that initial r and omization to a bypass surgery (BSX)-first strategy was associated with improvements in subsequent overall survival ( OS ) and amputation-free survival ( AFS ) of about 7 and 6 months , respectively . We describe the nature and timing of first , crossover , and re interventions and examine AFS and OS by first treatment received . We also compare vein with prosthetic BSX and transluminal with subintimal balloon angioplasty ( BAP ) and examine outcomes from BSX after failed BAP . METHODS We r and omly assigned 452 patients with SLI due to infrainguinal disease in 27 United Kingdom hospitals to a BSX first ( n = 228 ) or a BAP first ( n = 224 ) revascularization strategy . All patients have been monitored for 3 years and more than half for > 5 years . We prospect ively collected data on every procedure , major amputation , and death . RESULTS Patients r and omized to BAP were more likely to have their assigned treatment first ( 94 % vs 85 % , P = .01 , chi(2)test ) . BAP had a higher immediate technical failure rate of 20 % vs 2.6 % ( P = .01 , chi(2)test ) . By 12 weeks after r and omization 9 BAP ( 4 % ) vs 23 BSX ( 10 % ) patients had not undergone revascularization ; 3 BAP ( 1.3 % ) vs 13 BSX ( 5.8 % ) had undergone the opposite treatment first ; and 35 BAP ( 15.6 % ) and 2 ( 0.9 % ) BSX had received the assigned treatment and then undergone the opposite treatment . BSX distal anastomoses were divided approximately equally between the above and below knee popliteal and crural arteries ; most originated from the common femoral artery . About 25 % of the grafts were prosthetic and > 90 % of vein BSX used ipsilateral great saphenous vein . Most ( 80 % ) BAP patients underwent treatment of the SFA alone ( 38 % ) or combined with the popliteal artery ( 42 % ) and crural arteries ( 20 % ) . Outcome of vein BSX was better for AFS ( P = 0.003 ) but not OS ( P = 0.38 , log-rank tests ) than prosthetic BSX . There were no differences in outcome between approximately equal numbers of transluminal and subintimal BAP . AFS ( P = 0.006 ) but not OS ( P = 0.06 , log rank test ) survival was significantly worse after BSX after failed BAP than after BSX as a first revascularization attempt . CONCLUSIONS BAP was associated with a significantly higher early failure rate than BSX . Most BAP patients ultimately required surgery . BSX outcomes after failed BAP are significantly worse than for BSX performed as a first revascularization attempt . BSX with vein offers the best long term AFS and OS and , overall , BAP appears superior to prosthetic BSX Background Endovascular treatment options for the superficial femoral artery are evolving rapidly . For long lesions , the venous femoropopliteal bypass considered to be superior above the prosthetic bypass . An endoluminal bypass , however , may provide equal patency rates compared to the prosthetic above knee bypass . The introduction of heparin-bonded endografts may further improve patency rates . The SUrgical versus PERcutaneous Bypass ( SuperB ) study is design ed to assess whether a heparin-bonded endoluminal bypass provides equal patency rates compared to the venous bypass and to prove that it is associated with improved quality of life , related to a decreased complication rate , or not . Methods / design Two-hundred-twenty-two patients with peripheral arterial occlusive disease , category 3 - 6 according to Rutherford , will be r and omized in two treatment arms ; 1 . the surgical femoro-popliteal bypass , venous whenever possible , and 2 . the heparin-bonded endoluminal bypass . The power analysis was based on a non-inferiority principle , with an effect size of 90 % and 10 % margins ( alpha 5 % , power 80 % ) . Patients will be recruited from 5 teaching hospitals in the Netherl and s during a 2-year period . The primary endpoint is primary patency and quality of life evaluated by the R AND -36 question naire and the Walking Impairment Question naire . Secondary endpoints include secondary patency , freedom-from-TLR and complications . Discussion The SuperB trial is a multicentre r and omized controlled trial design ed to show non-inferiority in patency rates of the heparin-bonded endograft compared to the surgical bypass for treatment of long SFA lesions , and to prove a better quality of life using the heparin bonded-endograft compared to surgically treatment , related to a reduction in complications . Trial Registration Clinical trials : BACKGROUND A 2005 interim analysis of the Bypass versus Angioplasty in Severe Ischaemia of the Leg ( BASIL ) trial showed that in patients with severe lower limb ischemia ( SLI ; rest pain , ulceration , gangrene ) due to infrainguinal disease , bypass surgery (BSX)-first and balloon angioplasty (BAP)-first revascularization strategies led to similar short-term clinical outcomes , although BSX was about one-third more expensive and morbidity was higher . We have monitored patients for a further 2.5 years and now report a final intention-to-treat ( ITT ) analysis of amputation-free survival ( AFS ) and overall survival ( OS ) . METHODS Of 452 enrolled patients in 27 United Kingdom hospitals , 228 were r and omized to a BSX-first and 224 to a BAP-first revascularization strategy . All patients were monitored for 3 years and more than half for > 5 years . RESULTS At the end of follow-up , 250 patients were dead ( 56 % ) , 168 ( 38 % ) were alive without amputation , and 30 ( 7 % ) were alive with amputation . Four were lost to follow-up . AFS and OS did not differ between r and omized treatments during the follow-up . For those patients surviving 2 years from r and omization , however , BSX-first revascularization was associated with a reduced hazard ratio ( HR ) for subsequent AFS of 0.85 ( 95 % confidence interval [ CI ] , 0.5 - 1.07 ; P = .108 ) and for subsequent OS of 0.61 ( 95 % CI , 0.50 - 0.75 ; P = .009 ) in an adjusted , time-dependent Cox proportional hazards model . For those patients who survived for 2 years after r and omization , initial r and omization to a BSX-first revascularization strategy was associated with an increase in subsequent restricted mean overall survival of 7.3 months ( 95 % CI , 1.2 - 13.4 months , P = .02 ) and an increase in restricted mean AFS of 5.9 months ( 95 % CI , 0.2 - 12.0 months , P = .06 ) during the subsequent mean follow-up of 3.1 years ( range , 1 - 5.7 years ) . CONCLUSIONS Overall , there was no significant difference in AFS or OS between the two strategies . However , for those patients who survived for at least 2 years after r and omization , a BSX-first revascularization strategy was associated with a significant increase in subsequent OS and a trend towards improved AFS OBJECTIVE To derive formulae to predict the likely 12-month health-related quality of life outcome following different treatments for intermittent claudication ( IC ) . DESIGN A prospect i ve , r and omized , controlled study . MATERIAL S One hundred and seventy-one unselected patients with stable IC were sequentially r and omized to invasive therapy , supervised physical training or observation . Hierarchical analysis was used to identify significant predictors of outcome . RESULTS The strongest outcome predictors were baseline values of the respective outcome variables in all groups . No more than two significant secondary predictors were identified for each outcome variable and no outcome variable was a predictor of any other outcome variable . Result ing prediction equations achieved between 61 and 90 % concordance with improvement ( 75 % considered adequate ) , with best prediction for invasive therapy and poorest for observation . Suggested cutpoints for the various endpoints in the three groups had sensitivities ranging between 65 and 100 % and false positive rates between 5 and 50 % . CONCLUSIONS The derived equations adequately predicted improvement on the various outcome variables in invasive therapy and supervised physical training , and may serve as aids in selecting patients likely to benefit most from a particular treatment strategy . The uniqueness of the outcome variables underscores the importance of implementing a comprehensive set of endpoints relevant to the impacts of the condition Background — Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication , supervised exercise ( SE ) , or stent revascularization ( ST ) . Methods and Results — We r and omly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments : optimal medical care ( OMC ) , OMC plus SE , or OMC plus ST . The primary end point was the change in peak walking time on a grade d treadmill test at 6 months compared with baseline . Secondary end points included free-living step activity , quality of life with the Walking Impairment Question naire , Peripheral Artery Question naire , Medical Outcomes Study 12-Item Short Form , and cardiovascular risk factors . At the 6-month follow-up , change in peak walking time ( the primary end point ) was greatest for SE , intermediate for ST , and least with OMC ( mean change versus baseline , 5.8±4.6 , 3.7±4.9 , and 1.2±2.6 minutes , respectively ; P<0.001 for the comparison of SE versus OMC , P=0.02 for ST versus OMC , and P=0.04 for SE versus ST ) . Although disease-specific quality of life as assessed by the Walking Impairment Question naire and Peripheral Artery Question naire also improved with both SE and ST compared with OMC , for most scales , the extent of improvement was greater with ST than SE . Free-living step activity increased more with ST than with either SE or OMC alone ( 114±274 versus 73±139 versus −6±109 steps per hour ) , but these differences were not statistically significant . Conclusions — SE results in superior treadmill walking performance than ST , even for those with aortoiliac peripheral artery disease . The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study . Clinical Trial Registration — URL : http:// clinical trials.gov/ct/show/NCT00132743?order=1 . Unique identifier : NCT00132743 Current treatment of acute infrainguinal bypass occlusion consists of either surgical revascularization or catheter-guided intra-arterial thrombolysis with adjunctive correction of the underlying flow-limiting lesion . In maintaining long-term patency , improving the number of outflow vessels could be of utmost importance . To compare the efficiency of both thrombolysis and primary surgical revascularization and to study the effect of thrombolysis on the number of patent outflow vessels , a prospect i ve nonr and omized study was performed . Between February 2002 and August 2003 , 54 patients with 56 occluded bypasses were included . Thirty bypasses were treated with thrombolysis , 26 primarily with surgery . Thrombolysis was successful in 80 % of cases , with restoration of patency of the bypass but also with doubling of the amount of patent outflow vessels ; surgery was successful in 85.71 % of cases . However , in only 60 % of the successfully lysed bypasses no adjunctive major surgery was needed . Amputation-free survival was 87.5 % 1 year after surgery and 82.6 % 1 year after thrombolysis . One year after thrombolysis without adjunctive major surgery , the amputation-free survival was only 39.7 % . Therefore , a strategy could be to start with thrombolysis to improve outflow followed by a new bypass , whatever the underlying causative lesions are PURPOSE Early results of a prospect i ve study that compared surgical revascularization and thrombolysis for lower extremity arterial and graft occlusions have been published . This report details the final results in patients who have native artery occlusions . METHODS Two hundred thirty-seven patients who had lower extremity ischemia as a result of iliac-common femoral ( IF ; 69 patients ) or superficial femoral-popliteal ( FP ; 168 patients ) occlusion , and had symptomatically deteriorated within the past 6 months were r and omized to catheter-directed thrombolysis ( 150 patients ) or surgical revascularization ( 87 patients ) . After diagnostic arteriographic examination but before r and omization , the optimal surgical procedure was determined . Lytic patients were r and omized to recombinant tissue plasminogen activator ( rt-PA ; 84 patients ) or urokinase ( UK ; 66 patients ) . Recurrent ischemia , morbidity , amputation , and death rates were determined at 30 days , 6 months , and 1 year , and were analyzed on an intent-to-treat basis . RESULTS For patients r and omized to lysis , a catheter was properly positioned and the lytic agent delivered in 78 % . This provided a reduction in the predetermined surgical procedure in 58 % of patients who had an FP occlusion and 51 % of those who had an IF occlusion . rt-PA and UK were equally effective and safe , but lysis time was shorter with rt-PA ( 8 vs 24 hr ; p < 0.05 ) . At 1 year , the incidence of recurrent ischemia ( 64 % vs 35 % ; p < 0.0001 ) and major amputation ( 10 % vs 0 % ; p = 0.0024 ) was increased in patients who were r and omized to lysis . Factors associated with a poor lytic outcome included FP occlusion , diabetes , and critical ischemia . No differences in mortality rates were observed at 1 year between the lysis and surgical groups . CONCLUSION Surgical revascularization for lower extremity native artery occlusions is more effective and durable than thrombolysis . Thrombolysis used initially provides a reduction in the surgical procedure for a majority of patients ; however , long-term outcome is inferior , particularly for patients who have an FP occlusion , diabetes , or critical ischemia PURPOSE Surgical revascularization and angioplasty ( PTA ) are effective therapies for patients with peripheral arterial disease , but there are no data on long-term survival , limb salvage , and hemodynamic status from a r and omized study of such patients . A multicenter , prospect i ve trial compared PTA with bypass surgery ( BP ) in 263 men who had iliac , femoral , or popliteal artery obstruction . PATIENTS AND METHODS Lesions in the iliac versus the femoropopliteal artery and rest pain versus claudication were separately r and omized to the two treatment interventions . One hundred twenty-six patients underwent BP , 129 patients underwent PTA , and eight patients were not treated for lower extremity ischemia . RESULTS Three operative deaths occurred in the BP group and none in the PTA group . For the entire study , average annual mortality was higher in the BP group , but survival was not significantly different on life-table analysis ( P = .08 ) . Primary success favored BP , while limb salvage favored PTA , but differences were not statistically significant ( P = .08 and .35 , respectively ) . Patients with iliac disease or claudication fared better , but there was no statistical difference in response to PTA or BP . CONCLUSION Patients in both treatment groups had prompt and sustained increases in hemodynamics and quality of life . This study of patients r and omly assigned to BP or PTA shows no significant difference in outcomes during a median follow-up of 4 years BACKGROUND The Bypass versus Angioplasty in Severe Ischaemia of the Leg ( BASIL ) trial showed in patients with severe lower limb ischemia ( rest pain , tissue loss ) who survive for 2 years after intervention that initial r and omization to bypass surgery , compared with balloon angioplasty , was associated with an improvement in subsequent amputation-free survival and overall survival of about 6 and 7 months , respectively . The aim of this report is to describe the angiographic severity and extent of infrainguinal arterial disease in the BASIL trial cohort so that the trial outcomes can be appropriately generalized to other patient cohorts with similar anatomic ( angiographic ) patterns of disease . METHODS Preintervention angiograms were scored using the Bollinger method and the TransAtlantic Inter-Society Consensus ( TASC ) II classification system by three consultant interventional radiologists and two consultant vascular surgeons unaware of the treatment received or patient outcomes . RESULTS As was to be expected from the r and omization process , patients in the two trial arms were well matched in terms of angiographic severity and extent of disease as documented by Bollinger and TASC II . In patients with the least overall disease , it tended to be concentrated in the superficial femoral and popliteal arteries , which were the commonest sites of disease overall . The below knee arteries became increasingly involved as the overall severity of disease increased , but the disease in the above knee arteries did not tend to worsen . The posterior tibial artery was the most diseased crural artery , whereas the peroneal appeared relatively spared . There was less interobserver disagreement with the Bollinger method than with the TASC II classification system , which also appears inherently less sensitive to clinical ly important differences in infrapopliteal disease among patients with severe leg ischemia . CONCLUSIONS Anatomic ( angiographic ) disease description in patients with severe leg ischemia requires a reproducible scoring system that is sensitive to differences in crural artery disease . The Bollinger system appears well suited for this purpose , but the TASC II classification system less so . We hope this detailed analysis will facilitate appropriate generalization of the BASIL trial data to other groups of patients affected by similar anatomic ( angiographic ) patterns of disease IMPORTANCE To our knowledge , there is no level 1 evidence comparing open bypass with angioplasty and stenting in TransAtlantic Inter-Society Consensus ( TASC II ) B and C superficial femoral artery lesions . The Revascularization With Open Bypass vs Angioplasty and Stenting of the Lower Extremity Trial ( ROBUST ) is the first prospect i ve r and omized clinical trial comparing both treatments . OBJECTIVES To report the design of the ROBUST trial . The primary aim of the trial is to compare ( 1 ) the patency rate ( primary , primary assisted , and secondary patency at 6 and 12 months ) , ( 2 ) improvement of quality of life , ( 3 ) clinical improvement ( at least 1 Rutherford category ) , and ( 4 ) wound healing and limb salvage in patients presenting with critical limb ischemia ; secondary aims include ( 1 ) cost-effectiveness by factoring procedure and hospital admission costs including rehabilitation , readmission , and reintervention costs , ( 2 ) amputation-free survival , ( 3 ) reintervention rate , and ( 4 ) 30-day operative mortality , morbidity , and wound and access complications . DESIGN , SETTING , AND PARTICIPANTS ROBUST is a prospect i ve r and omized clinical trial with the aim to enroll 320 patients with intermittent claudication that does not respond to medical management and patients with critical limb ischemia . The maximum level of medical therapy will be administered using antiplatelet agents and statins , as well as measures to control hypertension and diabetes mellitus . INTERVENTIONS Patients with TASC II B or C lesions are prospect ively r and omized to receive either femoropopliteal bypass or percutaneous transluminal angioplasty and stenting ; patients with TASC II A and D lesions are not r and omized and receive percutaneous transluminal angioplasty and stenting or femoropopliteal bypass , respectively . All patients will be evaluated at 1 , 6 , and 12 months postoperatively with physical examination , ankle brachial index , duplex , and a quality -of-life question naire . RESULTS The trial is actively enrolling participants . At the time of writing , 29 patients have been enrolled ; most are male ( 60 % ) and white ( 65 % ) . CONCLUSIONS AND RELEVANCE Providing level 1 evidence , ROBUST may help to establish guidelines for the treatment of superficial femoral artery lesions , eliminate unnecessary procedures , and reduce health care costs . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01602159 Background Severe limb ischaemia is defined by ischaemic rest/night pain , tissue loss , or both , secondary to arterial insufficiency and is increasingly caused by infra-popliteal ( below the knee ) disease , mainly as a result of the increasing worldwide prevalence of diabetes . Currently , it is unknown whether vein bypass surgery or the best endovascular treatment ( angioplasty or stenting ) represents the optimal revascularisation strategy in terms of amputation-free survival , overall survival , relief of symptoms , quality of life and cost-effective use of health care re sources . Methods / Design The Bypass vs. Angioplasty in Severe Ischaemia of the Leg - 2 Trial is a UK National Institute of Health Research , Health Technology Assessment funded , multi-centre r and omised controlled trial that compares , at the point of clinical equipoise , the clinical and cost-effectiveness of a ‘ vein bypass first ’ and a ‘ best endovascular treatment first ’ revascularisation strategy for severe limb ischaemia due to infra-popliteal disease . The primary clinical outcome is amputation-free survival defined as the time to major ( above the ankle ) amputation of the trial limb or death from any cause . The primary outcome for the cost-effectiveness analysis is cost per quality -adjusted life year . Secondary outcomes include overall survival , quality of life , in-hospital mortality and morbidity , repeat and crossover interventions , healing of tissue loss and haemodynamic changes following revascularisation . Sample size is estimated at 600 patients . An economic evaluation will be conducted from the perspective of the National Health Service and comprise a ‘ within- study ’ analysis , based on prospect ively collected trial data and a ‘ model-based ’ analysis , which will extrapolate and compare costs and effects beyond the study follow-up period . Discussion The BASIL-2 trial is design ed to be pragmatic and represent current practice within the United Kingdom . Patients with severe limb ischaemia can only be r and omised into the trial where clinical equipose exists . The advent of hybrid operating procedures should not be a barrier to r and omisation , should a patient require inflow correction prior to tibial revascularisation . Trial registration IS RCT N:27728689 Date of registration : 12 May 2014 OBJECTIVE To compare a ' bypass-surgery-first ' with a ' balloon-angioplasty-first ' revascularisation strategy in patients with severe limb ischaemia ( SLI ) due to infrainguinal disease requiring immediate/early revascularisation . DESIGN A stratified r and omised controlled trial . A Delphi consensus study of vascular surgeons ' and interventional radiologists ' views on SLI treatment was performed before the trial . SETTING Twenty-seven UK hospitals . PARTICIPANTS Patients presenting with SLI as the result of infrainguinal atherosclerosis and who , in the opinion of the responsible consultant vascular surgeon and interventional radiologist , required and were suitable for both surgery and angioplasty . INTERVENTIONS Patients were r and omised to either ' bypass-surgery-first ' or ' balloon-angioplasty-first ' revascularisation strategies . MAIN OUTCOME MEASURES The primary end point was amputation-free survival ( AFS ) ; secondary end points were overall survival ( OS ) , health-related quality of life ( HRQoL ) and cost-effective use of hospital re sources . RESULTS AFS at 1 and 3 years was not significantly different for surgery and angioplasty . Interim analysis showed that surgery was associated with significantly lower immediate failure , higher 30-day morbidity and lower 12-month reintervention rates than angioplasty ; 30-day mortality was similar . Beyond 2 years from r and omisation , hazard ratios ( HRs ) were significantly reduced for both AFS ( adjusted HR 0.37 ; 95 % CI 0.17 to 0.77 ; p = 0.008 ) and OS ( HR 0.34 ; 95 % CI 0.17 to 0.71 ; p = 0.004 ) for surgery relative to angioplasty . By 2008 all but four patients had been followed for 3 years , some for over 7 years : 250 ( 56 % ) were dead , 168 ( 38 % ) were alive without amputation and 30 ( 7 % ) were alive with amputation . Considering the follow-up period as a whole , AFS and OS did not differ between treatments but for patients surviving beyond 2 years from r and omisation , bypass was associated with reduced HRs for AFS ( HR 0.85 ; 95 % CI 0.50 to 1.07 ; p = 0.108 ) and OS ( HR 0.61 ; 95 % CI 0.50 to 0.75 ; p = 0.009 ) , equating to an increase in restricted mean OS of 7.3 months ( p = 0.02 ) and AFS of 5.9 months ( p = 0.06 ) during the subsequent follow-up period . Vein bypasses and angioplasties performed better than prosthetic bypasses . HRQoL was non-significantly better in the surgery group ; amputation was associated with a significant reduction in HRQoL. Over the first year , hospital costs for bypass were significantly higher ( difference 5420 pounds ; 95 % CI 1547 pounds to 9294 pounds ) than for angioplasty . However , by 3 and at 7 years the differences in cost between the two strategies were no longer significant . Patients r and omised to surgery lived , on average , 29 days longer at an additional average cost of 2310 pounds . A 36-month perspective showed not significantly different mean quality -adjusted life times for angioplasty and surgery . The Delphi study revealed substantial disagreement between and among surgeons and radiologists on the appropriateness of bypass surgery or balloon angioplasty . CONCLUSIONS The findings of our study suggest that in patients with SLI due to infrainguinal disease the decision whether to perform bypass surgery or balloon angioplasty first appears to depend upon anticipated life expectancy . Patients expected to live less than 2 years should usually be offered balloon angioplasty first as it is associated with less morbidity and cost , and such patients are unlikely to enjoy the longer-term benefits of surgery . By contrast , those patients expected to live beyond 2 years should usually be offered bypass surgery first , especially where a vein is available as a conduit . Many patients who could not undergo a vein bypass would probably have been better served by a first attempt at balloon angioplasty than prosthetic bypass . The failure rate of angioplasty in SLI is high ( c. 25 % ) and patients who underwent bypass after failed angioplasty fared significantly worse than those who underwent surgery as their first procedure . The interests of a significant proportion of BASIL patients may have been best served by primary amputation followed by high- quality rehabilitation . Further research is required to confirm or refute the BASIL findings and recommendations ; vali date the BASIL survival prediction model in a separate cohort of patients with SLI ; examine the clinical and cost-effectiveness of new endovascular techniques and devices ; and compare revascularisation with primary amputation and with best medical and nursing care in those SLI patients with the poorest survival prospect s. TRIAL REGISTRATION Current Controlled Trials IS RCT N45398889 OBJECTIVES To compare graft patency and limb salvage rate following femoro-infrapopliteal bypass using ePTFE grafts with and without the addition of adjuvant arterio-venous fistula . DESIGN A prospect ively r and omised controlled trial . MATERIAL S Patients referred to two teaching hospital vascular surgery units in the U.K. for the treatment of critical limb ischaemia . METHODS Eighty-seven patients ( M : F ; 2.3:1 ) undergoing 89 femoro-intrapopliteal bypass operations with ePTFE grafts for critical limb ischaemia were r and omly allocated to have AVF included in the operative procedure ( n = 48 ) or to a control group without AVF ( n = 41 ) . An interposition vein-cuff was incorporated at the distal anastomosis in all patients . RESULTS The cumulative rates of primary patency and limb salvage at 1-year after operation for patients with AVF were 55.2 % and 54.1 % compared to 53.4 % and 43.2 % , respectively , for the control group . The differences between the AVF and control groups did not reach statistical significance , in terms of either graft patency or limb salvage , at any stage after operation ( Log-Rank test ) . CONCLUSIONS AVF confers no additional significant clinical advantage over interposition vein cuff in patients having femoro-infrapopliteal bypass with ePTFE grants for critical limb ischaemia UNLABELLED Early results of a thrupass endograft in the treatment of femoral lesions are promising . Less morbidity and better cost-effectiveness are suggested to be achieved in the treatment of chronic lower limb ischaemia with endovascular treatment compared to surgical treatment . PATIENTS AND METHODS This r and omised multicentre trial aim ed to enroll a group of 60 + 60 patients for the treatment of 5 - 25-cm occlusions of superficial femoral artery ( SFA ) to be followed up for 3 years . Patients were treated either with endoluminal PTFE thrupass ( WL Gore & Ass ) or with surgical polytetrafluoroethylene ( PTFE ) bypass to proximal popliteal artery . Primary patency at 3 years was scheduled to be the primary end-point and secondary patency , functional success , costs and quality of life the secondary end-points . RESULTS A sample of 100 consecutive SFA occlusions in one of the centres revealed that only 4 % of the lesions were amenable for the study . The trial was prematurely terminated due to the results of an interim analysis at the time when 44 patients were recruited : the 1-year primary patency ( excluding technical failures ) was 48 % for thrupass and 95 % for bypass ( p=0.02 ) . The patency difference in favour of surgical bypass over endovascular thrupass was also sustained after completion of 1-year follow-up , the primary patencies being 46 % and 84 % at 1 year with grossly equilinear life-table curves thereafter ( p=0.18 ) , respectively . The corresponding secondary patencies were 63 % and 100 % ( p=0.05 ) when excluding technical failures and 58 % and 100 % ( p=0.02 ) according to intention-to-treat analysis . Secondary outcomes were thus not analysed . CONCLUSION Treatment of SFA occlusions ( TASC IIB and C or Imelda Ia and II ) should be done by PTFE bypass rather than by PTFE thrupass , as thrupass is connected with worse early outcome . These results represent only a small category of femoral disease BACKGROUND This is a r and omized prospect i ve study comparing the treatment of superficial femoral artery occlusive disease percutaneously with an exp and ed polytetrafluoroethylene (ePTFE)/nitinol self-exp and ing stent graft ( stent graft ) versus surgical femoral to above-knee popliteal artery bypass with synthetic graft material . METHODS One hundred limbs in 86 patients with superficial femoral artery occlusive disease were evaluated from March 2004 to May 2005 . Patient symptoms included both claudication and limb threatening ischemia with or without tissue loss . Trans-Atlantic InterSociety Consensus ( TASC II ) A ( n = 18 ) , B ( n = 56 ) , C ( n = 11 ) , and D ( n = 15 ) lesions were included . Patients were r and omized prospect ively into one of two treatment groups ; a percutaneous treatment group ( group A ; n = 50 ) with angioplasty and placement of one or more stent grafts , or a surgical treatment group ( group B ; n = 50 ) with a femoral to above-knee popliteal artery bypass using synthetic conduit ( Dacron or ePTFE ) . Patients were followed for 48 months . Follow-up evaluation included clinical assessment , physical examination , ankle-brachial indices , and color flow duplex sonography at 3 , 6 , 9 , 12 , 18 , 24 , 36 , and 48 months . RESULTS Mean total lesion length of the treated arterial segment in the stent graft group was 25.6 cm ( SD = 15 cm ) . The stent graft group demonstrated a primary patency of 72 % , 63 % , 63 % , and 59 % with a secondary patency of 83 % , 74 % , 74 % , and 74 % at 12 , 24 , 36 , and 48 months , respectively . The surgical femoral-popliteal group demonstrated a primary patency of 76 % , 63 % , 63 % , and 58 % with a secondary patency of 86 % , 76 % , 76 % , and 71 % at 12 , 24 , 36 , and 48 months , respectively . No statistical difference was found between the two groups with respect to primary ( P = .807 ) or secondary ( P = .891 ) patency . CONCLUSION Management of superficial femoral artery occlusive disease with percutaneous stent grafts exhibits similar primary patency at 4-year ( 48 month ) follow up when compared with conventional femoral-popliteal artery bypass grafting with synthetic conduit . This treatment method may offer an alternative to treatment of the superficial femoral artery segment for revascularization when prosthetic bypass is being considered or when autologous conduit is unavailable OBJECTIVE Dacron was largely ab and oned for femoropopliteal bypass 30 years ago , because better patency rates were achieved with saphenous vein . Despite the range of potential prosthetics , polytetrafluoroethylne ( PTFE ) clearly predominates in current femoropopliteal practice . We compared heparin-bonded Dacron ( HBD ) with PTFE in a r and omized multicenter clinical trial . METHOD Over 28 months , 209 patients ( 179 above-knee disease , 30 below-knee disease ) were r and omized to receive HBD ( n = 106 ) or PTFE ( n = 103 ) grafts . Aspirin , 300 mg/d , was started before surgery , and was continued if tolerated . RESULTS At follow-up for a minimum of 5 years ( mean , 76 months ; range , 60 - 89 months ) , 37 patients ( 17.7 % ) had died with patent grafts and 121 ( 58 % ) grafts were occluded . Primary patency rate , measured with Kaplan-Meier survival analysis , was 46 % ( 95 % confidence interval [ CI ] , 35%-57 % ) at year 5 for HBD , compared with 35 % for PTFE ( CI , 25%-45 % ; P < .055 ) . Long-term patency was achieved in only 4 of 78 interventions performed in 55 thrombosed grafts . Secondary patency rate for HBD was 47 % ( CI , 36%-58 % ) , and for PTFE was 36 % ( CI , 26%-46 % ) . Risk factors for arterial disease did not significantly influence prosthetic patency . Major limb amputation was necessary in 9 patients with HBD grafts and 20 patients with PTFE grafts ( P < .025 ) . Two amputations in the HBD group and 8 amputations in the PTFE group were in patients undergoing bypass surgery to treat claudication only . Limb salvage rate was 86 % ( CI , 77%-95 % ) and 74 % ( CI , 64%-84 % ) , respectively . CONCLUSIONS Significantly better patency rates were achieved with HBD than with PTFE at 3 years ( P < .044 ) , but the difference was no longer statistically significant at 5 years ( P < .055 ) . The incidence of major limb amputation , however , was significantly greater ( P < .025 ) in the PTFE group compared with the HBD group at both 3 and 5 years of follow-up OBJECTIVES to compare the effect of surgery , exercise and simple observation on maximum exercise power in claudicants . DESIGN prospect i ve , r and omised study . METHODS a total of 264 unselected claudicants were r and omised to supervised exercise training , invasive treatment ( open surgical or endovascular procedures ) or observation . One year treatment outcomes were analysed on an intention to-treat basis . RESULTS invasively treated patients showed a significant improvement in maximum walking power , stopping distance , post-ischaemic blood flow and big toe pressure at one year . Patients r and omised to physical exercise training or to the control group did not improve in any outcome measure . CONCLUSION invasive treatment increased walking capacity , leg blood pressure and flow . Supervised physical exercise training offered no therapeutic advantage compared to untreated controls OBJECTIVE This r and omized prospect i ve study was design ed to compare the effectiveness of treating superficial femoral artery occlusive disease percutaneously with exp and ed polytetrafluoroethylene (ePTFE)/nitinol self-exp and ing stent grafts vs surgical femoral-to-above knee ( AK ) popliteal artery bypass with synthetic graft material . METHODS From March 2004 to May 2005 , 100 limbs in 86 patients with femoral-popliteal arterial occlusive disease were identified . Patients had symptoms ranging from claudication to rest pain , with or without tissue loss , and were prospect ively r and omized for treatment into one of two groups . The limbs were treated percutaneously with angioplasty and one or more self-exp and ing stent grafts ( n = 50 ) or surgically with femoral-to-AK popliteal artery bypass using synthetic Dacron or ePTFE grafts ( n = 50 ) . The mean + /- SD total length of artery stented was 25.6 + /- 15 cm . Follow-up evaluation with ankle-brachial indices and color flow duplex sonography imaging were performed at 3 , 6 , 9 , and 12 months after treatment . RESULTS Patients were monitored for a median of 18 months . No statistical difference was found in the primary patency ( P = .895 ) or secondary patency ( P = .861 ) between the two treatment groups . Primary patency at 3 , 6 , 9 , and 12 months of follow-up was 84 % , 82 % , 75.6 % , and 73.5 % for the stent graft group and 90 % , 81.8 % , 79.7 % , and 74.2 % for the femoral-popliteal surgical group . Thirteen patients in the stent graft group had 14 re interventions , and 12 re interventions occurred in the surgical group . This result ed in secondary patency rates of 83.9 % for the stent graft group and 83.7 % for the surgical group at the 12-month follow-up . CONCLUSIONS Management of femoral-popliteal arterial occlusive disease using percutaneous treatment with a stent graft is comparable with surgical revascularization with conventional femoral-to-AK popliteal artery bypass using synthetic material up to 12 months . Longer-term follow-up would be helpful in determining ongoing efficacy BACKGROUND To investigate the optimal surgical treatment , remote superficial femoral artery endarterectomy ( RSFAE ) or supragenicular bypass , for Transatlantic Inter-Society Consensus ( TASC ) C and D lesions of the superficial femoral artery . Medium-term results will be presented . METHODS The study r and omized 116 patients , 61 to RSFAE and 55 to supragenicular bypass surgery . Indications for surgery were claudication in 77 , rest pain in 21 , or tissue loss in 18 . RESULTS Primary patency after 3 years of follow-up was 47 % for RSFAE and 60 % for bypass ( p = 0.107 ) , assisted primary patency was 63 and 69 % ( p = 0.406 ) , and secondary patency was 69 and 73 % ( p = 0.541 ) , respectively . For venous ( n = 25 ) and prosthetic grafts ( n = 30 ) at 3-year follow-up , primary patency was 65 % and 56 versus 47 % for RSFAE ( p = 0.143 ) , assisted primary patency was 84 % and 56 versus 63 % for RSFAE ( p = 0.052 ) , and secondary patency was 89 % and 59 versus 69 % for RSFAE ( p = 0.046 ) , respectively . Limb salvage was 97 % after RSFAE and 95 % after bypass surgery ( p = 0.564 ) . CONCLUSION RSFAE is a minimally invasive option for surgical repair of TASC C and D superficial femoral artery obstructions , with assisted primary and secondary patency rates comparable with bypass surgery . Venous bypass grafting is superior to both RSFAE and polytetrafluoroethylene grafting , but only 45 % of patients had a sufficient saphenous vein available . If the saphenous vein is not applicable , RSFAE should be considered because it is less invasive and prosthetic graft material can be avoided OBJECTIVE There is continuing controversy as to whether surgical bypass or angioplasty should be first-line treatment of severe limb ischemia . We undertook this study to examine angiographic and clinical factors that influence the treatment of severe limb ischemia by vascular surgeons and interventional radiologists . METHODS Twenty consultant vascular surgeons and 17 consultant vascular interventional radiologists evaluated 596 hypothetical clinical or angiographic scenarios , and recorded whether , in their opinion , the most appropriate first-line treatment was surgical bypass , angioplasty , or primary amputation . Stepwise multiple linear regression was used to identify the factors that significantly affected responses from the entire group and from surgeons and radiologists separately . RESULTS There were significant differences between surgeons and radiologists with regard to how clinical and angiographic variables determined treatment preferences . Increasing disease severity , absence of runoff into the foot , presence of a suitable vein , and tissue loss as opposed to rest pain only ( the latter only significant to surgeons ) all increased the response score toward surgery . However , surgeons and radiologists weighted each of these factors quite differently . Even in the most complex statistical model , 19 % of surgical and 13 % of radiologic response variations remained unexplained . CONCLUSIONS Individual surgeons and radiologists vary considerably in their views of the relative merits of surgery and angioplasty in patients with severe limb ischemia . This broad gray area m and ates the need for r and omized controlled trial data to inform joint decision-making and to optimize patient outcome A prospect i ve , r and omized comparison of percutaneous transluminal angioplasty ( PTA ) with surgery in the treatment of occlusive disease of the iliac , superficial femoral , or popliteal arteries began in 1983 . Radiologists and vascular surgeons independently assessed index lesions on arteriograms to decide whether their respective treatments were appropriate . Of 263 male patients r and omized , 255 received vascular intervention ( surgery , 126 patients ; PTA , 129 patients ) . The groups were comparable when stratified for systemic risk factors and anatomic distribution of disease . Because eligibility criteria required that all lesions r and omized for treatment be suitable for PTA , the severity of disease was less than that of the general population having vascular disease . Claudication was the principal indication for intervention . The immediate failure rate for PTA was 15.5 % ( 20 of 129 patients ) . Surgery was performed with one in-hospital death ( 0.8 % ) and 17 complications ( 13.5 % ) . There were two late deaths ascribable to surgical complications and none to PTA . At 4.5 years , 50 deaths ( 20 % ) ( 28 from surgery ; 22 with PTA ) and 24 major amputations of legs included in the study ( 13 with surgery ; 11 with PTA ) have occurred . The baseline ankle-brachial indexes ( ABIs ) of 0.51 + /- 0.02 , respectively , after treatment and was not different between the groups through 36 months ( surgery , 0.28 + /- 0.04 ; PTA , 0.30 + /- 0.05 ) . The 17 patients undergoing surgery after unsuccessful PTA had a mean ABI increase of 0.32 + /- 0.07 ; the durability of hemodynamic improvement was similar in both groups of patients OBJECTIVES To provide estimates and confidence intervals for the performance ( detection and false-positive rates ) of screening for Down 's syndrome using repeated measures of biochemical markers from first and second trimester maternal serum sample s taken from the same woman . DESIGN Stored serum on Down 's syndrome cases and controls was used to provide independent test data for the assessment of screening performance of published risk algorithms and for the development and testing of new risk assessment algorithms . SETTING 15 screening centres across the USA , and at the North York General Hospital , Toronto , Canada . PARTICIPANTS 78 women with pregnancy affected by Down 's syndrome and 390 matched unaffected controls , with maternal blood sample s obtained at 11 - 13 and 15 - 18 weeks ' gestation , and women who received integrated prenatal screening at North York General Hospital at two time intervals : between 1 December 1999 and 31 October 2003 , and between 1 October 2006 and 23 November 2007 . INTERVENTIONS Repeated measurements ( first and second trimester ) of maternal serum levels of human chorionic gonadotrophin ( hCG ) , unconjugated estriol ( uE3 ) and pregnancy-associated plasma protein A ( PAPP-A ) together with alpha-fetoprotein ( AFP ) in the second trimester . MAIN OUTCOME MEASURES Detection and false-positive rates for screening with a threshold risk of 1 in 200 at term , and the detection rate achieved for a false-positive rate of 2 % . RESULTS Published distributional models for Down 's syndrome were inconsistent with the test data . When these test data were classified using these models , screening performance deteriorated substantially through the addition of repeated measures . This contradicts the very optimistic results obtained from predictive modelling of performance . Simplified distributional assumptions showed some evidence of benefit from the use of repeated measures of PAPP-A but not for repeated measures of uE3 or hCG . Each of the two test data sets was used to create new parameter estimates against which screening test performance was assessed using the other data set . The results were equivocal but there was evidence suggesting improvement in screening performance through the use of repeated measures of PAPP-A when the first trimester sample was collected before 13 weeks ' gestation . A Bayesian analysis of the combined data from the two test data sets showed that adding a second trimester repeated measurement of PAPP-A to the base test increased detection rates and reduced false-positive rates . The benefit decreased with increasing gestational age at the time of the first sample . There was no evidence of any benefit from repeated measures of hCG or uE3 . CONCLUSIONS If realised , a reduction of 1 % in false-positive rate with no loss in detection rate would give important benefits in terms of health service provision and the large number of invasive tests avoided . The Bayesian analysis , which shows evidence of benefit , is based on strong distributional assumptions and should not be regarded as confirmatory . The evidence of potential benefit suggests the need for a prospect i ve study of repeated measurements of PAPP-A with sample s from early in the first trimester . A formal clinical effectiveness and cost-effectiveness analysis should be undertaken . This study has shown that the established modelling methodology for assessing screening performance may be optimistically biased and should be interpreted with caution BACKGROUND A r and omized prospect i ve study comparing the treatment of superficial femoral artery occlusive disease percutaneously with an exp and ed polytetrafluoroethylene (ePTFE)/nitinol self-exp and ing stent graft ( stent-graft ) vs surgical femoral to above knee popliteal artery bypass with synthetic graft material . METHODS One hundred limbs in 86 patients with superficial femoral artery occlusive disease were evaluated from March 2004 to May 2005 . Patient symptoms included both claudication and limb threatening ischemia with or without tissue loss . The TransAtlantic InterSociety Consensus ( TASC ) II A ( N = 18 ) , B ( N = 56 ) , C ( N = 11 ) , and D ( N = 15 ) lesions were included . Patients were r and omized prospect ively into one of two treatment groups ; a percutaneous treatment group ( group A ; N = 50 ) with angioplasty and placement of one or more stent-grafts or a surgical treatment group ( group B ; N = 50 ) with a femoral to above knee popliteal artery bypass using synthetic conduit ( Dacron graft or ePTFE ) . Patients were followed for a total of 24 months . Follow-up evaluation included clinical assessment and physical examination , ankle-brachial indices ( ABI ) , and color flow duplex sonography at 3 , 6 , 9 , 12 , 18 , and 24 months . RESULTS The mean total lesion length of the treated arterial segment in the stent-graft group was 25.6 cm ( SD + /- 15 cm ) . The stent-graft group demonstrated a primary patency of 81 % , 72 % , and 63 % with a secondary patency of 86 % , 83 % , and 74 % at 6 , 12 , and 24 months , respectively . The surgical femoral-popliteal group demonstrated a primary patency of 84 % , 77 % , and 64 % with a secondary patency of 89 % , 86 % , and 76 % at 6 , 12 , and 24 months , respectively . No statistical difference was found between the two groups with respect to primary ( P = .716 ) or secondary patency ( P = .695 ) . Grouping of less severe ( TASC II A/B ) vs more severe ( TASC II C/D ) lesions demonstrated patency at 24 months for the femoral-popliteal arm of 63 % and 67 % , respectively while that of the stent-graft arm was 64 % and 47 % , respectively . Secondary patency was 76 % in both TASC classifications for the femoral-popliteal arm with 78 % and 47 % patency found respectively in the stent-graft group . These result ed in no significant difference for primary ( P = .978 ) or secondary ( P = .653 ) patency overall , although there is a trend for decreased patency with higher TASC II lesions . CONCLUSION Management of superficial femoral artery occlusive disease with percutaneous stent-grafts exhibits similar primary patency at 24-month follow-up when compared with conventional femoral-popliteal artery bypass grafting with synthetic conduit . This treatment method may offer an alternative to treatment of the superficial femoral artery segment for revascularization when prosthetic bypass is being considered or when autologous conduit is unavailable AIM To evaluate whether angioplasty or above-knee bypass is the best treatment for symptomatic superficial femoral artery occlusive lesions , we performed a multicentre r and omised trial . PATIENTS AND METHODS Between October 1995 and August 1998 , 56 patients were enrolled , all with symptoms related to a 5 - 15 cm long occlusive lesion of the superficial femoral artery . Thirty-one patients were r and omly assigned to percutaneous transluminal angioplasty ( PTA ) ; 25 patients to bypass surgery . All patients were followed at 1 , 6 and 12 months after the procedure . The primary outcome of our study was re-occlusion of the femoral artery . RESULTS Thirty patients underwent the allocated PTA and 24 patients underwent bypass surgery . Cumulative 1-year primary patency after PTA was 43 and 82 % after bypass surgery . After PTA more than half of the patients had a re-occlusion with an absolute risk reduction of 31 % ( CI : 6 - 56 % ) in favour of bypass surgery . The hazard ratio for occlusion comparing PTA with bypass surgery is 2.24 ( 95 % CI : 0.9 - 5.58 ) . CONCLUSION Despite 18 participating centres only 56 patients were r and omised to PTA our bypass surgery . Based on our results , for every three patients treated with bypass surgery instead of PTA , one additional re-occlusion is prevented . Therefore , we conclude that with respect to patency , for long superficial femoral artery ( SFA ) stenoses or occlusions , surgery is better than PTA OBJECTIVES Despite limited scientific evidence for the effectiveness of invasive treatment for intermittent claudication ( IC ) , revascularisation procedures for IC are increasingly often performed in Sweden . This r and omised controlled trial compares the outcome after 2 years of primary invasive ( INV ) versus primary non-invasive ( NON ) treatment strategies in unselected IC patients . MATERIAL S/ METHODS Based on arterial duplex and clinical examination , IC patients were r and omised to INV ( endovascular and /or surgical , n = 100 ) or NON ( n = 101 ) . NON patients could request invasive treatment if they deteriorated during follow-up . Primary outcome was maximal walking performance ( MWP ) on grade d treadmill test at 2 years and secondary outcomes included health-related quality of life ( HRQL ) , assessed with Short Form ( 36 ) Health Survey ( SF-36 ) . RESULTS MWP was not significantly ( p = 0.104 ) improved in the INV versus the NON group . Two SF-36 physical subscales , Bodily Pain ( p < 0.01 ) and Role Physical ( p < 0.05 ) improved significantly more in the INV versus the NON group . There were 7 % crossovers against the study protocol in the INV group . CONCLUSIONS Although invasive treatment did not show any significant advantage regarding MWP , the HRQL improvements associated with invasive treatment tentatively suggest secondary benefits of this regimen . On the other h and , a primary non-invasive treatment strategy seems to be accepted by most IC patients OBJECTIVE Techniques for surgical repair of Trans-Atlantic Inter-Society Consensus ( TASC ) C and D lesions of the superficial femoral artery ( SFA ) are supragenicular bypass grafting or the less invasive remote endarterectomy ( RSFAE ) . This trial compares the patency rates of both techniques . DESIGN R and omized , multicenter trial . MATERIAL S AND METHODS 116 patients were r and omized to RSFAE ( n=61 ) and supragenicular bypass surgery ( n=55 ) . Indications for surgery were claudication ( n=77 ) , rest pain ( n=21 ) , or tissue loss ( n=18 ) . RESULTS Median hospital stay was 4 days in the RSFAE group compared with 6 days in the bypass group ( p=0.004 ) . Primary patency after 1-year follow-up was 61 % for RSFAE and 73 % for bypass ( p=0.094 ) . Secondary patency was 79 % for both groups . Subdividing between venous ( n=25 ) and prosthetic grafts ( n=30 ) shows a primary patency of 89 % and 63 % respectively at 1-year follow-up ( p=0.086 ) . CONCLUSION RSFAE is a minimally invasive adjunct in the treatment of TASC C and D lesions of the SFA , with shorter admittance and a comparable secondary patency rate to bypass . The venous bypass is superior to both RSFAE and PTFE bypass surgery , but only 45 % of patients had a sufficient saphenous vein available . This study is registered with Clinical Trials.gov , number NCT00566436 This prospect i ve r and omized study reported early results of the treatment of 36 unreconstructable patients with critical lower limb ischemia . The patients were divided into two groups : 12 were treated with distal venous arterialization ( DVA ) and 24 were conservatively ( CT ) using antiplatelet drugs . There were seven men and five women with an average age 64.3 ± 9.9 in DVA and 13 men and 11 women with a average age 67.1 ± 10.8 in CT groups of patients . The aim of this study was to estimate the validity of DVA as the limb salvage procedure . During the period of monitoring , morbidity and mortality rates were 50 and 0 per cent at DVA versus a mortality rate in the CT group of 33.3 per cent ( P < 0.05 ) . The mean follow-up period for DVA was 4.8 ± 3.9 months ( range , 1 to 14 months ) versus 4.9 ± 2.4 months ( range , 1 to 9 months ) for the CT group ( P > 0.05 ) . Graft patency was 83.3 per cent with two early graft thromboses . There were significant differences between the two groups in limb salvage ( 91.7 % DVA vs 12.5 % CT , P < 0.001 ) , pain relief ( 75 % DVA vs 8.3 % CT , P < 0.001 ) , and wound healing rates ( 77.8 % DVA vs 0 % CT , P < 0.001 ) . Lactate level in the blood of deep venous system after repeated measuring was significantly decreased after the multivariate analysis of variance method was applied ( F = 7.691 , P < 0.01 ) . Hemodynamic parameters such as systolic digital pressure and digitobrachial systolic pressure index were increased after revascularization using Student 's t test ( P < 0.001 ) . The DVA may improve the outcome of the treatment of the patients for whom the conventional bypass procedure mainly was not possible Critical limb ischemia ( CLI ) is the most severe form of peripheral arterial disease and is associated with a significant risk of limb loss . It is currently treated with limb revascularization by a variety of specialists . Although both open vascular bypass and endovascular therapy are offered to patients with infrainguinal peripheral arterial disease and CLI , significant disagreement exists as to which therapy works best in c and i date s for both types of intervention . Persistent clinical equipoise in combination with a paucity of comparative effectiveness data to guide treatment of CLI has led to a multidisciplinary effort to organize the Best Endovascular versus Best Surgical Therapy in patients with CLI ( BEST-CLI ) trial . The BEST-CLI trial is a pragmatic , multicenter , open label , r and omized trial that compares best endovascular therapy with best open surgical treatment in patients eligible for both treatments . This trial is highly innovative in both its design and its collaborative nature . BEST-CLI aims to provide urgently needed clinical guidance for CLI management by using ( 1 ) a pragmatic design comparing the effectiveness of established techniques while allowing for the introduction of newer therapies as they become available ; ( 2 ) a novel primary end point that includes limb amputation rates , repeat intervention , and mortality ; ( 3 ) a multidisciplinary structure that fosters cooperation among interventional cardiologists , interventional radiologists , vascular surgeons , and vascular medicine specialists ; and ( 4 ) novel techniques to evaluate the cost-effectiveness and quality -of-life outcomes of the 2 treatment strategies being tested In a prospect i ve r and omised study , performed over a 6-year period , 102 patients with severe lower limb ischaemia or claudication resistant to exercise training were r and omised either to percutaneous transluminal angioplasty ( PTA ) or vascular surgery . Only patients who could be treated by both methods were included , constituting only 5 % of the total number of patients treated during this period . The two groups were similar regarding age , severity of symptoms and diabetes . The immediate and 1-year results showed similar success and complication rates . There was , however , a significantly shorter hospital stay for patients treated with PTA . Due to early complications and initial failures PTA should , however , only be used in institutions where vascular surgical facilities are available since PTA dem and s access to such treatment BACKGROUND An intention-to-treat analysis of the Bypass versus Angioplasty in Severe Ischaemia of the Leg ( BASIL ) trial showed that in patients with severe lower limb ischemia ( SLI ) due to infrainguinal disease who survived for 2 years after intervention , initial r and omization to a bypass surgery (BSX)-first vs balloon angioplasty (BAP)-first revascularization strategy was associated with improvements in subsequent overall survival ( OS ) and amputation-free survival ( AFS ) of about 7 and 6 months , respectively . This study explored the value of baseline factors to estimate the likelihood of survival to 2 years for the trial cohort ( Cox model ) and for individual BASIL trial patients ( Weibull model ) as an aid to clinical decision making . METHODS Of 452 patients presenting to 27 United Kingdom hospitals , 228 were r and omly assigned to a BSX-first and 224 to a BAP-first revascularization strategy . Patients were monitored for at least 3 years . Baseline factors affecting the survival of the entire cohort were examined with a multivariate Cox model . The chances of survival at 1 and 2 years for patients with given baseline characteristics were estimated with a Weibull parametric model . RESULTS At the end of follow-up , 172 patients ( 38 % ) were alive without major limb amputation of the trial leg , and 202 ( 45 % ) were alive . Baseline factors that were significant in the Cox model were BASIL r and omization stratification group , below knee Bollinger angiogram score , body mass index , age , diabetes , creatinine level , and smoking status . Using these factors to define five equally sized groups , we identified patients with 2-year survival rates of 50 % to 90 % . The factors that contributed to the Weibull predictive model were age , presence of tissue loss , serum creatinine , number of ankle pressure measurements detectable , maximum ankle pressure measured , a history of myocardial infa rct ion or angina , a history of stroke or transient ischemia attack , below knee Bollinger angiogram score , body mass index , and smoking status . CONCLUSIONS Patients in the BASIL trial were at high risk of amputation and death regardless of revascularization strategy . However , baseline factors can be used to stratify those risks . Furthermore , within a parametric Weibull model , certain of these factors can be used to help predict outcomes for individuals . It may thus be possible to define the clinical and anatomic ( angiographic ) characteristics of SLI patients who are likely- and not likely-to live for > 2 years after intervention . Used appropriately in the context of the BASIL trial outcomes , this may aid clinical decision making regarding a BSX- or BAP-first revascularization strategy in SLI patients like those r and omized in BASIL Forty-three patients with aortoiliac arteriosclerosis were preoperatively assigned in r and om fashion , to a thromboendarterectomy ( TEA ) or a bypass graft ( BPG ) group without regard to the historical data , the preoperative aortograms , or the preoperative physical findings . Of 21 patients in the BPG group , the immediate success rate was 100 % and all the patients left the hospital alive , though one died of an aortic suture line disruption six weeks postoperatively . Of 22 patients assigned to the TEA group , six required some form of BPG due to inability to complete TEA on one or both sides , an intraoperative failure rate of 27 % . One patient in this group died postoperatively of renal failure . Aortoiliofemoral TEA and BPG are not comparable procedures . Anatomic factors and technical skill must be considered in choosing the proper operation BACKGROUND The Bypass versus Angioplasty in Severe Ischaemia of the Leg ( BASIL ) trial showed that survival in patients with severe lower limb ischemia ( rest pain , tissue loss ) who survived postintervention for > 2 years after initial r and omization to bypass surgery ( BSX ) vs balloon angioplasty ( BAP ) was associated with an improvement in subsequent amputation-free and overall survival of about 6 and 7 months , respectively . We now compare the effect on hospital costs and health-related quality of life ( HRQOL ) of the BSX-first and BAP-first revascularization strategies using a within-trial cost-effectiveness analysis . METHODS We measured HRQOL using the Vascular Quality of Life Question naire ( VascuQol ) , the Short Form 36 ( SF-36 ) , and the EuroQol ( EQ-5D ) health outcome measure up to 3 years from r and omization . Hospital use was measured and valued using United Kingdom National Health Service hospital costs over 3 years . Analysis was by intention-to-treat . Incremental cost-effectiveness ratios were estimated for cost per quality -adjusted life-year ( QALY ) gained . Uncertainty was assessed using nonparametric bootstrapping of incremental costs and incremental effects . RESULTS No significant differences in HRQOL emerged when the two treatment strategies were compared . During the first year from r and omization , the mean cost of inpatient hospital treatment in patients allocated to BSX ( $ 34,378 ) was estimated to be about $ 8469 ( 95 % confidence interval , $ 2,417-$14,522 ) greater than that of patients allocated to BAP ( $ 25,909 ) . Owing to increased costs subsequently incurred by the BAP patients , this difference decreased at the end of follow-up to $ 5521 ( $ 45,322 for BSX vs $ 39,801 for BAP ) and was no longer significant . The incremental cost-effectiveness ratio of a BSX-first strategy was $ 184,492 per QALY gained . The probability that BSX was more cost-effective than BAP was relatively low given the similar distributions in HRQOL , survival , and hospital costs . CONCLUSIONS Adopting a BSX-first strategy for patients with severe limb ischemia does result in a modest increase in hospital costs , with a small positive but insignificant gain in disease-specific and generic HRQOL . However , the real-world choice between BSX-first and BAP-first revascularization strategies for severe limb ischemia due to infrainguinal disease can not depend on costs alone and will require a more comprehensive consideration of individual patient preferences conditioned by expectations of survival and other health outcomes This study reports the initial evaluation of treatment efficiency in 75 patients with intermittent claudication who were r and omized to three treatment groups : 1 ) reconstructive surgery , 2 ) recon structive surgery with subsequent physical training , and 3 ) physical training alone . Before treatment , there were no statistically significant differences between the groups in age , sex , smoking habits , symptom duration of claudication , ankle-arm blood pressure quotient ( ankle-index ) , maximal plethysmographic calf blood flow , symptom-free and maximal walking distance , the history of other atherosclerotic manifestations or in the medical treatment . The walking performance was improved in all three groups at follow-up 13 ± 0.5 months after r and omization . Surgery was most effective , but the addition of training to surgery improved the symptom-free walking distance even further . In pooled observations of the three groups , age , symptom duration , and a history of myocardial ischemic disease correlated negatively with walking performance after treatment . In the operated group , the duration of claudication and a history of myocardial ischemic disease correlated negatively with the walking performance . This was not the case when patients were censored if limited by other symptoms than intermittent claudication after treatment . In the trained group , the duration of claudication correlated negatively to symptom-free and maximal walking distance . Ankle-index and maximal plethysmographic calf blood flow after treatment and the change of these variables with treatment correlated positively with both symptom-free and maximal walking distance when results were pooled for all patients . Although this mainly was a consequence of the improved blood flow after surgery , the change of maximal plethysmographic calf blood flow also correlated with symptom-free but not with maximal walking distance in the trained group . The results demonstrate that , compared with physical training alone , operation alone or in combination with subsequent training are superior treatment modalities in patients with intermittent claudication OBJECTIVES To investigate differences between open and laparoscopic aortobifemoral bypass surgery for aorto-iliac occlusive disease on postoperative morbidity and mortality . DESIGN A multicentre r and omised controlled trial . METHODS Between January 2007 and November 2009 , 28 patients with severe aorto-iliac occlusive disease ( TASC II C or D ) were r and omised between laparoscopic and open approach at one community hospital and one university hospital ( TASC = Trans-Atlantic Inter-Society Consensus on the Management of Peripheral Arterial Disease ) . RESULTS The operation time was longer for the laparoscopic approach ( mean 4 h 19 min ( 2 h 00 min to 6 h 20 min ) vs. 3 h 30 min ( 1 h 42 min to 5 h 11 min ) ; p = 0.101 ) ) . Nevertheless , postoperative recovery and in-hospital stay were significantly shorter after laparoscopic surgery . Also oral intake could be restarted earlier ( mean 20 h 34 min ( 6 h 00 min to 26 h 55 min ) vs. 43 h 43 min ( 19 h 40 min to 77 h 30 min ) ; p = 0.00014 ) ) as well as postoperative mobilisation ( walking ) ( mean 46 h 15 min ( 16 h 07 min to 112 h 40 min ) vs. mean 94 h 14 min ( 66 h 10 min to 127 h 23 min ) ; p = 0.00016 ) ) . Length of hospitalisation was shorter ( mean 5.5 days ( 2.5 - 15 ) vs. mean 13.0 days ( 7 - 45 ) ; p = 0.0095 ) ) . Visual pain scores and visual discomfort scores were both lower after laparoscopic surgery . Also return to normal daily activities was achieved earlier . There were no major complications in both groups . CONCLUSION Laparoscopic aortobifemoral bypass surgery for aorto-iliac occlusive disease is a safe procedure with a significant decrease in postoperative morbidity and in-hospital stay and earlier recovery In the last few years the development of new and improved surgical procedures caused a more aggressive approach , by femoro-distal bypass , to the limb affected by critical ischaemia . A good surgical result is related to the crural vessel patency , the presence of an adequate autologous vein and the possibility to visualize inframalleolar and foot arteries by selective angiograms . Should all these conditions not be present , an outflow procedure might be at high risk for failure . On the other h and , several studies show that SCS relieves rest pain and improves trophic lesion healing although there is no evident increase in peripheral blood flow , but these studies refer to heterogeneous non-r and omized patients . In order to evaluate the effectiveness of SCS compared to distal arterial reconstruction , we started this prospect i ve and r and omized study . In a period of 15 months , 12 patients affected by critical limb ischaemia at 4th stage of Fontaine with angiographic multilevel distal lesions were r and omised for SCS ( 7 cases : group A ) and distal bypass ( 5 cases : group B ) . The result of the therapy was judged as good or fair when either complete or evident pain regression and trophic lesion healing were obtained ; otherwise the result was considered as poor . Actually the study is in progress , the follow-up is partial ( 3 - 12 months ) , the results are preliminary . In the patients of group A the results were good or fair in 5 cases ( 72 % ) and poor in 2 ( 28 % ) . In the patients of group B the results were good or fair in 2 cases ( 40 % ) and poor in 3 ( 60 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS The Claudication : Exercise vs Endoluminal Revascularization ( CLEVER ) Study is a prospect i ve multicenter r and omized clinical trial design ed to compare the relative clinical and cost-effectiveness of invasive revascularization with stents to supervised exercise rehabilitation in a cohort with moderate to severe claudication due to aortoiliac insufficiency . The study is currently enrolling at twenty-eight sites in the US and Canada . Enrollment of 217 participants is planned , with data collected at baseline , six months , and 18 months . The primary study endpoint is maximum walking duration ( MWD ) on a grade d treadmill test ; secondary endpoints include community-based walking , markers of cardiovascular disease risk ( body mass index , waist circumference , blood pressure , lipid profile , glucose tolerance , and plasma fibrinogen ) , health-related quality of life , and cost effectiveness . There are currently sixty r and omized participants ; recruitment is projected to end in July 2010 and final study results reported in June 2012 In review ing late morbidity of a multicenter clinical trial comparing balloon angioplasty ( percutaneous transluminal angioplasty ) with bypass surgery for lower-extremity ischemia , an unexpectedly high incidence of adverse systemic events in surgical patients was uncovered . The study was prospect i ve and r and omized , and included a total of 263 patients , with follow-up from 2 to 6 years . When end points of related deaths , amputations , and intervention failures were summed , surgery was favored over percutaneous transluminal angioplasty at 4 years . Progression of cardiac and renal dysfunction and mortality differed between groups . A total of 42 deaths were in the group who underwent surgery and 27 in those who underwent percutaneous transluminal angioplasty . The percentage difference in death rate between the two groups increased each year to reach 10 % at 5 years . A significant difference in renal function was noted in nine patients who underwent surgery and zero who underwent percutaneous transluminal angioplasty . Myocardial infa rct ions were greater on follow-up of surgical patients . After 6 years , congestive heart failure had occurred in 19 patients who underwent surgery and eight who underwent percutaneous transluminal angioplasty . The trends in this study of patients with only moderately severe peripheral arterial disease suggest an increased rate of deterioration of cardiac and renal function in patients who have arterial operations . In surgical patients , mortality was 13.1 % per year , whereas it was 8.4 % for patients treated with percutaneous transluminal angioplasty . Future intervention studies should include long-term follow-up of such cardiovascular events OBJECTIVES To compare the safety and efficacy of a bioresorbable paclitaxel-eluting wrap implanted with a synthetic vascular graft ( treatment ) versus the graft implanted alone ( control ) . DESIGN Prospect i ve , r and omized , controlled , multicentre , 2-year clinical study conducted in adults scheduled to undergo femoropopliteal peripheral bypass surgery with a polytetrafluoroethylene ( PTFE ) graft . MATERIAL S AND METHODS Hundred and nine subjects were r and omized 2:1 to treatment or control . All subjects were implanted with a 6 mm exp and ed PTFE vascular graft ; in addition , treated subjects had a 2.5 cm x 4 cm paclitaxel-eluting wrap ( 1.6 microg/mm(2 ) ) placed around the distal graft anastomosis . RESULTS The overall incidence of adverse events was similar in both groups . Treated subjects required fewer limb amputations than controls ( 15.5 % vs 18.4 % ) and time to amputation for those that required amputation was twice as long ( 153 days vs 76 days ) . Among diabetics , this effect was pronounced with 13.8 % of treated subjects requiring limb amputations compared with 23.5 % of controls . Over the course of study , the diameter at the distal graft anastomosis was greater in treated subjects than in controls ( difference of 2.1 mm at 2 yr , p=0.03 ) . CONCLUSIONS The paclitaxel-eluting wrap maintained graft patency at the distal anastomosis and was safe to use in patients who had received a peripheral bypass PTFE graft INTRODUCTION open transperitoneal aorto-bifemoral by-pass is still associated with a relatively high morbidity and mortality . To decrease this surgical stress , minimally invasive direct aortic surgery ( MIDAS ) was developed , utilizing a minilaparotomy and a retroperitoneal approach to the aorta . OBJECTIVES to compare in a r and omised controlled trial whether mortality and morbidity could be reduced with MIDAS . METHODS from October 1997 to September 2000 , 300 patients were r and omised to either MIDAS ( n=150 ) or conventional aorto-bifemoral by-pass surgery ( n=150 ) . RESULTS the perioperative ( 30 days ) mortality ( 2.6 % ) , was equal in both groups . MIDAS were significantly reduced length of hospital stay ( 3.1 days ) , and pulmonary dysfunction . CONCLUSIONS MIDAS reduced trauma and pain , which result ed in a shorter hospital stay , and a reduction in costs |
11,983 | 23,528,538 | Increased postoperative BNPs are independently associated with adverse cardiac events after noncardiac surgery | BACKGROUND It is unclear whether postoperative B-type natriuretic peptides ( i.e. , BNP and N-terminal proBNP ) can predict cardiovascular complications in noncardiac surgery . | CONTEXT Of the 200 million adults worldwide who undergo noncardiac surgery each year , more than 1 million will die within 30 days . OBJECTIVE To determine the relationship between the peak fourth-generation troponin T ( TnT ) measurement in the first 3 days after noncardiac surgery and 30-day mortality . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , international cohort study that enrolled patients from August 6 , 2007 , to January 11 , 2011 . Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery . MAIN OUTCOME MEASURES Patients ' TnT levels were measured 6 to 12 hours after surgery and on days 1 , 2 , and 3 after surgery . We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery , and the independent variables included 24 preoperative variables . We repeated this analysis , adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients ' risk of death . RESULTS A total of 15,133 patients were included in this study . The 30-day mortality rate was 1.9 % ( 95 % CI , 1.7%-2.1 % ) . Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL , occurring in 11.6 % of patients , were associated with higher 30-day mortality compared with the reference group ( peak TnT ≤ 0.01 ng/mL ) : peak TnT of 0.02 ng/mL ( adjusted hazard ratio [ aHR ] , 2.41 ; 95 % CI , 1.33 - 3.77 ) ; 0.03 to 0.29 ng/mL ( aHR , 5.00 ; 95 % CI , 3.72 - 6.76 ) ; and 0.30 ng/mL or greater ( aHR , 10.48 ; 95 % CI , 6.25 - 16.62 ) . Patients with a peak TnT value of 0.01 ng/mL or less , 0.02 , 0.03 - 0.29 , and 0.30 or greater had 30-day mortality rates of 1.0 % , 4.0 % , 9.3 % , and 16.9 % , respectively . Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without ( C index = 0.85 vs 0.81 ; difference , 0.4 ; 95 % CI , 0.2 - 0.5 ; P < .001 for difference between C index values ) . The net reclassification improvement with TnT was 25.0 % ( P < .001 ) . CONCLUSION Among patients undergoing noncardiac surgery , the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality This study considered if N-terminal prohormone brain natriuretic peptide ( NT-proBNP ) is associated with increased risk for postoperative cardiac events in high-risk patients undergoing noncardiac surgery . In addition , this report describes how levels of NT-proBNP are affected by noncardiac surgery . The study design was a prospect i ve cohort study that enrolled 83 patients age > or = 50 years with > or = 1 risk factor for coronary artery disease having intermediate or high-risk noncardiac surgery . NT-proBNP levels were measured preoperatively and on postoperative days 1 and 3 . During the month following surgery , 25 patients ( 33 % ) had a combined 37 postoperative cardiac events including 15 episodes of heart failure ( 20 % ) , 12 episodes of new dysrhythmia ( 16 % ) , 7 myocardial infa rct ions ( 9 % ) , and 3 cardiac arrests ( 4 % ) . Preoperative NT-proBNP level > or = 457 pg/ml was significantly associated with occurrence of a postoperative cardiac event ( odds ratio 10.5 , 95 % confidence interval 1.9 to 56.6 , p = 0.006 ) . After surgery , 64 of 72 patients ( 89 % ) had an increase in NT-proBNP from their preoperative level . In conclusion , this study determined there was a significant association between elevated preoperative NT-proBNP and occurrence of a postoperative cardiac event . In addition , increased NT-proBNP after noncardiac surgery is not uncommon even in the absence of clinical ly identifiable heart failure Background — Postoperative atrial fibrillation ( AF ) is a complication of thoracic surgery for lung cancer , with a reported incidence that can run as high as 42 % . Recently , it has been observed retrospectively that B-type natriuretic peptide predicts AF after cardiac surgery . We performed a prospect i ve study to evaluate the role of N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) as a marker for risk stratification of postoperative AF in patients undergoing thoracic surgery for lung cancer . Methods and Results — We measured NT-proBNP levels in 400 patients ( mean age , 62±10 years ; 271 men ) 24 hours before and 1 hour after surgery . The primary end point of the study was the incidence of postoperative AF . Overall , postoperative AF occurred in 72 patients ( 18 % ) . Eighty-eight patients ( 22 % ) showed an elevated perioperative NT-proBNP value . When patients with either preoperatively or postoperatively elevated NT-proBNP were pooled , a greater incidence of AF was observed compared with patients with normal values ( 64 % versus 5 % ; P<0.001 ) . At multivariable analysis , adjusted for age , gender , major comorbidities , echocardiography parameters , pneumonectomy , and medications , both preoperative and postoperative NT-proBNP values were independent predictors of AF ( relative risk , 27.9 ; 95 % CI , 13.2 to 58.9 ; P<0.001 for preoperative NT-proBNP elevation ; relative risk , 20.1 ; 95 % CI , 5.8 to 69.4 ; P<0.001 for postoperative NT-proBNP elevation ) . Conclusions — Elevation of perioperative NT-proBNP is a strong independent predictor of postoperative AF in patients undergoing thoracic surgery for lung cancer . This finding should facilitate studies of therapies to reduce AF in selected high-risk patients OBJECTIVES This study was design ed to evaluate B-type natriuretic peptide ( BNP ) for risk assessment and clinical decision making over a range of cut points , alone and with cardiac troponin I ( cTnI ) , in patients with non-ST-elevation acute coronary syndromes ( ACS ) . BACKGROUND B-type natriuretic peptide holds promise for risk stratification . Additional evidence regarding optimal decision limits , use in combination with troponin , and use in targeting therapy is needed before acceptance into clinical use for ACS . METHODS We evaluated BNP at baseline in 1,676 patients with non-ST-elevation ACS r and omized to early invasive versus conservative management . RESULTS Patients with elevated BNP ( > 80 pg/ml ; n = 320 ) were at higher risk of death at seven days ( 2.5 % vs. 0.7 % , p = 0.006 ) and six months ( 8.4 % vs. 1.8 % , p < 0.0001 ) . The association between BNP and mortality at six months ( adjusted odds ratio [ OR ] 3.3 ; 95 % confidence interval [ CI ] 1.7 to 6.3 ) was independent of important clinical predictors , including cTnI and congestive heart failure ( CHF ) . Patients with elevated BNP had a fivefold higher risk of developing new CHF by 30 days ( 5.9 % vs. 1.0 % , p < 0.0001 ) . B-type natriuretic peptide added prognostic information to cTnI , discriminating patients at higher mortality risk among those with negative ( OR 6.9 ; 95 % CI 1.9 to 25.8 ) and positive ( OR 4.1 ; 95 % CI 1.9 to 9.0 ) baseline cTnI results . No difference was observed in the effect of invasive versus conservative management when stratified by baseline levels of BNP ( p(interaction ) > or = 0.6 ) . CONCLUSIONS Elevated BNP ( > 80 pg/ml ) at presentation identifies patients with non-ST-elevation ACS who are at higher risk of death and CHF and adds incremental information to cTnI. Additional work is needed to identify therapies that may reduce the risk associated with increased BNP We performed a Monte Carlo study to evaluate the effect of the number of events per variable ( EPV ) analyzed in logistic regression analysis . The simulations were based on data from a cardiac trial of 673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality ; the number of events per predictive variable was ( 252/7 =) 36 for the full sample . For the simulations , at values of EPV = 2 , 5 , 10 , 15 , 20 , and 25 , we r and omly generated 500 sample s of the 673 patients , chosen with replacement , according to a logistic model derived from the full sample . Simulation results for the regression coefficients for each variable in each group of 500 sample s were compared for bias , precision , and significance testing against the results of the model fitted to the original sample . For EPV values of 10 or greater , no major problems occurred . For EPV values less than 10 , however , the regression coefficients were biased in both positive and negative directions ; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coefficients ; the 90 % confidence limits about the estimated values did not have proper coverage ; the Wald statistic was conservative under the null hypothesis ; and paradoxical associations ( significance in the wrong direction ) were increased . Although other factors ( such as the total number of events , or sample size ) may influence the validity of the logistic model , our findings indicate that low EPV can lead to major problems Background : Postoperative cognitive dysfunction ( POCD ) is a significant cause of morbidity after noncardiac surgery . Identified risk factors are largely limited to demographic characteristics . We hypothesized that POCD was associated with apolipoprotein E4 ( APOE4 ) genotype and plasma biomarkers of brain injury and inflammation . Methods : Three hundred ninety-four patients older than 55 yr undergoing major elective noncardiac surgery were enrolled in this prospect i ve observational study . Apolipoprotein E genotyping was performed at baseline . Plasma was collected at baseline and end of surgery and at 4.5 , 24 , and 48-h postoperatively . Six protein biomarkers were assayed ( B-type natriuretic peptide , C-reactive protein , D-dimer , matrix metalloproteinase-9 , neuron-specific enolase , and S-100B ) . Neurocognitive testing was conducted at baseline and at 6 weeks and 1 yr after surgery ; scores were subjected to factor analysis . The association of APOE4 and biomarkers with POCD was tested using multivariable regression modeling . Results : Three hundred fifty patients ( 89 % ) completed 6-week neurocognitive testing . POCD occurred in 54.3 % of participants at 6 weeks and 46.1 % at 1 yr . There was no difference in POCD between patients with or without the APOE4 allele ( 56.6 vs. 52.6 % ; P = 0.58 ) . The continuous cognitive change score ( mean ± SD ) was similar between groups ( APOE4 : 0.05 ± 0.27 vs. non-APOE4 : 0.07 ± 0.28 ; P = 0.53 ) . Two hundred ninety-one subjects ( 74 % ) completed testing at 1 yr . POCD occurred in 45.9 % of APOE4 subjects versus 46.3 % of non-APOE4 subjects ( P = 0.95 ) . The cognitive score was again similar ( APOE4 : 0.08 ± 0.27 vs. non-APOE4 : 0.05 ± 0.25 ; P = 0.39 ) . Biomarker levels were not associated with APOE4 genotype or cognition at 6 weeks or 1 yr . Conclusion : Cognitive decline after major noncardiac surgery is not associated with APOE4 genotype or plasma biomarker levels OBJECTIVES The aim of this study was to evaluate whether chronic heart failure ( HF ) therapy guided by concentrations of amino-terminal pro-B-type natriuretic peptide ( NT-proBNP ) is superior to st and ard of care ( SOC ) management . BACKGROUND It is unclear whether st and ard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with st and ard management alone . METHODS In a prospect i ve single-center trial , 151 subjects with HF due to left ventricular ( LV ) systolic dysfunction were r and omized to receive either st and ard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management . The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations . Secondary endpoints included effects of NT-proBNP-guided care on patient quality of life as well as cardiac structure and function , assessed with echocardiography . RESULTS Through a mean follow-up period of 10 ± 3 months , a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC ( 58 events vs. 100 events , p = 0.009 ; logistic odds for events 0.44 , p = 0.02 ) ; Kaplan-Meier curves demonstrated significant differences in time to first event , favoring NT-proBNP-guided care ( p = 0.03 ) . No age interaction was found , with elderly patients benefitting similarly from NT-proBNP-guided care as younger subjects . Compared with SOC , NT-proBNP-guided patients had greater improvements in quality of life , demonstrated greater relative improvements in LV ejection fraction , and had more significant improvements in both LV end-systolic and -diastolic volume indexes . CONCLUSIONS In patients with HF due to LV systolic dysfunction , NT-proBNP-guided therapy was superior to SOC , with reduced event rates , improved quality of life , and favorable effects on cardiac remodeling . ( Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting ; NCT00351390 ) OBJECTIVES To determine if troponin I and NT-proBNP were predictors of 6-month mortality after emergency orthopedic-geriatric surgery in a frail population . DESIGN Prospect i ve observational study . SETTING Orthopedic-geriatric unit of a metropolitan hospital in Australia . PARTICIPANTS A total of 383 patients were screened ; 44 were eligible for this study of which 33 patients consented who were receiving high-level care or had severe dementia or an illness with a prognosis of less than 12 months . MEASUREMENTS Troponin I and NT-proBNP were tested on one preoperative sample and at least one postoperative blood sample . Cardiac events were defined as acute myocardial infa rct ion , congestive cardiac failure , new onset or rapid atrial fibrillation , major arrhythmia , or cardiac arrest . RESULTS The mean age of the patients was 85.8 + /- 9.6 years and 93.9 % had a fractured neck of femur . Premorbid cardiac conditions were common ( 24.2 % had ischemic heart disease and 21.2 % congestive cardiac failure ) . A third of patients had a preoperative troponin elevation and 60.6 % had a postoperative elevation . The mortality within 30 days of surgery was 15.2 % ( 5/33 patients ) , rising to 39.4 % ( 13/33 ) at 6 months with 46.2 % ( 6/13 ) dying of a cardiac cause . The Kaplan-Meier survival curve was not significantly different between patients with and without a troponin elevation . A third of patients sustained a cardiac event at 6 months . The median preoperative NT-proBNP was 1651.50 pg/L , range 25 to 31,227 , and median postoperative NT-proBNP was 3038.50pg/L , range 44 to 27,348 . Troponin I and NT pro-BNP did not predict 6-month mortality or cardiac complications . Predictors of 6-month mortality using univariate analysis were number of comorbidities OR 2.0 ( 95 % CI 1.1 - 3.8 , P = .033 ) and premorbid atrial fibrillation OR 7.7 ( 95 % CI 1.2 - 47.8 , P = .028 ) . CONCLUSION Troponin I and NT-proBNP were not predictors of 6-month mortality or cardiac events in an older frailer population of patients undergoing orthopedic surgery . These patients sustained substantial cardiac morbidity and mortality at 6 months after surgery . The control of symptoms , rather than prolongation of life with cardiological intervention , may be more appropriate for this patient group BACKGROUND B-type natriuretic peptide is released from the cardiac ventricles in response to increased wall tension . METHODS We conducted a prospect i ve study of 1586 patients who came to the emergency department with acute dyspnea and whose B-type natriuretic peptide was measured with a bedside assay . The clinical diagnosis of congestive heart failure was adjudicated by two independent cardiologists , who were blinded to the results of the B-type natriuretic peptide assay . RESULTS The final diagnosis was dyspnea due to congestive heart failure in 744 patients ( 47 percent ) , dyspnea due to noncardiac causes in 72 patients with a history of left ventricular dysfunction ( 5 percent ) , and no finding of congestive heart failure in 770 patients ( 49 percent ) . B-type natriuretic peptide levels by themselves were more accurate than any historical or physical findings or laboratory values in identifying congestive heart failure as the cause of dyspnea . The diagnostic accuracy of B-type natriuretic peptide at a cutoff of 100 pg per milliliter was 83.4 percent . The negative predictive value of B-type natriuretic peptide at levels of less than 50 pg per milliliter was 96 percent . In multiple logistic-regression analysis , measurements of B-type natriuretic peptide added significant independent predictive power to other clinical variables in models predicting which patients had congestive heart failure . CONCLUSIONS Used in conjunction with other clinical information , rapid measurement of B-type natriuretic peptide is useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea Background and Objectives B-type natriuretic peptide ( BNP ) is an important marker for the diagnosis of heart failure and is useful towards predicting morbidity and mortality after non-cardiac surgery . Nevertheless , information on the relationship between postoperative BNP levels and perioperative prognosis after non-cardiac surgery is scarce . The purpose of the study was to assess whether postoperative BNP levels could be used as a predictor of prolonged hospitalization in elderly hypertensive patients after non-cardiac surgery . Subjects and Methods Ninety-seven ( 97 ) patients , aged 55 years or older ( mean age : 73.12±10.05 years , M : F=24 : 73 ) were enrolled in a prospect i ve study from May 2005 through August 2010 . All patients underwent total knee or hip replacement . Postoperative BNP and other diagnostic data were recorded within 24 hours of surgery . Patients that required a prolonged hospital stay due to operative causes , such as wound infection and re-operation , were excluded . Results The length of hospital stay was significantly correlated with postoperative BNP levels ( p=0.031 ) . Receiver operating characteristic curves demonstrated postoperative BNP levels as predictors of hospital stay ≥30 days with areas under the curve of 0.774 ( 95 % confidence interval : 0.679 - 0.87 , p<0.0001 ) . A BNP cut-off value above 217.5 pg/mL had a sensitivity of 80.6 % and a specificity of 66.7 % for predicting postoperative hospital stays of 30 days or more . Conclusion Postoperative BNP levels may predict the length of hospital stays after non-cardiac surgery in hypertensive patients . Elevated BNP levels were associated with prolonged hospitalization after elective orthopedic surgery OBJECTIVES Differentiating cardiogenic pulmonary edema ( CPE ) from respiratory causes of dyspnea is difficult in elderly patients . The aim of this study was to compare the usefulness of B-type natriuretic peptide ( BNP ) and amino-terminal fragment BNP ( proBNP ) , to diagnose CPE in patients aged 65 and older . DESIGN Prospect i ve study . SETTING Medical emergency department of a 2,000-bed urban teaching hospital . PARTICIPANTS Patients aged 65 and older presenting with acute dyspnea and a respiratory rate of 25 breaths/min or greater , a partial pressure of oxygen of 70 mmHg or less , or an oxygen saturation of 92 % or less were included . MEASUREMENTS Rapid BNP and proBNP assays , performed blind at admission , were compared with the final diagnosis ( CPE or no CPE ) as defined by an expert team . RESULTS Two hundred two patients ( mean age+/-st and ard deviation 80+/-9 ) were included ; 88 ( 44 % ) had CPE . There was a strong correlation between proBNP and BNP values ( correlation coefficient=0.91 , P<.001 ) . The median BNP and proBNP were higher in the group of patients with CPE ( 377 vs 74 pg/mL , P<.001 , and 3,851 vs 495 pg/mL , P<.001 , respectively ) . The best threshold values of BNP and proBNP were 250 pg/mL and 1,500 pg/mL , respectively . The area under the receiver operating characteristic curve was greater with BNP than with proBNP ( 0.85 vs 0.80 , P<.05 ) . BNP assay was more accurate in diagnosis than the emergency physician , whereas proBNP was not . Higher values of BNP and proBNP were associated with greater in-hospital mortality . CONCLUSION BNP assay is a more useful diagnostic indicator for CPE than proBNP in patients aged 65 and older Background Cardiovascular disease is the leading cause of perioperative death in surgical patients . A variety of clinical scoring systems have been developed to predict adverse cardiovascular events . B-type natriuretic peptide ( BNP ) is a sensitive and specific predictor of left ventricular systolic dysfunction and predicts first cardiovascular event and death in the general population . We present a prospect i ve , single-center , observational cohort study of patients undergoing major abdominal surgery and evaluate the role of BNP in predicting adverse cardiac events . Method A total of 205 patients were included in the study . All patients were assessed by a cardiological clinical evaluation , a 12-lead ECG report , and a preoperative and postoperative blood sample for plasmatic BNP assessment . The primary end point was the predictive power of preoperative BNP levels for adverse cardiac events until 30 days after discharge . Results Thirty-one of 205 ( 15 % ) patients had adverse cardiac events in the postoperative period up to 30 days after discharge . Five patients ( 2.4 % ) of these died of cardiac events . Preoperative BNP values were significantly increased in the 31 patients compared to the other patients in the postoperative period [ mean = 112.93 pg/ml ( range = 5–2,080 ) vs. 178.99 pg/ml ( range = 5–3,980 ) ; median = 117 vs. 23 pg/ml ; 95 % CI = 49–181 ; p < 0.0001 ] . At logistic regression , a preoperative BNP value of > 36 pg/ml was the only effective predictor of adverse cardiac events . Conclusion We have demonstrated that elevated preoperative BNP levels are independent predictors of adverse cardiac events in a cohort of patients undergoing major abdominal surgery in a general surgery department , and this is the first study about this specific cohort of patients OBJECTIVE Weight gain with oedema development is a complication of major surgical procedures with an incidence as high as 40 % . Fluid retention is not always clinical ly evident and it is reported despite fluid-restriction regime . The causes are several and not totally clear . We performed a prospect i ve study to assess the amount of fluid accumulation and redistribution observed after major thoracic surgery . METHODS In 49 patients su bmi tted to lobectomy with systematic lymph node dissection for lung cancer , we measured preoperatively and on the postoperative days 1 , 2 , 4 and 7 , body weight , fluid balance , brain natriuretic peptide ( BNP ) and bioimpedance analysis (BIA)-derived parameters resistance ( R ) and reactance ( X(c ) ) . RESULTS The postoperative course was characterised by significant changes . Mean increase in body weight was 2.7 kg ( ( 1.9 - 3.4 ) ; p<0.001 ) on postoperative day 2 . Most of the patients had a negative basal fluid balance ( -244 ml ( -520 to -50 ) ) , whereas , on postoperative day 2 , we observed a positive and significant change ( + 968 ml ( 646 - 1456 ) , p<0.001 ) ) . Total body R and X(c ) fell on the first day ( p<0.001 ) , anticipating the changes in weight and fluid balance . BNP increased on day 1 , immediately after surgery , and remained significantly above basal values for the entire observation period ( p<0.001 ) , in the absence of clinical signs of heart failure . CONCLUSION The three methods used consistently showed a significant fluid retention over the course of the study . BIA was an easy , reproducible and non-invasive method for the estimation and early detection of fluid retention . Increase in BNP may be related to the systemic reaction to stress and to the decreased pulmonary vascular bed . We found no correlation between fluid retention and length of anaesthesia , sex , age , blood loss and body mass index . The clinical and prognostic implication of weight gain may be relevant to patient 's health BACKGROUND Each year , millions of patients worldwide have a perioperative myocardial infa rct ion ( MI ) after noncardiac surgery . OBJECTIVE To examine the characteristics and short-term outcome of perioperative MI . DESIGN Cohort study . ( Clinical Trials.gov registration number : NCT00182039 ) SETTING 190 centers in 23 countries . PATIENTS 8351 patients included in the POISE ( PeriOperative ISchemic Evaluation ) trial . MEASUREMENTS Four cardiac biomarker or enzyme assays were measured within 3 days of surgery . The definition of perioperative MI included either autopsy findings of acute MI or an elevated level of a cardiac biomarker or enzyme and at least 1 of the following defining features : ischemic symptoms , development of pathologic Q waves , ischemic changes on electrocardiography , coronary artery intervention , or cardiac imaging evidence of MI . RESULTS Within 30 days of r and om assignment , 415 patients ( 5.0 % ) had a perioperative MI . Most MIs ( 74.1 % ) occurred within 48 hours of surgery ; 65.3 % of patients did not experience ischemic symptoms . The 30-day mortality rate was 11.6 % ( 48 of 415 patients ) among patients who had a perioperative MI and 2.2 % ( 178 of 7936 patients ) among those who did not ( P < 0.001 ) . Among patients with a perioperative MI , mortality rates were elevated and similar between those with ( 9.7 % ; adjusted odds ratio , 4.76 [ 95 % CI , 2.68 to 8.43 ] ) and without ( 12.5 % ; adjusted odds ratio , 4.00 [ CI , 2.65 to 6.06 ] ) ischemic symptoms . LIMITATION Cardiac markers were measured only until day 3 after surgery , and additional asymptomatic MIs may have been missed . CONCLUSION Most patients with a perioperative MI will not experience ischemic symptoms . Data suggest that routine monitoring of troponin levels in at-risk patients is needed after surgery to detect most MIs , which have an equally poor prognosis regardless of whether they are symptomatic or asymptomatic |
11,984 | 24,197,972 | Desarrollar y utilizar normas para medición del uso de condón ampliaría comparabilidad de result ados a través de estudios y beneficiaría investigación de la prevención de VIH . | When evaluating HIV prevention interventions , condom use is a common outcome measure used to assess changes in HIV-related behaviors ; however , no widely accepted st and ards exist for its measurement .
Using systematic review data on HIV prevention interventions conducted in low- and middle-income countries , we examined trends in condom use measurement since 1990 . | Among severely mentally ill ( SMI ) substance abusers , HIV rates are elevated and HIV risk reduction interventions have been shown to be less effective . An enhanced cognitive behavioral HIV risk reduction intervention ( E-CB ) for SMI was compared to a health promotion condition ( HPC ) in 222 psychiatric out patients at 6 months postintervention . Compared to females , males in the E-CB improved on intention to practice safer sex and in condom use skills and in unprotected vaginal sex , but did not differ in HIV knowledge , perceived susceptibility , anxiety , condom attitudes , safer sex self-efficacy , unprotected vaginal sex acts , or sex partners . Across intervention groups , there were improvements in all areas except self-efficacy and number of partners . Risk reduction among SMI may be facilitated by increasing awareness of health related behaviors and HIV-targeted content . However , meaningful changes in critical risk reduction skills and intentions may require a more focused intervention and may vary by gender Objective : The objective of this study was to assess the validity of women ’s reports of recent unprotected sex by testing for prostate-specific antigen ( PSA ) in vaginal sample s. Study Design : The authors conducted prospect i ve research with 332 female sex workers attending 2 public dispensaries in Madagascar . Results : Among women who reported no sex or protected sex only within the past 48 hours , 21 % and 39 % , respectively , tested positive for PSA . Among those testing positive for PSA , no differences in PSA concentrations were found among those reporting no sex , protected sex only , or at least one unprotected act . Conclusions : The substantial disagreement between self-reports and measurement of a biologic marker of semen exposure in vaginal specimens substantiates that self-reports of sexual behavior can not be assumed to be valid measures . Future sexually transmitted infection/HIV and pregnancy prevention studies should confirm the validity of self-reports or use end points that do not rely on self-reported data In a pilot study , young people in slums in Kampala , Ug and a received an HIV prevention program ( Street Smart ) and were r and omized to receive vocational training immediately ( Immediate ) or four months later ( Delayed ) . Youth were monitored at recruitment , 4 months ( 85 % retention ) , and 24 months ( 74 % retention ) . Employment increased dramatically : Only 48 % had ever been employed at recruitment , 86 % were employed from months 21 to 24 post recruitment . Over two years , decreases were recorded in the number of sexual partners , mental health symptoms , delinquent acts , and drug use ; condom use increased . Providing employment in low income countries , in conjunction with HIV prevention , may provide sustained support to young people to prevent HIV acquisition . ResumenEn un estudio piloto , los jóvenes en los barrios bajos de Kampala , Ug and a recibieron un programa de prevención del VIH ( Street Smart ) y fueron aleatorizados para recibir la formación profesional inmediatamente ( inmediato ) o cuatro meses más tarde ( en diferido ) . La juventud fue vigilada en el reclutamiento , 4 meses ( 85 % de retención ) , y 24 meses ( 74 % de retención ) . El empleo aumentó dramáticamente : sólo el 48 % había sido empleado en la contratación , el 86 % fue empleado de 21 a 24 meses después de la contratación . Más de dos años , se registraron disminuciones en el número de parejas sexuales , los síntomas de la salud mental , los actos delictivos y el consumo de drogas ; el uso del condón aumentó . La creación de empleo en los países de bajos ingresos , en conjunción con la prevención del VIH , puede proporcionar un apoyo sostenido a los jóvenes para prevenir la adquisición del VIH Challenges in the accurate measurement of sexual behavior in human immunodeficiency virus ( HIV ) prevention research are well documented and have prompted discussion about whether valid assessment s are possible . Audio computer-assisted self-interviewing ( ACASI ) may increase the validity of self-reported behavioral data . In 2006 - 2007 , Zimbabwean women participated in a r and omized , cross-sectional study that compared self-reports of recent vaginal sex and condom use collected through ACASI or face-to-face interviewing ( FTFI ) with a vali date d objective biomarker of recent semen exposure ( prostate-specific antigen ( PSA ) levels ) . Of 910 study participants , 196 ( 21.5 % ) tested positive for PSA , an indication of semen exposure during the previous 2 days . Of these 196 participants , 23 ( 11.7 % ) reported no sex in the previous 2 days , with no difference in reported sexual activity between interview modes ( 12.5 % ACASI vs. 10.9 % FTFI ; Fisher 's exact test : P = 0.72 ) . In addition , 71 PSA-positive participants ( 36.2 % ) reported condom-protected vaginal sex only ; their reports also indicated no difference between interview modes ( 33.7 % ACASI vs. 39.1 % FTFI ; P = 0.26 ) . Only 52 % of PSA-positive participants reported unprotected sex during the previous 2 days . Self-report was a poor predictor of recent sexual activity and condom use in this study , regardless of interview mode , providing evidence that such data should be interpreted cautiously A partner study was conducted in northern Thail and between March 1992 and June 1996 which included data that allowed an assessment of the reliability of self-reports of sexual behavior and contraceptive use among heterosexual couples . The authors enrolled 529 couples among whom all male subjects were human immunodeficiency virus ( HIV ) seropositive voluntary blood donors and their female sexual partners were either HIV infected ( n=246 ) or HIV seronegative ( n=283 ) . The levels of agreement within couples were assessed for recency of last sexual intercourse , sexual activity in the prior year , and contraceptive practice s. For HIV discordant couples , a prospect i ve study was conducted to examine risk factors for HIV transmission , the primary goal of the study . This allowed assessment of reliability of inter-partner reports over 6 - 12 months . Overall , agreement among couples was good for common sexual practice s , especially vaginal intercourse and time since last intercourse , but was lower for condom use . Anal and oral sex were infrequently reported by these couples and there was greater disagreement for the occurrence of these practice s. Partner agreement for contraceptive histories was good to excellent . Prospect i ve data showed less frequent intercourse and more condom use but reliability remained good . Common sexual practice s may be reliable for both HIV concordant and discordant couples in studies estimating prevalent infection . Estimates of incident heterosexually transmitted HIV may be made with greater reliability by studies which include assessment of reports of risk behavior by each member of a couple than studies of individuals This r and omized , controlled trial , conducted among out-of-treatment heroin/cocaine users at an emergency department visit , tests the impact on sexual risk of adding brief motivational intervention ( B-MI ) to point-of-service testing , counseling and drug treatment referral . 1,030 enrollees aged 18–54 received either voluntary counseling/testing ( VC/T ) with drug treatment referral , or VC/T , referral , and B-MI , delivered by an outreach worker . We measured number and proportion of non-protected sex acts ( last 30 days ) at 6 and 12 months ( n = 802 ) . At baseline , 70 % of past-30-days sex acts were non-protected ; 35 % of sex acts occurred while high ; 64 % of sexual acts involved main , 24 % casual and 12 % transactional sex partners ; 1.7 % tested positive for an STI , and 8.8 % for HIV . At six or 12 month follow-up , 20 enrollees tested positive for Chlamydia and /or Gonorrhea , and 6 enrollees HIV sero-converted . Self-reported high-risk behaviors declined in both groups with no significant between-group differences in behaviors or STI/HIV incidence Abstract This study assessed and compared the efficacy of culturally tailored behavioral interventions to increase use and acceptability of sexual barrier products among HIV-positive women in Zambia . It also sought to evaluate cultural preferences as facilitators or impediments to potential use of vaginal chemical barriers for sexual risk reduction within the Zambian context . Women ( N=240 ) , recruited from the University Teaching Hospital HIV Voluntary Counseling and Testing Center , were r and omized into group or individual intervention arms . Participants attended a baseline assessment , three intervention sessions and follow up assessment s at six and 12 months . All participants increased use and acceptability of female condoms and vaginal products and maintained male condom use at six and 12 months . Preliminary data indicated that group participants increased male condom use at six months and trial use and acceptability of female condoms and lubricants predicted their use in the group condition . Results support group interventions to increase sexual barrier use and acceptability in HIV-positive women within the Zambian context . From a public health st and point , groups may represent a cost-effective and culturally congruent intervention This article compares cross-sectional measures of condom use among 2,269 female sex workers in Cameroon r and omly assigned to receive one of five different question naires measuring condom use . We found that the level of reported condom use varied depending on the type of survey questions used . Measures based on 2-week coital logs or the past 10 acts categorized more women as " 100 % " or " 0 % " users than always-to-never scales categorized women as " always " or " never " users . Consistency of use also varied by type of partner . Internal consistency of responses was high . Future studies should assess differences in prospect i ve measures of condom use and the level of association between various measures and infection with sexually transmitted disease Research has established that voluntary medical male circumcision ( VMMC ) reduces HIV acquisition in heterosexual men by approximately 60 % ; however , engaging in sexual activity before the wound is healed may attenuate this protective effect . This prospect i ve study included VMMC clients who were circumcised in Kenya between November , 2008 and March , 2010 , aged ≥18 years , and r and omly selected for an interview and genital examination 28–45 days post-VMMC ( N = 1,344 ) . At the time of the interview , 91.3 % participants were healed . Overall , 30.7 % reported engaging in early sexual activity , usually 3–4 weeks post-VMMC . In a multivariable analysis , being married or cohabitating was the strongest predictor of engaging in early sexual activity . Strategies to reduce engaging in sexual activity during the recommended 42-day abstinence period following VMMC should be explored including re-energizing the effort to include female partners in counseling , mass education campaigns , and targeted text messaging programs for VMMC clients Culturally-specific HIV risk reduction interventions for Hispanic women are needed . SEPA ( Salud/Health , Educación/Education , Promoción/Promotion , y/ and Autocuidado/Self-care ) is a culturally-specific and theoretically-based group intervention for Hispanic women . The SEPA intervention consists of five sessions covering STI and HIV prevention ; communication , condom negotiation and condom use ; and violence prevention . A r and omized trial tested the efficacy of SEPA with 548 adult U.S. Hispanic women ( SEPA n = 274 ; delayed intervention control n = 274 ) who completed structured interviews at baseline and 3 , 6 , and 12 months post-baseline . Intent-to-treat analyses indicated that SEPA decreased positive urine sample s for Chlamydia ; improved condom use , decreased substance abuse and IPV ; improved communication with partner , improved HIV-related knowledge , improved intentions to use condoms , decreased barriers to condom use , and increased community prevention attitudes . Culturally-specific interventions have promise for preventing HIV for Hispanic women in the U.S. The effectiveness of SEPA should be tested in a translational community trial . ResumenIntervenciones culturalmente específicas son necesarias para la reducción de riesgo de contraer VIH en las mujeres hispanas . SEPA ( Salud/Health , Educación/Education , Promoción/Promotion , y Autocuidado/Self-care ) es una intervención grupal culturalmente específica con bases teóricas diseñada para mujeres Hispanas . La intervención SEPA consiste en cinco sesiones que cubren temas relacionados con la prevención de ITS - VIH , comunicación , negociación y uso del condón ; y prevención de la violencia . Utiliz and o un estudio r and omizado se probó la eficacia de SEPA con una muestra de 548 mujeres hispanas que viven en los Estados Unidos de Norteamérica ( SEPA n = 274 ; grupo control n = 274 ) . Las participantes respondieron una entrevistas estructuradas al inicio del estudio y a los 3 , 6 , y 12 meses posteriores a la intervención . Los result ados del análisis señalan que las mujeres que participaron en SEPA disminuyeron las muestras positivas de Chlamydia en orina , aumentaron el uso del condón , disminuyeron el abuso de sustancias y los episodios de violencia de pareja , mejoraron la comunicación de pareja , aumentaron el conocimiento sobre VIH , mejoraron la intención de utilizar condón , percibieron menores barreras para uso del condón , y mejoraron las actividades de prevención en la comunidad . Las intervenciones culturalmente específicas son promisorias para la prevención del VIH en las mujeres hispanas que viven en los Estados Unidos de Norteamérica . La efectividad de SEPA debe ser probada en la comunidad 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 Programs to help people living with HIV/AIDS practice safer sex are needed to prevent transmission of HIV and other sexually transmitted infections . We sought to assess the impact of SafeTalk , a multicomponent motivational interviewing-based safer sex program , on HIV-infected patients ’ risky sexual behavior . We enrolled sexually active adult HIV-infected patients from one of three clinical sites in North Carolina and r and omized them to receive the 4-session SafeTalk intervention versus a hearthealthy attention-control . There was no significant difference in the proportion of people having unprotected sex between the two arms at enrollment . SafeTalk significantly reduced the number of unprotected sex acts with at-risk partners from baseline , while in controls the number of unprotected sex acts increased . Motivational interviewing can provide an effective , flexible prevention intervention for a heterogeneous group of people living with HIV.ResumenProgramas para ayudar a las personas que viven con VIH/SIDA practicar el sexo seguro es necesario para prevenir la transmisión del VIH y otras infecciones de transmisión sexual . Hemos tratado de evaluar el impacto de SafeTalk , un multe-componente motivacional programa basado en el sexo más seguro , sobre el comportamiento de pacientes infectados por VIH-sexuales de riesgo . Se incluyó a adultos sexualmente activos pacientes infectados por VIH de uno de los tres centros clínicos en Carolina del Norte y al azar a recibir la intervención SafeTalk de 4 sesiones en comparación con un corazón sano control de atención . No hubo diferencias significativas en la proporción de personas que tienen relaciones sexuales sin protección entre los dos grupos en la inscripción . SafeTalk redujo significativamente el número de relaciones sexuales sin protección con parejas en situación de riesgo desde el inicio , mientras que en los controles del número de actos sexuales sin protección mayor . La entrevista motivacional puede proporcionar una intervención eficaz , flexible para la prevención de un grupo heterogéneo de personas que viven con el VIH This study compares condom use reported two ways . 251 heterosexual participants ( 63 % female ) reported condom use on a prospect i ve daily diary and on a retrospective question naire . Proportion of condom use with vaginal sex was calculated from the diary data and contrasted with retrospective categories . Responses were consistent for some participants , especially those who used condoms never or always , but responses from others showed considerable variability . Participants with few sexual encounters were more likely than those with more encounters to use “ never ” and “ every time ” endpoints . The results call into question the way participants interpret the meaning of retrospective categories We assessed the validity of self-reported sex and condom use by comparing self-reports with prostate-specific antigen ( PSA ) detection in a prospect i ve study of 210 female sex workers in Mombasa , Kenya . Participants were interviewed on recent sexual behaviours at baseline and 12-month follow-up visits . At both visits , a trained nurse instructed participants to self-swab to collect vaginal fluid specimens , which were tested for PSA using enzyme-linked immunosorbent assay ( ELISA ) . Eleven percent of sample s ( n = 329 ) from women reporting no unprotected sex for the prior 48 hours tested positive for PSA . The proportions of women with this type of discordant self-reported and biological data did not differ between the enrolment and 12-month visit ( odds ratio [ OR ] 1.1 ; 95 % confidence interval [ CI ] 0.99 , 1.2 ) . The study found evidence that participants failed to report recent unprotected sex . Furthermore , because PSA begins to clear immediately after exposure , our measures of misreported semen exposure likely are underestimations Background Studies of sexual behavior and of interventions design ed to reduce human immunodeficiency virus risk usually depend on self-report . Validation of self-reported condom use measures has not been previously reported in an urban population at high risk for sexually transmitted diseases and human immunodeficiency virus . Methods A prospect i ve cohort study was performed in subjects recruited from sexually transmitted disease clinics in Baltimore . At enrollment , a question naire was administered that assessed human immunodeficiency virus risk factors and sexually transmitted disease history , and used a retrospective calendar to assess sexual events and condom use over the previous 30 days . Clinical evaluation was performed for sexually transmitted diseases . At follow-up 3 months later , the same procedures were repeated . Incident sexually transmitted diseases at follow-up were defined as new culture or serologically documented diagnoses of gonorrhea , chlamydia , syphilis , or trichomoniasis . Results In the 323 male and 275 female ( total = 598 ) subjects who completed a follow-up visit , 21 % reported using condoms for every act of sexual intercourse over the previous 30 days , 21 % reported occasionally using condoms , and 59 % reported not using condoms . At follow-up , 21 % of subjects had new incident gonorrhea , chlamydia , syphilis , or trichomoniasis . Fifteen percent of the men who were “ always ” condom users had incident sexually transmitted diseases compared with 15.3 % of “ never users ; ” 23.5 % of women who were “ always ” users had incident sexually transmitted diseases compared with 26.8 % of “ never ” users . Conclusions In this high-risk population , self-reported condom use is not associated with lower sexually transmitted disease incidence . This finding suggests that self-reported condom use measures , even in a research setting , may be subject to substantial reporting bias Objective : To assess the impact and costs of adding female condoms to a male condom promotion and distribution peer education programme for sex workers in Mombasa , Kenya . Design : A 12 month , prospect i ve study of 210 female sex workers . Methods : We interviewed participants about their sexual behaviour every 2 months for a total of seven times and introduced female condoms after the third interview . We also collected cost data and calculated the cost and cost effectiveness of adding the female condom component to the existing programme . Results : Introduction of the female condom in an HIV/AIDS prevention project targeting sex workers led to small , but significant , increases in consistent condom use with all sexual partners . However , there was a high degree of substitution of the female condom for male condoms . The cost per additional consistent condom user at a programme level is estimated to be $ 2160 ( £ 1169 , € 1711 ) ( 95 % CI : 1338 to 11 179 ) . Conclusions : The female condom has some potential for reducing unprotected sex among sex workers . However , given its high cost , and the marginal improvements seen here , governments should limit promotion of the female condom in population s that are already successfully using the male condom . More research is needed to identify effective methods of encouraging sex workers to practise safer sex with their boyfriends Background : Many studies measure sex behavior to determine the efficacy of sexually transmitted disease (STD)/HIV prevention interventions . Goal : To determine how well measured behavior reflects STD incidence . Study Design : Data from a trial ( Project RESPECT ) were analyzed to compare behavior and incidence of STD ( gonorrhea , chlamydia , syphilis , HIV ) during two 6‐month intervals . Results : A total of 2879 persons had 5062 six‐monthly STD exams and interviews ; 8.9 % had a new STD in 6 months . Incidence was associated with demographic factors but only slightly associated with number of partners and number of unprotected sex acts with occasional partners . Many behaviors had paradoxical associations with STD incidence . After combining behavior variables to compare persons with highest and lowest risk behaviors , the STD incidence ratio was only 1.7 . Conclusion : Behavioral interventions have prevented STD . We found people tend to have safe sex with risky partners and risky sex with safe partners . Therefore , it is difficult to extrapolate the disease prevention efficacy of an intervention from a measured effect on behavior alone |
11,985 | 25,252,002 | There were mixed findings for changes in professionals ' behaviors and impact on practitioners ' and patients ' outcomes : some outcomes improved , while others showed no difference . | BACKGROUND Mentoring as a knowledge translation ( KT ) intervention uses social influence among healthcare professionals to increase use of evidence in clinical practice .
AIM To determine the effectiveness of mentoring as a KT intervention design ed to increase healthcare professionals ' use of evidence in clinical practice . | Although evidence -based practice ( EBP ) improves health care quality , decreases costs , and empowers nurses , there is a paucity of intervention studies design ed to test models of how to enhance nurses ' use of EBP . Therefore , the specific aim of this study was to determine the preliminary effects of implementing the Advancing Research and Clinical practice through close Collaboration ( ARCC ) model on nurses ' EBP beliefs , EBP implementation behaviors , group cohesion , productivity , job satisfaction , and attrition/turnover rates . A 2-group r and omized controlled pilot trial was used with 46 nurses from the Visiting Nurse Service of New York . The ARCC group versus an attention control group had stronger EBP beliefs , higher EBP implementation behaviors , more group cohesion , and less attrition/turnover . Implementation of the ARCC model in health care systems may be a promising strategy for enhancing EBP and improving nurse and cost outcomes Background Little is known about the impact of implementing nursing-oriented best practice guidelines on the delivery of patient care in either hospital or community setting s. Methods A naturalistic study with a prospect i ve , before and after design documented the implementation of six newly developed nursing best practice guidelines ( asthma , breastfeeding , delirium-dementia-depression ( DDD ) , foot complications in diabetes , smoking cessation and venous leg ulcers ) . Eleven health care organisations were selected for a one-year project . At each site , clinical re source nurses ( CRNs ) worked with managers and a multidisciplinary steering committee to conduct an environmental scan and develop an action plan of activities ( i.e. education sessions , policy review ) . Process and patient outcomes were assessed by chart audit ( n = 681 pre-implementation , 592 post-implementation ) . Outcomes were also assessed for four of six topics by in-hospital/home interviews ( n = 261 pre-implementation , 232 post-implementation ) and follow-up telephone interviews ( n = 152 pre , 121 post ) . Interviews were conducted with 83/95 ( 87 % ) CRN 's , nurses and administrators to describe recommendations selected , strategies used and participants ' perceived facilitators and barriers to guideline implementation . Results While statistically significant improvements in 5 % to 83 % of indicators were observed in each organization , more than 80 % of indicators for breastfeeding , DDD and smoking cessation did not change . Statistically significant improvements were found in > 50 % of indicators for asthma ( 52 % ) , diabetes foot care ( 83 % ) and venous leg ulcers ( 60 % ) . Organizations with > 50 % improvements reported two unique implementation strategies which included h and s-on skill practice sessions for nurses and the development of new patient education material s. Key facilitators for all organizations included education sessions as well as support from champions and managers while key barriers were lack of time , workload pressure and staff resistance . Conclusion Implementation of nursing best practice guidelines can result in improved practice and patient outcomes across diverse setting s yet many indicators remained unchanged . Mobilization of the nursing workforce to actively implement guidelines and to monitor the delivery of their care is important so that patients may learn about and receive recommended healthcare Background . The influence of an opinion leader intervention on adherence to Unstable Angina ( UA ) guidelines compared with a traditional quality improvement model was investigated . Research Design . A group-r and omized controlled trial with 2210 patients from 21 hospitals was design ed . There were three intervention arms : ( 1 ) no intervention ( NI ) ; ( 2 ) a traditional Health Care Quality Improvement Program ( HCQIP ) ; and ( 3 ) a physician opinion leader in addition to the HCQIP model ( OL ) . Quality indicators included : electrocardiogram within 20 minutes , antiplatelet therapy within 24 hours and at discharge , and heparin and & bgr;-blockers during hospitalization . Hospitals could determine the specific indicators they wished to target . Potential cases of UA were identified from Medicare cl aims data . UA confirmation was determined by a clinical algorithm based on data abstract ed from medical records . Data analyses included both hospital level analysis ( analysis of variance ) and patient level analysis ( generalized linear models ) . Results . The only statistically significant postintervention difference in percentage compliant was greater improvement for the OL group in the use of antiplatelet therapy at 24 hours in both hospital level ( P = 0.01 ) and patient level analyses ( P < 0.05 ) compared with the HCQIP and NI groups . When analyses were confined to hospitals that targeted specific indicators , compared with the HCQIP hospitals , the OL hospitals showed significantly greater change in percentage compliant postintervention in both antiplatelet therapy during the first 24 hours ( 20.2 % vs. −3.9 % , P = 0.02 ) and heparin ( 31.0 % vs.9.1 % , P = 0.05 ) . Conclusions . The influence of physician opinion leaders was unequivocally positive for only one of five quality indicators . To maximize adherence to best practice s through physician opinion leaders , more research on how these physicians influence health care delivery in their organizations will be required BACKGROUND Very little effort has been directed to enable GPs to better informed decisions about PSA screening among their male patients . OBJECTIVES To evaluate an innovative programme design ed to enhance GPs ' capacity to promote informed decision making by male patients about PSA screening . METHODS The study design was a cluster r and omised controlled trial set in New South Wales , Australia 's most populous state . 277 GPs were recruited through a major pathology laboratory . The interventions were three telephone-administered ' peer coaching ' sessions integrated with educational re sources for GPs and patients and the main outcome measures were : GP knowledge ; perceptions of patient involvement in informed decision making ; GPs ' own decisional conflict ; and perceptions of medicolegal risk . RESULTS Compared with GPs allocated to the control group , GPs allocated to our intervention gained significantly greater knowledge about PSA screening and related information [ Mean 6.1 out of 7 ; 95 % confidence interval ( CI ) = 5.9 - 6.3 versus 4.8 ; 95 % CI = 4.6 - 5.0 ; P < 0.001 ] . They were less likely to agree that patients should remain passive when making decisions about PSA screening [ Odds ratio ( OR ) = 0.11 ; 95 % CI = 0.04 - 0.31 ; P < 0.001 ] . They perceived less medicolegal risk when not acceding to an ' uninformed ' patient request for a PSA test ( OR = 0.31 ; 95 % CI 0.19 - 0.51 ) . They also demonstrated lower levels of personal decisional conflict about the PSA screening ( Mean 25.4 ; 95 % CI 24.5 - 26.3 versus 27.8 ; 95 % CI 26.6 - 29.0 ; P = 0.0002 ) . CONCLUSION A ' peer coaching ' programme , supplemented by education material s , holds promise as a strategy to equip GPs to facilitate informed decision making amongst their patients Studies at area hospitals revealed many gaps between research evidence and intrapartum nursing practice s. A r and omized controlled trial involving 20 hospitals was used to evaluate the effectiveness of a marketing strategy to promote research -based nursing care . It was hypothesized that the strategy would result in lower rates of epidural analgesia , through increasing the amount of support nurses provided to their patients . Other outcomes included rates of narcotic analgesia , episiotomy , and operative delivery . The marketing strategy was unsuccessful in improving intrapartum nursing care . Much more research is needed about the factors that facilitate improvements in nursing practice Background . As familial cancer genetic services moves into community practice increased numbers of trained health professionals are needed to counsel individuals seeking cancer risk information . Nurses have been targeted to provide cancer risk assessment and counseling . To help prepare nurses for this role , a 5-day training in familial cancer risk assessment and counseling followed by a long-distance mentorship to support continued skill development in the work environment was conducted by Fox Chase Cancer Center , Philadelphia , PA . Methods . Four cohorts ( N = 41 ) have completed the training and were r and omized to either an immediate or delayed mentorship . A formative evaluation assessed the nurse ’s ability to consult with other genetic health professionals and build self-efficacy in counseling skills via responses to question naire . A post-mentorship interview evaluated the usefulness , timing and length of the mentorship . Results . For both groups , there was a statistically significant improvement in self-efficacy for all skills from baseline to 6 months and an increased number of nurses consulting with genetic health professionals . All the nurses reported the value of the mentorship and those with less cancer risk counseling experience prior to the training needed support and re sources for further skill and program development . Lessons learned from this formative evaluation are provided Pain in children is infrequently assessed and managed by nurses . One-on-one coaching based on audit with feedback and the use of opinion leaders have been effective in changing professional health care practice s. Coaching by an opinion leader for changing pediatric nurses ' pain practice s was tested in a clustered r and omized trial in six Canadian pediatric hospitals . The rate of pain assessment s , nurses ' knowledge , and nonpharmacological interventions increased in the coaching group . However , there were significant site differences that could not be attributed to the coaching but to factors inherent in the sites . The context in which interventions are implemented will influence the effectiveness of individualized interventions A r and omized controlled trial with 76 physicians in 16 community hospitals evaluated audit and feedback and local opinion leader education as methods of encouraging compliance with a guideline for the management of women with a previous cesarean section . The guideline recommended clinical actions to increase trial of labor and vaginal birth rates . Charts for all 3552 cases in the study groups were audited . After 24 months the trial of labor and vaginal birth rates in the audit and feedback group were no different from those in the control group , but rates were 46 % and 85 % higher , respectively , among physicians educated by an opinion leader . Duration of hospital stay was lower in the opinion leader education group than in the other two groups . The overall cesarean section rate was reduced only in the opinion leader education group . There were no adverse clinical outcomes attributable to the interventions . The use of opinion leaders improved the quality of care BACKGROUND The paradigm shift to evidence -based nursing practice in the United States has been slow . Although multiple barriers to evidence -based practice ( EBP ) have been identified through prior studies , there is a gap in the literature specifically identifying key variables ( e.g. , belief that EBP produces quality outcomes ) that are correlated with the extent to which nurses engage in EBP . AIM The primary aims of this study were to ( 1 ) describe nurses ' knowledge , beliefs , skills , and needs regarding EBP ; ( 2 ) determine whether relationships exist among these variables ; and ( 3 ) describe major barriers and facilitators to EBP . METHODS A descriptive survey was conducted with a convenience sample of 160 nurses who were attending EBP conferences or workshops in four states located within the Eastern Region of the United States . RESULTS Although participant beliefs about the benefit of EBP were high , knowledge of EBP was relatively low . Significant relationships were found between the extent to which the nurses ' practice is evidence -based and ( 1 ) nurses ' knowledge of EBP , ( 2 ) nurses ' beliefs about the benefits of EBP , ( 3 ) having an EBP mentor , and ( 4 ) using the Cochrane Data base of Systematic Review s and the National Guideline Clearinghouse . CONCLUSION AND IMPLICATION S Health care systems need to implement interventions that not only increase nurses ' EBP knowledge and skills , but also strengthen their beliefs about the benefit of evidence -based care . EBP mentors may be key in accelerating a more rapid shift toward evidence -based nursing practice . Theoretically driven r and omized controlled trials are urgently needed to test the effectiveness of interventions on advancing evidence -based care CONTEXT The effectiveness of recruiting local medical opinion leaders to improve quality of care is poorly understood . OBJECTIVE To evaluate a guideline -implementation intervention of clinician education by local opinion leaders and performance feedback to ( 1 ) increase use of lifesaving drugs ( aspirin and thrombolytics in eligible elderly patients , beta-blockers in all eligible patients ) for acute myocardial infa rct ion ( AMI ) , and ( 2 ) decrease use of a potentially harmful therapy ( prophylactic lidocaine ) . DESIGN R and omized controlled trial with hospital as the unit of r and omization , intervention , and analysis . SETTING Thirty-seven community hospitals in Minnesota . PATIENTS All patients with AMI admitted to study hospitals over 10 months before ( 1992 - 1993 , N=2409 ) or after ( 1995 - 1996 , N=2938 ) the intervention . INTERVENTION Using a vali date d survey , we identified opinion leaders at 20 experimental hospitals who influenced peers through small and large group discussion s , informal consultations , and revisions of protocol s and clinical pathways . They focused on ( 1 ) evidence ( drug efficacy ) , ( 2 ) comparative performance , and ( 3 ) barriers to change . Control hospitals received mailed performance feedback . MAIN OUTCOME MEASURES Hospital-specific changes before and after the intervention in the proportion of eligible patients receiving each study drug . RESULTS Among experimental hospitals , the median change in the proportion of eligible elderly patients receiving aspirin was + 0.13 ( 17 % increase from 0.77 at baseline ) , compared with a change of -0.03 at control hospitals ( P=.04 ) . For beta-blockers , the respective changes were + 0.31 ( 63 % increase from 0.49 at baseline ) vs + 0.18 ( 30 % increase from baseline ) for controls ( P=.02 ) . Lidocaine use declined by about 50 % in both groups . The intervention did not increase thrombolysis in the elderly ( from 0.73 at baseline ) , but nearly two thirds of eligible nonrecipients were older than 85 years , had severe comorbidities , or presented after at least 6 hours . CONCLUSIONS Working with opinion leaders and providing performance feedback can accelerate adoption of some beneficial AMI therapies ( eg , aspirin , beta-blockers ) . Secular changes in knowledge and hospital protocol s may extinguish out date d practice s ( eg , prophylactic lidocaine ) . However , it is more difficult to increase use of effective but riskier treatments ( eg , thrombolysis ) for frail elderly patients |
11,986 | 26,346,329 | Authors ' conclusions H and washing promotion probably reduces diarrhoea episodes in both child day‐care centres in high‐income countries and among communities living in LMICs by about 30 % .
However , less is known about how to help people maintain h and washing habits in the longer term . | Abstract Background Diarrhoea accounts for 1.8 million deaths in children in low‐ and middle‐income countries ( LMICs ) .
One of the identified strategies to prevent diarrhoea is h and washing .
Objectives To assess the effects of h and washing promotion interventions on diarrhoeal episodes in children and adults . | The impact of improved water , sanitation , and hygiene ( WASH ) access on mitigating illness is well documented , although impact of school-based WASH on school-aged children has not been rigorously explored . We conducted a cluster-r and omized trial in Nyanza Province , Kenya to assess the impact of a school-based WASH intervention on diarrhoeal disease in primary -school pupils . Two study population s were used : schools with a nearby dry season water source and those without . Pupils attending ' water-available ' schools that received hygiene promotion and water treatment ( HP&WT ) and sanitation improvements showed no difference in period prevalence or duration of illness compared to pupils attending control schools . Those pupils in schools that received only the HP&WT showed similar results . Pupils in ' water-scarce ' schools that received a water-supply improvement , HP&WT and sanitation showed a reduction in diarrhoea incidence and days of illness . Our study revealed mixed results on the impact of improvements to school WASH improvements on pupil diarrhoea BACKGROUND The promotion of household water treatment and h and washing with soap has led to large reductions in child diarrhoea in r and omized efficacy trials . Currently , we know little about the health effectiveness of behaviour-based water and hygiene interventions after the conclusion of intervention activities . METHODS We present an extension of previously published design ( propensity score matching ) and analysis ( targeted maximum likelihood estimation ) methods to evaluate the behavioural and health impacts of a pre-existing but non-r and omized intervention ( a 3-year , combined household water treatment and h and washing campaign in rural Guatemala ) . Six months after the intervention , we conducted a cross-sectional cohort study in 30 villages ( 15 intervention and 15 control ) that included 600 households , and 929 children < 5 years of age . RESULTS The study design created a sample of intervention and control villages that were comparable across more than 30 potentially confounding characteristics . The intervention led to modest gains in confirmed water treatment behaviour [ risk difference = 0.05 , 95 % confidence interval ( CI ) 0.02 - 0.09 ] . We found , however , no difference between the intervention and control villages in self-reported h and washing behaviour , spot-check hygiene conditions , or the prevalence of child diarrhoea , clinical acute lower respiratory infections or child growth . CONCLUSIONS To our knowledge this is the first post-intervention follow-up study of a combined household water treatment and h and washing behaviour change intervention , and the first post-intervention follow-up of either intervention type to include child health measurement . The lack of child health impacts is consistent with unsustained behaviour adoption . Our findings highlight the difficulty of implementing behaviour-based household water treatment and h and washing outside of intensive efficacy trials Background H and hygiene is considered as an important means of infection control . We explored whether guided h and hygiene together with transmission-limiting behaviour reduces infection episodes and lost days of work in a common work environment in an open cluster-r and omized 3-arm intervention trial . Methods A total of 21 clusters ( 683 persons ) were r and omized to implement h and hygiene with soap and water ( 257 persons ) , with alcohol-based h and rub ( 202 persons ) , or to serve as a control ( 224 persons ) . Participants in both intervention arms also received st and ardized instructions on how to limit the transmission of infections . The intervention period ( 16 months ) included the emergence of the 2009 influenza p and emic and the subsequent national h and hygiene campaign influencing also the control arm . Results In the total follow-up period there was a 6.7 % reduction of infection episodes in the soap- and water arm ( p = 0.04 ) . Before the onset of the anti-p and emic campaign , a statistically significant ( p = 0.002 ) difference in the mean occurrence of infection episodes was observed between the control ( 6.0 per year ) and the soap- and -water arm ( 5.0 per year ) but not between the control and the alcohol-rub arm ( 5.6 per year ) . Neither intervention had a decreasing effect on absence from work . Conclusions We conclude that intensified h and hygiene using water and soap together with behavioural recommendations can reduce the occurrence of self-reported acute illnesses in common work environment . Surprisingly , the occurrence of reported sick leaves also increased in the soap- and water-arm . Trial Registration Clinical Trials.gov : NCT00981877 Source of funding The Finnish Work Environment Fund and the National Institute for Health and Welfare Elementary school-age children are particularly vulnerable to infections . While h and washing is the best method of preventing infections , many elementary schools are housed in buildings that have barriers to effective h and hygiene . The purpose of this study was to determine the effectiveness of an alcohol gel as an adjunct to h and washing in reducing absenteeism secondary to infectious illness . Two-hundred and fifty-three elementary school children were r and omized by classroom into an experimental or control group . With a crossover design , all children participated in both groups , with a one-week washout period between phases . A 45-minute “ Germ Unit ” was taught to all children as they started the experimental phase and a st and ard unit on h and hygiene was taught as they started the control phase . Sixty-nine children were absent due to illness while in the control group . Thirty-nine children became ill while in the experimental group . Alcohol gel as an adjunct to h and washing was shown to be effective in reducing absenteeism due to infectious illness by 43 % H and washing is thought to be effective for the prevention of transmission of diarrhoea pathogens . However it is not conclusive that h and washing with soap is more effective at reducing contamination with bacteria associated with diarrhoea than using water only . In this study 20 volunteers contaminated their h and s deliberately by touching door h and les and railings in public spaces . They were then allocated at r and om to ( 1 ) h and washing with water , ( 2 ) h and washing with non-antibacterial soap and ( 3 ) no h and washing . Each volunteer underwent this procedure 24 times , yielding 480 sample s overall . Bacteria of potential faecal origin ( mostly Enterococcus and Enterobacter spp . ) were found after no h and washing in 44 % of sample s. H and washing with water alone reduced the presence of bacteria to 23 % ( p < 0.001 ) . H and washing with plain soap and water reduced the presence of bacteria to 8 % ( comparison of both h and washing arms : p < 0.001 ) . The effect did not appear to depend on the bacteria species . H and washing with non-antibacterial soap and water is more effective for the removal of bacteria of potential faecal origin from h and s than h and washing with water alone and should therefore be more useful for the prevention of transmission of diarrhoeal diseases Background Day care center attendance has been recognized as a risk factor for acquiring gastrointestinal and respiratory infections , which can be prevented with adequate h and hygiene ( HH ) . Based on previous studies on environmental and sociocognitive determinants of caregivers ’ compliance with HH guidelines in day care centers ( DCCs ) , an intervention has been developed aim ing to improve caregivers ’ and children ’s HH compliance and decrease infections among children attending DCCs . The aim of this paper is to describe the design of a cluster r and omized controlled trial to evaluate the effectiveness of this intervention . Methods / design The intervention will be evaluated in a two-arm cluster r and omized controlled trial among 71 DCCs in the Netherl and s. In total , 36 DCCs will receive the intervention consisting of four components : 1 ) HH products ( dispensers and refills for paper towels , soap , alcohol-based h and sanitizer , and h and cream ) ; 2 ) training to educate about the Dutch national HH guidelines ; 3 ) two team training sessions aim ed at goal setting and formulating specific HH improvement activities ; and 4 ) reminders and cues to action ( posters/stickers ) . Intervention DCCs will be compared to 35 control DCCs continuing usual practice . The primary outcome measure will be observed HH compliance of caregivers and children , measured at baseline and one , three , and six months after start of the intervention . The secondary outcome measure will be the incidence of gastrointestinal and respiratory infections in 600 children attending DCCs , monitored over six months by parents using a calendar to mark the days their child has diarrhea and /or a cold . Multilevel logistic regression will be performed to assess the effect of the intervention on HH compliance . Multilevel poisson regression will be performed to assess the incidence of gastrointestinal and respiratory infections in children attending DCCs . Discussion This is one of the first DCC intervention studies to assess HH compliance of both caregivers and children , as well as the incidence of gastrointestinal and respiratory infections in children , as outcome measures . When an effect of the intervention on improving HH compliance and /or reducing incidence of infections is shown , (inter)national dissemination of the intervention in other DCCs may be considered . Trial registration Netherl and s trial registry : OBJECTIVES Improving school water , sanitation and hygiene ( WASH ) conditions reduces pupil absence and illness . However , these benefits may depend on the conditions of the latrines and availability of consumables . We sought to determine whether a low-cost , policy-relevant , environmental-level latrine cleaning intervention could improve latrine cleanliness , increase its use and reduce absenteeism . METHODS In a three-arm , cluster-r and omized trial we assessed absence via periodical roll-call among 17 564 pupils in 60 schools that had previously received WASH improvements as part of the SWASH+ project . Latrine conditions and use were also assessed using structured observation . Latrine cleanliness increased significantly during the post-intervention period among schools receiving the latrine cleaning package compared to controls , as did h and washing with soap . We found no difference in latrine use and absence across arms . CONCLUSIONS The additive impact of cleaning may not have been strong enough to impact absence above and beyond reductions attributable to the original WASH infrastructure improvements and basic hygiene education the schools previously received . Improving latrine conditions is important for the dignity and well-being of pupils , and investments and strategies are necessary to ensure that school toilets are clean and pupil-friendly Introduction Enteric infections are common during the first years of life in low-income countries and contribute to growth faltering with long-term impairment of health and development . Water quality , sanitation , h and washing and nutritional interventions can independently reduce enteric infections and growth faltering . There is little evidence that directly compares the effects of these individual and combined interventions on diarrhoea and growth when delivered to infants and young children . The objective of the WASH Benefits study is to help fill this knowledge gap . Methods and analysis WASH Benefits includes two cluster-r and omised trials to assess improvements in water quality , sanitation , h and washing and child nutrition — alone and in combination — to rural households with pregnant women in Kenya and Bangladesh . Geographically matched clusters ( groups of household compounds in Bangladesh and villages in Kenya ) will be r and omised to one of six intervention arms or control . Intervention arms include water quality , sanitation , h and washing , nutrition , combined water+sanitation+h and washing ( WSH ) and WSH+nutrition . The studies will enrol newborn children ( N=5760 in Bangladesh and N=8000 in Kenya ) and measure outcomes at 12 and 24 months after intervention delivery . Primary outcomes include child length-for-age Z-scores and caregiver-reported diarrhoea . Secondary outcomes include stunting prevalence , markers of environmental enteropathy and child development scores ( verbal , motor and personal/social ) . We will estimate unadjusted and adjusted intention-to-treat effects using semiparametric estimators and permutation tests . Ethics and dissemination Study protocol s have been review ed and approved by human subjects review boards at the University of California , Berkeley , Stanford University , the International Centre for Diarrheal Disease Research , Bangladesh , the Kenya Medical Research Institute , and Innovations for Poverty Action . Independent data safety monitoring boards in each country oversee the trials . This study is funded by a grant from the Bill & Melinda Gates Foundation to the University of California , Berkeley . Registration Trial registration identifiers ( http://www . clinical trials.gov ) : NCT01590095 ( Bangladesh ) , NCT01704105 ( Kenya ) OBJECTIVE To evaluate a simple low cost method for measuring h and contamination as an objective assessment of h and washing practice s. METHOD As part of a larger r and omized controlled trial of h and washing promotion with soap conducted in squatter settlements of Karachi , Pakistan , a r and omly selected subset of 52 mothers in households receiving soap and h and washing promotion and 28 mothers in control households directly pressed three fingers of their right h and onto MacConkey agar plates on weekly unannounced visits from April to September 2002 , and monthly from October 2002 to March 2003 . The MacConkey plates were incubated at 44 degrees C for 24 h , and evaluated for growth of thermotolerant coliform bacteria . RESULTS The proportion of sample s that had detectable thermotolerant coliforms ( 50 % ) was similar in households that received soap and control households ( 52 % , P = 0.40 ) . In the week after evaluation of the mothers ' h and s , the proportion of households that reported diarrhoea was similar regardless of whether or not the mother had thermotolerant coliforms detected by direct finger imprint ( 18.6%vs . 19.1 % , Relative Risk 0.99 , 95 % CI 0.96 , 1.03 ) . CONCLUSIONS A three finger direct imprint test using MacConkey agar for thermotolerant coliforms was not a useful method to assess regular h and washing practice s with soap in Karachi . Developing better measures of h and washing behaviour remains an important research priority From October 1981 to September 1984 , the authors conducted a three-year longitudinal study of diarrhea among infants and toddlers attending day care centers in Maricopa County , Arizona . In the third year of study , they evaluated the effects on diarrhea rates of staff training without external monitoring and of active surveillance conducted throughout the study . From 21 study day care centers , they r and omly selected 10 ( " intervention day care centers " ) to receive staff training in procedures to reduce transmission of infectious diarrhea . Continuing active surveillance in the 10 intervention and 11 control day care centers found no difference between diarrhea rates in intervention day care centers in the pre- and posttraining years and no difference between diarrhea rates in the two groups of centers either before or after the training intervention . Biweekly family-based surveys during the two months after training also demonstrated no difference between infant-toddler diarrhea rates in intervention and control day care centers . These surveys found the 21 study day care centers to have significantly higher diarrhea rates than did day care homes or households not using day care , but significantly lower rates than day care centers not included in the active surveillance . Continuous surveillance without training was associated with a significant decrease in diarrheal illness during the course of longitudinal study . One-time staff training without subsequent monitoring did not result in additional decreases and did not lower day care center diarrhea rates to the levels observed in day care homes and households not using day care The objective of this study was to assess the effectiveness of a hygiene program in reducing the incidence of respiratory and diarrheal diseases in toddlers attending day care centers . A r and omized field trial was conducted in 52 day care centers in Quebec , Canada , between September 1 , 1996 and November 30 , 1997 . Absences for any reasons and the daily occurrence of colds and /or diarrhea in toddlers were recorded on calendars by the educators . The number of fecal coliforms on children 's h and s and on educators ' h and s was measured during three unannounced visits . Overall , 1,729 children were followed in 47 day care centers for a total of 153,643 child-days . The incidence rate of diarrhea was considerably reduced by the effect of monitoring ( IRR = 0.73 , 95 % CI = 0.54,0.97 ) , and the intervention reduced the incidence rate of upper respiratory tract infections ( IRR = 0.80 , 95 % CI = 0.68,0.93 ) . Monitoring alone also had an important effect in reducing the level of bacterial contamination on children 's and educators ' h and s. The results indicate that both an intervention program and monitoring alone play a role in reducing infections in children attending day care centers Diarrhea has been recognized as a frequent health problem among children enrolled in day-care centers . Thus , we evaluated the effect of a h and washing program in two day-care centers ( HWC ) on the incidence of diarrhea among children when compared to children in two control centers ( CC ) . After the program was begun , the incidence of diarrhea at the HWC began to fall and after the second month of the study was consistently lower than that at the CC . The incidence of diarrhea in the HWC was approximately half that of the CC for the entire 35-week study period . Adenoviruses , rotavirus , Giardia lamblia , and enteropathogenic Escherichia coli were found in the stools of a small number of ill children , but not pathogen was identified in the stools of most children with diarrhea . These results suggest that a h and washing program will probably prevent at least some of the diarrhea in day-care centers INTRODUCTION Pneumonia and diarrhoea are leading causes of death in children . There is a need to develop effective interventions . OBJECTIVE We present the design and baseline findings of a community-r and omised controlled trial in rural Peru to evaluate the health impact of an Integrated Home-based Intervention Package in children aged 6 to 35 months . METHODS We r and omised 51 communities . The intervention was developed through a community-participatory approach prior to the trial . They comprised the construction of improved stoves and kitchen sinks , the promotion of h and washing , and solar drinking water disinfection ( SODIS ) . To reduce the potential impact of non-blinding bias , a psychomotor stimulation intervention was implemented in the control arm . The baseline survey included anthropometric and socio-economic characteristics . In a sub- sample we determined the level of faecal contamination of drinking water , h and s and kitchen utensils and the prevalence of diarrhoegenic Escherichia coli in stool specimen . RESULTS We enrolled 534 children . At baseline all households used open fires and 77 % had access to piped water supplies . E. coli was found in drinking water in 68 % and 64 % of the intervention and control households . Diarrhoegenic E. coli strains were isolated from 45/139 stool sample s. The proportion of stunted children was 54 % . CONCLUSIONS R and omization result ed in comparable study arms . Recently , several critical review s raised major concerns on the reliability of open health intervention trials , because of uncertain sustainability and non-blinding bias . In this regard , the presented trial featuring objective outcome measures , a simultaneous intervention in the control communities and a 12-month follow up period will provide valuable evidence Transmission of enteric pathogens is facilitated in child day care centers , including family day care homes , by frequent and intimate exposure among susceptible hosts , with diaper changing as the highest-risk procedure for such transmission . The objective of this study was to evaluate the effectiveness of an intervention program in decreasing the incidence of infectious disease symptoms in children attending family day care homes during a 12-month period . Each of 24 family day care homes was r and omly assigned to an intervention or control group . The intervention included four components : ( 1 ) a h and washing educational program and ( 2 ) use of vinyl gloves , ( 3 ) use of disposable diaper changing pads , and ( 4 ) use of an alcohol-based h and rinse by the day care provider . Symptoms of enteric disease ( diarrhea and vomiting ) were significantly reduced in intervention family day care homes ( p less than or equal to 0.05 ) , whereas respiratory symptoms were not significantly different between intervention and control family day care homes ( p = 0.35 ) . Diarrhea was reported in 1 of every 100 child care days , representing one diarrhea episode per month in a typical family day care home OBJECTIVES To evaluate the effectiveness of point of use water treatment with flocculent-disinfectant on reducing diarrhoea and the additional benefit of promoting h and washing with soap . METHODS The study was conducted in squatter settlements of Karachi , Pakistan , where diarrhoea is a leading cause of childhood death . Interventions were r and omly assigned to 47 neighbourhoods . Households in 10 neighbourhoods received diluted bleach and a water vessel ; nine neighbourhoods received soap and were encouraged to wash h and s ; nine neighbourhoods received flocculent-disinfectant water treatment and a water vessel ; 10 neighbourhoods received disinfectant-disinfectant water treatment and soap and were encouraged to wash h and s ; and nine neighbourhoods were followed as controls . Field workers visited households at least once a week from April to December 2003 to promote use of the interventions and to collect data on diarrhoea . RESULTS Study participants in control neighbourhoods had diarrhoea on 5.2 % of days . Compared to controls , participants living in intervention neighbourhoods had a lower prevalence of diarrhoea : 55 % ( 95 % CI 17 % , 80 % ) lower in bleach and water vessel neighbourhoods , 51 % ( 95 % CI 12 % , 76 % ) lower in h and washing promotion with soap neighbourhoods , 64 % lower ( 95 % CI 29 % , 90 % ) in disinfectant-disinfectant neighbourhoods , and 55 % ( 95 % CI 18 % , 80 % ) lower in disinfectant-disinfectant plus h and washing with soap neighbourhoods . CONCLUSIONS With an intense community-based intervention and supplies provided free of cost , each of the home-based interventions significantly reduced diarrhoea . There was no benefit by combining h and washing promotion with water treatment Intensive h and washing promotion can reduce diarrheal and respiratory disease incidence . To determine whether less intensive , more scalable interventions can improve health , we evaluated a school-based h and washing program . We r and omized 87 Chinese schools to usual practice s : st and ard intervention ( h and washing program ) or exp and ed intervention ( h and washing program , soap for school sinks , and peer hygiene monitors ) . We compared student absence rates , adjusting for cluster design . In control schools , children experienced a median 2.0 episodes ( median 2.6 days ) of absence per 100 student-weeks . In st and ard intervention schools , there were a median 1.2 episodes ( P = 0.08 ) and 1.9 days ( P = 0.14 ) of absence per 100 student-weeks . Children in exp and ed intervention schools experienced a median 1.2 episodes ( P = 0.03 ) and 1.2 days ( P = 0.03 ) of absence per 100 student-weeks . Provision of a large-scale h and washing promotion program and soap was associated with significantly reduced absenteeism . Similar programs could improve the health of children worldwide Background The economical impact of absenteeism and reduced productivity due to acute infectious respiratory and gastrointestinal disease is normally not in the focus of surveillance systems and may therefore be underestimated . However , large community studies in Europe and USA have shown that communicable diseases have a great impact on morbidity and lead to millions of lost days at work , school and university each year . H and disinfection is acknowledged as key element for infection control , but its effect in open , work place setting s is unclear . Methods Our study involved a prospect i ve , controlled , intervention-control group design to assess the epidemiological and economical impact of alcohol-based h and disinfectants use at work place . Volunteers in public administrations in the municipality of the city of Greifswald were r and omized in two groups . Participants in the intervention group were provided with alcoholic h and disinfection , the control group was unchanged . Respiratory and gastrointestinal symptoms and days of work were recorded based on a monthly question naire over one year . On the whole , 1230 person months were evaluated . Results H and disinfection reduced the number of episodes of illness for the majority of the registered symptoms . This effect became statistically significant for common cold ( OR = 0.35 [ 0.17 - 0.71 ] , p = 0.003 ) , fever ( OR = 0.38 [ 0.14 - 0.99 ] , p = 0.035 ) and coughing ( OR = 0.45 [ 0.22 - 0.91 ] , p = 0.02 ) . Participants in the intervention group reported less days ill for most symptoms assessed , e.g. colds ( 2.07 vs. 2.78 % , p = 0.008 ) , fever ( 0.25 vs. 0.31 % , p = 0.037 ) and cough ( 1.85 vs. 2.00 % , p = 0.024 ) . For diarrhoea , the odds ratio for being absent became statistically significant too ( 0.11 ( CI 0.01 - 0.93 ) . Conclusion H and disinfection can easily be introduced and maintained outside clinical setting s as part of the daily h and hygiene . Therefore it appears as an interesting , cost-efficient method within the scope of company health support programmes . Trial registration numberIS RCT N : IS RCT This paper describes the effect of a preschool hygiene intervention program on psychosocial measures of educators regarding h and washing and communicable pediatric disease . A cluster-r and omized trial , with r and omization at the level of the preschool , was run in 40 Jerusalem preschool classrooms . Eighty preschool educators participated . The program used a multipronged approach which included elements aim ed at staff , children , parents , school nurses and the classroom environment . Frontal lectures by medical , epidemiological and educational experts , along with printed material s and experiential learning , were provided to staff . Responses from a vali date d survey instrument were used to build four scales for each respondent regarding beliefs , attitudes , self-efficacy and knowledge . The scales were built on a Likert-type 1 - 7 scale ( 1 = minimum , 7 = maximum ) . The effect of the intervention was tested using mixed model analysis of variance . Response was received from 92.5 % of educators . Educators believed that h and washing could affect health ( mean = 5.5 , SD = 1.1 ) , had high levels of self-efficacy ( mean = 6.1 , SD = 0.9 ) and had positive attitudes toward h and washing ( mean = 5.7 , SD = 1.2 ) . Knowledge was affected by the intervention ( intervention : mean = 6.2 , SD = 0.7 ; control : mean = 5.8 , SD = 0.8 ) . The combination of positive attitudes toward h and washing among educators and the program 's effectiveness in imparting knowledge helped to create a sustained social norm of h and washing among many children in disparate locations OBJECTIVE . The objective of this study was to determine whether the installation of equipment for diaper-changing , h and -washing , and food preparation that is specifically design ed to reduce the transmission of infectious agents would result in a decrease in the rate of diarrheal illness among children and their teachers in child care centers . METHODS . Twenty-three pairs of child care centers were matched on size and star-rated license level . One member of each pair was r and omly assigned to an intervention group and the other to a control group . Intervention centers received new diaper-changing , h and -washing , and food-preparation equipment , and both intervention and control centers received hygiene and sanitation training with reinforcement and follow-up as needed . Families with children in participating classrooms were called biweekly to ascertain the frequency and severity of any diarrheal illness episodes . Staff attendance was monitored , and staff hygiene and sanitation behaviors were observed and recorded monthly . RESULTS . Although hygiene and sanitation behaviors improved in both intervention and control centers , there was a significant difference favoring the intervention centers with respect to frequency of diarrheal illness ( 0.90 vs 1.58 illnesses per 100 child-days in control centers ) and proportion of days ill as a result of diarrhea ( 4.0 % vs 5.0 % in control centers ) among the children . Staff in those same classrooms were reported to have a significantly lower proportion of days absent as a result of any illness ( 0.77 % in treatment centers versus 1.73 % in control centers ) . CONCLUSION . Diapering , h and -washing , and food-preparation equipment that is specifically design ed to reduce the spread of infectious agents significantly reduced diarrheal illness among the children and absence as a result of illness among staff in out-of-home child care centers BACKGROUND Diarrhoeal disease is a leading cause of morbidity in young children in rural Zaire . Few diarrhoea prevention programmes have been implemented in B and undu Province , where available data suggest an annual prevalence rate of 10 % . The urgent need to reduce diarrhoeal morbidity in Zaire , together with the potential effectiveness and feasibility of hygiene education as a diarrhoea prevention strategy , led to the development of the present research project . METHODS A r and omized , controlled trial of an education intervention to reduce diarrhoea through improved personal and domestic hygiene behaviours was conducted in 18 geographically separate village clusters ( sites ) in rural Zaire . For 12 weeks baseline information on the diarrhoeal morbidity of 2082 children aged 3 - 35 months was collected at weekly home visits , and structured observations of hygiene practice s related to diarrhoea were made on a subset of 300 families . Intervention messages addressed disposal of animal faeces from the yard , h and washing after defecation and before meal preparation and eating , and disposal of children 's faeces . Three months after the start of the intervention and exactly 1 year after the baseline studies , a second diarrhoeal morbidity study and a second observational study were conducted in order to evaluate the intervention . RESULTS Children in intervention communities experienced an 11 % reduction in the risk of reporting diarrhoea during the peak diarrhoeal season , compared to controls ( P < 0.025 ) . The largest differences were seen among children aged 24 - 35 months , with those from intervention communities reporting significantly fewer episodes , shorter mean duration s and hence fewer days of diarrhoea . There was some evidence that greater reductions in diarrhoea occurred in sites where the quality of the intervention , a scored measure of volunteer efficacy and community participation , was highest . CONCLUSIONS The results of this study suggest that hygiene education may be an effective approach to reduce the incidence and duration of diarrhoeal episodes in rural Zaire . Children aged 2 years appear to benefit the most . A Hawthorne effect of the education may contribute to diarrhoeal reductions A case-control study was performed to develop an empirically based intervention for improving water-sanitation practice s and rates of childhood diarrhea among families residing in urban Bangladesh . For three months fortnightly , histories of diarrhea were taken for all children under six years of age among 1,350 families to estimate age-specific rates of diarrhea in the population . A total of 247 r and omly sample d families , termed sentinel families , were visited once during the study for prolonged observations of water-sanitation practice s. Behaviors potentially affecting incidence of diarrhea were compared in a case group ( n = 45 ) , defined as sentinel families whose children had rates at least 1.7 times the rates expected for similarly aged children , and in a control group ( n = 53 ) , defined as sentinel families without any episodes of childhood diarrhea during the period of observation . Three practice s differentiated the two groups : more control ( 82 % ) than case ( 53 % ) mothers who were observed to prepare food washed their h and s before beginning the preparation ( p less than 0.01 ) ; fewer control families ( 33 % ) than case families ( 80 % ) had ambulatory children who , when observed to defecate , did so in the family 's living area ( p less than 0.01 ) ; and fewer control ( 30 % ) than case ( 47 % ) families had children who were observed to place garbage or waste products in their mouth ( p less than 0.10 ) . Focus on these three empiric associations enabled the design of a community-specific educational intervention which is simple in construction and based upon naturally occurring , financially feasible , salutory practice BACKGROUND Diarrhoea and respiratory infections are the two biggest causes of child death globally . H and washing with soap could substantially reduce diarrhoea and respiratory infections , but prevalence of adequate h and washing is low . We tested whether a scalable village-level intervention based on emotional drivers of behaviour , rather than knowledge , could improve h and washing behaviour in rural India . METHODS The study was done in Chittoor district in southern And hra Pradesh , India , between May 24 , 2011 , and Sept 10 , 2012 . Eligible villages had a population of 700 - 2000 people , a state-run primary school for children aged 8 - 13 years , and a preschool for children younger than 5 years . 14 villages ( clusters ) were selected , stratified by population size ( < 1200 vs > 1200 ) , and r and omly assigned in a 1:1 ratio to intervention or control ( no intervention ) . Clusters were enrolled by the study manager . R and om allocation was done by the study statistician using a r and om number generator . The intervention included community and school-based events incorporating an animated film , skits , and public pledging ceremonies . Outcomes were measured by direct observation in 20 - 25 households per village at baseline and at three follow-up visits ( 6 weeks , 6 months , and 12 months after the intervention ) . Observers had no connection with the intervention and observers and participant households were told that the study was about domestic water use to reduce the risk of bias . No other masking was possible . The primary outcome was the proportion of h and washing with soap at key events ( after defecation , after cleaning a child 's bottom , before food preparation , and before eating ) at all follow-up visits . The control villages received a shortened version of the intervention before the final follow-up round . Outcome data are presented as village-level means . FINDINGS H and washing with soap at key events was rare at baseline in both the intervention and control groups ( 1 % [ SD 1 ] vs 2 % [ 1 ] ) . At 6 weeks ' follow-up , h and washing with soap at key events was more common in the intervention group than in the control group ( 19 % [ SD 21 ] vs 4 % [ 2 ] ; difference 15 % , p=0·005 ) . At the 6-month follow-up visit , the proportion h and washing with soap was 37 % ( SD 7 ) in the intervention group versus 6 % ( 3 ) in the control group ( difference 31 % ; p=0·02 ) . At the 12-month follow-up visit , after the control villages had received the shortened intervention , the proportion h and washing with soap was 29 % ( SD 9 ) in the intervention group and 29 % ( 13 ) in the control group . INTERPRETATION This study shows that substantial increases in h and washing with soap can be achieved using a scalable intervention based on emotional drivers . FUNDING Wellcome Trust , SHARE Context Household cleaning products containing antibacterial ingredients are widely available and popular . Although manufacturers use cl aims of health benefits to market these products , evidence linking the use of antibacterial products to health outcomes has been lacking . Contribution This innovative trial found no difference in episodes of infectious disease symptoms over one year in 228 inner-city households r and omly assigned to use antibacterial household cleaning products or identically packaged products without antibacterial ingredients . Implication s These findings highlight the need to better educate consumers about the use and limitations of household antibacterial cleaning products . The Editors Changing demographic and social patterns , such as more working parents , increased numbers of meals eaten in restaurants , and more child-care outside of the home , are causing concomitant changes in patterns of infectious diseases ( 1 ) . For example , recent foodborne outbreaks have result ed from widespread distribution of contaminated foods , such as meat or ice cream . Media attention to such outbreaks and the result ant public concern about disease transmission may be one reason for the burgeoning of various products that are labeled antibacterial and that are readily available for personal hygiene and general cleaning . These demographic and social shifts raise the question of the relative importance of home hygienic practice s in the prevention of infectious diseases . The home environment has been implicated as one important source of spread of infectious diseases ( 2 - 4 ) , and hygienic interventions have result ed in reduced incidence , particularly in less-developed countries ( 5 ) . In the United States , several studies have demonstrated the effectiveness of hygienic interventions in reducing transmission of infections in child-care centers and schools ( 6 - 9 ) . However , despite the fact that 75 % of liquid and 29 % of bar soaps available in the U.S. consumer market contain antibacterial ingredients ( 10 ) , their benefits in terms of reducing the incidence of infectious diseases in households have not been demonstrated . In addition , concerns have been raised about the potential for long-term use of such products to increase resistance to antiseptics or cross-resistance with antibiotics ( 11 , 12 ) . Therefore , we sought to evaluate the effect of antibacterial cleaning and h and washing products on the occurrence of infectious disease symptoms in households . Methods In this double-blind clinical trial , we r and omly assigned households to one of 2 intervention groups : those who used h and washing and household cleaning products with antibacterial ingredients and those who used products without such ingredients . The interventions lasted for 48 weeks . Sample and Setting We conducted the study in an inner-city neighborhood in northern Manhattan , New York , with a predominantly immigrant population in multigenerational households . Almost 30 % of residents spoke little or no English , and about 90 % of the households had telephones ( 13 ) . To qualify for the study , a household unit had to include 3 or more persons with at least one preschool-age child and had to have access to a telephone . In addition , household members had to speak English or Spanish . In a preliminary survey ( 14 ) conducted in this neighborhood , 78.5 % of 398 households reported infectious disease symptoms within the previous month , and in 37.9 % of these households , at least one person sought medical attention and received specific treatment or antibiotics for an infectious disease symptom or symptoms . On the basis of this pilot work , we concluded that a r and omized clinical trial with sufficient statistical power was feasible . Recruitment was by word of mouth , referral , and English- and Spanish- language flyers ( preapproved by the institutional review board ) posted throughout the community . Participants were recruited by an experienced , trained interviewer who resided in the community and who was a native Spanish speaker . We determined sample size by power analysis . With 100 households for each intervention group and a household incidence of infectious disease symptoms of about 35 % per month , on the basis of the pilot study , it would be possible to detect an absolute difference between the 2 intervention groups of 20 percentage points or more ( for example , from 35 % to 15 % ) with a power of 80 % and an value of less than 0.05 ( 15 ) . We recruited an additional 19 % above this desired sample size to account for potential loss to follow-up and dropouts . A total of 238 households were r and omly assigned , and 224 ( 94.1 % ) completed the entire 48 weeks of data collection . Fourteen households ( 5.9 % ) did not complete the entire study period , 9 ( 64.3 % ) because the household moved out of the study area , 3 ( 21.4 % ) because the household did not continue to use the products , and 2 ( 14.3 % ) because the household was inadvertently supplied with the wrong product ( Figure 1 ) . Figure 1 . Profile of r and omized , clinical trial . Intervention Criteria for selecting products to be tested were as follows : The products had to be readily available over the counter ; have the same or similar formulation , except for the presence or absence of an antibacterial ingredient ; be representative of a particular category of product so that results could be generalized to other similar products ; and be developed by reputable companies known for good manufacturing practice s. Antibacterial was defined as the presence of triclosan , quaternary ammonium compounds , hypochlorite , or another recognized microbicidal agent in amounts greater than preservative levels . Also , the product label had to include the term antibacterial or disinfectant . Households r and omly assigned to the antibacterial group were provided with the following : a liquid kitchen spray and all- purpose hard-surface cleaner containing a quaternary ammonium compound , liquid h and washing soap containing triclosan , and a laundry detergent containing oxygenated bleach . The nonantibacterial group received parallel products with similar compositions that did not contain antibacterial ingredients . Both intervention groups were provided with the same liquid dishwashing detergent and bar soap , neither of which contained antibacterial ingredients . Procedures The study was approved by the Columbia Presbyterian Medical Center Institutional Review Board . After we obtained written informed consent , households were r and omly assigned to one of the intervention groups ; the master key code was retained by the biostatistician . All products were provided without cost , were packaged identically with a generic label indicating their use , and were delivered to the household monthly . On the initial home visit , we collected baseline data on home hygiene practice s and the presence of infectious disease symptoms within the previous month for each household member by using our Home Hygiene Assessment Form . We made a weekly telephone call and a monthly home visit to each household . During the monthly visit , we assessed adherence to the product regimens by weighing the remainder of products with a postal scale and inspecting the home for the presence of other products . Every 3 months , we assessed symptoms in individual household members , and the Home Hygiene Assessment Form was readministered to determine whether any hygienic practice s had changed . We conducted an average of 226 interviews each week . For most of the households ( 98.8 % ) , at least 20 weekly interviews were completed , and for 89.0 % of households , 45 or more weekly interviews were completed . Data were collected by 3 interviewers who received extensive training using a written orientation manual , practice sessions with return demonstrations , and inter-rater reliability assessment s. The interviewers and project director were native Spanish speakers ; 3 were physicians , and the fourth was a trained community health worker . Initially and on a r and om monthly basis , each interviewer was accompanied by the project director on 10 % of the home visits for ongoing quality control . Instrument Because cleaning and hygiene practice s within the home would probably affect the dependent variable , infectious disease symptoms , we collected extensive data on cleaning and hygiene practice s at baseline and at quarterly intervals . The Home Hygiene Assessment Form is a 31-page interview booklet that includes questions about demographic characteristics and illness ( age , sex , ethnicity , country of birth , hours per week spent outside the home , type of work for adults , school or child-care arrangements for children , state of health , and presence of chronic diseases ) , home hygiene practice s ( 54 items ) , and other relevant household factors ( numbers and ages of household members , size of living space , presence of pets and visitors , type of building , and heating and cooling systems ) . We also asked participants about their attitudes and beliefs about how germs are spread and what they did to prevent infections in their home . The components of the instrument were originally derived from a literature search , focus groups of consumers , and a panel of environmental sanitation experts . The Home Hygiene Assessment Form was tested extensively for validity and reliability ( 16 ) . Whenever possible , direct observations were made to confirm self-reports . Measurement of Dependent Variable ( Infectious Disease Symptoms ) The presence of infections was assessed symptomatically . We instructed participants to call their interviewer if any member of the household had vomiting , diarrhea , fever , sore throat , cough , runny nose , skin infection , or conjunctivitis ( pinkeye ) . We provided each household with a supply of single-use thermometers ( Tempa-DOT , 3 M Health Care , St. Paul , Minnesota ) and gave instructions for their use . In the weekly telephone call from the interviewer , we also solicited information on symptoms . If participants reported a cough , they were queried by a physician about whether BACKGROUND More than 3.5 million children aged less than 5 years die from diarrhoea and acute lower respiratory-tract infection every year . We undertook a r and omised controlled trial to assess the effect of h and washing promotion with soap on the incidence of acute respiratory infection , impetigo , and diarrhoea . METHODS In adjoining squatter settlements in Karachi , Pakistan , we r and omly assigned 25 neighbourhoods to h and washing promotion ; 11 neighbourhoods ( 306 households ) were r and omised as controls . In neighbourhoods with h and washing promotion , 300 households each were assigned to antibacterial soap containing 1.2 % triclocarban and to plain soap . Fieldworkers visited households weekly for 1 year to encourage h and washing by residents in soap households and to record symptoms in all households . Primary study outcomes were diarrhoea , impetigo , and acute respiratory-tract infections ( ie , the number of new episodes of illness per person-weeks at risk ) . Pneumonia was defined according to the WHO clinical case definition . Analysis was by intention to treat . FINDINGS Children younger than 5 years in households that received plain soap and h and washing promotion had a 50 % lower incidence of pneumonia than controls ( 95 % CI ( -65 % to -34 % ) . Also compared with controls , children younger than 15 years in households with plain soap had a 53 % lower incidence of diarrhoea ( -65 % to -41 % ) and a 34 % lower incidence of impetigo ( -52 % to -16 % ) . Incidence of disease did not differ significantly between households given plain soap compared with those given antibacterial soap . INTERPRETATION H and washing with soap prevents the two clinical syndromes that cause the largest number of childhood deaths globally-namely , diarrhoea and acute lower respiratory infections . H and washing with daily bathing also prevents impetigo BACKGROUND Soil-transmitted helminths are among the most prevalent sources of human infections globally . We determined the effect of an educational package at rural schools in Linxiang City District , Hunan province , China , where these worms are prevalent . The intervention aim ed to increase knowledge about soil-transmitted helminths , induce behavioral change , and reduce the rate of infection . METHODS We conducted a single-blind , unmatched , cluster-r and omized intervention trial involving 1718 children , 9 to 10 years of age , in 38 schools over the course of 1 school year . Schools were r and omly assigned to the health-education package , which included a cartoon video , or to a control package , which involved only the display of a health-education poster . Infection rates , knowledge about soil-transmitted helminths ( as assessed with the use of a question naire ) , and h and -washing behavior were assessed before and after the intervention . Albendazole was administered in all the participants at baseline and in all the children who were found to be positive for infection with soil-transmitted helminths at the follow-up assessment at the end of the school year . RESULTS At the follow-up assessment , the mean score for the knowledge of helminths , calculated as a percentage of a total of 43 points on a question naire , was 90 % higher in the intervention group than in the control group ( 63.3 vs. 33.4 , P<0.001 ) , the percentage of children who washed their h and s after using the toilet was nearly twice as high in the intervention group ( 98.9 % , vs. 54.2 % in the control group ; P<0.001 ) , and the incidence of infection with soil-transmitted helminths was 50 % lower in the intervention group than in the control group ( 4.1 % vs. 8.4 % , P<0.001 ) . No adverse events were observed immediately ( within 15 minutes ) after albendazole treatment . CONCLUSIONS The health-education package increased students ' knowledge about soil-transmitted helminths and led to a change in behavior and a reduced incidence of infection within 1 school year . ( Funded by UBS Optimus Foundation , Zurich , Switzerl and ; Australian New Zeal and Clinical Trials Registry number , ACTRN12610000048088 . ) OBJECTIVE To evaluate associations between h and washing promotion and child growth and development . DESIGN Cluster r and omized controlled trial . SETTING Informal settlements in Karachi , Pakistan . PARTICIPANTS A total of 461 children who were enrolled in a trial of household-level h and washing promotion in 2003 and were younger than 8 years at re assessment in 2009 . INTERVENTIONS In 2003 , neighborhoods were r and omized to control ( n = 9 ) , h and washing promotion ( n = 9 ) , or h and washing promotion and drinking water treatment ( n = 10 ) ; intervention households received free soap and weekly h and washing promotion for 9 months . MAIN OUTCOME MEASURES Anthropometrics and developmental quotients measured with the Battelle Developmental Inventory II at 5 to 7 years of age . RESULTS Overall , 24.9 % ( 95 % CI , 20.0%-30.6 % ) and 22.1 % ( 95 % CI , 18.0%-26.8 % ) of children had z scores that were more than 2 SDs below the expected z scores for height and body mass index for age , respectively ; anthropometrics did not differ significantly across study groups . Global developmental quotients averaged 104.4 ( 95 % CI , 101.9 - 107.0 ) among intervention children and 98.3 ( 95 % CI , 93.1 - 103.4 ) among control children ( P = .04 ) . Differences of similar magnitude were measured across adaptive , personal-social , communication , cognitive , and motor domains . CONCLUSIONS Although growth was similar across groups , children r and omized to the h and washing promotion during their first 30 months of age attained global developmental quotients 0.4 SDs greater than those of control children at 5 to 7 years of age . These gains are comparable to those of at-risk children enrolled in publicly funded preschools in the United States and suggest that h and washing promotion could improve child well-being and societal productivity . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01538953 Little is known about effects of public use of antimicrobial h and washing soap . A double-blinded , r and omized clinical trial of h and s of primary caretakers in 238 inner city households was conducted in which effects of plain or antimicrobial ( containing 0.2 % triclosan ) h and washing soap on bacterial counts of the h and s were compared before and after a single wash and before and after h and washing following a year of product use . The r and omly assigned product was provided without cost to each household during monthly home visits , and compliance with product use was monitored . Households were contacted by telephone weekly and with a home visit monthly for 11 months . H and cultures were obtained before and after h and washing at baseline and after 11 months , using a modified glove juice technique . Overall , there were no significant differences in pre-to-post h and washing counts at baseline ( p = 0.41 ) , but by the end of one year , post-wash counts were significantly lower than pre-wash ( p = 0.000 ) for those using either antimicrobial or plain soap . There were no significant differences in mean log counts either before or after h and washing between those using the antimicrobial or plain soap at baseline or after a year of use ( all p values > 0.28 ) . For the group using antimicrobial soap , higher counts were observed post-h and washing in 31.3 % of paired sample s at baseline and 26.7 % after one year ( p = 0.03 ) . A single h and wash had minimal effect on quantity of h and flora , but there were significant effects over time , regardless of whether antimicrobial or plain soap was used . In the absence of more definitive evidence , the risk-benefit ratio argues in favor of targeted rather than ubiquitous , general household use of antimicrobial soap CONTEXT Washing h and s with soap prevents diarrhea , but children at the highest risk of death from diarrhea are younger than 1 year , too young to wash their own h and s. Previous studies lacked sufficient power to assess the impact of household h and washing on diarrhea in infants . OBJECTIVE To evaluate the effect of promoting household h and washing with soap among children at the highest risk of death from diarrhea . DESIGN , SETTING , AND PARTICIPANTS A cluster r and omized controlled trial of 36 low-income neighborhoods in urban squatter settlements in Karachi , Pakistan . Field workers visited participating households at least weekly from April 15 , 2002 , to April 5 , 2003 . Eligible households located in the study area had at least 2 children younger than 15 years , at least 1 of whom was younger than 5 years . INTERVENTIONS Weekly visits in 25 neighborhoods to promote h and washing with soap after defecation and before preparing food , eating , and feeding a child . Within intervention neighborhoods , 300 households ( 1523 children ) received a regular supply of antibacterial soap and 300 households ( 1640 children ) received plain soap . Eleven neighborhoods ( 306 households and 1528 children ) comprised the control group . MAIN OUTCOME MEASURE Incidence density of diarrhea among children , defined as the number of diarrheal episodes per 100 person-weeks of observation . RESULTS Children younger than 15 years living in households that received h and washing promotion and plain soap had a 53 % lower incidence of diarrhea ( 95 % confidence interval [ CI ] , -65 % to -41 % ) compared with children living in control neighborhoods . Infants living in households that received h and washing promotion and plain soap had 39 % fewer days with diarrhea ( 95 % CI , -61 % to -16 % ) vs infants living in control neighborhoods . Severely malnourished children ( weight for age z score , < -3.0 ) younger than 5 years living in households that received h and washing promotion and plain soap had 42 % fewer days with diarrhea ( 95 % CI , -69 % to -16 % ) vs severely malnourished children in the control group . Similar reductions in diarrhea were observed among children living in households receiving antibacterial soap . CONCLUSION In a setting in which diarrhea is a leading cause of child death , improvement in h and washing in the household reduced the incidence of diarrhea among children at high risk of death from diarrhea In an earlier study in rural Guatemala , 257 households that received flocculant-disinfectant to treat their drinking water had 39 % less diarrhea than 257 control households . Three weeks after completion of the study , national marketing of the flocculant-disinfectant was extended into the study communities . Six months later , we assessed frequency of and characteristics associated with purchase and use of the flocculant-disinfectant by revisiting the original study households and administering a question naire . Four hundred sixty-two households ( 90 % ) completed the follow-up survey ; 22 households ( 5 % ) purchased the flocculant-disinfectant within the preceding 2 weeks and used it within the last week . Neither being r and omized to the intervention group during the efficacy study nor combined spending on laundry soap , toothpaste , and h and soap in the preceding week was associated with active repeat use . Even after efficacy was demonstrated within their community and an aggressive sophisticated marketing approach , few households purchased flocculant-disinfectant for point-of-use water treatment OBJECTIVE To evaluate the effectiveness of alcohol-based h and rubs ( ABH ) in reducing acute diarrheal diseases ( ADD ) and acute respiratory infections ( ARI ) among children 1 - 5 years of age in childcare centers with limited tap water . METHODS This was the first cluster-r and omized controlled trial in a developing country . The study took place at 42 childcare centers with sporadic and limited water availability in six towns in Colombia . Participants were r and omly assigned to use ABH as a complement to h and washing ( intervention arm : 21 centers/794 children ) ; or to continue existing h and washing practice s ( control arm : 21 centers/933 children ) . ADD and ARI cases were identified through teacher-reported signs and symptoms of illness . Adverse events were monitored . Hazard ratios ( HR ) were obtained using Cox proportional hazards multivariate regression shared frailty models . RESULTS Child-days of surveillance totaled 336 038 . Loss to follow up was 14.5 % . For both ADD and ARI , there were no differences in hazard ratios during the first trimester of the study . In the second and third trimesters , significant reductions in the risk of ADD were found in the intervention compared to control arm ( HR = 0.55 , P < 0.001 and HR = 0.44 , P < 0.001 , respectively ) . There were also significant risk reductions for ARI in the second trimester ( HR = 0.80 , P < 0.05 ) and in the third trimester ( HR = 0.69 , P < 0.001 ) . No adverse events occurred . CONCLUSIONS ABH effectively prevent ADD and ARI , and are safe . Colombia 's national public health policies for prevention of these diseases should include use of ABH , especially in setting s where h and washing with soap and water is limited by water availability SUMMARY Infections are common in children attending daycare centres ( DCCs ) . We evaluated the effect of a h and hygiene ( HH ) intervention for caregivers on the incidence of gastrointestinal and respiratory infections in children . The intervention was evaluated in a two-arm cluster r and omized controlled trial . Thirty-six DCCs received the intervention including HH products , training sessions , and posters/stickers . Thirty-five control DCCs continued usual practice . Incidence of episodes of diarrhoea and the common cold in children was monitored by parents during 6 months . Using multilevel Poisson regression , incidence rate ratios ( IRRs ) with 95 % confidence intervals ( CIs ) were obtained . Diarrhoeal incidence was monitored in 545 children for 91 937 days . During follow-up , the incidence was 3·0 episodes per child-year in intervention DCCs vs. 3·4 in control DCCs ( IRR 0·90 , 95 % CI 0·73–1·11 ) . Incidence of the common cold was monitored in 541 children for 91 373 days . During follow-up , the incidence was 8·2 episodes per child-year in intervention DCCs vs. 7·4 in control DCCs ( IRR 1·07 , 95 % CI 0·97–1·19 ) . In this study , no evidence for an effect of the intervention was demonstrated on the incidence of episodes of diarrhoea and the common cold Background : Acute gastroenteritis ( AGE ) is one of the most common diseases among children and an important cause of school absenteeism . The aim of this study was to assess the effectiveness of a h and washing program using h and sanitizers for the prevention of school absenteeism due to AGE Methods : A r and omized , controlled and open study of a sample of 1341 children between 4 and 12 years of age , attending 5 state schools in Almería ( Spain ) , with an 8-month follow up ( academic year ) . The experimental group ( EG ) washed their h and s with soap and water , complementing this with the use of a h and sanitizer , and the control group ( CG ) followed the usual h and washing procedure . Absenteeism rates due GI were compared between the 2 groups through the multivariate Poisson regression analysis . Percent days absent in both groups were compared with a Z-test Results : 446 cases of school absenteeism due to AGE were registered . The school children from the EG had a 36 % lower risk of absenteeism due to AGE ( IRR : 0.64 , 95 % confidence interval : 0.52–0.78 ) and a decrease in absenteeism of 0.13 episodes/child/academic year ( 0.27 of EG vs 0.40 CG/episodes/child/academic year , P < 0.001 ) . Pupils missed 725 school days due to AGE and absent days was significantly lower in the EG ( EG : 0.31 % , 95 % confidence interval : 0.28–0.35 vs. CG : 0.44 % , 95 % confidence interval : 0.40–0.48 , P < 0.001 ) Conclusions : The use of h and sanitizer as a complement to h and washing with soap is an efficient measure to reduce absent days and the number of school absenteeism cases due to AGE OBJECTIVE To evaluate h and washing behaviour 5 years after a h and washing intervention in Karachi , Pakistan . METHODS In 2003 , we r and omised neighbourhoods to control , h and washing promotion , or h and washing promotion and water treatment . Intervention households were given soap + /- water treatment product and weekly h and washing education for 9 months . In 2009 , we re-enrolled 461 households from the three study groups : control ( 160 ) , h and washing ( 141 ) , and h and washing + water treatment ( 160 ) and assessed hygiene-related outcomes , accounting for clustering . RESULTS Intervention households were 3.4 times more likely than controls to have soap at their h and washing stations during the study visit [ 293/301 ( 97 % ) vs. 45/159 ( 28 % ) , P < 0.0001 ] . While nearly all households reported h and washing after toileting , intervention households more commonly reported h and washing before cooking [ relative risk ( RR ) 1.2 ( 95 % confidence interval ( CI ) 1.0 - 1.4 ) ] and before meals [ RR 1.7 ( 95 % CI , 1.3 - 2.1 ) ] . Control households cited a mean of 3.87 occasions for washing h and s ; h and washing households , 4.74 occasions ; and h and washing + water treatment households , 4.78 occasions ( P < 0.0001 ) . Households reported purchasing a mean of 0.65 ( control ) , 0.91 ( h and washing ) and 1.1 ( h and washing + water treatment ) bars of soap/person/month ( P < 0.0001 ) . CONCLUSIONS Five years after receiving h and washing promotion , intervention households were more likely to have soap at the household h and washing station , know key times to wash h and s and report purchasing more soap than controls , suggesting habituation of improved h and washing practice s in this population . Intensive h and washing promotion may be an effective strategy for habituating hygiene behaviours and improving health OBJECTIVES To pilot two intensive h and hygiene promotion interventions , one using soap and one using a waterless h and sanitizer , in low-income housing compounds in Dhaka , Bangladesh and assess subsequent changes in h and washing behaviour and h and microbiology . METHODS Fieldworkers r and omized 30 housing compounds : 10 received h and washing promotion with free soap , 10 received h and washing promotion with free waterless h and sanitizer and 10 were non-intervention controls . Fieldworkers assessed h and washing behaviour by structured observation and collected h and rinse specimens . RESULTS At baseline , compound residents washed their h and s with soap 26 % of the time after defecation and 30 % after cleaning a child 's anus but < 1 % at other times . Compared with baseline , residents of soap intervention compounds were much more likely to wash their h and s with soap after faecal contact ( 85 - 91 % ) , before preparing food ( 26 % ) and before eating ( 26 % ) . Compounds that received waterless h and sanitizer cleansed their h and s more commonly than control compounds that used soap ( 10.4%vs . 2.3 % ) , but less commonly than soap intervention compounds used soap ( 25 % ) . Post-intervention h and rinse sample s from soap and sanitizer compounds had lower concentrations of faecal indicator bacteria compared with baseline and control compounds . CONCLUSIONS Waterless h and sanitizer was readily adopted by this low-income community and reduced h and contamination but did not improve the frequency of h and washing compared with soap . Future deployments of waterless h and sanitizers may improve h and hygiene more effectively by targeting setting s where soap and water is unavailable OBJECTIVES We examined the impact of school water , sanitation , and hygiene ( WASH ) interventions on diarrhea-related outcomes among younger siblings of school-going children . METHODS We conducted a cluster-r and omized trial among 185 schools in Kenya from 2007 to 2009 . We assigned schools to 1 of 2 study groups according to water availability . Multilevel logistic regression models , adjusted for baseline measures , assessed differences between intervention and control arms in 1-week period prevalence of diarrhea and 2-week period prevalence of clinic visits among children younger than 5 years with at least 1 sibling attending a program school . RESULTS Among water-scarce schools , comprehensive WASH improvements were associated with decreased odds of diarrhea ( odds ratio [ OR ] = 0.44 ; 95 % confidence interval [ CI ] = 0.27 , 0.73 ) and visiting a clinic ( OR = 0.36 ; 95 % CI = 0.19 , 0.68 ) , relative to control schools . In our separate study group of schools with greater water availability , school hygiene promotion and water treatment interventions and school sanitation improvements were not associated with differences in diarrhea prevalence between intervention and control schools . CONCLUSIONS In water-scarce areas , school WASH interventions that include robust water supply improvements can reduce diarrheal diseases among young children Patients with AIDS frequently develop diarrhoeal illness . In this r and omized , controlled study , 260 patients were screened for those who had not had diarrhoea in the preceding 3 months and who had received a stable highly active antiretroviral therapy regimen for at least 6 weeks prior to the study enrollment . A total of 148 patients met the inclusion criteria and were enrolled : 75 patients were r and omly assigned to an intensive h and washing intervention ( i.e. h and washing after defecation , after cleaning infants who had defecated , before preparing food , before eating , and before and after sex ) and 73 patients were r and omly assigned to the control group . Patients in both groups were called weekly by telephone to determine compliance with h and washing and to determine the number of diarrhoeal episodes for the preceding week . Patients were observed for 1 year . Patients assigned to the intensive h and washing intervention group washed their h and s more frequently compared with the control group ( seven vs four times a day , respectively ; P < 0.05 ) and developed fewer episodes of diarrhoeal illness ( 1.24+/-0.9 vs 2.92+/-0.6 new episodes of diarrhoea , respectively ; P < 0.001 ) during the 1 year observation . The most common pathogens identified in both groups in patients who developed diarrhoeal illness were Giardia lamblia , Cryptosporidium , Entamoeba histolytica and Shigella flexneri . These data suggest that intensive h and washing reduces diarrhoeal illness in patients with AIDS UNLABELLED BACKGROUND AND HYPOTHESES : A substantial percentage of school absenteeism among children is related to transmissible infection . Rates of transmission can be reduced by h and washing with soap and water , but such washing occurs infrequently . This study tested whether an alcohol-free instant h and sanitizer ( CleanH and s ) could reduce illness absenteeism in school-age children . METHODS A 10-week , open-label , crossover study was performed on 420 elementary school-age children ( ages 5 - 12 ) . Students were given a brief orientation immediately prior to the start of the study on the relationship of germs , illness , and h and washing . Each student in the treatment group then received the test product in individual bottles , with instructions to apply one to two sprays to the h and s after coming into the classroom , before eating , and after using the restroom , in addition to their normal h and washing with soap and water . The control group was instructed to continue h and washing as normal with non-medicated soap . After 4 weeks of treatment and a 2-week wash-out period , the control and experimental groups were reversed . Data gathered on absenteeism were classified as gastrointestinal or respiratory related and normalized for nonillness-related absenteeism and school holidays . RESULTS Compared to the h and washing-only control group , students using CleanH and s were found to have 41.9 % fewer illness-related absence days , representing a 28.9 % and a 49.7 % drop in gastrointestinal- and respiratory-related illnesses , respectively . Likewise , absence incidence decreased by 31.7 % , consisting of a 44.2 % and 50.2 % decrease in incidence of gastrointestinal- and respiratory-related illnesses , respectively . No adverse events were reported during the study . CONCLUSIONS Daily use of the instant h and sanitizer was associated with significantly lower rates of illness-related absenteeism BACKGROUND AND OBJECTIVES H and washing prevents communicable illness . We evaluated the effect of a m and atory , scheduled h and -washing program in elementary school children on absenteeism due to acute communicable illness . METHODS The study was conducted at Trombley Elementary School in Grosse Pointe Park , Mich. The intervention group , approximately half of the school children ( n = 143 , including all grade s 1 - 5 ) , washed their h and s a minimum of four scheduled times a day . The control group ( n = 162 ) continued h and -washing practice s as usual . RESULTS Of the 37 school days examined , children in the h and -washing group were absent fewer days than the control group due to all acute communicable illness ( relative risk = .75 ) . There were less days of absence due to gastrointestinal symptoms ( relative risk = .43 ) . The difference in absence due to respiratory symptoms was not statistically significant . CONCLUSIONS A scheduled h and -washing program will reduce acute communicable ( gastrointestinal ) illnesses in elementary school-age children Diarrheal diseases pose a major threat to the health of people living in developing countries , particularly where there is poverty and a poor environment . The effect of h and washing in reducing the incidence of diarrhea in day-care centers has been reported recently . The present study is a prospect i ve community based study conducted to evaluate the effect of h and washing on the incidence of diarrheal disease in Calcutta slums . H and washing was implemented in 1 slum and the other nearby slum , without h and washing program , served as control . The incidence of watery diarrhea during the 13 month period , between the study and control groups was not significantly different . However , the incidence of dysentery in individuals above 5 years of age in the control group was significantly higher as compared to those in the study group ( p 0.05 ) . The results of this study indicate that h and washing with soap may reduce the incidence of dysenteric cases in the community by interruption of transmission of the pathogens from 1 person to the other This study examines the effect of maternal personal and domestic hygiene on the incidence of diarrhoea in children aged 6 - 23 months from rural areas around Teknaf , Bangladesh . The intervention area received augmented water supply through h and pumps and health education while the control area received no project inputs . From July 1980 to June 1983 , diarrhoea incidence was recorded weekly while mothers ' personal and domestic hygiene was observed yearly . Annual incidence of diarrhoea in 314 children from the intervention area and 309 children from the control area was analysed in relation to maternal personal and domestic hygiene , controlling for education and occupation of household head and household size . Results show that , in both areas , use of h and pump water for drinking and washing , removal of child 's faeces from the yard , and maternal h and washing before h and ling food and after defaecation of self and child , observed together , decreased yearly diarrhoea incidence in children by more than 40 % compared to children living in households where none or only one of these practice s was observed To evaluate the effectiveness of an intensive h and hygiene campaign on reducing absenteeism caused by influenza-like illness ( ILI ) , diarrhea , conjunctivitis , and laboratory-confirmed influenza , we conducted a r and omized control trial in 60 elementary schools in Cairo , Egypt . Children in the intervention schools were required to wash h and s twice each day , and health messages were provided through entertainment activities . Data were collected on student absenteeism and reasons for illness . School nurses collected nasal swabs from students with ILI , which were tested by using a qualitative diagnostic test for influenza A and B. Compared with results for the control group , in the intervention group , overall absences caused by ILI , diarrhea , conjunctivitis , and laboratory-confirmed influenza were reduced by 40 % , 30 % , 67 % , and 50 % , respectively ( p<0.0001 for each illness ) . An intensive h and hygiene campaign was effective in reducing absenteeism caused by these illnesses BACKGROUND A third of the 2·5 billion people worldwide without access to improved sanitation live in India , as do two-thirds of the 1·1 billion practising open defecation and a quarter of the 1·5 million who die annually from diarrhoeal diseases . We aim ed to assess the effectiveness of a rural sanitation intervention , within the context of the Government of India 's Total Sanitation Campaign , to prevent diarrhoea , soil-transmitted helminth infection , and child malnutrition . METHODS We did a cluster-r and omised controlled trial between May 20 , 2010 , and Dec 22 , 2013 , in 100 rural villages in Odisha , India . Households within villages were eligible if they had a child younger than 4 years or a pregnant woman . Villages were r and omly assigned ( 1:1 ) , with a computer-generated sequence , to undergo latrine promotion and construction or to receive no intervention ( control ) . R and omisation was stratified by administrative block to ensure an equal number of intervention and control villages in each block . Masking of participants was not possible because of the nature of the intervention . However , households were not told explicitly that the purpose of enrolment was to study the effect of a trial intervention , and the surveillance team was different from the intervention team . The primary endpoint was 7-day prevalence of reported diarrhoea in children younger than 5 years . We did intention-to-treat and per- protocol analyses . This trial is registered with Clinical Trials.gov , number NCT01214785 . FINDINGS We r and omly assigned 50 villages to the intervention group and 50 villages to the control group . There were 4586 households ( 24,969 individuals ) in intervention villages and 4894 households ( 25,982 individuals ) in control villages . The intervention increased mean village-level latrine coverage from 9 % of households to 63 % , compared with an increase from 8 % to 12 % in control villages . Health surveillance data were obtained from 1437 households with children younger than 5 years in the intervention group ( 1919 children younger than 5 years ) , and from 1465 households ( 1916 children younger than 5 years ) in the control group . 7-day prevalence of reported diarrhoea in children younger than 5 years was 8·8 % in the intervention group and 9·1 % in the control group ( period prevalence ratio 0·97 , 95 % CI 0·83 - 1·12 ) . 162 participants died in the intervention group ( 11 children younger than 5 years ) and 151 died in the control group ( 13 children younger than 5 years ) . INTERPRETATION Increased latrine coverage is generally believed to be effective for reducing exposure to faecal pathogens and preventing disease ; however , our results show that this outcome can not be assumed . As efforts to improve sanitation are being undertaken worldwide , approaches should not only meet international coverage targets , but should also be implemented in a way that achieves uptake , reduces exposure , and delivers genuine health gains . FUNDING Bill & Melinda Gates Foundation , International Initiative for Impact Evaluation ( 3ie ) , and Department for International Development-backed SHARE Research Consortium at the London School of Hygiene & Tropical Medicine An educational intervention was design ed to improve three water-sanitation behaviors empirically shown to be associated with high rates of childhood diarrhea in Dhaka , Bangladesh : lack of h and washing before preparing food , open defecation by children in the family compound , and inattention to proper disposal of garbage and feces , increasing the opportunity for young children to place waste products in their mouth . Fifty-one communities , each comprising 38 families , were r and omized either to receive ( n = 25 ) or not to receive ( n = 26 ) the intervention . During the six months after the intervention , the rate of diarrhea ( per 100 person-weeks ) in children under six years of age was 4.3 in the intervention communities and 5.8 in the control communities ( 26 % protective efficacy ; p less than 0.0001 ) . A corresponding improvement in h and washing practice s before preparing food was noted , although no improvement was observed for defecation and waste disposal practice s. These data suggest that educational interventions for water-sanitation practice s can have an important beneficial effect upon childhood diarrhea in developing countries , particularly when the interventions are design ed in a simple way to promote naturally occurring salutory behaviors that are empirically associated with lower rates of childhood diarrhea OBJECTIVE To evaluate common h and hygiene methods for efficacy in removing Clostridium difficile . DESIGN R and omized crossover comparison among 10 volunteers with h and s experimentally contaminated by nontoxigenic C. difficile . METHODS Interventions included warm water with plain soap , cold water with plain soap , warm water with antibacterial soap , antiseptic h and wipes , alcohol-based h and rub , and a control involving no intervention . All interventions were evaluated for mean reduction in colony-forming units ( CFUs ) under 2 contamination protocol s : " whole h and " and " palmar surface . " Results were analyzed according to a Bayesian approach , by using hierarchical models adjusted for multiple observations . RESULTS Under the whole-h and protocol , the greatest adjusted mean reductions were achieved by warm water with plain soap ( 2.14 log(10 ) CFU/mL [ 95 % credible interval ( CrI ) , 1.74 - 2.54 log(10 ) CFU/mL ] ) , cold water with plain soap ( 1.88 log(10 ) CFU/mL [ 95 % CrI , 1.48 - 2.28 log(10 ) CFU/mL ) , and warm water with antibacterial soap ( 1.51 log(10 ) CFU/mL [ 95 % CrI , 1.12 - 1.91 log(10 ) CFU/mL ] ) , followed by antiseptic h and wipes ( 0.57 log(10 ) CFU/mL [ 95 % CrI , 0.17 - 0.96 log(10 ) CFU/mL ] ) . Alcohol-based h and rub ( 0.06 log(10 ) CFU/mL [ 95 % CrI , -0.34 to 0.45 log(10 ) CFU/mL ] ) was equivalent to no intervention . Under the palmar surface protocol , warm water with plain soap , cold water with plain soap , and warm water with antibacterial soap again yielded the greatest mean reductions , followed by antiseptic h and wipes ( 26.6 , 26.6 , 26.6 , and 21.9 CFUs per plate , respectively ) , when compared with alcohol-based h and rub . Hypothenar ( odds ratio , 10.98 [ 95 % CrI , 1.96 - 37.65 ] ) and thenar ( odds ratio , 6.99 [ 95 % CrI , 1.25 - 23.41 ] ) surfaces were more likely than fingertips to remain heavily contaminated after h and washing . CONCLUSIONS H and washing with soap and water showed the greatest efficacy in removing C. difficile and should be performed preferentially over the use of alcohol-based h and rubs when contact with C. difficile is suspected or likely Background Infectious illnesses such as influenza and diarrhea are leading causes of absenteeism among Danish school children . Interventions in school setting s addressing h and hygiene have shown to reduce the number of infectious illnesses . However , most of these studies include small population s and almost none of them are conducted as r and omized controlled trials . The overall aim of the Hi Five study was to develop , implement and evaluate a multi-component school-based intervention to improve h and hygiene and well-being and to reduce the prevalence of infections among school children in intervention schools by 20 % compared to control schools . This paper describes the development and the evaluation design of Hi Five . Methods / design The Hi Five study was design ed as a tree-armed cluster-r and omized controlled trial . A national r and om sample of schools ( n = 44 ) was r and omized to one of two intervention groups ( n = 29 ) or to a control group with no intervention ( n = 15 ) . A total of 8,438 six to fifteen-year-old school children were enrolled in the study . The Hi Five intervention consisted of three components : 1 ) a curriculum component 2 ) m and atory daily h and washing before lunch 3 ) extra cleaning of school toilets during the school day . Baseline data was collected from December 2011 to April 2012 . The intervention period was August 2012 to June 2013 . The follow-up data was collected from December 2012 to April 2013 . Discussion The Hi Five study fills a gap in international research . This large r and omized multi-component school-based h and hygiene intervention is the first to include education on healthy and appropriate toilet behavior as part of the curriculum . No previous studies have involved supplementary cleaning at the school toilets as an intervention component . The study will have the added value of providing new knowledge about usability of short message service ( SMS , text message ) for collecting data on infectious illness and absenteeism in large study population s . Trial registration Current Controlled Trials IS RCT N19287682 , 21 December 2012 A community-based intervention was developed through direct participation of the target population in assessment and iterative trials to improve hygiene practice s and to reduce childhood diarrhoea in lowl and rural Bangladesh . A total of 185 ( 98 % ) households with children ages 0 - 18 months in five contiguous villages were targeted for the interventions . A comparison site was selected for a detailed observational study and for use as a control for the intervention . About 97 % of all households with children ages 0 - 18 months were enrolled for study at the control site . Children in this age group were targeted because at this developmental stage they were most vulnerable to diarrhoeal morbidity and malnutrition ( related to unhygienic practice s ) . The intervention was implemented with the assistance of village leaders through a " Clean Life " campaign by local project workers and volunteer mothers who were chosen from the target households . The intervention activities started in January 1986 and lasted for 7 months . Higher adoption rates of the intervention were associated with better cleanliness status , which was related to lower diarrhoea and malnutrition rates in the intervention site . The results of between-site longitudinal analyses showed that after the intervention , the intervention site had substantially higher cleanliness scores , lower diarrhoeal morbidity , and better growth status compared to those of the control site , with differences increasing over time . The findings suggest that this type of community-based intervention can be very beneficial in modifying hygiene behaviours and lowering childhood diarrhoea and malnutrition Background . Diarrheal infections are common in children who attend child care , and preventing transmission of disease in this setting depends on actions by child care staff . We set out to discover whether transmission of gastrointestinal infections in child care could be reduced by improved infection control procedures . Methods . We performed a cluster r and omized , controlled trial of an infection control intervention conducted in child care centers for 1 city in Australia . The intervention was training of child care staff about transmission of infection and h and washing and focused on both staff and child behavior . Implementation of the intervention was recorded by an observer . Illness was measured by parent report in telephone interviews every 2 weeks . Results . There were 311 child-years of surveillance for diarrheal episodes . The rate of episodes of diarrhea was 1.9 per child-year in intervention centers and 2.7 per child-year in control centers . Multivariable analysis showed that diarrheal episodes were significantly reduced in intervention center children by 50 % . However , the impact of the intervention was confined to children over 24 months of age . For those centers in which children 's compliance with h and washing was high , diarrheal episodes were reduced by 66 % . Conclusions . This trial supports education about infection control , for staff and children in child care , as a means of reducing transmission of diarrhea . Reduction in episodes of diarrhea in children in child care was limited to children over 24 months of age To assess the health impact of reusable , antimicrobial h and towels , we conducted a cluster r and omized , yearlong field trial . At baseline , we surveyed mothers , and gave four towels plus hygiene education to intervention households and education alone to controls . At biweekly home visits , we asked about infections in children < 2 years old and tested post-h and washing h and rinse sample s of 20 % of mothers for Escherichia coli . At study 's conclusion , we tested 50 % of towels for E. coli . Baseline characteristics between 188 intervention and 181 control households were similar . Intervention and control children had similar rates of diarrhea ( 1.47 versus 1.48 , P = 0.99 ) , respiratory infections ( 1.38 versus 1.48 , P = 0.92 ) , skin infections ( 1.76 versus 1.79 , P = 0.81 ) , and subjective fever ( 2.62 versus 3.40 , P = 0.04 ) per 100 person-visits . Post-h and washing h and contamination was similar ; 67 % of towels exhibited E. coli contamination . Antimicrobial h and towels became contaminated over time , did not improve h and hygiene , or prevent diarrhea , respiratory infections , or skin infections BACKGROUND Several studies have indicated a connection between h and washing and illness-related absenteeism in school setting s. The difficulty of ensuring consistent and effective h and washing among student population s has also been noted . The purpose of this study was to assess the effectiveness of the use of an alcohol gel h and sanitizer in the classroom to help decrease the illness-related absentee rate for elementary school students . METHODS This study involved 5 individual school districts , 16 individual schools , and more than 6000 students in Delaware , Ohio , Tennessee , and California . Individual schools in each district were paired into product and control groups . In the product group schools , an alcohol gel h and sanitizer was used by the students and staff when entering and leaving the classroom . Absenteeism due to infection was recorded , and the data were statistically analyzed . RESULTS The overall reduction in absenteeism due to infection in the schools included in this study was 19.8 % for schools that used an alcohol gel h and sanitizer compared with the control schools ( P < .05 ) . Data from the school system with the largest teacher population ( n = 246 ) showed that teacher absenteeism decreased 10.1 % ( trend ) in the schools where sanitizer was used . CONCLUSION Elementary school absenteeism due to infection is significantly reduced when an alcohol gel h and sanitizer is used in the classroom as part of a h and hygiene program In a cluster r and omized trial , Patricia Priest and colleagues find that providing h and sanitizer along with h and hygiene education in primary school classrooms , compared with h and hygiene alone , does not reduce school absences . Please see later in the article for the Editors ' OBJECTIVE To investigate the effectiveness of a hygiene promotion intervention based on germ awareness in increasing h and washing with soap on key occasions ( after faecal contact and before eating ) in rural Indian households . METHODS Cluster r and omised trial of a hygiene promotion intervention in five intervention and five control villages . H and washing was assessed through structured observation in a r and om sample of 30 households per village . Additionally , soap use was monitored in a sub- sample of 10 households per village using electronic motion detectors embedded in soap bars . RESULTS The intervention reached 40 % of the target population . Germ awareness increased as well as reported h and washing ( a possible indicator of perceived social norms ) . Observed h and washing with soap on key occasions was rare ( 6 % ) , especially after faecal contact ( 2 % ) . Observed h and washing with soap on key occasions did not change 4 weeks after the intervention in either the intervention arm ( -1 % , 95 % CI -2%/+0.3 % ) , or the control arm ( + 0.4 % , 95 % CI -1%/+2 % ) . Data from motion detectors indicated a significant but small increase in overall soap use in the intervention arm . We can not confidently identify the nature of this increase except to say that there was no change in a key measure of h and washing after defecation . CONCLUSION The intervention proved scalable and effective in raising hygiene awareness . There was some evidence of an impact on soap use but not on the primary outcome of h and washing at key times . However , the results do not exclude that changes in knowledge and social norms may lay the foundations for behaviour change in the longer term |
11,987 | 26,678,635 | CONCLUSIONS Pooled data provide moderate-certainty evidence that performance of multivessel PCI will provide an appreciable reduction in nonfatal MI and high-certainty evidence that it will reduce need for repeat revascularization .
Patients are likely to place a high value on these benefits | BACKGROUND Guidelines suggest percutaneous intervention ( PCI ) of only the culprit artery in patients presenting with ST-segment elevation myocardial infa rct ion ( STEMI ) and multivessel coronary artery disease .
However , recent r and omized controlled trials ( RCTs ) suggest benefit to performing PCI of other stenotic vessels at the same time as culprit vessel PCI . | In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Background Few reports described outcomes of complete compared with infa rct -related artery (IRA)-only revascularisation in patients with ST-elevation myocardial infa rct ion ( STEMI ) and multivessel coronary artery disease ( CAD ) . Moreover , no studies have compared the simultaneous treatment of non-IRA with the IRA treatment followed by an elective procedure for the other lesions ( staged revascularisation ) . Methods The outcomes of 214 consecutive patients with STEMI and multivessel CAD undergoing primary angioplasty were studied . Before the first angioplasty patients were r and omly assigned to three different strategies : culprit vessel angioplasty-only ( COR group ) ; staged revascularisation ( SR group ) and simultaneous treatment of non-IRA ( CR group ) . Results During a mean follow-up of 2.5 years , 42 ( 50.0 % ) patients in the COR group experienced at least one major adverse cardiac event ( MACE ) , 13 ( 20.0 % ) in the SR group and 15 ( 23.1 % ) in the CR group , p<0.001 . Inhospital death , repeat revascularisation and re-hospitalisation occurred more frequently in the COR group ( all p<0.05 ) , whereas there was no significant difference in re-infa rct ion among the three groups . Survival free of MACE was significantly reduced in the COR group but was similar in the CR and SR groups . Conclusions Culprit vessel-only angioplasty was associated with the highest rate of long-term MACE compared with multivessel treatment . Patients scheduled for staged revascularisation experienced a similar rate of MACE to patients undergoing complete simultaneous treatment of non-IRA BACKGROUND As compared with thrombolytic therapy , primary coronary angioplasty results in a higher rate of patency of the infa rct -related coronary artery , lower rates of stroke and reinfa rct ion , and higher in-hospital or 30-day survival rates . However , the comparative long-term efficacy of these two approaches has not been carefully studied . METHODS We r and omly assigned a total of 395 patients with acute myocardial infa rct ion to treatment with angioplasty or intravenous streptokinase . Clinical information was collected for a mean ( + /-SD ) of 5+/-2 years , and medical charges associated with the two treatments were compared . RESULTS A total of 194 patients were assigned to undergo primary angioplasty , and 201 to receive streptokinase . Mortality was 13 percent in the angioplasty group , as compared with 24 percent in the streptokinase group ( relative risk , 0.54 ; 95 percent confidence interval , 0.36 to 0.87 ) . Nonfatal reinfa rct ion occurred in 6 percent and 22 percent of the two groups , respectively ( relative risk , 0.27 ; 95 percent confidence interval , 0.15 to 0.52 ) . The combined incidence of death and nonfatal reinfa rct ion was also lower among patients assigned to angioplasty than among those assigned to streptokinase , with a relative risk of 0.13 ( 95 percent confidence interval , 0.05 to 0.37 ) for early events ( within the first 30 days ) and a relative risk of 0.62 ( 95 percent confidence interval , 0.43 to 0.91 ) for late events ( after 30 days ) . The rates of readmission for heart failure and ischemia were also lower among patients in the angioplasty group than among patients in the streptokinase group . Total medical charges per patient were lower in the angioplasty group ( 16,090 dollars ) than in the streptokinase group ( 16,813 dollars , P=0.05 ) . CONCLUSIONS During five years of follow-up , primary coronary angioplasty for acute myocardial infa rct ion was associated with lower rates of early and late death and nonfatal reinfa rct ion , fewer hospital readmissions for ischemia or heart failure , and lower total medical charges than treatment with intravenous streptokinase BACKGROUND Patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease . We aim ed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infa rct -related artery only . METHODS We undertook an open-label , r and omised controlled trial at two university hospitals in Denmark . Patients presenting with STEMI who had one or more clinical ly significant coronary stenosis in addition to the lesion in the infa rct -related artery were included . After successful percutaneous coronary intervention ( PCI ) of the infa rct -related artery , patients were r and omly allocated ( in a 1:1 ratio ) either no further invasive treatment or complete FFR-guided revascularisation before discharge . R and omisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI . All patients received best medical treatment . The primary endpoint was a composite of all-cause mortality , non-fatal reinfa rct ion , and ischaemia-driven revascularization of lesions in non-infa rct -related arteries and was assessed when the last enrolled patient had been followed up for 1 year . Analysis was on an intention-to-treat basis . This trial is registered with Clinical Trials.gov , number NCT01960933 . FINDINGS From March , 2011 , to February , 2014 , we enrolled 627 patients to the trial ; 313 were allocated no further invasive treatment after primary PCI of the infa rct -related artery only and 314 were assigned complete revascularization guided by FFR values . Median follow-up was 27 months ( range 12–44 months ) . Events comprising the primary endpoint were recorded in 68 ( 22 % ) patients who had PCI of the infa rct -related artery only and in 40 ( 13 % ) patients who had complete revascularisation ( hazard ratio 0∙56 , 95 % CI 0∙38–0∙83 ; p=0∙004 ) . INTERPRETATION In patients with STEMI and multivessel disease , complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI . This effect is driven by significantly fewer repeat revascularisations , because all-cause mortality and non-fatal reinfa rct ion did not differ between groups . Thus , to avoid repeat revascularisation , patients can safely have all their lesions treated during the index admission . Future studies should clarify whether complete revascularization should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints . FUNDING Danish Agency for Science , Technology and Innovation and Danish Council for Strategic Research In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted BACKGROUND In acute ST-segment elevation myocardial infa rct ion ( STEMI ) , the use of percutaneous coronary intervention ( PCI ) to treat the artery responsible for the infa rct ( infa rct , or culprit , artery ) improves prognosis . The value of PCI in noninfa rct coronary arteries with major stenoses ( preventive PCI ) is unknown . METHODS From 2008 through 2013 , at five centers in the United Kingdom , we enrolled 465 patients with acute STEMI ( including 3 patients with left bundle-branch block ) who were undergoing infa rct -artery PCI and r and omly assigned them to either preventive PCI ( 234 patients ) or no preventive PCI ( 231 patients ) . Subsequent PCI for angina was recommended only for refractory angina with objective evidence of ischemia . The primary outcome was a composite of death from cardiac causes , nonfatal myocardial infa rct ion , or refractory angina . An intention-to-treat analysis was used . RESULTS By January 2013 , the results were considered conclusive by the data and safety monitoring committee , which recommended that the trial be stopped early . During a mean follow-up of 23 months , the primary outcome occurred in 21 patients assigned to preventive PCI and in 53 patients assigned to no preventive PCI ( infa rct -artery-only PCI ) , which translated into rates of 9 events per 100 patients and 23 per 100 , respectively ( hazard ratio in the preventive-PCI group , 0.35 ; 95 % confidence interval [ CI ] , 0.21 to 0.58 ; P<0.001 ) . Hazard ratios for the three components of the primary outcome were 0.34 ( 95 % CI , 0.11 to 1.08 ) for death from cardiac causes , 0.32 ( 95 % CI , 0.13 to 0.75 ) for nonfatal myocardial infa rct ion , and 0.35 ( 95 % CI , 0.18 to 0.69 ) for refractory angina . CONCLUSIONS In patients with STEMI and multivessel coronary artery disease undergoing infa rct -artery PCI , preventive PCI in noninfa rct coronary arteries with major stenoses significantly reduced the risk of adverse cardiovascular events , as compared with PCI limited to the infa rct artery . ( Funded by Barts and the London Charity ; PRAMI Current Controlled Trials number , IS RCT N73028481 . ) DESIGN : Prospect i ve r and omized , multicentre study . RATIONALE : Recanalisation of the culprit lesion is the main goal of primary angioplasty for acute myocardial infa rct ion . With the exception of cardiogenic shock , staged procedures are performed in the presence of multivessel disease . The study hypothesis is that with modern non-thrombogenic stents ( heparin coated ) complete revascularization with multivessel treatment can be safely achieved during the primary angioplasty procedure with a lower need of subsequent revascularization procedures and at a lower cost . ENDPOINTS : PRIMARY : 12-month incidence of repeat revascularization ( any revascularization , infa rct related artery as well as non-infa rct -related artery ) . SECONDARY : ( 1 ) in hospital repeat revascularization , reinfa rct ion and death ; ( 2 ) total hospital cost ( including a 12 months follow-up period ) . METHODS : 69 patients with ST elevation Acute Myocardial Infa rct ion ( AMI ) , < 12 hours after symptoms onset , undergoing primary angioplasty , with documented multivessel disease and both culprit lesion and 1 to 3 other lesions suitable for stent implantation . Unbalanced r and omization between culprit lesion treatment only ( n = 17 ) and complete multivessel treatment ( n = 52 , with 71 additional lesions treated ) . RESULTS : The two groups were well balanced in terms of clinical characteristics , number of diseased vessels and angiographic characteristics of the culprit lesion . In the complete multivessel treatment group 2.36 ± 0.64 lesions per patient were treated using 2.73 ± 0.78 heparin coated stents ( 1.00 lesions and 1.29 ± 0.61 stents in the culprit treatment group , bothp < 0.001 ) . The duration of the procedure increased from 53 ± 21 min ( culprit treatment group ) to 69 ± 32 min ( p = 0.032 ) and the amount of contrast used from 242 ± 102 ml ( culprit treatment group ) to 341 ± 163 ml ( multivessel complete treatment),p = 0.025 . A similar low incidence of in-hospital major adverse cardiac events was observed in the 2 groups ( 0 and 3.8 % in culprit and multivessel treatment groups , p = 0.164 ) . The increase in the incidence of new revascularisation in the culprit treatment group at 12 month follow-up was not significant ( 35 vs 17%,p = 0.247 ) but was sufficient to compensate the initial higher in-hospital cost , with a similar 12 month hospital cost in the 2 groups ( € 22 330 ± € 13 653 vs € 20 382 ± € 11 671,p = 0.231 ) . CONCLUSION : Multivessel treatment during primary PTCA was safe in this controlled trial . However , when only the culprit lesion was initially treated , the need for subsequent clinical ly driven revascularization remained low and no clinical or economical advantages were obtainable with a more aggressive initial approach . In clinical practice , a staged approach to multivessel treatment during primary angioplasty avoids to treat unnecessarily non clinical ly relevant lesions . ( Int J Cardiovasc Intervent 2004 ; 6 : 128 - 133 Background The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention ( P-PCI ) for ST-segment elevation myocardial infa rct ion is uncertain . Objectives CvLPRIT ( Complete versus Lesion-only Primary PCI trial ) is a U.K. open-label r and omized study comparing complete revascularization at index admission with treatment of the infa rct -related artery ( IRA ) only . Methods After they provided verbal assent and underwent coronary angiography , 296 patients in 7 U.K. centers were r and omized through an interactive voice-response program to either in-hospital complete revascularization ( n = 150 ) or IRA-only revascularization ( n = 146 ) . Complete revascularization was performed either at the time of P-PCI or before hospital discharge . R and omization was stratified by infa rct location ( anterior/nonanterior ) and symptom onset ( ≤3 h or > 3 h ) . The primary endpoint was a composite of all-cause death , recurrent myocardial infa rct ion ( MI ) , heart failure , and ischemia-driven revascularization within 12 months . Results Patient groups were well matched for baseline clinical characteristics . The primary endpoint occurred in 10.0 % of the complete revascularization group versus 21.2 % in the IRA-only revascularization group ( hazard ratio : 0.45 ; 95 % confidence interval : 0.24 to 0.84 ; p = 0.009 ) . A trend toward benefit was seen early after complete revascularization ( p = 0.055 at 30 days ) . Although there was no significant reduction in death or MI , a nonsignificant reduction in all primary endpoint components was seen . There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding , contrast-induced nephropathy , or stroke between the groups . Conclusions In patients presenting for P-PCI with multivessel disease , index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA . In such patients , inpatient total revascularization may be considered , but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival . ( Complete Versus Lesion-only Primary PCI Pilot Study [ CvLPRIT ] ; IS RCT N70913605 |
11,988 | 21,604,942 | Interestingly , only limited numbers of patients under active surveillance require additional treatment .
Recent data suggest that delayed treatment does not appear to alter the clinical outcome among those highly selected patients . | Surgery or radiation therapy remain the st and ard curative treatments for newly diagnosed prostate cancer patients .
Nonetheless , these aggressive treatments are associated with decreased quality of life with altered sexual and urinary functions .
The objective was a systematic review of active surveillance protocol s to investigate the role of histopathology and molecular markers in the active surveillance of prostate cancer .
Using modern risk stratification , several centres have gained significant experience in identifying patients with a low risk of prostate cancer progression and have adopted an active surveillance program with delayed curative therapy . | In a population -based study , disease progression and survival were evaluated in untreated patients with newly diagnosed cancer of the prostate without distant metastases . Complete follow-up was achieved in 223 of 227 ( 98 % ) consecutively diagnosed , eligible patients of all ages . After 5 years , the cumulative progression-free survival ( with 95 % confidence interval ) was 71.8 (65.5 - 78.1)% and survival corrected for causes of death other than prostatic cancer was 93.8 (88.3 - 97.6)% . Univariate and multivariate analyses showed no association between age at diagnosis and the natural course . Local progression was less common in localised , non-palpable tumours than in larger tumours . The rate of progression was 18.7 ( 6.1 - 57.1 ) times higher and that of disease-specific death 216.0 ( 31.2 - 1496 ) times higher in patients with poorly than in those with highly differentiated tumours . It is concluded that tumour grade at diagnosis is an excellent predictor of local and distant progression . The low death rate , especially in patients with highly and moderately differentiated tumours , means that any local or systemic therapy intended for patients with early prostatic cancer must be evaluated in clinical trials with untreated controls for comparison Active surveillance followed by selective treatment for men who have evidence of disease progression may be an option for select patients with early‐stage prostate cancer . In this article , the authors report their experience in a contemporary cohort of men with prostate cancer who were managed with active surveillance BACKGROUND In 2008 , we reported that radical prostatectomy , as compared with watchful waiting , reduces the rate of death from prostate cancer . After an additional 3 years of follow-up , we now report estimated 15-year results . METHODS From October 1989 through February 1999 , we r and omly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy . Follow-up was complete through December 2009 , with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death . Relative risks , with 95 % confidence intervals , were estimated with the use of a Cox proportional-hazards model . RESULTS During a median of 12.8 years , 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died ( P=0.007 ) . In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting , death was due to prostate cancer . This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6 % and 20.7 % , respectively ( a difference of 6.1 percentage points ; 95 % confidence interval [ CI ] , 0.2 to 12.0 ) , and a relative risk with surgery of 0.62 ( 95 % CI , 0.44 to 0.87 ; P=0.01 ) . The survival benefit was similar before and after 9 years of follow-up , was observed also among men with low-risk prostate cancer , and was confined to men younger than 65 years of age . The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age . Among men who underwent radical prostatectomy , those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth ( relative risk , 6.9 ; 95 % CI , 2.6 to 18.4 ) . CONCLUSIONS Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer . Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment . ( Funded by the Swedish Cancer Society and the National Institutes of Health . ) OBJECTIVES Outcome data from a prospect i ve study of active surveillance of localised prostate cancer were analysed to identify factors , present at the time of diagnosis , that predict subsequent radical treatment . METHODS Eligible patients had clinical stage T1-T2a , N0-Nx , M0-Mx adenocarcinoma of the prostate with serum PSA<15 ng/ml , Gleason score < or= 7 , primary Gleason grade < or= 3 , and % positive biopsy cores ( pbc ) < or= 50 % . Monitoring included serial PSA measurement and repeat prostate biopsies . Radical treatment was initiated in the event of biochemical progression ( PSA velocity > 1 ng/ml/yr ) or histological progression ( primary Gleason grade > or= 4 , or % pbc > 50 % ) . Multivariate Cox regression analysis of baseline variables was performed with respect to time to radical treatment . RESULTS The 326 men recruited from 2002 to 2006 have been followed for a median of 22 mo . Median age was 67 yr , and median initial PSA ( iPSA ) 6.4 ng/ml . Sixty-five patients ( 20 % ) had deferred radical treatment , 16 ( 5 % ) changed to watchful waiting because of increasing comorbidity , 7 ( 2 % ) died of other causes , and 238 ( 73 % ) remain on surveillance . On multivariate Cox regression analysis , the free/total PSA ratio ( p<0.001 ) and clinical T stage ( p=0.006 ) were independent determinants of time to radical treatment . CONCLUSIONS In addition to established prognostic factors , the free/total PSA ratio may predict time to radical treatment in patients with untreated , localised prostate cancer managed by active surveillance . This possibility warrants further study |
11,989 | 20,382,722 | The available evidence to date supports the use of antibiotic prophylaxis for the prevention of Lyme disease in endemic areas following an Ixodes tick bite . | BACKGROUND The clinical value of antibiotic prophylaxis in preventing Lyme disease remains uncertain , owing to a meta- analysis lacking sufficient power to demonstrate efficacy and a more recent trial showing effectiveness but lacking precision .
Our objective was to up date our prior meta- analysis on antibiotic prophylaxis for the prevention of Lyme disease , to obtain a more precise estimate of treatment effect . | BACKGROUND Tests to determine serum antibody levels-the 2-tier sonicate immunoglobulin M ( IgM ) and immunoglobulin G ( IgG ) enzyme-linked immunosorbent assay ( ELISA ) and Western blot method or the IgG of the variable major protein-like sequence-expressed ( VlsE ) sixth invariant region ( C6 ) peptide ELISA method -are the major tests available for support of the diagnosis of Lyme disease . However , these tests have not been assessed prospect ively . METHODS We used these tests prospect ively to determine serologic responses in 134 patients with various manifestations of Lyme disease , 89 patients with other illnesses ( with or without a history of Lyme disease ) , and 136 healthy subjects from areas of endemicity and areas in which the infection was not endemic . RESULTS With 2-tier tests and the C6 peptide ELISA , only approximately one-third of 76 patients with erythema migrans had results that were positive for IgM or IgG seroreactivity with Borrelia burgdorferi in acute-phase sample s. During convalescence , 3 - 4 weeks later , almost two-thirds of patients had seroreactivity with the spirochete B. burgdorferi . The frequencies of seroreactivity were significantly greater among patients with spirochetal dissemination than they were among those who lacked evidence of disseminated disease . Of the 44 patients with Lyme disease who had neurologic , heart , or joint involvement , all had positive C6 peptide ELISA results , 42 had IgG responses with 2-tier tests , and 2 patients with facial palsy had only IgM responses . However , among the control groups , the IgG Western blot was slightly more specific than the C6 peptide ELISA . The differences between the 2 test systems ( 2-tier testing and C6 peptide ELISA ) with respect to sensitivity and specificity were not statistically significant . CONCLUSIONS Except in patients with erythema migrans , both test systems were sensitive for support of the diagnosis of Lyme disease . However , with current methods , 2-tier testing was associated with slightly better specificity BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences OBJECTIVE To determine if the early antibiotic treatment of deer tick bites prevented Lyme disease . DESIGN Prospect i ve , double-blind , placebo-controlled , antibiotic treatment . SETTING Private practice in an area endemic for Lyme disease . STUDY PARTICIPANTS Patients between 3 and 19 years of age who received antibiotic treatment within 3 days following a deer tick bite . INTERVENTIONS Patients received an antibiotic or placebo and were followed up for stage I and II disease . All patients had blood drawn at the time of presentation and 6 weeks later for immunofluorescent antibodies ( IFA ) . MEASUREMENTS /MAIN RESULTS One patient in the placebo group developed clinical Lyme disease associated with an IFA titer of 1:32 , considered weakly positive . Three other patients in the placebo group developed an IFA titer of 1:32 ; one had an influenzalike illness and two had no symptoms . None of the study patients developed any neurologic , cardiac , or arthritic symptoms in the 1- to 3-year follow-up . CONCLUSION Based on the low frequency of illness , the absence of stage II disease , and the inability to establish the efficacy of early antibiotic treatment , we suggest that physicians not routinely use prophylactic antibiotics for deer tick bites Animal studies have shown an exponential increase in the risk of Borrelia burgdorferi infection after 48 - 72 h of deer tick attachment . Persons with tick bites were prospect ively studied to determine if those with prolonged tick attachment constitute a high-risk group for infection . Ticks were identified , measured for engorgement , and assayed by polymerase chain reaction ( PCR ) for B. burgdorferi DNA . Duration of attachment was determined from the scutal index of engorgement . Of 316 su bmi ssions , 229 were deer ticks ; 14 % were positive by PCR . Paired sera and an intact tick for determination of duration of attachment were available for 105 subjects ( 109 bites ) . There were 4 human cases ( 3.7 % of bites ) of B. burgdorferi infection . The incidence was significantly higher for duration of attachment > or = 72 h than for < 72 h : 3 ( 20 % ) of 15 vs. 1 ( 1.1 % ) of 94 ( P = .008 ; odds ratio , 23.3 ; 95 % confidence interval , 2.2 - 242 ) . PCR was an unreliable predictor of infection . Tick identification and measurement of engorgement can be used to identify a small , high-risk subset of persons who may benefit from antibiotic prophylaxis BACKGROUND Tick-borne relapsing fever ( TBRF ) is an acute febrile illness . In Israel , TBRF is caused by Borrelia persica and is transmitted by Ornithodoros tholozani ticks . We examined the safety and efficacy of postexposure treatment to prevent TBRF . METHODS In a double-blind , placebo-controlled trial , 93 healthy subjects with suspected tick exposure ( 52 with signs of tick bites and 41 close contacts -- those without signs but with a similar risk of contact with ticks ) were r and omly assigned to receive either doxycycline ( Dexxon , in a dose of 200 mg the first day and then 100 mg per day for four days ) or placebo after presumed exposure to TBRF . Cases of TBRF were defined by fever and a positive blood smear . Serologic analysis for cross-reactivity to Borrelia burgdorferi and polymerase chain reaction ( PCR ) for the borrelia glpQ gene were also performed . RESULTS After r and omization , 47 subjects ( 26 with signs of tick bites and 21 close contacts ) received doxycycline . Forty-six other subjects ( 26 with signs of tick bites and 20 close contacts ) received placebo . All 10 cases of TBRF identified by a positive blood smear were in the placebo group of subjects with signs of a tick bite ( P<0.001 ) . These findings suggested a 100 percent efficacy of preemptive treatment ( 95 percent confidence interval , 46 to 100 percent ) . PCR for the borrelia glpQ gene was negative at baseline for all subjects and subsequently positive in all subjects with fever and a positive blood smear . Seroconversion was detected in eight of nine cases of TBRF . PCR and serum sample s were negative for all of the other subjects tested . No major treatment-associated adverse effects were identified . CONCLUSIONS Treatment with doxycycline is safe and efficacious in preventing TBRF after suspected exposure to ticks in a high-risk environment . ( Clinical Trials.gov number , NCT00237016 [ Clinical Trials.gov ] . ) We compared the efficacy of three antibiotics ( ceftriaxone , erythromycin and clarithromycin ) against Borrelia garinii infection in mice . The nymphal ticks of Ixodes persulcatus infected with the strain JEM6 of Japanese B. garinii were allowed to feed on female C3H mice . The mice were treated with each of the antibiotics for 5 consecutive days 1 , 3 , or 7 weeks after tick detachment . The doses of antibiotics per day were as follows : 5 mg intraperitoneal injection of ceftriaxone , 2 mg intraperitoneal injection of erythromycin and 1 mg peroral administration of clarithromycin . The infection status in treated mice was monitored by culturing their earlobes , hearts and urinary bladders in BSK II medium . Ceftriaxone eliminated borreliae completely ; however , a recurrence of infection was observed in mice treated with erythromycin and clarithromycin During 1980 and 1981 , we compared antibiotic regimens in 108 adult patients with early Lyme disease . Erythema chronicum migrans and its associated symptoms resolved faster in penicillin- or tetracycline-treated patients than in those given erythromycin ( mean duration , 5.4 and 5.7 versus 9.2 days , F = 3.38 , p less than 0.05 ) . None of 39 patients given tetracycline developed major late complications ( meningoencephalitis , myocarditis , or recurrent attacks of arthritis ) compared with 3 of 40 penicillin-treated patients and 4 of 29 given erythromycin ( chi square with 2 degrees of freedom = 5.33 , p = 0.07 ) . In 1982 , all 49 adult patients were given tetracycline ; again , none of them developed major complications . However , with all three antibiotic agents nearly half of the patients had minor late symptoms such as headache , musculoskeletal pain , and lethargy . These complications correlated significantly with the initial severity of illness . For patients with early Lyme disease , tetracycline appears to be the most effective drug , then penicillin , and finally erythromycin Summary A study on prevention of borreliosis in humans bitten by infected ticks was performed in 1992–1994 in the Perm ' region of Russia . AdultIxodes persulcatus ticks were removed from the study subjects , and live preparations made from the material obtained from the gut of each tick were microscopically analyzed ( up to 250 microscopic fields per preparation ) . Persons were divided into experimental and control groups ( 261 and 97 persons , respectively ) . The experimental group received doxycycline ( 100 mg twice daily ) for 3–5 days after the tick bite . In the control ( untreated ) group , 12 persons contracted borreliosis . In the experimental group , the disease was diagnosed in three subjects . Morbidity per 100 patients in the experimental group was 1.1 , i.e. 11 times lower than that in the control group . Identification ofBorrelia in ticks by microscopic analysis , followed by a short-term treatment with antibiotics according to microbiological indications , is an efficient method for preventing persons from contracting borreliosis . ZusammenfassungIn der Perm-Region , Rußl and , wurde von 1992–1994 eine Studie bei Personen , die von borrelieninfizierten Zecken gestochen worden waren , durchgeführt . Erwachsene Zecken der SpeziesIxodes persulcatus wurden abgenommen und nach Sektion auf Anwesenheit von Borrelien i m Darm mikroskopisch untersucht ( bis zu 250 Gesichtsfelder pro Präparat wurden untersucht ) . In der experimentellen Gruppe waren 261 und in der Kontrollgruppe 97 Personen eingeschlossen . Die experimentelle Gruppe erhielt eine Therapie mit 100 mg Doxycyclin zweimal täglich für 3–5 Tage nach dem Zeckenstich . In der unbeh and elten Kontrollgruppe zogen sich 12 Personen eine Borrelieninfektion zu . In der experimentellen Gruppe wurde bei drei Personen eine Borreliose diagnostiziert . Die Morbidität war in der beh and elten Gruppe mit 1,1/100 11 mal geringer als in der Kontrollgruppe . Identifizierung von Borrelien in den Zecken unter dem Mikroskop und kurzzeitige Antibiotikabeh and lung entsprechend dem mikroskopischen Befund erwies sich als effiziente Method e , um nach Zeckenstick eine Borrelia-Infektion zu verhüten Etude des mesures de prevention et du traitement au cours d'une etude faite dans le BACKGROUND Borrelia burgdorferi , which causes Lyme disease , is transmitted by deer ticks ( lxodes dammini ) in the northeastern and midwestern United States . Although deer-tick bites are common in areas in which the disease is endemic , there is uncertainty about how to manage the care of persons who are bitten . METHODS To assess the risk of infection with B. burgdorferi and the efficacy of prophylactic antimicrobial treatment after a deer-tick bite , we conducted a double-blind , placebo-controlled trial in an area of southeastern Connecticut in which Lyme disease is endemic . Children and adults who had been bitten by deer ticks were r and omly assigned to receive either amoxicillin or placebo for 10 days . Subjects were followed for one year for clinical manifestations of Lyme disease . Serum sample s obtained at enrollment and six weeks and three months later were tested for antibodies against B. burgdorferi . RESULTS Of the 387 subjects , 205 ( 53 percent ) were assigned to receive amoxicillin and 182 ( 47 percent ) to receive placebo . Of 344 deer ticks su bmi tted and analyzed by the polymerase chain reaction , 15 percent were infected with B. burgdorferi . Erythema migrans developed in two subjects , both of whom had received placebo . There were no asymptomatic seroconversions and no late manifestations of Lyme disease . The risk of infection with B. burgdorferi in the placebo-treated subjects was 1.2 percent ( 95 percent confidence interval , 0.1 to 4.1 percent ) , which was not significantly different ( P = 0.22 ) from the risk in the amoxicillin-treated subjects ( 0 percent ; 95 percent confidence interval , 0 to 1.5 percent ) . CONCLUSIONS Even in an area in which Lyme disease is endemic , the risk of infection with B. burgdorferi after a recognized deer-tick bite is so low that prophylactic antimicrobial treatment is not routinely indicated BACKGROUND It is unclear whether antimicrobial treatment after an Ixodes scapularis tick bite will prevent Lyme disease . METHODS In an area of New York where Lyme disease is hyperendemic we conducted a r and omized , double-blind , placebo-controlled trial of treatment with a single 200-mg dose of doxycycline in 482 subjects who had removed attached I. scapularis ticks from their bodies within the previous 72 hours . At base line , three weeks , and six weeks , subjects were interviewed and examined , and serum antibody tests were performed , along with blood cultures for Borrelia burgdorferi . Entomologists confirmed the species of the ticks and classified them according to sex , stage , and degree of engorgement . RESULTS Erythema migrans developed at the site of the tick bite in a significantly smaller proportion of the subjects in the doxycycline group than of those in the placebo group ( 1 of 235 subjects [ 0.4 percent ] vs. 8 of 247 subjects [ 3.2 percent ] , P<0.04 ) . The efficacy of treatment was 87 percent ( 95 percent confidence interval , 25 to 98 percent ) . Objective extracutaneous signs of Lyme disease did not develop in any subject , and there were no asymptomatic seroconversions . Treatment with doxycycline was associated with more frequent adverse effects ( in 30.1 percent of subjects , as compared with 11.1 percent of those assigned to placebo ; P<0.001 ) , primarily nausea ( 15.4 percent vs. 2.6 percent ) and vomiting ( 5.8 percent vs. 1.3 percent ) . Erythema migrans developed more frequently after untreated bites from nymphal ticks than after bites from adult female ticks ( 8 of 142 bites [ 5.6 percent ] vs. 0 of 97 bites [ 0 percent ] , P=0.02 ) and particularly after bites from nymphal ticks that were at least partially engorged with blood ( 8 of 81 bites [ 9.9 percent ] , as compared with 0 of 59 bites from unfed , or flat , nymphal ticks [ 0 percent ] ; P=0.02 ) . CONCLUSIONS A single 200-mg dose of doxycycline given within 72 hours after an I. scapularis tick bite can prevent the development of Lyme disease |
11,990 | 26,237,632 | No clear advantage of MRI/US fusion-guided TBs was seen for cancer detection rates ( CDRs ) of all prostate cancers .
However , MRI/US fusion-guided TBs tended to give higher CDRs for clinical ly significant prostate cancers in our analysis .
Today , a limited number of prospect i ve studies have reported the CDRs of fusion platforms . | Despite limitations considering the presence , staging and aggressiveness of prostate cancer , ultrasonography (US)-guided systematic biopsies ( SBs ) are still the ' gold st and ard ' for the diagnosis of prostate cancer .
Recently , promising results have been published for targeted prostate biopsies ( TBs ) using magnetic resonance imaging ( MRI ) and ultrasonography (MRI/US)-fusion platforms .
Different platforms are USA Food and Drug Administration registered and have , mostly subjective , strengths and weaknesses .
To our knowledge , no systematic review exists that objective ly compares prostate cancer detection rates between the different platforms available .
To assess the value of the different MRI/US-fusion platforms in prostate cancer detection , we compared platform-guided TB with SB , and other ways of MRI TB ( cognitive fusion or in-bore MR fusion ) . | BACKGROUND Increasing evidence supports the use of magnetic resonance (MR)-targeted prostate biopsy . The optimal method for such biopsy remains undefined , however . OBJECTIVE To prospect ively compare targeted biopsy outcomes between MR imaging (MRI)-ultrasound fusion and visual targeting . DESIGN , SETTING , AND PARTICIPANTS From June 2012 to March 2013 , prospect i ve targeted biopsy was performed in 125 consecutive men with suspicious regions identified on prebiopsy 3-T MRI consisting of T2-weighted , diffusion-weighted , and dynamic-contrast enhanced sequences . INTERVENTION Two MRI-ultrasound fusion targeted cores per target were performed by one operator using the ei-Nav|Artemis system . Targets were then blinded , and a second operator took two visually targeted cores and a 12-core biopsy . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Biopsy information yield was compared between targeting techniques and to 12-core biopsy . Results were analyzed using the McNemar test . Multivariate analysis was performed using binomial logistic regression . RESULTS AND LIMITATIONS Among 172 targets , fusion biopsy detected 55 ( 32.0 % ) cancers and 35 ( 20.3 % ) Gleason sum ≥7 cancers compared with 46 ( 26.7 % ) and 26 ( 15.1 % ) , respectively , using visual targeting ( p=0.1374 , p=0.0523 ) . Fusion biopsy provided informative nonbenign histology in 77 targets compared with 60 by visual ( p=0.0104 ) . Targeted biopsy detected 75.0 % of all clinical ly significant cancers and 86.4 % of Gleason sum ≥7 cancers detected on st and ard biopsy . On multivariate analysis , fusion performed best among smaller targets . The study is limited by lack of comparison with whole-gl and specimens and sample size . Furthermore , cancer detection on visual targeting is likely higher than in community setting s , where experience with this technique may be limited . CONCLUSIONS Fusion biopsy was more often histologically informative than visual targeting but did not increase cancer detection . A trend toward increased detection with fusion biopsy was observed across all study subsets , suggesting a need for a larger study size . Fusion targeting improved accuracy for smaller lesions . Its use may reduce the learning curve necessary for visual targeting and improve community adoption of MR-targeted biopsy PURPOSE We compared the accuracy of visual targeted biopsies vs computerized transrectal ultrasound-magnetic resonance imaging registration using a rigid ( Esaote ® , nondeformable ) or elastic ( Koelis ® , deformable ) approach . MATERIAL S AND METHODS A total of 391 consecutive patients with suspected localized prostate cancer were prospect ively included in analysis . All patients underwent prostate magnetic resonance imaging , followed by 10 to 12-core r and om prostate biopsies . When magnetic resonance imaging detected suspicious findings , targeted biopsy was performed , including visual , rigid system and elastic system targeted biopsies in the first 127 patients , the next 131 and the last 133 , respectively . Cancer detection rates were assessed by conditional logistic regression . Targeted biopsies alone and r and om biopsies were further compared for the amount of tissue sample d and microfocal cancer detection , the latter defined as a single core with 5 mm or less of Gleason 6 cancer . RESULTS Patient characteristics and r and om biopsy detection rates were similar among the groups . Magnetic resonance imaging detected at least 1 suspicious area in 54 ( 42 % ) , 78 ( 59 % ) and 82 patients ( 62 % ) in groups 1 , 2 and 3 , respectively . The cancer detection rates of rigid and elastic system targeted biopsies were significantly higher than the r and om biopsy rate ( p = 0.0065 and 0.0016 , respectively ) . Visual targeted biopsy did not perform better than r and om biopsy ( p = 0.66 ) . Rigid and elastic system targeted biopsies allowed for decreasing the number of cores and the detection of microfocal cancer , while increasing the detection of high grade cancer . CONCLUSIONS When performed with computerized magnetic resonance imaging-transrectal ultrasound image registration , targeted biopsy alone improved cancer detection over r and om biopsies , decreased the detection rate of microfocal cancer and increased the detection rate of cancer with a Gleason score of greater than 6 IMPORTANCE Targeted magnetic resonance (MR)/ultrasound fusion prostate biopsy has been shown to detect prostate cancer . The implication s of targeted biopsy alone vs st and ard extended-sextant biopsy or the 2 modalities combined are not well understood . OBJECTIVE To assess targeted vs st and ard biopsy and the 2 approaches combined for the diagnosis of intermediate- to high-risk prostate cancer . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1003 men undergoing both targeted and st and ard biopsy concurrently from 2007 through 2014 at the National Cancer Institute in the United States . Patients were referred for elevated level of prostate-specific antigen ( PSA ) or abnormal digital rectal examination results , often with prior negative biopsy results . Risk categorization was compared among targeted and st and ard biopsy and , when available , whole-gl and pathology after prostatectomy as the " gold st and ard . " INTERVENTIONS Patients underwent multiparametric prostate magnetic resonance imaging to identify regions of prostate cancer suspicion followed by targeted MR/ultrasound fusion biopsy and concurrent st and ard biopsy . MAIN OUTCOMES AND MEASURES The primary objective was to compare targeted and st and ard biopsy approaches for detection of high-risk prostate cancer ( Gleason score ≥ 4 + 3 ) ; secondary end points focused on detection of low-risk prostate cancer ( Gleason score 3 + 3 or low-volume 3 + 4 ) and the biopsy ability to predict whole-gl and pathology at prostatectomy . RESULTS Targeted MR/ultrasound fusion biopsy diagnosed 461 prostate cancer cases , and st and ard biopsy diagnosed 469 cases . There was exact agreement between targeted and st and ard biopsy in 690 men ( 69 % ) undergoing biopsy . Targeted biopsy diagnosed 30 % more high-risk cancers vs st and ard biopsy ( 173 vs 122 cases , P < .001 ) and 17 % fewer low-risk cancers ( 213 vs 258 cases , P < .001 ) . When st and ard biopsy cores were combined with the targeted approach , an additional 103 cases ( 22 % ) of mostly low-risk prostate cancer were diagnosed ( 83 % low risk , 12 % intermediate risk , and 5 % high risk ) . The predictive ability of targeted biopsy for differentiating low-risk from intermediate- and high-risk disease in 170 men with whole-gl and pathology after prostatectomy was greater than that of st and ard biopsy or the 2 approaches combined ( area under the curve , 0.73 , 0.59 , and 0.67 , respectively ; P < .05 for all comparisons ) . CONCLUSIONS AND RELEVANCE Among men undergoing biopsy for suspected prostate cancer , targeted MR/ultrasound fusion biopsy , compared with st and ard extended-sextant ultrasound-guided biopsy , was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer . Future studies will be needed to assess the ultimate clinical implication s of targeted biopsy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00102544 PURPOSE Given the limitations of prostate specific antigen and st and ard biopsies for detecting prostate cancer , we evaluated the cancer detection rate and external validity of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system used at the National Institutes of Health . MATERIAL S AND METHODS We performed a phase III trial of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system with participants enrolled between 2012 and 2013 . A total of 153 men consented to the study and underwent 3 Tesla multiparametric magnetic resonance imaging with an endorectal coil for clinical suspicion of prostate cancer . Lesions were classified as low or moderate/high risk for prostate cancer . Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and st and ard 12-core prostate biopsy were performed and 105 men were eligible for analysis . RESULTS Mean patient age was 65.8 years and mean prostate specific antigen was 9.5 ng/ml . The overall cancer detection rate was 62.9 % ( 66 of 105 patients ) . The cancer detection rate in those with moderate/high risk on imaging was 72.3 % ( 47 of 65 ) vs 47.5 % ( 19 of 40 ) in those classified as low risk for prostate cancer ( p<0.05 ) . Mean tumor core length was 4.6 and 3.7 mm for fusion biopsy and st and ard 12-core biopsy , respectively ( p<0.05 ) . Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detected prostate cancer that was missed by st and ard 12-core biopsy in 14.3 % of cases ( 15 of 105 ) , of which 86.7 % ( 13 of 15 ) were clinical ly significant . This biopsy up grade d 23.5 % of cancers ( 4 of 17 ) deemed clinical ly insignificant on 12-core biopsy to clinical ly significant prostate cancer necessitating treatment . CONCLUSIONS Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy can improve prostate cancer detection . The results of this trial support the external validity of this platform and may be the next step in the evolution of prostate cancer management PURPOSE We evaluated biochemical parameters and pathological features , as well as biopsy related morbidity of prostate cancer detected on biopsies 2 , 3 and 4 in men with total serum prostate specific antigen ( PSA ) between 4 and 10 ng./ml . These features were compared to those detected on prostate biopsy 1 . MATERIAL S AND METHODS In this prospect i ve European Prostate Cancer Detection study 1,051 men with total PSA between 4 and 10 ng./ml . underwent transrectal ultrasound guided sextant biopsy and 2 additional transition zone biopsies . All patients in whom biopsy sample s were negative for prostate cancer underwent biopsy 2 after 6 weeks . If also negative , biopsies 3 and even 4 were performed at 8-week intervals . Those patients with clinical ly localized cancer underwent radical prostatectomy . Pathological and clinical features of patients diagnosed with cancer on either biopsy 1 or 2 and clinical ly organ confined disease who agreed to undergo radical prostatectomy were compared . RESULTS Cancer detection rates on biopsies 1 , 2 , 3 and 4 were 22 % ( 231 of 1,051 ) , 10 % ( 83 of 820 ) , 5 % ( 36 of 737 ) and 4 % ( 4 of 94 ) , respectively . Overall , of the patients with clinical ly localized disease , which was 67 % of cancers detected , 86 % underwent radical prostatectomy and 14 % opted for watchful waiting or radiation therapy . Overall , 58.0 % , 60.9 % , 86.3 % and 100 % of patients had organ confined disease on biopsies 1 , 2 , 3 and 4 , respectively . Despite statistically significant differences in regard to multifocality ( p = 0.009 ) and cancer location ( p = 0.001 ) , including cancer on biopsy 2 showing a lower rate of multifocality and a more apico-dorsal location , there were no differences in regard to stage ( p = 0.2 ) , Gleason score ( p = 0.3 ) , percent Gleason grade 4/5 ( p = 0.2 ) , serum PSA and patient age between biopsies 1 and 2 . However , cancer detected on biopsies 3 and 4 had a significantly lower Gleason score ( p = 0.001 and 0.001 ) , lower rate of grade 4/5 ( p = 0.02 ) , and lower volume ( p = 0.001 and 0.001 ) and stage ( p = 0.001 ) , respectively . CONCLUSIONS Despite differences in location and multifocality , pathological and biochemical features of cancer detected on biopsies 1 and 2 were similar , suggesting comparable biological behaviors . Cancer detected on biopsies 3 and 4 had a lower grade , stage and volume compared with that on biopsies 1 and 2 . Morbidity on biopsies 1 and 2 was similar , whereas biopsies 3 and 4 had a slightly higher complication rate . Therefore , biopsy 2 in all cases of a negative finding on biopsy 1 appears justified . However , biopsies 3 and 4 should only be obtained in select patients with a high suspicion of cancer and /or poor prognostic factors on biopsy 1 or 2 Purpose : To evaluate multiparametric magnetic resonance imaging/transrectal ultrasound ( mpMRI/TRUS ) fusion targeted biopsy ( TB ) of the prostate for prostate cancer ( PCa ) diagnosis . Patients and Methods : From April 2013 to January 2014 , 53 men were included in this prospect i ve single-centre study . The degree of PCa suspicion from mpMRI findings was classified according to the PI-RADS scoring system . Of these , 50 patients underwent both an mpMRI/TRUS fusion TB and a 10-core systematic biopsy ( SB ) of the prostate and were eligible for analysis . Results : 225 targeted and 500 systematic cores were included in this study . PCa was histologically confirmed in 52.0 % of patients ( 26/50 ) , whereas TB revealed PCa in 46.0 % ( 23/50 ) and SB in 36.0 % ( 18/50 ) . TB identified PCa in 16.0 % of all patients ( 8/50 ) that were missed by SB . All told , the targeted core was 2.8 times more likely to be PCa-positive than the systematic core ( 29.3 vs. 10.4 % ) . Conclusions : mpMRI/TRUS fusion TB of the prostate is safe , practicable and may improve PCa diagnosis using fewer biopsy cores compared to SB PURPOSE Diagnosis and precise risk stratification of prostate cancer is essential for individualized treatment decisions . Magnetic resonance imaging/transrectal ultrasound fusion has shown encouraging results for detecting clinical ly significant prostate cancer . We critically evaluated magnetic resonance imaging targeted , transrectal ultrasound guided transperineal fusion biopsy in routine clinical practice . MATERIAL S AND METHODS Included in this prospect i ve study were 347 consecutive patients with findings suspicious for prostate cancer . Median age was 65 years ( range 42 to 84 ) and mean prostate specific antigen was 9.85 ng/ml ( range 0.5 to 104 ) . Of the men 49 % previously underwent transrectal ultrasound guided biopsies , which were negative , and 51 % underwent primary biopsy . In all patients 3 Tesla multiparametric magnetic resonance imaging was done . Systematic stereotactic prostate biopsies plus magnetic resonance imaging targeted , transrectal ultrasound guided biopsies were performed in those with abnormalities on magnetic resonance imaging . Imaging data and biopsy results were analyzed . A self- design ed question naire was sent to all men on further clinical history and biopsy adverse effects . RESULTS Of 347 patients biopsy sample s of 200 ( 58 % ) showed prostate cancer and 73.5 % of biopsy proven prostate cancer were clinical ly relevant according to National Comprehensive Cancer Network ( NCCN ) criteria . On multiparametric magnetic resonance imaging 104 men had findings highly suspicious for prostate cancer . The tumor detection rate was 82.6 % ( 86 of 104 men ) with a Gleason score of 7 or greater in 72 % . Overall targeted cores detected significantly more cancer than systematic biopsies ( 30 % vs 8.2 % ) . Of 94 patients without cancer suspicious lesions on magnetic resonance imaging 11 ( 11.7 % ) were diagnosed with intermediate risk disease . Regarding adverse effects , 152 of 300 patients ( 50.6 % ) reported mild hematuria , 26 % had temporary erectile dysfunction and 2.6 % needed short-term catheterization after biopsy . Nonseptic febrile urinary tract infections developed in 3 patients ( 1 % ) . CONCLUSIONS Magnetic resonance imaging targeted , transrectal ultrasound guided transperineal fusion biopsy provides high detection of clinical ly significant tumors . Since multiparametric magnetic resonance imaging still has some limitations , systematic biopsies should currently not be omitted . The morbidity of the transperineal saturation approach is reasonable and mainly self-limiting The diagnosis of prostatic carcinoma is most commonly made today by transrectal ultrasound guided needle biopsy . Often hypoechoic and peripheral zone lesions are the only areas sample d. Recently , we showed that this approach missed a quarter of the cancers that would be detected by a systematic biopsy technique . We term these missed cancers isoechoic carcinomas . We review ed 1,549 systematic sextant prostate needle biopsies , of which 417 cancers were detected and subdivided into hypoechoic cancers ( cancers detected on biopsy of a hypoechoic sector and isoechoic cancers ( cancers found only in normal [ isoechoic ] peripheral zone ) . We noted in men with only isoechoic cancers that fewer biopsy cores per prostate revealed cancer ( mean 1.6 versus 3.0 , p < 0.0001 ) and that these men had lower serum prostate specific antigen levels ( mean 14.4 versus 43.7 , p < 0.001 ) . The Gleason scores for the isoechoic and hypoechoic cancers were indistinguishable . The pathological staging of hypoechoic and isoechoic cancers was also similar . This study suggests that while isoechoic cancers are generally smaller than hypoechoic cancers , they do not represent low grade clinical ly insignificant carcinomas . A systematic approach to performing prostate biopsy is recommended OBJECTIVES To report our early experience with manually controlled targeted biopsy with real-time multiparametric magnetic resonance imaging and transrectal ultrasound fusion images for the diagnosis of prostate cancer . METHODS A total of 20 consecutive patients suspicious of prostate cancer at the multiparametric magnetic resonance imaging scan were recruited prospect ively . Targeted biopsies were carried out for each cancer-suspicious lesion , and 12 systematic biopsies using the BioJet system . Pathological findings of targeted and systematic biopsies were analyzed . RESULTS The median age of the patients was 70 years ( range 52 - 83 years ) . The median preoperative prostate-specific antigen value was 7.4 ng/mL ( range 3.54 - 19.9 ng/mL ) . Median preoperative prostate volume was 38 mL ( range 24 - 68 mL ) . The number of cancer-detected cases was 14 ( 70 % ) . The median Gleason score was 6.5 ( range 6 - 8 ) . Cancer-detected rates of the systematic and targeted biopsy cores were 6.7 and 31.8 % , respectively ( P < 0.0001 ) . In six patients who underwent radical prostatectomy , the geographic locations and pathological grade s of clinical ly significant cancers and index lesions corresponded to the pathological results of the targeted biopsies . CONCLUSION Prostate cancers detected by targeted biopsies with manually controlled targeted biopsy using real-time multiparametric magnetic resonance imaging and transrectal ultrasound fusion imaging have significantly higher grade s and longer length compared with those detected by systematic biopsies . Further studies and comparison with the pathological findings of whole-gl and specimens have the potential to determine the role of this biopsy methodology in patients selected for focal therapy and those under active surveillance PURPOSE We identified histological differences between prostate cancer foci that are detected and missed using multiparametric magnetic resonance imaging . MATERIAL S AND METHODS A total of 49 patients who underwent multiparametric magnetic resonance imaging , including T2-weighted imaging , including diffusion weighted imaging and dynamic contrast enhanced imaging , before prostatectomy were enrolled in the study . One radiologist identified areas highly suspicious for tumor . One pathologist identified and categorized tumors in terms of size , Gleason score , solid tumor growth , intermixed benign gl and s , loose stroma , desmoplastic stroma and a high malignant epithelium-to-stroma ratio . Differences between detected and missed tumors were assessed using logistic regression analyses based on generalized estimating equations for correlated data . RESULTS All histological features showed significant differences between detected and missed tumors on multiparametric magnetic resonance imaging ( p<0.0001 ) . Independent predictors of detection on multivariate analysis were size ( OR 5.38 , p=0.0077 ) , Gleason score ( OR 5.12 , p=0.0094 ) and solid growth ( OR 17.83 , p<0.0001 ) . Size , Gleason score and loose stroma were significant predictors of identification with diffusion weighted imaging on univariate analysis ( p≤0.0245 ) , while Gleason score ( OR 17.05 , p=0.0212 ) and solid growth ( OR 34.90 , p=0.0103 ) were independent predictors of identification with diffusion weighted imaging on multivariate analysis . Identification with T2-weighted imaging was associated with size and Gleason score ( p≤0.01876 ) . Identification with dynamic contrast enhanced imaging was associated with intermixed benign epithelium , loose stroma and a high malignant epithelium-to-stroma ratio ( p≤0.0499 ) . No combination of features served as independent predictors on multivariate analysis for T2-weighted imaging or dynamic contrast enhanced imaging . CONCLUSIONS There are fundamental histological differences between detected and missed prostate tumors using magnetic resonance imaging . Insights into these differences may facilitate the prospect i ve role of magnetic resonance imaging in counseling and treatment selection for patients with prostate cancer OBJECTIVE To prove the feasibility and evaluate the initial clinical results of targeted prostate biopsies using the Urostation novel platform using magnetic resonance imaging (MRI)/transrectal ultrasound ( TRUS ) registration to help steer the biopsy needle to suspicious areas . METHODS We prospect ively included 30 patients for suspicion of prostate cancer from November 2011 to August 2012 . All patients were previously evaluated by a multiparametric MRI , interpreted by a single radiologist who attributed a Prostate Imaging-Reporting and Data System ( PI-RADS ) score to each lesion . A conventional 12-core r and omized biopsy protocol was performed and 2 additional targeted biopsies were performed on suspicious area(s ) . The results of r and omized and targeted biopsies were compared . RESULTS Among the 30 patients , suspicious area(s ) were found on MRI in 20 cases ( 67 % ) . Median procedure time was 23 minutes . Targeting success rate ( biopsy visualized inside the target ) was 83 % , with at least 1 biopsy reaching the target in all cases . Prostate cancer was detected in 14 cases ( 47 % ) , including 11 cases with an abnormal MRI . Targeted biopsies detected cancer in all 11 cases and all but 1 were clinical ly significant . R and omized biopsies detected 10 of these 11 cases , and 3 more cases that MRI considered normal . Sensitivity to detect a significant cancer was 91 % in both modalities . CONCLUSION This initial clinical study showed encouraging results for targeted MRI-guided prostate biopsies using MRI-TRUS fusion . Although further studies are needed to determine the role of prostate MRI before biopsy and the relevance of targeted biopsies , the Urostation is an MRI-TRUS fusion device that has good accuracy for targeting suspicious areas on MRI |
11,991 | 31,765,002 | Based on our four pre-selected comparisons of interest , continuous treatment with VRD had the largest survival benefit compared with MP , while RD and TMP also probably considerably increase survival .
However , treatment combinations of V , R , and T also substantially increase the incidence of AEs , and lead to a higher risk of treatment discontinuation . | BACKGROUND Multiple myeloma is a bone marrow-based hematological malignancy accounting for approximately two per cent of cancers .
First-line treatment for transplant-ineligible individuals consists of multiple drug combinations of bortezomib ( V ) , lenalidomide ( R ) , or thalidomide ( T ) .
However , access to these medicines is restricted in many countries worldwide .
OBJECTIVES To assess and compare the effectiveness and safety of multiple drug combinations of V , R , and T for adults with newly diagnosed transplant-ineligible multiple myeloma and to inform an application for the inclusion of these medicines into the World Health Organization 's ( WHO ) list of essential medicines . | Abstract In the MM-015 trial , melphalan – prednisone – lenalidomide followed by lenalidomide maintenance ( MPR-R ) significantly prolonged progression-free survival versus melphalan – prednisone ( MP ) in newly diagnosed patients with multiple myeloma aged ≥ 65 years . Health-related quality of life ( HRQoL ) , a secondary endpoint of MM-015 , was also improved with MPR-R. This sub- analysis evaluated the impact of individual predictive factors on HRQoL. Patients completed HRQoL question naires at baseline , every third cycle and at progressive disease (PD)/treatment discontinuation . In a mixed-effects model female gender , advanced age and PD negatively affected HRQoL while better treatment responses showed positive effects . Compared to PD , HRQoL during MPR-R treatment was statistically significantly better in two of six preselected domains both of which were also clinical ly meaningful . HRQoL scores at end of treatment were all either improved or not statistically significantly different versus baseline . In conclusion , continuous treatment with MPR-R , which delays PD , appears to be associated with clinical ly meaningful improvements in We have carried out the largest r and omised trial to date of newly diagnosed myeloma patients , in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy ( SPM ) incidence and pathology . After review , 104 SPMs were confirmed in 96 of 2732 trial patients . The cumulative incidence of SPM was 0.7 % ( 95 % confidence interval ( CI ) 0.4–1.0 % ) , 2.3 % ( 95 % CI 1.6–2.7 % ) and 3.8 % ( 95 % CI 2.9–4.6 % ) at 1 , 2 and 3 years , respectively . Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall ( P=0.011 ) . Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged > 74 years receiving lenalidomide maintenance . The 3-year cumulative incidence in this group was 17.3 % ( 95 % CI 8.2–26.4 % ) , compared with 6.5 % ( 95 % CI 0.2–12.9 % ) in observation only patients ( P=0.049 ) . There was a low overall incidence of haematological SPM ( 0.5 % ) . The higher SPM incidence in patients receiving lenalidomide maintenance therapy , especially in advanced age , warrants ongoing monitoring although the benefit on survival is likely to outweigh risk We compared thalidomide-dexamethasone ( TD ) with melphalan-prednisolone ( MP ) in 289 elderly patients with multiple myeloma ( MM ) . Patients received either thalidomide 200 mg plus dexamethasone 40 mg , days 1 to 4 and 15 to 18 on even cycles and days 1 to 4 on odd cycles , during a 28-day cycle or to melphalan 0.25 mg/kg and prednisolone 2 mg/kg orally on days 1 to 4 during a 28- to 42-day cycle . Patients achieving stable disease or better were r and omly assigned to maintenance therapy with either thalidomide 100 mg daily and 3 MU interferon alpha-2b thrice weekly or to 3 MU interferon alpha-2b thrice weekly only . TD result ed in a higher proportion of complete and very good remissions ( 26 % vs 13 % ; P= .006 ) and overall responses ( 68 % vs 50 % ; P= .002 ) compared with MP . Time to progression ( 21.2 vs 29.1 months ; P= .2 ) , and progression-free survival was similar ( 16.7 vs 20.7 months ; P= .1 ) , but overall survival was significantly shorter in the TD group ( 41.5 vs 49.4 months ; P= .024 ) . Toxicity was higher with TD , particularly in patients older than 75 years with poor performance status . The study was registered at Clinical Trials.gov as NCT00205751 Because interleukin-6 ( IL-6 ) is considered important in the proliferation of early multiple myeloma ( MM ) , we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone ( VMP ) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM . One hundred and six patients were r and omized to receive 9 cycles of VMP or VMP plus siltuximab ( 11 mg/kg every 3 weeks ) followed by siltuximab maintenance . Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions . With a complete response ( CR ) rate of 27 % on siltuximab plus VMP ( S+VMP ) and 22 % on VMP , the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10 % . Overall response rate was 88 % on S+VMP and 80 % on VMP , and at least very good partial response rates were 71 % and 51 % ( P = .0382 ) , respectively . Median progression-free survival ( 17 months ) and 1-year overall survival ( 88 % ) were identical in the 2 arms . Grade ≥3 adverse-event incidence was 92 % on S+VMP and 81 % on VMP ( P = .09 ) , with trends toward more hematologic events and infections on S+VMP . Maintenance therapy with siltuximab was well tolerated . In conclusion , the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes . This study was registered at http:// clinical trials.gov as # NCT00911859 Oral melphalan and prednisone remain an effective and tolerable treatment for patients with multiple myeloma . For approximately 40 years , this combination has been the st and ard of care for patients not proceeding to stem cell transplant . Within the last 10 years , new agents have been found to be efficacious in the relapsed/refractory setting . Within the last year , two trials of added thalidomide in the newly diagnosed setting have demonstrated outcomes superior to those achieved with melphalan and prednisone alone . This improved outcome comes at the cost of increased toxicity . The National Cancer Institute of Canada Clinical Trials Group ( ncic ctg ) has recently developed a r and omized phase ii trial ( MY.11 ) that uses a combination of lenalidomide with melphalan for patients with newly diagnosed multiple myeloma . Lenalidomide is a thalidomide analogue and , like thalidomide , is thought to work through immunomodulatory effects . It was shown to have activity in patients with relapsed or refractory disease and , in combination with dexamethasone , is superior to dexamethasone alone . Lenalidomide holds promise as a more effective and potentially less toxic derivative of thalidomide . Experience with lenalidomide in combination with chemotherapy is very limited , and the purpose of MY.11 is to establish tolerability and to gain knowledge about efficacy . The information gained from MY.11 is expected to help inform dosing levels and schedules for a large phase iii trial being developed by the Eastern Cooperative Oncology Group that will include participation by the ncic ctg Purpose This analysis of the FIRST trial in patients with newly diagnosed multiple myeloma ( MM ) ineligible for stem-cell transplantation examined up date d outcomes and impact of patient age . Patients and Methods Patients with untreated symptomatic MM were r and omly assigned at a one-to-one-to-one ratio to lenalidomide plus low-dose dexamethasone until disease progression ( Rd continuous ) , Rd for 72 weeks ( 18 cycles ; Rd18 ) , or melphalan , prednisone , and thalidomide ( MPT ; 72 weeks ) , stratified by age ( ≤ 75 v > 75 years ) , disease stage ( International Staging System stage I/II v III ) , and country . The primary end point was progression-free survival . Rd continuous and MPT were primary comparators . Results Between August 21 , 2008 , and March 7 , 2011 , 1,623 patients were enrolled ( Rd continuous , n = 535 ; Rd18 , n = 541 ; MPT , n = 547 ) , including 567 ( 35 % ) age older than 75 years . Higher rates of advanced-stage disease and renal impairment were observed in patients older than 75 versus 75 years of age or younger . Rd continuous reduced the risk of progression or death compared with MPT by 31 % ( hazard ratio [ HR ] , 0.69 ; 95 % CI , 0.59 to 0.80 ; P < .001 ) overall , 36 % ( HR , 0.64 ; 95 % CI , 0.53 to 0.77 ; P < .001 ) in patients age 75 years or younger , and 20 % ( HR , 0.80 ; 95 % CI , 0.62 to 1.03 ; P = .084 ) in those age older than 75 years . Median overall survival was longer with Rd continuous than with MPT , including a 14-month difference in patients age older than 75 years . Progression-free survival with Rd18 was similar to that with MPT , and overall survival with Rd18 was marginally inferior to that with Rd continuous . Rates of grade 3 to 4 treatment-emergent adverse events were similar for Rd continuous-treated patients age 75 years or older and those age older than 75 years ; however , older patients had more frequent lenalidomide dose reductions . Conclusion Results support Rd continuous treatment as a new st and ard of care for stem-cell transplantation-ineligible patients with newly diagnosed MM of all ages Bortezomib plus melphalan and prednisone ( VMP ) and lenalidomide plus low-dose dexamethasone ( Rd ) are 2 st and ards of care for elderly untreated multiple myeloma ( MM ) patients . We planned to use VMP and Rd for 18 cycles in a sequential or alternating scheme . Patients ( 233 ) with untreated MM , > 65 years , were r and omized to receive 9 cycles of VMP followed by 9 cycles of Rd ( sequential scheme ; n = 118 ) vs 1 cycle of VMP followed by 1 cycle of Rd , and so on , up to 18 cycles ( alternating scheme ; n = 115 ) . VMP consisted of one 6-week cycle of bortezomib using a biweekly schedule , followed by eight 5-week cycles of once-weekly VMP . Rd included nine 4-week cycles of Rd . The primary end points were 18-month progression free survival ( PFS ) and safety profile of both schemes . The 18-month PFS was 74 % and 80 % in the sequential and alternating arms , respectively ( P = .21 ) . The sequential and alternating groups exhibited similar hematologic and nonhematologic toxicity . Both arms yielded similar complete response rate ( 42 % and 40 % ) , median PFS ( 32 months vs 34 months , P = .65 ) , and 3-year overall survival ( 72 % vs 74 % , P = .63 ) . The benefit of both schemes was remarkable in patients aged 65 to 75 years . In addition , achieving complete and immunophenotypic response was associated with better outcome . The present approach , based on VMP and Rd , is associated with high efficacy and acceptable toxicity profile with no differences between the sequential and alternating regimens . This trial was registered at www . clinical trials.gov as # NCT00443235 Thalidomide with melphalan/prednisone ( MPT ) was defined as st and ard treatment in elderly patients with multiple myeloma ( MM ) based on five r and omized trials . In one of these trials , HOVON49 , a prospect i ve health-related quality -of-life ( HRQoL ) study was initiated in order to assess the impact of thalidomide on QoL. Patients aged > 65 years with newly diagnosed MM were r and omized to receive melphalan plus prednisone ( MP ) or MPT , followed by thalidomide maintenance in the MPT arm . Two hundred eighty-four patients were included in this side study ( MP , n = 149 ; MPT n = 135 ) . HRQoL was assessed with the EORTC Core QoL Question naire ( QLQ-C30 ) and the myeloma-specific module ( QLQ-MY24 ) at baseline and at predetermined intervals during treatment . The QLQ-C30 subscales physical function ( P = 0.044 ) and constipation ( P < 0.001 ) showed an improvement during induction in favour of the MP arm . During thalidomide maintenance , the scores for the QLQ-MY24 paraesthesia became significantly higher in the MPT arm ( P<0.001 ) . The QLQ-C30 subscales pain ( P = 0.12 ) , insomnia ( P = 0.068 ) , appetite loss ( P = 0.074 ) and the QLQ-MY24 item sick ( P = 0.086 ) scored marginally better during thalidomide maintenance . The overall QoL-scale QLQ-C30-HRQoL showed a significant time trend towards more favourable mean values during protocol treatment without differences between MP and MPT . For the QLQ-C30 subscales emotional function and future perspectives , difference in favour of the MPT arm from the start of treatment was observed ( P = 0.018 and P = 0.045 , respectively ) with no significant ‘ time × arm ’ interaction , indicating a persistent better patient perspective with MPT treatment . This study shows that the higher frequency of toxicity associated with MPT does not translate into a negative effect on HRQoL and that MPT holds a better patient perspective We assessed efficacy , safety , and reversal of renal impairment ( RI ) in untreated patients with multiple myeloma given bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide ( VMPT-VT ) maintenance or bortezomib-melphalan-prednisone ( VMP ) . Exclusion criteria included serum creatinine ≥ 2.5 mg/dL. In the VMPT-VT/VMP arms , severe RI ( estimated glomerular filtration rate [ eGFR ] ≤ 30 mL/min ) , moderate RI ( eGFR 31 - 50 mL/min ) , and normal renal function ( eGFR > 50 mL/min ) , were 6%/7.9 % , 24.1%/24.9 % , and 69.8%/67.2 % , respectively . Statistically significant improvements in overall response rates and progression-free survival were observed in VMPT-VT versus VMP arms across renal cohorts , except in severe RI patients . In the VMPT group , severe RI reduced overall survival ( OS ) . RI was reversed in 16/63 ( 25.4 % ) patients receiving VMPT-VT versus 31/77 ( 40.3 % ) receiving VMP . Multivariate analysis showed male sex ( P = .022 ) and moderate RI ( P = .003 ) significantly predicted RI recovery . VMP patients achieving renal response showed longer OS . In both arms , greater rates of severe hematologic adverse events were associated with RI ( eGFR < 50 mL/min ) , however , therapy discontinuation rates were unaffected . VMPT-VT was superior to VMP for cases with normal renal function and moderate RI , whereas VMPT-VT failed to outperform VMP in patients with severe RI , although the relatively low number of cases analyzed preclude drawing definitive conclusions . VMPT-VT had no advantage in terms of RI reversal over VMP The introduction of agents such as thalidomide , lenalidomide , and bortezomib has changed the management of patients with multiple myeloma who are not eligible for autologous transplantation , many of whom are elderly . We sought to compare three thalidomide-based oral regimens among such patients in Latin America . We r and omized patients with newly diagnosed multiple myeloma with measurable disease to one of the following regimens : melphalan , prednisone , and thalidomide ( MPT ) ; cyclophosphamide , thalidomide , and dexamethasone ( CTD ) ; and thalidomide and dexamethasone ( TD ) . The TD arm was closed prematurely and was analyzed only descriptively . The primary endpoint was the overall response rate ( ORR ) , whereas progression-free survival ( PFS ) and overall survival ( OS ) were secondary endpoints . The accrual rate was slower than expected , and the study was terminated after 82 patients had been r and omized . The ORRs were 67.9 % with MPT , 89.7 % with CTD , and 68.7 % with TD ( p = 0.056 for the comparison between MPT and CTD ) . The median PFS was 24.1 months for MPT , 25.9 months for CTD , and 21.5 months for TD . There were no statistically significant differences in PFS or OS between MPT and CTD . In an unplanned logistic regression analysis , ORR was significantly associated with treatment with CTD ( p = 0.046 ) and with performance status of 0 or 1 ( p = 0.035 ) . Based on the current results , no definitive recommendations can be made regarding the comparative merit of the regimens tested . Nevertheless and until the results of further studies become available , we recommend either CTD or MPT as suitable frontline regimens for patients with multiple myeloma who are not c and i date s to transplantation in setting s where lenalidomide and bortezomib are not available BACKGROUND In multiple myeloma , combination chemotherapy with melphalan plus prednisone is still regarded as the st and ard of care in elderly patients . We assessed whether the addition of thalidomide to this combination , or reduced-intensity stem cell transplantation , would improve survival . METHODS Between May 22 , 2000 , and Aug 8 , 2005 , 447 previously untreated patients with multiple myeloma , who were aged between 65 and 75 years , were r and omly assigned to receive either melphalan and prednisone ( MP ; n=196 ) , melphalan and prednisone plus thalidomide ( MPT ; n=125 ) , or reduced-intensity stem cell transplantation using melphalan 100 mg/m2 ( MEL100 ; n=126 ) . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00367185 . FINDINGS After a median follow-up of 51.5 months ( IQR 34.4 - 63.2 ) , median overall survival times were 33.2 months ( 13.8 - 54.8 ) for MP , 51.6 months ( 26.6-not reached ) for MPT , and 38.3 months ( 13.0 - 61.6 ) for MEL100 . The MPT regimen was associated with a significantly better overall survival than was the MP regimen ( hazard ratio 0.59 , 95 % CI 0.46 - 0.81 , p=0.0006 ) or MEL100 regimen ( 0.69 , 0.49 - 0.96 , p=0.027 ) . No difference was seen for MEL100 versus MP ( 0.86 , 0.65 - 1.15 , p=0.32 ) . INTERPRETATION The results of our trial provide strong evidence to indicate that the use of thalidomide in combination with melphalan and prednisone should , at present , be the reference treatment for previously untreated elderly patients with multiple myeloma BACKGROUND Since 1960 , oral melphalan and prednisone ( MP ) has been regarded as the st and ard of care in elderly multiple myeloma patients . This multicentre r and omised trial compared oral MP plus thalidomide ( MPT ) with MP alone in patients aged 60 - 85 years . METHODS Patients with newly diagnosed multiple myeloma were r and omly assigned to receive oral MP for six 4-week cycles plus thalidomide ( n=129 ; 100 mg per day continuously until any sign of relapse or progressive disease ) or MP alone ( n=126 ) . Analysis was intention-to-treat . This study is registered at , number NCT00232934 . RESULTS Patients treated with thalidomide had higher response rates and longer event-free survival ( primary endpoints ) than patients who were not . Combined complete or partial response rates were 76.0 % for MPT and 47.6 % for MP alone ( absolute difference 28.3 % , 95 % CI 16.5 - 39.1 ) , and the near-complete or complete response rates were 27.9 % and 7.2 % , respectively . 2-year event-free survival rates were 54 % for MPT and 27 % for MP ( hazard ratio [ HR ] for MPT 0.51 , 95 % CI 0.35 - 0.75 , p=0.0006 ) . 3-year survival rates were 80 % for MPT and 64 % for MP ( HR for MPT 0.68 , 95 % CI 0.38 - 1.22 , p=0.19 ) . Rates of grade 3 or 4 adverse events were 48 % in MPT patients and 25 % in MP patients ( p=0.0002 ) . Introduction of enoxaparin prophylaxis reduced rate of thromboembolism from 20 % to 3 % ( p=0.005 ) . CONCLUSION Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma . Anticoagulant prophylaxis reduces frequency of thrombosis . Longer follow-up is needed to assess effect on overall survival In this double-blind , placebo-controlled study , 363 patients with untreated multiple myeloma were r and omized to receive either melphalan-prednisone and thalidomide ( MPT ) or melphalan-prednisone and placebo ( MP ) . The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase . The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression . A total of 357 patients were analyzed . Partial response was 34 % and 33 % , and very good partial response or better was 23 % and 7 % in the MPT and MP arms , respectively ( P < .001 ) . There was no significant difference in progression-free or overall survival , with median survival being 29 months in the MPT arm and 32 months in the MP arm . Most quality of life outcomes improved equally in both arms , apart from constipation , which was markedly increased in the MPT arm . Constipation , neuropathy , nonneuropathy neurologic toxicity , and skin reactions were significantly more frequent in the MPT arm . The number of thromboembolic events was equal in the 2 treatment arms . In conclusion , MPT had a significant antimyeloma effect , but this did not translate into improved survival . This trial was registered at www . clinical trials.gov as # NCT00218855 We compared the health-related quality -of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal , phase III FIRST trial . Patients received : i ) continuous lenalidomide and low-dose dexamethasone until disease progression ; ii ) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months ; or iii ) fixed cycles of melphalan , prednisone , thalidomide for 18 months . Data were collected using the vali date d question naires ( QLQ-MY20 , QLQ-C30 , and EQ-5D ) . The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance . Lenalidomide and low-dose dexamethasone , and melphalan , prednisone , thalidomide improved patients ’ health-related quality -of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D . In the QLQ-MY20 , lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan , prednisone , thalidomide at Month 3 , and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessment s except Month 18 . Linear mixed-model repeated- measures analyses confirmed the results observed in the cross-sectional analysis . Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan , prednisone , thalidomide and has been associated with a clinical ly meaningful improvement in health-related quality -of-life . These results further establish continuous lenalidomide and low-dose dexamethasone as a new st and ard of care for initial therapy of myeloma by demonstrating superior health-related quality -of-life during treatment , compared with melphalan , prednisone , thalidomide Combinations of bortezomib ( V ) and dexamethasone ( D ) with either lenalidomide ( R ) or cyclophosphamide ( C ) have shown significant efficacy . This r and omized phase 2 trial evaluated VDC , VDR , and VDCR in previously untreated multiple myeloma ( MM ) . Patients received V 1.3 mg/m2 ( days 1 , 4 , 8 , 11 ) and D 40 mg ( days 1 , 8 , 15 ) , with either C 500 mg/m2 ( days 1 , 8) and R 15 mg ( days 1 - 14 ; VDCR ) , R 25 mg ( days 1 - 14 ; VDR ) , C 500 mg/m2 ( days 1 , 8 ; VDC ) or C 500 mg/m2 ( days 1 , 8 , 15 ; VDC-mod ) in 3-week cycles ( maximum 8 cycles ) , followed by maintenance with V 1.3 mg/m2 ( days 1 , 8 , 15 , 22 ) for four 6-week cycles ( all arms)≥very good partial response was seen in 58 % , 51 % , 41 % , and 53 % ( complete response rate of 25 % , 24 % , 22 % , and 47 % ) of patients ( VDCR , VDR , VCD , and VCD-mod , respectively ) ; the corresponding 1-year progression-free survival was 86 % , 83 % , 93 % , and 100 % , respectively . Common adverse events included hematologic toxicities , peripheral neuropathy , fatigue , and gastrointestinal disturbances . All regimens were highly active and well tolerated in previously untreated MM , and , based on this trial , VDR and VCD-mod are preferred for clinical practice and further comparative testing . No substantial advantage was noted with VDCR over the 3-drug combinations . This trial is registered at www . clinical trials.gov ( NCT00507442 ) High-dose therapy is an effective st and ard treatment for multiple myeloma patients . Evidence that intermediate-dose therapy improves survival is limited . At diagnosis , about 70 % of patients are older than 65 . Intermediate-dose regimen is very well tolerated in older patients . In a multicenter study , 194 patients were r and omized to receive at diagnosis either conventional chemotherapy ( 6 courses of oral melphalan and prednisone [ MP ] ) or intermediate-dose therapy ( 2 courses of melphalan at 100 mg/m(2 ) [ MEL100 ] ) with stem cell support . Response rate was higher after MEL100 . Near-complete remission ( nCR ) was 6 % after MP and 25 % after MEL100 ( P = .0002 ) . At 3 years , MEL100 increased event-free survival ( EFS ) from 16 % to 37 % and overall survival ( OS ) from 62 % to 77 % ( P < .001 ) . Similar results were observed in patients aged 65 to 70 : nCR was 8 % after MP and 25 % after MEL100 ( P = .05 ) ; at 3 years , MEL100 improved EFS from 18 % to 31 % ( P = .01 ) and OS from 58 % to 73 % ( P = .01 ) . Patients aged 65 to 70 had a median OS of 37.2 months ( MP ) versus 58 months ( MEL100 ) . Intermediate-dose melphalan improves response rate , EFS , and OS in myeloma patients , specifically in those aged 65 to 70 . It constitutes a more effective first-line regimen than st and ard treatment for elderly patients Dexamethasone alone increases life expectancy in patients with relapsed multiple myeloma ( MM ) ; however , no large r and omized study has compared dexamethasone and dexamethasone-based regimens with st and ard melphalan-prednisone in newly diagnosed MM patients ineligible for high-dose therapy . In the Intergroupe Francophone du Myélome ( IFM ) 95 - 01 trial , 488 patients aged 65 to 75 years were r and omized between 4 regimens of treatment : melphalan-prednisone , dexamethasone alone , melphalan-dexamethasone , and dexamethasone-interferon alpha . Response rates at 6 months ( except for complete response ) were significantly higher among patients receiving melphalan-dexamethasone , and progression-free survival was significantly better among patients receiving melphalan ( P < .001 , for both comparisons ) , but there was no difference in overall survival between the 4 treatment groups . Moreover , the morbidity associated with dexamethasone-based regimens was significantly higher than with melphalan-prednisone , especially for severe pyogenic infections in the melphalan-dexamethasone arm and hemorrhage , severe diabetes , and gastrointestinal and psychiatric complications in the dexamethasone arms . Overall , these results indicated that dexamethasone should not be routinely recommended as first-line treatment in elderly patients with MM . In the context of the IFM 95 - 01 trial , the st and ard melphalan-prednisone remained the best treatment choice when efficacy and patient comfort were both considered . These results might be useful in the context of future combinations with innovative drugs Melphalan ( M ) , in combination with prednisone ( MP ) , has been the backbone of new combinations , including bortezomib plus MP ( VMP ) . However , new alkylator-free schemes , such as lenalidomide plus low-dose dexamethasone , are challenging the role of alkylators in myeloma treatment of elderly patients . Here we have up date d , after a long follow-up ( median 6 years ) , the results of the GEM2005 study that addressed this question by comparing VMP with bortezomib plus thalidomide and prednisone ( VTP ) as induction . Between April 2005 and October 2008 , 260 patients were r and omized to receive 6 cycles of VMP or VTP as induction . The median progression-free survival was 32 months for the VMP and 23 months for the VTP arms ( P 5 .09 ) . VMP significantly prolonged the overall survival ( OS ) compared with VTP ( median of 63 and 43 months , respectively ; hazard ratio [ HR ] : 0.67 , P 5 .01 ) . Achieving immunophenotypic complete response was associated with a significantly longer OS , especially in the VMP arm ( 66%remain alive after 8 years ) . Melphalan , plus bortezomib , should be maintained as st and ard care for the treatment of elderly multiple myeloma patients . This trial was registered at www . clinical trials.gov as # NCT00443235 The combination of melphalan , prednisone , and thalidomide ( MPT ) is considered st and ard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation . Long-term treatment with thalidomide is hampered by neurotoxicity . Melphalan , prednisone , and lenalidomide , followed by lenalidomide maintenance therapy , showed promising results without severe neuropathy emerging . We r and omly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity ( MPT-T ) and the same MP regimen with thalidomide being replaced by lenalidomide ( MPR-R ) . This multicenter , open-label , r and omized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group ( the HOVON87/NMSG18 trial ) . The primary end point was progression-free survival ( PFS ) . A total of 318 patients were r and omly assigned to receive MPT-T , and 319 received MPR-R. After a median follow-up of 36 months , PFS with MPT-T was 20 months ( 95 % confidence interval [ CI ] , 18 - 23 months ) vs 23 months ( 95 % CI , 19 - 27 months ) with MPR-R ( hazard ratio , 0.87 ; 95 % CI , 0.72 - 1.04 ; P = .12 ) . Response rates were similar , with at least a very good partial response of 47 % and 45 % , respectively . Hematologic toxicity was more pronounced with MPR-R , especially grade s 3 and 4 neutropenia : 64 % vs 27 % . Neuropathy of at least grade 3 was significantly higher in the MPT-T arm : 16 % vs 2 % in MPR-R , result ing in a significant shorter duration of maintenance therapy ( 5 vs 17 months in MPR-R ) , irrespective of age . MPR-R has no advantage over MPT-T concerning efficacy . The toxicity profile differed with clinical ly significant neuropathy during thalidomide maintenance vs myelosuppression with MPR As part of the r and omized MRC Myeloma IX trial , we compared an attenuated regimen of cyclophosphamide , thalidomide , and dexamethasone ( CTDa ; n = 426 ) with melphalan and prednisolone ( MP ; n = 423 ) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation . The primary endpoints were overall response rate , progression-free survival , and overall survival ( OS ) . The overall response rate was significantly higher with CTDa than MP ( 63.8 % vs 32.6 % ; P < .0001 ) , primarily because of increases in the rate of complete responses ( 13.1 % vs 2.4 % ) and very good partial responses ( 16.9 % vs 1.7 % ) . Progression-free survival and OS were similar between groups . In this population , OS correlated with the depth of response ( P < .0001 ) and favorable interphase fluorescence in situ hybridization profile ( P < .001 ) . CTDa was associated with higher rates of thromboembolic events , constipation , infection , and neuropathy than MP . In elderly patients with newly diagnosed multiple myeloma ( median age , 73 years ) , CTDa produced higher response rates than MP but was not associated with improved survival outcomes . We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events . This trial was registered at International St and ard R and omized Controlled Trials Number as # 68454111 Maintenance therapy has become a hot field in myeloma , and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy . We report the results of a r and omized comparison of maintenance with bortezomib plus thalidomide ( VT ) or prednisone ( VP ) in 178 elderly untreated myeloma patients who had received 6 induction cycles with bortezomib plus either melphalan and prednisone or thalidomide and prednisone . The complete response ( CR ) rate increased from 24 % after induction up to 42 % , higher for VT versus VP ( 46 % vs 39 % ) . Median progression-free survival ( PFS ) was superior for VT ( 39 months ) compared with VP ( 32 months ) and overall survival ( OS ) was also longer in VT patients compared with VP ( 5-year OS of 69 % and 50 % , respectively ) but the differences did not reach statistical significance . CR achievement was associated with a significantly longer PFS ( P < .001 ) and 5-year OS ( P < .001 ) . The incidence of G3 - 4 peripheral neuropathy was 9 % for VT and 3 % for VP . Unfortunately , this approach was not able to overcome the adverse prognosis of cytogenetic abnormalities . In summary , these maintenance regimens result in a significant increase in CR rate , remarkably long PFS , and acceptable toxicity profile . The trial is registered at www . clinical trials.gov as NCT00443235 In a recent phase 3 trial , bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone . To decrease neurologic toxicities , the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions : 372 patients received once-weekly and 139 twice-weekly bortezomib . In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety . Long-term outcomes appeared similar : 3-year progression-free survival rate was 50 % in the once-weekly and 47 % in the twice-weekly group ( P > .999 ) , and 3-year overall survival rate was 88 % and 89 % , respectively ( P = .54 ) . The complete response rate was 30 % in the once-weekly and 35 % in the twice-weekly group ( P = .27 ) . Nonhematologic grade 3/4 adverse events were reported in 35 % of once-weekly patients and 51 % of twice-weekly patients ( P = .003 ) . The incidence of grade 3/4 peripheral neuropathy was 8 % in the once-weekly and 28 % in the twice-weekly group ( P < .001 ) ; 5 % of patients in the once-weekly and 15 % in the twice-weekly group discontinued therapy because of peripheral neuropathy ( P < .001 ) . This improvement in safety did not appear to affect efficacy . This study is registered at http://www . clinical trials.gov as NCT01063179 Although haematological toxicities , such as anaemia , are common in multiple myeloma ( MM ) , no clear consensus exists on the use and impact of erythropoiesis‐stimulating agents ( ESA ) on outcomes in MM . This analysis characterizes haematological toxicities and associated interventions in the phase III VISTA ( Velcade ® as Initial St and ard Therapy in Multiple Myeloma : Assessment with Melphalan and Prednisone ) study of bortezomib plus melphalan/prednisone ( VMP , n = 344 ) versus MP ( n = 338 ) in previously untreated MM patients ineligible for high‐dose therapy , and evaluates the impact of ESA use or red‐blood‐cell ( RBC ) transfusions on outcomes and thromboembolic risk . Incidence of haematological toxicities was similar with VMP and MP ; similar rates of interventions and associated complications ( e.g. bleeding , febrile neutropenia ) were observed . Two hundred thirty three patients received ESA ; 204 had RBC transfusions . Frequency of thromboembolic events was low and not affected by ESA use . Median time‐to progression ( TTP ) was similar between ESA/non‐ESA [ hazard ratio : 1·03 ( 95 % confidence interval 0·76–1·39 ) ; P = 0·8478 ] in both arms ( VMP : 19·9/not reached ; MP : 15·0/17·5 months ) . Three‐year overall survival ( OS ) rates were similar between ESA/non‐ESA in each arm . Patients receiving RBC transfusions had significantly shorter OS ( P < 0·0001 ) versus non‐RBC‐transfusion patients . In conclusion , bortezomib did not add to melphalan haematological toxicity . Concomitant ESA use with VMP/MP in previously untreated MM patients did not adversely affect TTP or OS , or increase thromboembolic risk . However , RBC transfusion was associated with significantly shorter survival 6508 Background : A phase III trial comparing thalidomide plus dexamethasone ( Thal/Dex ) versus dexamethasone alone ( Dex ) as first line therapy in newly diagnosed multiple myeloma ( MM ) . METHODS Pts with newly diagnosed , untreated , symptomatic MM were eligible . Pts in the Thal/Dex arm ( Arm A ) received Thal 200 mg/day PO with Dex 40 mg on days 1 - 4 , 9 - 12 , and 17 - 20 PO . Pts in the Dex arm ( Arm B ) received Dex alone , at the same dose as Arm A. Therapy was repeated monthly . The primary endpoint was best response at 4 months on intention to treat basis . At 4 months pts could go off study for stem cell transplant or elect to continue therapy . Response was defined as a decrease in serum and urine monoclonal ( M ) protein by 50 % or higher . If the serum M protein was unmeasurable , a 90 % or higher decrease in urine M protein was required . RESULTS 207 pts were enrolled as planned : 103 r and omized to Thal/Dex and 104 to Dex alone . Median age was 65 yrs . At this planned analysis , response data were available on 109 pts . Response rate with Thal/Dex was significantly higher than with Dex : 80 % versus 53 % , respectively , ( p=0.0023 ; one-sided Fisher 's exact test ) . Toxicity data is available on 192 pts . As a planned analysis , incidence rates of grade 3 or higher deep vein thrombosis ( DVT ) , rash , bradycardia , and neuropathy and any grade 4 - 5 toxicity in the first 4 months were compared ( Table ) . In this period , 14 pts died , 6 in arm A and 8 in Arm B. Grade 3 or higher cardiac ischemia occurred in 3 pts in Arm A and 2 pts in Arm B. CONCLUSIONS Thal/Dex demonstrates superior response rates in newly diagnosed MM compared to Dex , comparable to historical results with complex intravenous regimens like VAD . Thal/Dex has higher toxicity compared to Dex , especially DVT . The use of Thal/Dex must be weighed in each pt given the higher toxicities compared to Dex alone . [ Figure : see text ] [ Table : see text ] PURPOSE To determine if thalidomide plus dexamethasone yields superior response rates compared with dexamethasone alone as induction therapy for newly diagnosed multiple myeloma . PATIENTS AND METHODS Patients were r and omly assigned to receive thalidomide plus dexamethasone or dexamethasone alone . Patients in arm A received thalidomide 200 mg orally for 4 weeks ; dexamethasone was administered at a dose of 40 mg orally on days 1 to 4 , 9 to 12 , and 17 to 20 . Cycles were repeated every 4 weeks . Patients in arm B received dexamethasone alone at the same schedule as in arm A. RESULTS Two hundred seven patients were enrolled : 103 were r and omly assigned to thalidomide plus dexamethasone and 104 were r and omly assigned to dexamethasone alone ; eight patients were ineligible . The response rate with thalidomide plus dexamethasone was significantly higher than with dexamethasone alone ( 63 % v 41 % , respectively ; P = .0017 ) . The response rate allowing for use of serum monoclonal protein levels when a measurable urine monoclonal protein was unavailable at follow-up was 72 % v 50 % , respectively . The incidence rates of grade 3 or higher deep vein thrombosis ( DVT ) , rash , bradycardia , neuropathy , and any grade 4 to 5 toxicity in the first 4 months were significantly higher with thalidomide plus dexamethasone compared with dexamethasone alone ( 45 % v 21 % , respectively ; P < .001 ) . DVT was more frequent in arm A than in arm B ( 17 % v 3 % ) ; grade 3 or higher peripheral neuropathy was also more frequent ( 7 % v 4 % , respectively ) . CONCLUSION Thalidomide plus dexamethasone demonstrates significantly superior response rates in newly diagnosed myeloma compared with dexamethasone alone . However , this must be balanced against the greater toxicity seen with the combination Multiple myeloma , a plasma cell neoplasm , is the second most common hematologic malignancy after non-Hodgkins lymphoma and is responsible for 2 % of cancer deaths . Melphalan and prednisone ( MP ) has been the st and ard treatment in elderly patients for many decades . The VISTA study evaluated the effect of this combination with or without the first-in-class proteasome inhibitor bortezomib in newly diagnosed myeloma patients who were not c and i date s for autologous stem cell transplantation . Altogether 682 patients were enrolled and prospect ively r and omized in this trial . All patients received nine 6-week cycles of oral melphalan ( 9 mg/m(2 ) ) and prednisone ( 60 mg/m(2 ) ) on days 1 - 4 , either alone or with bortezomib administered intravenously ( 1.3 mg/m(2 ) on days 1 , 4 , 8 , 11 , 22 , 25 , 29 and 32 during the first four cycles and on days 1 , 8 , 22 , 29 during remaining course of therapy ) . Median time to progression ( the primary end point of the trial ) was 24 months in the bortezomib-containing group compared with 16.6 months in the control group ( p < 0.001 ) . Response was evaluated in 337 patients receiving bortezomib compared with 331 patients in the control group who received MP alone ; the percentages of partial response or better was 71 vs 35 % ( p < 0.001 ) , with complete response seen in 30 vs 4 % , respectively ( p < 0.001 ) . Median response duration in both groups was 19.9 versus 13.1 months , respectively . Median overall survival has not been reached in VMP group compared with 43 months in the MP group ( p < 0.001 ) , and this benefit is maintained after long term follow-up and subsequent antimyeloma therapies . Hematological adverse events ( AEs ) were similar in both groups , although patients in the bortezomib group experienced more frequent peripheral sensory neuropathy ( including 13 % grade 3 , with less than 1 % grade 4 ) . Overall , the occurrence of grade 3 AEs was higher in patients receiving bortezomib ( 53 vs 44 % , p = 0.02 ) , but the risk of grade 4 AEs was identical ( 28 vs 27 % ) . These results confirm the superiority of MP plus bortezomib combination over MP therapy in treatment-naive patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation 7517 Background : Thalidomide plus dexamethasone ( Thal/Dex ) yields superior response rates versus dexamethasone ( Dex ) but its impact as primary therapy for multiple myeloma ( MM ) is unknown . METHODS Patients ( pts ) with previously untreated , symptomatic MM were eligible and were r and omized in this double-blind trial to Thal/Dex ( Arm A ) or placebo plus Dex ( Arm B ) . Pts in Arm A received Thal 50 mg PO daily , escalated to 100 mg on day 15 , and to 200 mg from day 1 of cycle 2 ; Dex 40 mg PO was given on days 1 - 4 , 9 - 12 , and 17 - 20 . Pts in Arm B received placebo instead of Thal , and Dex as in Arm A. Cycles were 28 days long , repeated until progression or undue toxicity . The primary endpoint was time to progression ( TTP ) defined using EBMT criteria . All analyses were intent to treat . Planned sample size was 218 eligible pts in each arm . Full information for one-sided log rank test with significance level of 0.025 ( allowing for 1interim analysis ) to have 80 % power to detect a 40 % improvement in TTP ( 16.8 mo in Arm A vs. 12 mo in Arm B ) would be achieved when 282 pts have progressed . A pre-planned interim analysis of the primary endpoint and safety was performed by an independent Data Monitoring Committee ( DMC ) . P value < 0.0015 at this interim analysis would indicate that Arm A is superior to Arm B based on an alpha-spending function of the O'Brien-Fleming type . The DMC recommended release of results . RESULTS 470 pts were enrolled : 235 r and omized to Thal/Dex and 235 to placebo/Dex . Median follow-up was 25 months . Median age was 65 yrs . TTP was significantly superior with Thal/Dex vs placebo/Dex , median TTP 17.4 months ( 95 % CI : 8.1 months-NE ) vs 6.4 months ( 95 % CI : 5.6 - 7.4 months ) , respectively , P < 0.000065 , crossing the upper boundary for superiority . DVT was higher with Thal/Dex vs placebo/Dex , 15.4 % vs 4.3 % , respectively . Median survival was not reached in either arm . CONCLUSIONS Thal/Dex is significantly superior to Dex alone as first-line therapy for multiple myeloma . [ Table : see text ] [ Table : see text ] PURPOSE Bortezomib-melphalan-prednisone ( VMP ) has improved overall survival in multiple myeloma . This r and omized trial compared VMP plus thalidomide ( VMPT ) induction followed by bortezomib-thalidomide maintenance ( VMPT-VT ) with VMP in patients with newly diagnosed multiple myeloma . PATIENTS AND METHODS We r and omly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT ( nine 5-week cycles of VMPT followed by 2 years of VT maintenance ) or VMP ( nine 5-week cycles without maintenance ) . RESULTS In the initial analysis with a median follow-up of 23 months , VMPT-VT improved complete response rate from 24 % to 38 % and 3-year progression-free-survival ( PFS ) from 41 % to 56 % compared with VMP . In this analysis , median follow-up was 54 months . The median PFS was significantly longer with VMPT-VT ( 35.3 months ) than with VMP ( 24.8 months ; hazard ratio [ HR ] , 0.58 ; P < .001 ) . The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group ( HR , 0.52 ; P < .001 ) . The 5-year overall survival ( OS ) was greater with VMPT-VT ( 61 % ) than with VMP ( 51 % ; HR , 0.70 ; P = .01 ) . Survival from relapse was identical in both groups ( HR , 0.92 ; P = .63 ) . In the VMPT-VT group , the most frequent grade 3 to 4 adverse events included neutropenia ( 38 % ) , thrombocytopenia ( 22 % ) , peripheral neuropathy ( 11 % ) , and cardiologic events ( 11 % ) . All of these , except for thrombocytopenia , were significantly more frequent in the VMPT-VT patients . CONCLUSION Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation BACKGROUND Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma . This double-blind , multicenter , r and omized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance ( MPR-R ) with melphalan-prednisone-lenalidomide ( MPR ) or melphalan-prednisone ( MP ) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma . METHODS We r and omly assigned patients who were ineligible for transplantation to receive MPR-R ( nine 4-week cycles of MPR followed by lenalidomide maintenance therapy until a relapse or disease progression occurred [ 152 patients ] ) or to receive MPR ( 153 patients ) or MP ( 154 patients ) without maintenance therapy . The primary end point was progression-free survival . RESULTS The median follow-up period was 30 months . The median progression-free survival was significantly longer with MPR-R ( 31 months ) than with MPR ( 14 months ; hazard ratio , 0.49 ; P<0.001 ) or MP ( 13 months ; hazard ratio , 0.40 ; P<0.001 ) . Response rates were superior with MPR-R and MPR ( 77 % and 68 % , respectively , vs. 50 % with MP ; P<0.001 and P=0.002 , respectively , for the comparison with MP ) . The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age ( P=0.001 for treatment-by-age interaction ) . After induction therapy , a l and mark analysis showed a 66 % reduction in the rate of progression with MPR-R ( hazard ratio for the comparison with MPR , 0.34 ; P<0.001 ) that was age-independent . During induction therapy , the most frequent adverse events were hematologic ; grade 4 neutropenia was reported in 35 % , 32 % , and 8 % of the patients in the MPR-R , MPR , and MP groups , respectively . The 3-year rate of second primary tumors was 7 % with MPR-R , 7 % with MPR , and 3 % with MP . CONCLUSIONS MPR-R significantly prolonged progression-free survival in patients with newly diagnosed multiple myeloma who were ineligible for transplantation , with the greatest benefit observed in patients 65 to 75 years of age . ( Funded by Celgene ; MM-015 Clinical Trials.gov number , NCT00405756 . ) BACKGROUND The combination melphalan-prednisone-thalidomide ( MPT ) is considered a st and ard therapy for patients with myeloma who are ineligible for stem-cell transplantation . However , emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospect i ve comparison of the two approaches . METHODS We r and omly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression ( 535 patients ) , to the same combination for 72 weeks ( 18 cycles ; 541 patients ) , or to MPT for 72 weeks ( 547 patients ) . The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT . RESULTS The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone , 20.7 months with 18 cycles of lenalidomide-dexamethasone , and 21.2 months with MPT ( hazard ratio for the risk of progression or death , 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone ; P<0.001 for both comparisons ) . Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points , including overall survival ( at the interim analysis ) . Overall survival at 4 years was 59 % with continuous lenalidomide-dexamethasone , 56 % with 18 cycles of lenalidomide-dexamethasone , and 51 % with MPT . Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT ( 70 % vs. 78 % ) . As compared with MPT , continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events , a moderate increase in infections , and fewer second primary hematologic cancers . CONCLUSIONS As compared with MPT , continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival , with an overall survival benefit at the interim analysis , among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation . ( Funded by Intergroupe , Francophone du Myélome and Celgene ; FIRST Clinical Trials.gov number , NCT00689936 ; European Union Drug Regulating Authorities Clinical Trials number , 2007 - 004823 - 39 . ) This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma ( NDMM ) treated with lenalidomide and low-dose dexamethasone until disease progression ( Rd continuous ) , Rd for 72 weeks ( 18 cycles ; Rd18 ) , or melphalan , prednisone , and thalidomide ( MPT ; 72 weeks ) . The primary endpoint was progression-free survival ( PFS ; primary comparison : Rd continuous vs MPT ) . Overall survival ( OS ) was a key secondary endpoint ( final analysis prespecified ≥60 months ' follow-up ) . Patients were r and omized to Rd continuous ( n = 535 ) , Rd18 ( n = 541 ) , or MPT ( n = 547 ) . At a median follow-up of 67 months , PFS was significantly longer with Rd continuous vs MPT ( hazard ratio [ HR ] , 0.69 ; 95 % confidence interval [ CI ] , 0.59 - 0.79 ; P < .00001 ) and was similarly extended vs Rd18 . Median OS was 10 months longer with Rd continuous vs MPT ( 59.1 vs 49.1 months ; HR , 0.78 ; 95 % CI , 0.67 - 0.92 ; P = .0023 ) , and similar with Rd18 ( 62.3 months ) . In patients achieving complete or very good partial responses , Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 ( 69.5 vs 39.9 months ) . Over half of all patients who received second-line treatment were given a bortezomib-based therapy . Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT . No new safety concerns , including risk for secondary malignancies , were observed . Treatment with Rd continuous significantly improved survival outcomes vs MPT , supporting Rd continuous as a st and ard of care for patients with transplant-ineligible NDMM . This trial was registered at www . clinical trials.gov as # NCT00689936 and EudraCT as 2007 - 004823 - 39 In recent years , we have seen tremendous progress in our ability to achieve durable responses in patients with multiple myeloma . At the center of this progress , we have the development of 2 unrelated classes of drugs : proteasome inhibitors such as bortezomib and immunomodulatory drugs such as thalidomide and lenalidomide . The depth and durability of responses attained with these agents in the first-line setting has raised the possibility that they may be considered primary therapy . The Eastern Cooperative Oncology Group E1A05 clinical trial addresses the potential role of bortezomib and dexamethasone ( VD ) or VD plus lenalidomide ( VRD ) as primary first-line therapy . This clinical trial enrolls patients who have completed a dexamethasone-based induction ( excluding patients using bortezomib ) . Assuming that most patients entering this clinical trial have been previously treated with thalidomide or lenalidomide , the trial will test whether switching to a proteasome inhibitor ( VD arm ) versus adding a proteasome inhibitor ( VRD ) results in superior longterm disease control . Patients entering this clinical trial will have deferred stem cell transplantation until the time of relapse . The primary endpoint of the trial is progression-free survival . By using an alkylator-free consolidation and reserving stem cell transplantation until the time of relapse , we hope that these treatment strategies will further prolong the survival of patients with myeloma 8515 Background : In MM patients VMP is superior to MP . In relapsed-refractory patients the 4 drug combination VMPT induced a high proportion of complete responses ( CR ) . METHODS 500 newly diagnosed MM patients ≥ 65 years were r and omly assigned to receive VMPT ( N=247 ) or VMP ( N=253 ) . Patients were treated with nine 5-week cycles of VMPT ( bortezomib 1.3 mg/m2 days 1 , 8 , 15 , 22 ; melphalan 9 mg/m2 days 1 - 4 ; prednisone 60 mg/m2 days 1 - 4 and thalidomide 50 mg days 1 - 35 ) or VMP ( bortezomib , melphalan and prednisone at the same doses and schedules previously described ) . Primary end-point was progression-free survival ( PFS ) . Assuming the hazard ratio ( VMP vs VMPT ) of 1.35 , the total sample size is 500 ( 250/arm ) subjects ( power 80 % , 2-side alpha 0.05 ) . RESULTS 354 patients ( median age 71 years ) , who received at least 1 cycle were evaluated : 177 VMPT and 177 VMP . Data were analyzed in intention-to-treat . The VGPR rate was 55 % in the VMPT group and 45 % in the VMP group ( p<0.001 ) . After a median follow-up of 14.5 months , the 3-year PFS was 74 % in the VMPT group and 70 % in the VMP group ( HR=0.75 , 95 % CI 0.45 - 1.26 , p=0.28 ) . The 3-year overall survival ( OS ) was 88 % in the VMPT group and 87 % in the VMP group ( HR=0.89 , 95 % CI 0.42 - 1.87 , p=0.75 ) . Subgroup analyses did not show any statistical difference between responses/PFS and either ISS or chromosomal abnormalities ( t(4;14 ) or t(14;16 ) or del17 ) in both groups . Age > 75 years was associated with lower VGPR rate ( p=0.02 ) in VMPT but not in VMP . Factors predictive of longer PFS were age ≤ 75 years ( p=0.003 ) and the achievement of VGPR ( p=0.0005 ) in VMPT but not in VMP . The incidence of grade 3 - 4 adverse events ( AEs ) was similar in both groups . In the VMPT patients and in the VMP patients , the more frequent AEs were neutropenia ( 36 % vs 31 % ) , thrombocytopenia ( 20 % vs 19 % ) , peripheral neuropathy ( 18 % vs 12 % ) and infections ( 14 % vs 10 % ) , respectively . CONCLUSIONS VMPT is superior to VMP in terms of response rates . Longer follow-up is needed to assess their effects on PFS and OS . Both regimens appeared to overcome the poor prognosis of ISS and chromosomal abnormalities . An up date of these data will be presented . [ Table : see text ] PURPOSE For several decades , the treatment of elderly patients with multiple myeloma ( MM ) has consisted of melphalan and prednisone ( MP ) . The Dutch-Belgium Hemato-Oncology Cooperative Group ( HOVON ) investigated the efficacy of thalidomide added to MP ( MP-T ) in a r and omized phase III trial . The objective of this study was to investigate the efficacy , toxicity , and effects on quality of life of MP-T. PATIENTS AND METHODS A r and omized phase III trial compared st and ard MP with MP-T ( thalidomide 200 mg/d ) in newly diagnosed patients with multiple myeloma older than age 65 years . Maintenance therapy with thalidomide 50 mg/d was administered to patients after MP-T until relapse . The primary end point was event-free survival ( EFS ) ; response rate , overall survival ( OS ) , and progression-free survival ( PFS ) were secondary end points . RESULTS An intent-to-treat analysis of 333 evaluable patients showed significantly higher response rates in MP-T-treated patients compared with MP-treated patients a response ( > or = partial response : 66 % v 45 % , respectively ; P < .001 ; and > or = very good partial response [ VGPR ] : 27 % v 10 % , respectively ; P < .001 ) . EFS was 13 months with MP-T versus 9 months with MP ( P < .001 ) . OS was 40 months with MP-T versus 31 months with MP ( P = .05 ) . CONCLUSION This study demonstrates that thalidomide improves the response rate and VGPR in elderly patients with newly diagnosed MM . MP-T also results in a better EFS , PFS , and OS 8072 Background : The multicenter , phase IIIb UPFRONT study compares the efficacy and safety of 3 bortezomib (Vc)-based induction regimens , VcD ( Vc-dexamethasone ) , VcTD ( Vc-thalidomide-dexamethasone ) and VcMP ( Vc-melphalan-prednisone ) , followed by weekly Vc maintenance , in newly diagnosed MM patients ineligible for HDT-SCT . METHODS Patients were r and omized ( 1:1:1 ) to receive 8 three-week cycles of induction followed by 5 five-week cycles of maintenance . Efficacy and safety data were analyzed by patient and disease baseline characteristics including age , gender , Charlson comorbidity index ( CCI ) and ISS stage after 300 patients ( 100 patients per arm ) had the opportunity to complete all 13 cycles . Data were pooled across all three treatment arms . Response was assessed using IMWG criteria . AEs were grade d by NCI-CTCAE v3.0 . RESULTS Rates of ≥VGPR were higher in patients age < 75 years ( p=0.034 ) . Patients with a CCI of 0 showed a trend to better ≥VGPR ( p=0.078 ) . A multivariate analysis showed similar results . There was no significant difference in ≥VGPR by gender , race , or ISS stage . Grade ≥3 AE rates appeared lower in patients < 75 years , and PN rates ( all grade ) tended to be lower in males and in white patients . There were no apparent trends in the rates of grade ≥3 AEs or PN ( all grade ) by CCI or ISS stage . Previous reports from this study have shown that ≥VGPR rates were similar by treatment arm , but that rates of grade ≥3 AEs and PN were higher in the VcTD arm ( Niesvizky , ASH 2010 ) . CONCLUSIONS The results of this subgroup analysis show that patients < 75 years had higher rates of ≥VGPR and lower rates of grade ≥3 AEs in the UPFRONT study . These results suggest that Vc-containing regimens are active across various patient subgroups including gender , race , co-morbidity status , and ISS stage . [ Table : see text ] Melphalan – prednisone ( MP ) has been the gold st and ard treatment for more than 30 years in elderly multiple myeloma ( MM ) patients . In order to assess whether the combination of dexamethasone with melphalan ( MD ) could improve on the efficacy of MP , we have carried out a r and omized trial comparing both treatment approaches . A total of 201 patients ≥70 years old were included in the study . The overall response rate was similar after six cycles ( MP : 67·9%versus MD : 64·5 % ) and after 12 cycles ( MP : 49·4%versus MD : 46·1 % ) . However , the proportion of complete responses ( CR ) was higher in the MD arm , particularly after 12 cycles ( MD : 22·4%versus MP : 9·1 % ; P < 0·05 ) . There was no significant difference in event‐free survival ( MP : 15·9 months versus MD : 23·3 months ) . The median overall survival in both arms was almost identical ( MP : 29·4 months versus MD : 27·2 months ; P = 0·63 ) . No significant differences in haematological toxicity were observed , but non‐haematological toxicity was significantly higher in the MD arm . According to these results MP remains as the gold st and ard for treatment of MM and should be the reference for comparison of new therapeutic approaches involving novel agents BACKGROUND Bortezomib plus melphalan and prednisone ( VMP ) is significantly better than melphalan plus prednisone alone for elderly patients with untreated multiple myeloma ; however , toxic effects are high . We investigated a novel and less intensive bortezomib-based regimen to maintain efficacy and to reduce toxic effects . METHODS Between March , 2006 , and October , 2008 , 260 patients with untreated multiple myeloma , 65 years and older , from 63 Spanish centres , were r and omly assigned to receive six cycles of VMP ( n=130 ) or bortezomib plus thalidomide and prednisone ( VTP ; n=130 ) as induction therapy , consisting of one cycle of bortezomib twice per week for 6 weeks ( 1·3 mg/m² on days 1 , 4 , 8 , 11 , 22 , 25 , 29 , and 32 ) , plus either melphalan ( 9 mg/m² on days 1 - 4 ) or daily thalidomide ( 100 mg ) , and prednisone ( 60 mg/m² on days 1 - 4 ) . The first cycle was followed by five cycles of bortezomib once per week for 5 weeks ( 1·3 mg/m² on days 1 , 8 , 15 , and 22 ) plus the same doses of melphalan plus prednisone and thalidomide plus prednisone . 178 patients completed the six induction cycles and were r and omly assigned to maintenance therapy with bortezomib plus prednisone ( n=87 ) or bortezomib plus thalidomide ( n=91 ) , consisting of one conventional cycle of bortezomib for 3 weeks ( 1·3 mg/m² on days 1 , 4 , 8 , and 11 ) every 3 months , plus either prednisone ( 50 mg every other day ) or thalidomide ( 50 mg per day ) , for up to 3 years . Treatment codes were generated with a computerised r and om number generator , and neither participants nor study personnel were masked to treatment . The primary endpoint was response rate in induction and maintenance phases . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00443235 . FINDINGS In the induction phase , 105 ( 81 % ) patients in the VTP group and 104 ( 80 % ) in the VMP group achieved partial responses or better ( p=0·9 ) , including 36 ( 28 % ) and 26 ( 20 % ) complete remissions , respectively ( p=0·2 ) . Treatment with VTP result ed in more serious adverse events ( 40 [ 31 % ] vs 20 [ 15 % ] , p=0·01 ) and discontinuations ( 22 [ 17 % ] vs 15 [ 12 % ] , p=0·03 ) than did treatment with VMP . The most common toxicities ( grade 3 or worse ) were infections ( one [ 1 % ] in the VTP group vs nine [ 7 % ] in the VMP group ) , cardiac events ( 11 [ 8 % ] vs 0 ) , and peripheral neuropathy ( nine [ 7 % ] vs 12 [ 9 % ] ) . After maintenance therapy , the complete remission rate was 42 % ( 40 [ 44 % ] patients in complete remission in the bortezomib plus thalidomide group , 34 [ 39 % ] in the bortezomib plus prednisone group ) . No grade 3 or worse haematological toxicities were recorded during maintenance therapy ; two ( 2 % ) patients in the bortezomib plus prednisone group and six ( 7 % ) in the bortezomib plus thalidomide group developed peripheral neuropathy . INTERPRETATION Reduced-intensity induction with a bortezomib-based regimen , followed by maintenance , is a safe and effective treatment for elderly patients with multiple myeloma . FUNDING Pethema ( Spanish Program for the Treatment of Hematologic Diseases ) Renal impairment is associated with poor prognosis in myeloma . This analysis of the pivotal phase 3 FIRST trial examined the impact of renally adapted dosing of lenalidomide and dexamethasone on outcomes of patients with different degrees of renal impairment . Transplant-ineligible patients not requiring dialysis were r and omized 1:1:1 to receive continuous lenalidomide and dexamethasone until disease progression ( n=535 ) or for 18 cycles ( 72 weeks ; n=541 ) , or melphalan , prednisone , and thalidomide for 12 cycles ( 72 weeks ; n=547 ) . Follow-up is ongoing . Patients were grouped by baseline creatinine clearance into no ( ≥ 80 mL/min [ n=389 ] ) , mild ( ≥ 50 to < 80 mL/min [ n=715 ] ) , moderate ( ≥ 30 to < 50 mL/min [ n=372 ] ) , and severe impairment ( < 30 mL/min [ n=147 ] ) subgroups . Continuous lenalidomide and dexamethasone therapy reduced the risk of progression or death in no , mild , and moderate renal impairment subgroups vs. melphalan , prednisone , and thalidomide therapy ( HR = 0.67 , 0.70 , and 0.65 , respectively ) . Overall survival benefits were observed with continuous lenalidomide and dexamethasone treatment vs. melphalan , prednisone , and thalidomide treatment in no or mild renal impairment subgroups . Renal function improved from baseline in 52.6 % of lenalidomide and dexamethasone – treated patients . The safety profile of continuous lenalidomide and dexamethasone was consistent across renal subgroups , except for grade 3/4 anemia and rash , which increased with increasing severity of renal impairment . Continuous lenalidomide and dexamethasone treatment , with renally adapted lenalidomide dosing , was effective for most transplant-ineligible patients with myeloma and renal impairment PURPOSE The combination of bortezomib-melphalan-prednisone ( VMP ) is a new st and ard of care for newly diagnosed multiple myeloma . This phase III study examined the efficacy of the four-drug combination of bortezomib-melphalan-prednisone-thalidomide ( VMPT ) followed by maintenance with bortezomib-thalidomide ( VMPT-VT ) compared with VMP treatment alone in untreated multiple myeloma patients who are ineligible for autologous stem-cell transplantation . PATIENTS AND METHODS A total of 511 patients were r and omly assigned to receive nine cycles of VMPT followed by continuous VT as maintenance , or nine cycles of VMP at the same doses with no additional therapy . The primary end point was progression-free survival . RESULTS The 3-year estimates of progression-free survival were 56 % in patients receiving VMPT-VT and 41 % in those receiving VMP ( hazard ratio [ HR ] , 0.67 ; 95 % CI , 0.50 to 0.90 ; P = .008 ) . At 3 years , the cumulative proportions of patients who did not go on to the next therapy were 72 % with VMPT-VT and 60 % with VMP ( HR , 0.58 ; 95 % CI , 0.50 to 0.90 ; P = .007 ) . Complete response rates were 38 % in the VMPT-VT group and 24 % in the VMP group ( P < .001 ) . The 3-year overall survival was 89 % with VMPT-VT and 87 % with VMP ( HR , 0.92 ; 95 % CI , 0.53 to 1.60 ; P = .77 ) . Grade 3 to 4 neutropenia ( 38 % v 28 % ; P = .02 ) , cardiologic events ( 10 % v 5 % ; P = .04 ) , and thromboembolic events ( 5 % v 2 % ; P = .08 ) were more frequent among patients assigned to the VMPT-VT group than among those assigned to the VMP group ; treatment-related deaths were 4 % with VMPT-VT and 3 % with VMP . CONCLUSION VMPT followed by VT as maintenance was superior to VMP alone in patients with multiple myeloma who are ineligible for autologous stem-cell transplantation Thalidomide , the prototype of a new class of agents active against multiple myeloma ( MM ) , exerts synergistic/additive effects when combined with other drugs . The aim of this study was to compare the toxicity and efficacy of thalidomide alone and in combination with oral melphalan . Patients with advanced MM received 100 mg/day oral thalidomide escalated weekly up to 600 mg/day ( n=23 ; T group ) , alone or with 0.20 oral mg/kg/die melphalan administered monthly for four consecutive days ( n=27 ; TM group ) . A>/=50 % paraprotein reduction was observed in 59 % of TM compared with 26 % of T patients ( P=0.009 ) ; three TM patients were found to have an absence of paraprotein by immunofixation . After a median follow-up of 13 months ( range 6 - 32 ) , progression-free survival ( PFS ) at 2 years was significantly longer in the TM group ( 61 versus 45 % ; P=0.0376 ) , whereas overall survival did not differ significantly . Toxicity was not significantly greater with the combination therapy ; although DVT was more frequent ( 11 versus 4 % ) , as was grade 3 leukopenia ( 30 versus 13 % ; P=0.073 ) , there were no cases of severe infection . Thalidomide administered with oral melphalan improved response rates and PFS in patients with advanced MM without significantly increasing severe toxicity Objectives : This sub analysis of the phase 3 VISTA trial aim ed to assess the frequency , characteristics and reversibility of , and prognostic factors for , bortezomib‐associated peripheral neuropathy ( PN ) in newly diagnosed patients with multiple myeloma ineligible for high‐dose therapy who received bortezomib plus melphalan – prednisone PURPOSE Continuous therapy ( CT ) prolongs progression-free survival 1 ( PFS1 ; time from r and om assignment until the first progression or death ) , but chemotherapy-resistant relapse may negatively impact overall survival ( OS ) . Progression-free survival 2 ( PFS2 ; time from r and om assignment until the second progression or death ) may represent an additional tool to estimate outcome . This study evaluates the benefit of novel agent-based CT versus fixed duration of therapy ( FDT ) in patients with newly diagnosed myeloma . METHODS We included patients enrolled onto three phase III trials that r and omly assigned patients to novel agent-based CT versus FDT . Primary analyses were restricted to the intent-to-treat population eligible for CT ( patients progression free and alive at 1 year after r and om assignment ) . Primary end points were PFS1 , PFS2 , and OS . All hazard ratios ( HRs ) and 95 % CIs were adjusted for several potential confounders using Cox models . RESULTS In the pooled analysis of the three trials , 604 patients were r and omly assigned to CT and 614 were assigned to FDT . Median follow-up was 52 months . In the intent-to-treat CT population , CT ( n = 417 ) , compared with FDT ( n = 410 ) , significantly improved PFS1 ( median , 32 v 16 months , respectively ; HR , 0.47 ; 95 % CI , 0.40 to 0.56 ; P < .001 ) , PFS2 ( median , 55 v 40 months , respectively ; HR , 0.61 ; 95 % CI , 0.50 to 0.75 ; P < .001 ) , and OS ( 4-year OS , 69 % v 60 % , respectively ; HR , 0.69 ; 95 % CI , 0.54 to 0.88 ; P = .003 ) . CONCLUSION In this pooled analysis , CT significantly improved PFS1 , PFS2 , and OS . The improvement in PFS2 suggests that the benefit reported during first remission is not cancelled by a shorter second remission . PFS2 is a valuable end point to estimate long-term clinical benefit and should be included in future trials The phase 3 , r and omized Frontline Investigation of Revlimid and Dexamethasone Versus St and ard Thalidomide ( FIRST ) trial investigating lenalidomide plus low-dose dexamethasone until disease progression ( Rd continuous ) vs melphalan , prednisone and thalidomide for 12 cycles ( MPT ) and Rd for 18 cycles ( Rd18 ) in transplant-ineligible patients with newly diagnosed multiple myeloma ( NDMM ) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT . A sub analysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response . Patients r and omized 1:1:1 to Rd continuous , Rd18 or MPT were divided into subgroups based on best response : complete response ( CR ; n=290 ) , ⩾very good partial response ( VGPR ; n=679 ) , ⩾partial response ( PR ; n=1 225 ) or ⩽stable disease ( n=299 ) . Over 13 % of patients receiving Rd continuous who achieved ⩾VGPR as best response did so beyond 18 months of treatment . Rd continuous reduced the risk of progression or death by 67 % , 51 % and 35 % vs MPT in patients with CR , ⩾VGPR and ⩾PR , respectively . Similarly , Rd continuous reduced the risk of progression or death by 61 % , 54 % and 38 % vs Rd18 in patients with CR , ⩾VGPR and ⩾PR , respectively . In patients with CR , ⩾VGPR or ⩾PR , 4-year survival rates in the Rd continuous arm ( 81.1 % , 73.1 % or 64.6 % , respectively ) were higher vs MPT ( 70.8 % , 59.8 % or 57.2 % , respectively ) and similar vs Rd18 ( 76.5 % , 67.7 % and 62.5 % , respectively ) . Rd continuous improved efficacy outcomes in all responding patients , including those with CR , compared with fixed duration treatment The combination of melphalan-prednisone-thalidomide ( MPT ) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules . This prospect i ve trial differs from previous melphalan-prednisone ( MP ) vs. MPT trials by treatment dosing , duration , routine anticoagulation , and permission for a crossover . Newly diagnosed patients with multiple myeloma ( MM ) ( n=122 ) aged greater than 55 yr , not eligible for transplantation were r and omized to receive 8 cycles of M ( 9 mg/m(2 ) /d ) and P ( 60 mg/m(2 ) /d ) for 4d every 6 wk ( n=62 ) or MP and thalidomide ( 100 mg/d ) continuously ( n=60 ) . Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy . Secondary endpoints were disease-free ( DFS ) and overall survival ( OS ) . Overall , MPT-treated patients were younger ( median 69 yr vs. 72 yr ; P=0.016 ) and had a higher incidence of renal impairment ( RI , 19 % vs. 7 % , respectively ; P=0.057 ) . After 4 cycles of treatment ( n=115 ) , there were more partial responses or better in the MPT arm than in the MP arm ( 57.9 % vs. 37.5 % ; P=0.030 ) . However , DFS and OS were not significantly different between the arms after a median of 23 months follow-up ( median OS 26.0 vs. 28.0 months , P=0.655 ; DFS 21.0 vs. 14.0 months , P=0.342 , respectively ) . Crossover to MPT was required in 11 patients , 57 % of whom responded to treatment . A higher rate of grade 3 - 4 infections was observed in the MPT arm compared with the MP arm ( 22.4 % vs. 7.0 % ; P=0.033 ) . However , none of these infections were associated with febrile neutropenia . Death within the first 3 months was observed more frequently in the MP arm ( n=8 , 14.0 % ) than in the MPT arm ( n=2 , 3.4 % ; P=0.053 ) . Long-term discontinuation and dose reduction rates were also analyzed ( MPT : 15.5 % vs. MP : 5.3 % ; P=0.072 ) . Although patients treated with MPT were relatively younger and had more frequent RI , better responses and less early mortality were observed in all age groups despite more frequent discontinuation PURPOSE The purpose of this study was to confirm overall survival ( OS ) and other clinical benefits with bortezomib , melphalan , and prednisone ( VMP ) versus melphalan and prednisone ( MP ) in the phase III VISTA ( Velcade as Initial St and ard Therapy in Multiple Myeloma ) trial after prolonged follow-up , and evaluate the impact of subsequent therapies . PATIENTS AND METHODS Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP ( n = 344 ) or MP ( n = 338 ) . RESULTS With a median follow-up of 36.7 months , there was a 35 % reduced risk of death with VMP versus MP ( hazard ratio , 0.653 ; P < .001 ) ; median OS was not reached with VMP versus 43 months with MP ; 3-year OS rates were 68.5 % versus 54.0 % . Response rates to subsequent thalidomide- ( 41 % v 53 % ) and lenalidomide-based therapies ( 59 % v 52 % ) appeared similar after VMP or MP ; response rates to subsequent bortezomib-based therapy were 47 % versus 59 % . Among patients treated with VMP ( n = 178 ) and MP ( n = 233 ) , median survival from start of subsequent therapy was 30.2 and 21.9 months , respectively , and there was no difference in survival from salvage among patients who received subsequent bortezomib , thalidomide , or lenalidomide . Rates of adverse events were higher with VMP versus MP during cycles 1 to 4 , but similar during cycles 5 to 9 . With VMP , 79 % of peripheral neuropathy events improved within a median of 1.9 months ; 60 % completely resolved within a median of 5.7 months . CONCLUSION VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy . First-line bortezomib use does not induce more resistant relapse . VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent-based treatment until relapse 8007 Background : MM pts have an 8 - 10 fold higher risk of developing acute myeloid leukemia ( AML ) than the general population . MM-015 compared MPR-R vs fixed- duration MP or MPR in transplant-ineligible pts ≥65 yrs . This analysis evaluated SPM incidence rates ( IRs ) and st and ardized incidence ratios ( SIR ) . METHODS IRs were calculated for AML and solid tumor ( ST ) malignancies . Expected IRs used to calculate SIR were derived from 23,838 MM pts identified in the Surveillance , Epidemiology , and End Results ( SEER ) Cancer Registries between 1973 - 2000 ( Dores 2006 ) . RESULTS As of May 2010 cut-off , total cases of SPM were 4/150 in MPR-R ( IR=1.40 ) , 6/152 in MPR ( IR=2.05 ) and 2/153 in MP ( IR=0.67 ) , including 2 myelodysplastic syndromes cases in MPR-R and 2 AML cases in each of MPR-R and MPR . 11 pts with complex cytogenetics were r and omized to MPR-R/MPR and none r and omized to MP . Of these , 3 developed AML ; 2 MDS . ST were of heterogeneous tumor types . No B-cell malignancies were reported . Median progression-free survival ( PFS ) of MPR-R vs MP was 31 vs 13 mos ( P < .001 ; median follow-up : 25 months ) , with a reduced risk of progression of 60 % ( hazard ratio [ HR ] = 0.395 ) . When SPM were added as additional events for PFS , results remained unchanged ( HR = 0.408 ; P < .001 ) . CONCLUSIONS An imbalance of AML incidence was observed in MPR/MPR-R vs MP , but incidence was low ( 0.7 % vs 0 % ) and associated with complex baseline cytogenetics . ST IRs were low and similar for all arms . At present , the SPM risk is similar to that reported in other studies . Longer follow-up is needed to definitively assess the risk of SPM in NDMM pts receiving lenalidomide and alkylating agents . Evaluation will continue with up date d data at the meeting . [ Table : see text ] BACKGROUND The st and ard treatment for patients with multiple myeloma who are not c and i date s for high-dose therapy is melphalan and prednisone . This phase 3 study compared the use of melphalan and prednisone with or without bortezomib in previously untreated patients with multiple myeloma who were ineligible for high-dose therapy . METHODS We r and omly assigned 682 patients to receive nine 6-week cycles of melphalan ( at a dose of 9 mg per square meter of body-surface area ) and prednisone ( at a dose of 60 mg per square meter ) on days 1 to 4 , either alone or with bortezomib ( at a dose of 1.3 mg per square meter ) on days 1 , 4 , 8 , 11 , 22 , 25 , 29 , and 32 during cycles 1 to 4 and on days 1 , 8 , 22 , and 29 during cycles 5 to 9 . The primary end point was the time to disease progression . RESULTS The time to progression among patients receiving bortezomib plus melphalan-prednisone ( bortezomib group ) was 24.0 months , as compared with 16.6 months among those receiving melphalan-prednisone alone ( control group ) ( hazard ratio for the bortezomib group , 0.48 ; P<0.001 ) . The proportions of patients with a partial response or better were 71 % in the bortezomib group and 35 % in the control group ; complete-response rates were 30 % and 4 % , respectively ( P<0.001 ) . The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group . The hazard ratio for overall survival was 0.61 for the bortezomib group ( P=0.008 ) . Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan-prednisone . Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group ( 53 % vs. 44 % , P=0.02 ) , but there were no significant differences in grade 4 events ( 28 % and 27 % , respectively ) or treatment-related deaths ( 1 % and 2 % ) . CONCLUSIONS Bortezomib plus melphalan-prednisone was superior to melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy . ( Clinical Trials.gov number , NCT00111319 . OBJECTIVES Bone disease is a key presenting feature of myeloma . This post hoc analysis of the phase III VISTA trial of bortezomib plus melphalan-prednisone ( VMP ) vs. MP in previously untreated myeloma patients assessed clinical bone disease events and changes in alkaline phosphatase ( ALP ) , a marker for osteoblast activation , and serum Dickkopf-1 ( DKK-1 ) , an inhibitor of osteoblast differentiation , during treatment . METHODS Patients received nine 6-wk cycles of VMP ( bortezomib 1.3 mg/m(2 ) , days 1 , 4 , 8 , 11 , 22 , 25 , 29 , 32 , cycles 1 - 4 , days 1 , 8 , 22 , 29 , cycles 5 - 9 , plus melphalan 9mg/m(2 ) and prednisone 60mg/m(2 ) , days 1 - 4 , cycles 1 - 9 ; N=344 ) or MP alone ( N=338 ) . RESULTS Rates of bisphosphonates use during treatment ( 73 % vs. 82 % ) , progression because of worsening bone disease ( 3 % vs. 11 % ) , and requirement for subsequent radiotherapy ( 3 % vs. 8 % ) were lower with VMP vs. MP . Median maximum ALP increase was significantly higher with VMP vs. MP overall ( 49.7 % vs. 30.3 % , P=0.029 ) , and higher by response group ( complete response [ CR ] : 68.7 % vs. 43.9 % ; partial response [ PR ] : 41.5 % vs. 31.2 % ) . Greater maximum ALP increase was strongly associated with achievement of CR ( P≤0.0001 ) and CR/PR ( P≤0.01 ) . Median DKK-1 decreased with VMP by 694.4pg/mL and increased with MP by 1273.3pg/mL from baseline to day 4 ( P=0.0069 ) . Available radiologic data revealed evidence of bone healing in 6/11 VMP-treated patients , who achieved best responses of three CR , one PR , and two stable disease . CONCLUSIONS These results suggest a positive effect of bortezomib on bone metabolism and potentially bone healing in myeloma PURPOSE The US community-based , phase IIIB UPFRONT trial was design ed to compare three frontline bortezomib-based regimens in transplantation-ineligible patients with myeloma . PATIENTS AND METHODS Patients ( N = 502 ) were r and omly assigned 1:1:1 to 24 weeks ( eight 21-day cycles ) of induction with bortezomib-dexamethasone ( VD ; n = 168 ; intravenous bortezomib 1.3 mg/m(2 ) , days 1 , 4 , 8 , and 11 plus oral dexamethasone 20 mg , days 1 , 2 , 4 , 5 , 8 , 9 , 11 , and 12 [ cycles 1 to 4 ] , or 1 , 2 , 4 , and 5 [ cycles 5 to 8 ] ) , bortezomib-thalidomide-dexamethasone ( VTD ; n = 167 ; bortezomib and dexamethasone as before plus oral thalidomide 100 mg , days 1 to 21 ) , or bortezomib-melphalan-prednisone ( VMP ; n = 167 ; bortezomib as before plus oral melphalan 9 mg/m(2 ) and oral prednisone 60 mg/m(2 ) , days 1 to 4 , every other cycle ) , followed by 25 weeks ( five 35-day cycles ) of bortezomib maintenance ( 1.6 mg/m(2 ) , days 1 , 8 , 15 , and 22 ) . The primary end point was progression-free survival . RESULTS After 42.7 months ' median follow-up , median progression-free survival with VD , VTD , and VMP was 14.7 , 15.4 , and 17.3 months , respectively ; median overall survival was 49.8 , 51.5 , and 53.1 months , with no significant differences among treatments for either end point ( global P = .46 and P = .79 , respectively , Wald test ) . Overall response rates were 73 % ( VD ) , 80 % ( VTD ) , and 70 % ( VMP ) . Adverse events were more common with VTD than VD or VMP . Bortezomib maintenance was feasible without producing cumulative toxicity . CONCLUSION Although all bortezomib-containing regimens produced good outcomes , VTD and VMP did not appear to offer an advantage over VD in transplantation-ineligible patients with myeloma treated in US community practice BACKGROUND Patients with myeloma who relapse after high-dose chemotherapy have few therapeutic options . Since increased bone marrow vascularity imparts a poor prognosis in myeloma , we evaluated the efficacy of thalidomide , which has antiangiogenic properties , in patients with refractory disease . METHODS Eighty-four previously treated patients with refractory myeloma ( 76 with a relapse after high-dose chemotherapy ) received oral thalidomide as a single agent for a median of 80 days ( range , 2 to 465 ) . The starting dose was 200 mg daily , and the dose was increased by 200 mg every two weeks until it reached 800 mg per day . Response was assessed on the basis of a reduction of the myeloma protein in serum or Bence Jones protein in urine that lasted for at least six weeks . RESULTS The serum or urine levels of paraprotein were reduced by at least 90 percent in eight patients ( two had a complete remission ) , at least 75 percent in six patients , at least 50 percent in seven patients , and at least 25 percent in six patients , for a total rate of response of 32 percent . Reductions in the paraprotein levels were apparent within two months in 78 percent of the patients with a response and were associated with decreased numbers of plasma cells in bone marrow and increased hemoglobin levels . The microvascular density of bone marrow did not change significantly in patients with a response . At least one third of the patients had mild or moderate constipation , weakness or fatigue , or somnolence . More severe adverse effects were infrequent ( occurring in less than 10 percent of patients ) , and hematologic effects were rare . As of the most recent follow-up , 36 patients had died ( 30 with no response and 6 with a response ) . After 12 months of follow-up , Kaplan-Meier estimates of the mean ( + /-SE ) rates of event-free survival and overall survival for all patients were 22+/-5 percent and 58+/-5 percent , respectively . CONCLUSIONS Thalidomide is active against advanced myeloma . It can induce marked and durable responses in some patients with multiple myeloma , including those who relapse after high-dose chemotherapy This phase 3 trial ( Eastern Cooperative Oncology Group [ ECOG ] E1A06 ) compared melphalan , prednisone , and thalidomide ( MPT-T ) with melphalan , prednisone , and lenalidomide ( mPR-R ) in patients with untreated multiple myeloma ( MM ) . A noninferiority design was used , and inferiority was defined as a progression-free survival ( PFS ) hazard ratio ( HR ) of MPT-T/mPR-R ≤0.82 . A total of 306 patients enrolled , with a median age of 75.7 years . Median follow-up was 40.7 months . Median time on therapy was 12.1 months and 23.1 months for the 46.6 % of treated patients who received maintenance , with no differences by arm . Median PFS was 21 months on MPT-T and 18.7 months on mPR-R ( HR , 0.84 ; 95 % confidence interval , 0.64 - 1.09 ) . Overall survival was 52.6 months ( MPT-T ) vs 47.7 months ( mPR-R ) ( P = .476 ) . Per- protocol response rates were 63.6 % ( MPT-T ) and 59.9 % ( mPR-R ) ( P = .557 ) . Grade ≥3 nonhematologic toxicity was 59.5 % for MPT-T vs 40.0 % for mPR-R ( P = .001 ) . Second malignancies were observed in 18 MPT-T patients vs 14 mPR-R patients . Quality -of-life analysis favored mPR-R by induction end ( P = .007 ) . Use of MPT-T or mPR-R in elderly patients with untreated MM demonstrates no statistical or clinical ly relevant differences in response rates , PFS , and OS ; however , quality of life at end of induction was improved and lower toxicity reported with mPR-R. This trial was registered at www . clinical trials.gov as # NCT00602641 PURPOSE To provide up date d recommendations about prophylaxis and treatment of venous thromboembolism ( VTE ) in patients with cancer . METHODS PubMed and the Cochrane Library were search ed for r and omized controlled trials ( RCTs ) and meta-analyses of RCTs published from August 1 , 2014 , through December 4 , 2018 . ASCO convened an Expert Panel to review the evidence and revise previous recommendations as needed . RESULTS The systematic review included 35 publications on VTE prophylaxis and treatment and 18 publications on VTE risk assessment . Two RCTs of direct oral anticoagulants ( DOACs ) for the treatment of VTE in patients with cancer reported that edoxaban and rivaroxaban are effective but are linked with a higher risk of bleeding compared with low-molecular-weight heparin ( LMWH ) in patients with GI and potentially genitourinary cancers . Two additional RCTs reported on DOACs for thromboprophylaxis in ambulatory patients with cancer at increased risk of VTE . RECOMMENDATIONS Changes to previous recommendations : Clinicians may offer thromboprophylaxis with apixaban , rivaroxaban , or LMWH to selected high-risk out patients with cancer ; rivaroxaban and edoxaban have been added as options for VTE treatment ; patients with brain metastases are now addressed in the VTE treatment section ; and the recommendation regarding long-term postoperative LMWH has been exp and ed . Re-affirmed recommendations : Most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis throughout hospitalization . Thromboprophylaxis is not routinely recommended for all out patients with cancer . Patients undergoing major cancer surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days . Patients with cancer should be periodically assessed for VTE risk , and oncology professionals should provide patient education about the signs and symptoms of VTE.Additional information is available at www.asco.org/supportive-care- guidelines BACKGROUND The combination of bortezomib , melphalan , and prednisone is a st and ard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem‐cell transplantation . Daratumumab has shown efficacy in combination with st and ard‐of‐care regimens in patients with relapsed or refractory multiple myeloma . METHODS In this phase 3 trial , we r and omly assigned 706 patients with newly diagnosed multiple myeloma who were ineligible for stem‐cell transplantation to receive nine cycles of bortezomib , melphalan , and prednisone either alone ( control group ) or with daratumumab ( daratumumab group ) until disease progression . The primary end point was progression‐free survival . RESULTS At a median follow‐up of 16.5 months in a prespecified interim analysis , the 18‐month progression‐free survival rate was 71.6 % ( 95 % confidence interval [ CI ] , 65.5 to 76.8 ) in the daratumumab group and 50.2 % ( 95 % CI , 43.2 to 56.7 ) in the control group ( hazard ratio for disease progression or death , 0.50 ; 95 % CI , 0.38 to 0.65 ; P<0.001 ) . The overall response rate was 90.9 % in the daratumumab group , as compared with 73.9 % in the control group ( P<0.001 ) , and the rate of complete response or better ( including stringent complete response ) was 42.6 % , versus 24.4 % ( P<0.001 ) . In the daratumumab group , 22.3 % of the patients were negative for minimal residual disease ( at a threshold of 1 tumor cell per 105 white cells ) , as compared with 6.2 % of those in the control group ( P<0.001 ) . The most common adverse events of grade 3 or 4 were hematologic : neutropenia ( in 39.9 % of the patients in the daratumumab group and in 38.7 % of those in the control group ) , thrombocytopenia ( in 34.4 % and 37.6 % , respectively ) , and anemia ( in 15.9 % and 19.8 % , respectively ) . The rate of grade 3 or 4 infections was 23.1 % in the daratumumab group and 14.7 % in the control group ; the rate of treatment discontinuation due to infections was 0.9 % and 1.4 % , respectively . Daratumumab‐associated infusion‐related reactions occurred in 27.7 % of the patients . CONCLUSIONS Among patients with newly diagnosed multiple myeloma who were ineligible for stem‐cell transplantation , daratumumab combined with bortezomib , melphalan , and prednisone result ed in a lower risk of disease progression or death than the same regimen without daratumumab . The daratumumab‐containing regimen was associated with more grade 3 or 4 infections . ( Funded by Janssen Research and Development ; ALCYONE Clinical Trials.gov number , NCT02195479 . There are currently no direct head‐to‐head clinical trials evaluating bortezomib‐melphalan‐prednisone ( VMP ) versus lenalidomide and low‐dose dexamethasone ( Rd ) . VMP ( 257 cases ) and Rd ( 222 cases ) arms of two r and omized phase III trials were employed to assess the treatment influence on outcome in untreated elderly MM patients BACKGROUND Lenalidomide plus dexamethasone is a reference treatment for patients with newly diagnosed myeloma . The combination of the proteasome inhibitor bortezomib with lenalidomide and dexamethasone has shown significant efficacy in the setting of newly diagnosed myeloma . We aim ed to study whether the addition of bortezomib to lenalidomide and dexamethasone would improve progression-free survival and provide better response rates in patients with previously untreated multiple myeloma who were not planned for immediate autologous stem-cell transplant . METHODS In this r and omised , open-label , phase 3 trial , we recruited patients with newly diagnosed multiple myeloma aged 18 years and older from participating Southwest Oncology Group ( SWOG ) and National Clinical Trial Network ( NCTN ) institutions ( both inpatient and outpatient setting s ) . Key inclusion criteria were presence of CRAB ( C = calcium elevation ; R = renal impairment ; A = anaemia ; B = bone involvement ) criteria with measurable disease ( measured by assessment of free light chains ) , Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 3 , haemoglobin concentration 9 g/dL or higher , absolute neutrophil count 1 × 103 cells per mm3 or higher , and a platelet count of 80 000/mm3 or higher . We r and omly assigned ( 1:1 ) patients to receive either an initial treatment of bortezomib with lenalidomide and dexamethasone ( VRd group ) or lenalidomide and dexamethasone alone ( Rd group ) . R and omisation was stratified based on International Staging System stage ( I , II , or III ) and intent to transplant ( yes vs no ) . The VRd regimen was given as eight 21-day cycles . Bortezomib was given at 1·3 mg/m2 intravenously on days 1 , 4 , 8 , and 11 , combined with oral lenalidomide 25 mg daily on days 1 - 14 plus oral dexamethasone 20 mg daily on days 1 , 2 , 4 , 5 , 8 , 9 , 11 , and 12 . The Rd regimen was given as six 28-day cycles . The st and ard Rd regimen consisted of 25 mg oral lenalidomide once a day for days 1 - 21 plus 40 mg oral dexamethasone once a day on days 1 , 8 , 15 , and 22 . The primary endpoint was progression-free survival using a prespecified one-sided stratified log rank test at a significance level of 0·02 . Analyses were intention to treat . This trial is registered with Clinical Trials.gov , number NCT00644228 . FINDINGS Between April , 2008 , and February , 2012 , we r and omly assigned 525 patients at 139 participating institutions ( 264 to VRd and 261 to Rd ) . In the r and omly assigned patients , 21 patients in the VRd group and 31 in the Rd group were deemed ineligible based mainly on missing , insufficient , or early or late baseline laboratory data . Median progression-free survival was significantly improved in the VRd group ( 43 months vs 30 months in the Rd group ; stratified hazard ratio [ HR ] 0·712 , 96 % CI 0·56 - 0·906 ; one-sided p value 0·0018 ) . The median overall survival was also significantly improved in the VRd group ( 75 months vs 64 months in the Rd group , HR 0·709 , 95 % CI 0·524 - 0·959 ; two-sided p value 0·025 ) . The rates of overall response ( partial response or better ) were 82 % ( 176/216 ) in the VRd group and 72 % ( 153/214 ) in the Rd group , and 16 % ( 34/216 ) and 8 % ( 18/214 ) of patients who were assessable for response in these respective groups had a complete response or better . Adverse events of grade 3 or higher were reported in 198 ( 82 % ) of 241 patients in the VRd group and 169 ( 75 % ) of 226 patients in the Rd group ; 55 ( 23 % ) and 22 ( 10 % ) patients discontinued induction treatment because of adverse events , respectively . There were no treatment-related deaths in the Rd group , and two in the VRd group . INTERPRETATION In patients with newly diagnosed myeloma , the addition of bortezomib to lenalidomide and dexamethasone result ed in significantly improved progression-free and overall survival and had an acceptable risk-benefit profile . FUNDING NIH , NCI , NCTN , Millennium Pharmaceuticals , Takeda Oncology Company , and Celgene Corporation Results from a r and omised phase 3 trial show that the addition of daratumumab to the st and ard treatment regimen of bortezomib , melphalan , and prednisone improves progression-free survival in patients with multiple myeloma who are ineligible for stem-cell transplantation . In the study by Maria-Victoria Mateos ( University of Salamanca , Salamanca , Spain ) and colleagues , 706 patients with newly diagnosed multiple myeloma who were not eligible for stem-cell transplantation were enrolled and r and omly assigned in a 1:1 ratio to receive nine cycles of bortezomib , melphalan , and prednisone with daratumumab ( n=350 ) or without daratumumab ( control group ; n=356 ) . The primary endpoint was progressionfree survival . Secondary endpoints included overall response and safety . On the basis of a prespecified interim analysis done at a median follow-up of 16·5 months , when 231 events of disease progression or death had occurred ( 88 in the daratumumab group vs 143 in the control group ) , median progressionfree survival was not estimable in the daratumumab group versus 18·1 months in the control group ( hazard ratio 0·50 [ 95 % CI 0·38–0·65 ] , p<0·001 ) . Estimated progressionfree survival at 18 months was 71·6 % ( 95 % CI 65·5–76·8 ) in the daratumumab group and 50·2 % ( 43·2–56·7 ) in the control group . The number of patients who achieved an overall response was 318 ( 90·9 % [ 95 % CI 87·3–93·7 ] ) of 350 in the daratumumab group versus 263 ( 73·9 % [ 69·0–78·4 ] ) of 356 in the control group . Common grade 3–4 adverse events included neutropenia in 138 ( 39·9 % ) of 346 patients in the daratumumab group versus 137 ( 38·7 % ) of 354 in the control group , thrombocytopenia in 119 ( 34·4 % ) versus 133 ( 37·6 % ) , and anaemia in 55 ( 15·9 % ) versus 70 ( 19·8 % ) . Mateos said , “ Our results support the use of this regimen with daratumumab as st and ard of care for newly diagnosed myeloma patients who are not eligible for transplant . Ongoing trials will evaluate the role of daratumumab in combination with other backbones for this population and could explore intensification of bortezomib administration beyond cycle nine ” . Gordon Cook ( St James ’s University Hospital , Leeds , UK ) added , “ This is the first of several frontline studies that demonstrate the superiority of adding an active monoclonal antibody to novel agent backbones in terms of disease response durability . Daratumumab is clearly a significant agent in myeloma treatment ” The initial analysis of the oral combination melphalan , prednisone , and thalidomide ( MPT ) in newly diagnosed patients with myeloma showed significantly higher response rate and longer progression-free survival ( PFS ) than did the st and ard melphalan and prednisone ( MP ) combination and suggested a survival advantage . In this up date d analysis , efficacy and safety end points were up date d. Patients were r and omly assigned to receive oral MPT or MP alone . Up date d analysis was by intention to treat and included PFS , overall survival ( OS ) , and survival after progression . After a median follow-up of 38.1 months , the median PFS was 21.8 months for MPT and 14.5 months for MP ( P = .004 ) . The median OS was 45.0 months for MPT and 47.6 months for MP ( P = .79 ) . In different patient subgroups , MPT improved PFS irrespective of age , serum concentrations of beta(2)-microglobulin , or high International Staging System . Thalidomide or bortezomib administration as salvage regimens significantly improved survival after progression in the MP group ( P = .002 ) but not in the MPT group ( P = .34 ) . These data confirm activity of MPT for PFS but failed to show any survival advantage . New agents in the management of relapsed disease could explain this finding . The study is registered at www . clinical trials.gov as # NCT00232934 The phase 3 Velcade as Initial St and ard Therapy in Multiple Myeloma : Assessment with Melphalan and Prednisone study in newly diagnosed multiple myeloma patients ineligible for high-dose therapy demonstrated that bortezomib-melphalan-prednisone ( VMP ) was superior to melphalan-prednisone across all efficacy end points . We assessed the prognostic impact of response on time-to-event parameters in the intent-to-treat population . Patients received nine 6-week cycles of treatment . Time to progression , time to next therapy , and treatment-free interval were associated with quality of response . When European Group for Blood and Marrow Transplantation criteria were used , complete response ( CR ) was associated with significantly longer time to progression ( hazard ratio [ HR ] = 0.45 , P = .004 ) , time to next therapy ( HR = 0.46 , P = .0004 ) , and treatment-free interval ( HR = 0.38 , P < .0001 ) versus partial response , but there was no significant difference in overall survival ( HR = 0.87 , P = .54 ) ; similar differences were seen with CR versus very good partial response by uniform criteria . Quality of response improved with prolonged VMP treatment , with 28 % of CRs achieved during cycles 5 - 9 . CR duration appeared similar among patients with " early " ( cycles 1 - 4 ) and " late " CRs ( cycles 5 - 9 ) and among patients receiving 9 versus < 9 cycles of bortezomib within VMP . These results highlight that CR is an important treatment goal and support prolonged VMP therapy to achieve maximal response . This study is registered at http://www . clinical trials.gov as NCT00111319 The Southwest Oncology Group conducted a r and omized trial comparing lenalidomide ( LEN ) plus dexamethasone ( DEX ; n = 97 ) to placebo ( PLC ) plus DEX ( n = 95 ) in newly diagnosed myeloma . Three 35-day induction cycles applied DEX 40 mg/day on days 1 to 4 , 9 to 12 , and 17 to 20 together with LEN 25 mg/day for 28 days or PLC . Monthly maintenance used DEX 40 mg/day on days 1 to 4 and 15 to 18 along with LEN 25 mg/day for 21 days or PLC . Crossover from PLC-DEX to LEN-DEX was encouraged on progression . One-year progression-free survival , overall response rate , and very good partial response rate were superior with LEN-DEX ( 78 % vs 52 % , P = .002 ; 78 % vs 48 % , P < .001 ; 63 % vs 16 % , P < .001 ) , whereas 1-year overall survival was similar ( 94 % vs 88 % ; P = .25 ) . Toxicities were more pronounced with LEN-DEX ( neutropenia grade 3 or 4 : 21 % vs 5 % , P < .001 ; thromboembolic events despite aspirin prophylaxis : 23.5 % [ initial LEN-DEX or crossover ] vs 5 % ; P < .001 ) . This trial was registered at www . clinical trials.gov as # NCT00064038 Lenalidomide-dexamethasone improved outcome in newly diagnosed elderly multiple myeloma patients . We r and omly assigned 662 patients who were age ≥65 years or transplantation-ineligible to receive induction with melphalan-prednisone-lenalidomide ( MPR ) or cyclophosphamide-prednisone-lenalidomide ( CPR ) or lenalidomide plus low-dose dexamethasone ( Rd ) . The primary end point was progression-free survival ( PFS ) in triplet ( MPR and CPR ) vs doublet ( Rd ) lenalidomide-containing regimens . After a median follow-up of 39 months , the median PFS was 22 months for the triplet combinations and 21 months for the doublet ( P = .284 ) . The median overall survival ( OS ) was not reached in either arms , and the 4-year OS was 67 % for the triplet and 58 % for the doublet arms ( P = .709 ) . By considering the 3 treatment arms separately , no difference in outcome was detected among MPR , CPR , and Rd . The most common grade ≥3 toxicity was neutropenia : 64 % in MPR , 29 % in CPR , and 25 % in Rd patients ( P < .0001 ) . Grade ≥3 nonhematologic toxicities were similar among arms and were mainly infections ( 6.5 % to 11 % ) , constitutional ( 3.5 % to 9.5 % ) , and cardiac ( 4.5 % to 6 % ) , with no difference among the arms . In conclusion , in the overall population , the alkylator-containing triplets MPR and CPR were not superior to the alkylator-free doublet Rd , which was associated with lower toxicity . This study was registered at www . clinical trials.gov as # NCT01093196 PURPOSE The long-term impact of thalidomide plus dexamethasone ( thal/dex ) as primary therapy for newly diagnosed multiple myeloma ( MM ) is unknown . The goal of this study was to compare thalidomide plus dexamethasone versus placebo plus dexamethasone (placebo/dex)as primary therapy for newly diagnosed MM . PATIENTS AND METHODS In this double-blind , placebo-controlled trial , patients with untreated symptomatic MM were r and omized to thal/dex ( arm A ) or to placebo plus dexamethasone ( dex ) ( arm B ) . Patients in arm A received oral thalidomide 50 mg daily , escalated to 100 mg on day 15 , and to 200 mg from day 1 of cycle 2 ( 28-day cycles ) . Oral dex 40 mg was administered on days 1 through 4 , 9 through 12 , and 17 through 20 during cycles 1 through 4 and on days 1 through 4 only from cycle 5 onwards . Patients in arm B received placebo and dex , administered as in arm A. The primary end point of the study was time to progression . This study is registered at http:// Clinical Trials.gov ( NCT00057564 ) . RESULTS A total of 470 patients were enrolled ( 235 r and omly assigned to thal/dex and 235 to placebo/dex ) . The overall response rate was significantly higher with thal/dex compared with placebo/dex ( 63 % v 46 % ) , P < .001 . Time to progression ( TTP ) was significantly longer with thal/dex compared with placebo/dex ( median , 22.6 v 6.5 months , P < .001 ) . Grade 4 adverse events were more frequent with thal/dex than with placebo/dex ( 30.3 % v 22.8 % ) . CONCLUSION Thal/dex results in significantly higher response rates and significantly prolongs TTP compared with dexamethasone alone in patients with newly diagnosed MM PURPOSE Until recently , melphalan and prednisone were the st and ards of care in elderly patients with multiple myeloma . The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years . This r and omized , placebo-controlled , phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma . PATIENTS AND METHODS Between April 2002 and December 2006 , 232 previously untreated patients with myeloma , age 75 years or older , were enrolled and 229 were r and omly assigned to treatment . All patients received melphalan ( 0.2 mg/kg/d ) plus prednisone ( 2 mg/kg/d ) for 12 courses ( day 1 to 4 ) every 6 weeks . Patients were r and omly assigned to receive 100 mg/d of oral thalidomide ( n = 113 ) or placebo ( n = 116 ) , continuously for 72 weeks . The primary end point was overall survival . RESULTS After a median follow-up of 47.5 months , overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo ( median , 44.0 v 29.1 months ; P = .028 ) . Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group ( median , 24.1 v 18.5 months ; P = .001 ) . Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group : grade 2 to 4 peripheral neuropathy ( 20 % v 5 % in the melphalan and prednisone plus placebo group ; P < .001 ) and grade 3 to 4 neutropenia ( 23 % v 9 % ; P = .003 ) . CONCLUSION This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma . Toxicity was acceptable PURPOSE To assess bortezomib plus melphalan and prednisone ( VMP ) and melphalan and prednisone ( MP ) in previously untreated patients with multiple myeloma ( MM ) with renal impairment enrolled on the phase III VISTA study , and to evaluate renal impairment reversibility . PATIENTS AND METHODS Patients received nine 6-week cycles of VMP ( bortezomib 1.3 mg/m(2 ) , melphalan 9 mg/m(2 ) , prednisone 60 mg/m(2 ) ) or MP . Patients with serum creatinine higher than 2 mg/dL were excluded . Results In the VMP/MP arms , 6%/4 % , 27%/30 % , and 67%/66 % of patients had baseline glomerular filtration rate ( GFR ) of < or = 30 , 31 to 50 , and higher than 50 mL/min , respectively . Response rates were higher and time to progression ( TTP ) and overall survival ( OS ) longer with VMP versus MP across renal cohorts . Response rates with VMP and TTP in both arms did not appear significantly different between patients with GFR < or = 50 or higher than 50 mL/min ; OS appeared somewhat longer in patients with normal renal function in both arms . Renal impairment reversal ( baseline GFR < 50 improving to > 60 mL/min ) was seen in 49 ( 44 % ) of 111 patients receiving VMP versus 40 ( 34 % ) of 116 patients receiving MP . By multivariate analysis , younger age ( < 75 years ; P = .006 ) and less severe impairment ( GFR > or = 30 mL/min ; P = .027 ) were associated with higher reversal rates . In addition , treatment with VMP approached significance ( P = .07 ) . In both arms , rates of grade 4 and 5 adverse events ( AEs ) and serious AEs appeared higher in patients with renal impairment ; with VMP , rates of discontinuations/bortezomib dose reductions due to AEs did not appear affected . CONCLUSION VMP is a feasible , active , and well-tolerated treatment option for previously untreated patients with MM with moderate renal impairment , result ing in 44 % renal impairment reversal The MM-015 trial assessed the effect of lenalidomide-based therapy on health-related quality of life . Patients ( n=459 ) with newly diagnosed multiple myeloma aged 65 years or over were r and omized 1:1:1 to nine 4-week cycles of lenalidomide , melphalan , and prednisone , followed by lenalidomide maintenance ; or lenalidomide , melphalan , and prednisone , or melphalan and prednisone , with no maintenance therapy . Patients completed health-related quality of life question naires at baseline , after every third treatment cycle , and at treatment end . Health-related quality of life improved in all treatment groups during induction therapy . Patients receiving lenalidomide maintenance had the most pronounced improvements , Global Health Status/ Quality of Life ( P<0.05 ) , Physical Functioning ( P<0.01 ) , and Side Effects of Treatment ( P<0.05 ) out of 6 pre-selected health-related quality of life domains . More patients receiving lenalidomide maintenance achieved minimal important differences ( P<0.05 for Physical Functioning ) . Therefore , lenalidomide , melphalan , and prednisone , followed by lenalidomide maintenance , improves health-related quality of life in patients with newly diagnosed multiple myeloma . ( Clinical trials.gov identifier NCT00405756 ) |
11,992 | 31,893,034 | The seasonality of RSV in the WPR countries follows the latitude , with the peak of RSV season occurring in the winter in temperate countries , and during the rainy season in tropical countries . | Background Respiratory syncytial virus ( RSV ) is the leading cause of viral pneumonia and bronchiolitis , especially in younger children .
The burden of RSV infection in adults , particularly in the older age group , is increasingly recognised .
However , RSV disease burden and molecular epidemiology in the World Health Organization ( WHO ) Western Pacific Region ( WPR ) has not been review ed systematic ally .
The aim of this systematic review is to investigate the epidemiological aspects of RSV ( incidence , prevalence , seasonality and hospitalisation status ) and the associated molecular data in the WPRO countries . | Objectives : To determine virologically confirmed hospitalization rates associated with respiratory syncytial virus ( RSV ) , adenovirus , and parainfluenza viruses in Hong Kong children . Methods : All patients < 18 years of age living on Hong Kong Isl and ( within Hong Kong SAR ) admitted for a febrile acute respiratory infection to 1 of the 2 public hospitals on 1 fixed day of the week between October 2003 and September 2006 were prospect ively recruited . Hong Kong Isl and has a known population denominator and these 2 hospitals managed 72.5 % of all general pediatric admissions for this population . Nasopharyngeal aspirates were tested for RSV , adenovirus , and parainfluenzae types 1 , 2 , and 3 by direct antigen detection and culture . Results : The annual hospitalization rate for RSV in infants < 6 months of age was 233.4 to 311.2 per 10,000 . Parainfluenza type 3 had a hospitalization rate of 27.3 to 122.8 per 10,000 in the 1 to < 2 years group . Adenovirus was associated with significant hospitalization in those 6 months to 1 year ( 25.9–77.8 per 10,000 ) , and in those 2 to < 5 years ( 38.1–59.2 per 10,000 ) . The mean duration of hospitalization for RSV was 4.04 ± 2.61 days , significantly longer than the 3.12 ± 1.41 days for adenovirus and the 2.93 ± 2.54 days for parainfluenza infections ( P = 0.013 and P = 0.038 , respectively ) . Conclusion : We documented that the overall pediatric hospitalization burden of RSV was high and comparable to that of influenza . The burden for all the studied viruses was mainly in previously healthy children < 5 years of age OBJECTIVE To explore the distribution and clinical manifestations of rhinovirus infection in wheezing children , and compare the clinical differences between rhinovirus- and respiratory syncytial virus-induced wheezing . MATERIAL S AND METHODS This prospect i ve cohort study was carried out in Children 's Hospital of Soochow University from Dec 2012 to Nov 2014 . We enrolled consecutive hospitalized children < 60 months of age presented with wheezing . Clinical data including cough , fever , dyspnea , crackles were recorded by pediatricians on the first day of admission . Meanwhile , nasopharyngeal aspirates were obtained to test for respiratory viruses , by using polymerase chain reaction method for rhinovirus , human bocavirus , and human metapneumovirus , and direct immunofluorescence assay to test for respiratory syncytial virus , adenovirus , parainfluenza virus types 1 - 3 , and influenza virus types A and B. RESULTS Rhinovirus was a main causative agent isolated in 14.7 % of the hospitalized wheezing children in Suzhou , China , being second to respiratory syncytial virus ( 21.0 % ) . Different from respiratory syncytial virus infection , which peaked in winter months , rhinovirus could be detected all year round , peaked between July and September , and in November . Children with rhinovirus infection were older and presented with more often allergic sensitizations , blood eosinophilia , and leukocytosis than those of respiratory syncytial virus infection . Logistic regression analysis revealed that rhinovirus-infected children experienced earlier wheezing more often than respiratory syncytial virus children ( odds ratio , 3.441 ; 95 % confidence interval , 1.187 - 9.979 ; p=0.023 ) . CONCLUSION Rhinovirus was a main viral pathogen in wheezing children , especially in summer time . Rhinovirus-induced wheezing was different from respiratory syncytial virus , apart from seasonal epidemics ; these two groups differed with regard to age , allergic sensitizations , laboratory test , and history of wheezing episodes Background Human respiratory syncytial virus ( RSV ) is an important community and nosocomial pathogen in developed countries but data regarding the importance of RSV in developing countries are relatively scarce . Methods During a 1-year surveillance study in 2010 , we took serial sample s from children admitted to the Emergency Unit of the Respiratory Ward of Children 's Hospital 1 in Ho Chi Minh City , Vietnam . RSV was detected within 72 hours of admission to the ward in 26 % ( 376/1439 ; RSV A : n = 320 ; RSV B : n = 54 ; and RSV A and B : n = 2 ) . Among those negative in the first 72 hours after admission , 6·6 % ( 25/377 ) acquired nosocomial RSV infection during hospitalization ( RSV A : n = 22 ; and RSV B : n = 3 ) . Results Children with nosocomial RSV infection were younger ( P = 0·001 ) and had a longer duration of hospitalization ( P < 0·001 ) . The rate of incomplete recovery among children with nosocomial RSV infection was significantly higher than among those without ( P < 0·001 ) . Phylogenetic analysis of partial G gene sequences obtained from 79 % ( 316/401 ) of positive specimens revealed the co-circulation of multiple genotypes with RSV A NA1 being predominant ( A NA1 : n = 275 ; A GA5 : n = 5 ; B BA3 : n = 3 ; B BA9 : n = 26 ; and B BA10 : n = 7 ) . The RSV A GA5 and RSV B BA3 genotypes have not been reported from Vietnam , previously . Conclusion Besides emphasizing the importance of RSV as a cause of respiratory infection leading to hospitalization in young children and as a nosocomial pathogen , data from this study extend our knowledge on the genetic diversity of RSV circulating in Vietnam Background and objective Clinical characteristics of human bocavirus ( HBoV ) infection have been studied worldwide , but their importance of those characteristics remains unknown . We investigated distinctive clinical features of HBoV-positive children with lower respiratory tract infection ( LRTI ) . Methods and results During April 2007–July 2009 , for 402 hospitalized children younger than 2 years with LRTI , we prospect ively examined virus genomes in nasopharyngeal swabs for HBoV , respiratory syncytial virus ( RSV ) , rhinovirus , metapneumovirus , parainfluenzavirus , and adenovirus . The HBoV genomes were identified in 34 patients ( 8.5 % ) . Clinical and laboratory data of HBoV-positive and other virus/bacteria-negative patients ( n = 18 ) were analyzed and compared with data of RSV-single positive patients ( n = 99 ) . The seasonal distribution of HBoV exhibits a concentration of cases during March – September , with most RSV cases occurring during winter in Japan . The minimum age of HBoV-positive patients was 5 months , although 44 patients ( 44 % ) with RSV were younger than 6 months . The main clinical features were respiratory distress and hypoxia . Hypoxia advances within 3 days after onset . The mean oxygen saturation on arrival was 92.8 % , which was significantly lower than that in patients with RSV ( p < 0.001 ) . White blood cell counts were similar among groups . However , the percentage of neutrophils in white blood cells were significantly higher in HBoV-positive patients ( 62 vs. 45 % , p < 0.001 ) . Their prognoses were good . Their hospital stays were 6.6 days . Conclusions HBoV-single positive patients show several clinical characteristics , such as seasonality , age , hypoxia , and neutrophilia , which differ from those with RSV infection Summary In a multicenter , prospect i ve case-control study involving 1758 children aged < 5 years in developing and emerging countries , the main microorganisms associated with pneumonia were Streptococcus pneumoniae , human metapneumovirus , rhinovirus , and respiratory syncytial virus Background The dominant viral etiologies responsible for acute respiratory infections ( ARIs ) are poorly understood , particularly among hospitalized children in re source -limited tropical countries where morbidity and mortality caused by ARIs are highest . Improved etiological insight is needed to improve clinical management and prevention . Objectives We conducted a three-year prospect i ve descriptive study of severe respiratory illness among children from 2 months to 13 years of age within the largest referral hospital for infectious diseases in southern Vietnam . Methods Molecular detection for 15 viral species and subtypes was performed on three types of respiratory specimens ( nose , throat swabs and nasopharyngeal aspirates ) using a multiplex RT-PCR kit ( Seeplex ™ RV detection , Seegene ) and additional monoplex real-time RT-PCRs . Results A total of 309 children were enrolled from November 2004 to January 2008 . Viruses were identified in 72 % ( 222/309 ) of cases , including respiratory syncytial virus ( 24 % ) , influenza virus A and B ( 17 % ) , human bocavirus ( 16 % ) , enterovirus ( 9 % ) , human coronavirus ( 8 % ) , human metapneumovirus ( 7 % ) , parainfluenza virus 1–3 ( 6 % ) , adenovirus ( 5 % ) , and human rhinovirus A ( 4 % ) . Co-infections with multiple viruses were detected in 20 % ( 62/309 ) of patients . When combined , diagnostic yields in nose and throat swabs were similar to nasopharyngeal aspirates . Conclusion Similar to other parts in the world , RSV and influenza were the predominant viral pathogens detected in Vietnamese hospitalized children . Combined nasal and throat swabs are the specimens of choice for sensitive molecular detection of a broad panel of viral agents . Further research is required to better underst and the clinical significance of single versus multiple viral coinfections and to address the role of bacterial (co-)infections involved in severe respiratory illness Since the initial discovery of RSV-A ON1 in Canada in 2010 , ON1 has been reported worldwide , yet information regarding its clinical impact and severity has been controversial . To investigate the clinical relevance of RSV-A ON1,acute respiratory infection ( ARI ) cases enrolled to our population -based prospect i ve pediatric ARI surveillance at Khanh Hoa General Hospital , Central Vietnam from January 2010 through December 2012 were studied . Clinical -epidemiological information and nasopharyngeal sample s were collected . Multiplex PCR assays were performed for screening 13 respiratory viruses . RSV-positive sample s were further tested for subgroups ( A/B ) and genotypes information by sequencing the G-glycoprotein 2nd hypervariable region . Statistical analysis was performed to evaluate the clinical -epidemiological characteristics of RSV-A ON1 . A total of 1854 ARI cases were enrolled and 426 ( 23.0 % ) of them were RSV-positive . During the study period , RSV-A and B had been co-circulating . NA1 was the predominant RSV-A genotype until the appearance of ON1 in 2012 . RSV-related ARI hospitalization incidence significantly increased after the emergence of ON1 . Moreover , multivariate analysis revealed that risk of lower respiratory tract infection was 2.26 ( 95 % CI : 1.37–3.72 ) times , and radiologically-confirmed pneumonia was 1.98 ( 95 % CI : 1.01–3.87 ) times greater in ON1 compared to NA1 cases . Our result suggested that ON1 ARI cases were clinical ly more severe than NA1 BACKGROUND Respiratory syncytial virus ( RSV ) is the most important viral pathogen in infants and children . It is important to analyze RSV epidemic patterns and related relevant factors in order to prevent further infections and related complications . OBJECTIVE To explore the relationship between RSV infection rate in hospitalized children from Suzhou area and climatic factors . STUDY DESIGN 42,664 nasopharyngeal specimens from hospitalized children with acute respiratory infections were screened for RSV antigens using direct immunofluorescence . 472 RSV positive sample s were r and omly selected and performed real-time PCR to identify RSV subtype . Monthly meteorological data in Suzhou area was collected ( average temperature , relative humidity , precipitation , total sunshine , and average wind speed ) from 2001 to 2011 . The relation between RSV infections and climatic factors was evaluated using correlation and stepwise regression analyses . RESULTS The annual RSV infection rate in hospitalized children in Suzhou from 2001 to 2011 varied between 11.85 % and 27.30 % . The highest monthly infection rates occurred from November to April . The time interval from November to April was considered the infection season . Seasonal RSV infection rates from 2001 to 2010 were 40.75 % , 22.72 % , 39.93 % , 27.37 % , 42.71 % , 21.28 % , 38.57 % , 19.86 % , and 29.73 % . The infection rate of any season was statistically different from the next season . There was no significant difference in RSV infection rates in the 2010 - 2011 and 2009 - 2010 epidemic seasons . Among the 472 r and omly selected RSV positive sample s , 412 were found to be RSV subtype A ( RSV-A ) , while 60 subtype B ( RSV-B ) . The monthly RSV infection rate was negatively correlated with monthly average temperature ( r=-0.84 ) , total sunshine ( r=-0.47 ) , precipitation ( r=-0.31 ) , relative humidity ( r=-0.20 ) , and average wind speed ( r=-0.20 ) , ( P<0.05 ) . Stepwise regression analysis showed monthly average temperature fit into a linear model ( R(2)=0.64 , P<0.01 ) with a regression coefficient of -1.52 ( t=15.21 , P<0.01 ) . CONCLUSIONS RSV infection in Suzhou occurred most frequently between November and April . The number of infections peaked every other year . Abnormally high infection rate in non-epidemic season only caused by RSV-A. Ambient temperature played an important role in the development of RSV infection Comprehensive population -based data on the role of respiratory viruses in the development of lower respiratory tract infections ( LRTIs ) remain unclear . We investigated the incidence and effect of single and multiple infections with respiratory viruses on the risk of LRTIs in Vietnam . Population -based prospect i ve surveillance and a case – control study of hospitalised paediatric patients with acute respiratory infection ( ARI ) were conducted from April 2007 through to March 2010 . Healthy controls were r and omly recruited from the same community . Nasopharyngeal sample s were collected and tested for 13 respiratory viruses using multiplex PCRs . 1992 hospitalised ARI episodes , including 397 ( 19.9 % ) with LRTIs , were enrolled . Incidence of hospitalised LRTIs among children aged < 24 months was 2171.9 per 100 000 ( 95 % CI 1947.9–2419.7 ) . The majority of ARI cases ( 60.9 % ) were positive for at least one virus . Human rhinovirus ( 24.2 % ) , respiratory syncytial virus ( 20.1 % ) and influenza A virus ( 12.0 % ) were the most common and 9.5 % had multiple-viral infections . Respiratory syncytial virus and human metapneumovirus infections independently increased the risk of LRTIs . Respiratory syncytial virus further increased the risk , when co-infected with human rhinovirus , human metapneumovirus and parainfluenza virus-3 but not with influenza A virus . The case – control analysis revealed that respiratory syncytial virus and influenza A virus increased the risk of ARI hospitalisation but not human rhinovirus . Respiratory syncytial virus is the leading pathogen associated with risk of ARI hospitalisation and LRTIs in Vietnam We performed a prospect i ve cohort study from September 2003 to December 2004 to delineate attributing the effect of different respiratory viral infections including newly discovered ones to asthma exacerbations in children in Hong Kong . One hundred and fourteen children aged 6–14 years with chronic stable asthma and on regular inhaled steroid were monitored for respiratory symptoms over a full calendar year from recruitment . They would attend the study clinic if peak expiratory flow rate decreased to below 80 % of their baselines , if they met a predefined symptom score , or if parents subjectively felt them developing a cold . Virological diagnosis using virus culture , antigen detection , and polymerase chain reaction methods on nasal swab specimens would be attempted for all these visits irrespective of triggers . Physician diagnosed outcome of each episode was documented . Three hundred and five episodes of respiratory illnesses were captured in the cohort . Nasal specimens were available in 166 episodes , 92 of which were diagnosed as asthma exacerbations , and 74 non-asthma related episodes . Respiratory viruses were detected in 61 of 166 episodes ( 36.7 % ) . There was no significant difference in virus detection rate between asthma exacerbations ( 32 out of 97 episodes , 34.8 % ) and non-asthma respiratory illnesses ( 29 out of 79 episodes , 39.2 % ) . Although newly discovered respiratory viruses were identified in these episodes , rhinovirus was the commonest organism associated with both asthma exacerbations and non-asthma related episodes . Plausible explanations for much lower virus detection rate than previously reported include improved personal hygiene and pre caution ary measures taken during respiratory tract infections in the immediate post-severe acute respiratory syndrome period together with a significant contribution of other adverse factors like environmental air pollution . We conclude that not all viral infections in children with asthma lead to an asthma exacerbation and the attributing effect of different triggers of asthma exacerbations in children vary across different time periods and across different localities Background / Purpose To investigate the prevalence of common viruses and Mycoplasma pneumoniae ( MP ) in hospitalized infants with acute bronchiolitis and study the relationship between bronchiolitis and meteorological conditions . Methods A 2-year prospect i ve study was conducted on infants with a first episode of bronchiolitis admitted to Respiratory Department of Suzhou Children 's Hospital . Demographic and clinical characteristics and meteorological conditions were obtained and analyzed . Results Pathogens were identified in 59.6 % of 998 cases analyzed . The most frequent pathogen identified was respiratory syncytial virus ( 28.7 % ) , followed by human bocavirus ( 11.6 % ) , MP ( 9.0 % ) , human parainfluenza virus-3 ( 7.8 % ) , human metapneumovirus ( 6.6 % ) , influenza A ( 3.5 % ) , adenovirus ( 1.0 % ) , and human parainfluenza virus-1 ( 0.3 % ) . The clinical scores in children with MP or human metapneumovirus single infections , based on the assessment of severity of acute bronchiolitis , were significantly lower than in children with respiratory syncytial virus single infections . Respiratory syncytial virus had the strongest inverse correlation with mean temperature , followed by influenza A and human metapneumovirus . In addition , MP and human parainfluenza virus-3 showed positive correlations with mean temperature . Conclusion Although respiratory syncytial virus was the most frequent pathogen in patients in whom bronchiolitis was diagnosed , other pathogens , including newly identified viruses and MP , also play important roles in infants with bronchiolitis . Different respiratory pathogens have different traits in response to certain meteorological conditions Children and elderly individuals are often infected easily and repeatedly with human respiratory syncytial virus ( HRSV ) ; however , the features of recurrent infection in the same individual are defined poorly . To clarify the clinical significance of repeated HRSV infections in relation to subgroup epidemiology , this study performed prospect i ve and longitudinal analyses in children with lower respiratory tract infections over 20 consecutive epidemics between 1985 and 2005 at a pediatric outpatient clinic in Kawasaki , Japan . HRSV infections were confirmed by 2 types of reverse-transcription PCR . Sample s obtained from patients with repeated infections were subjected to sequence analysis and cloning analysis . A total of 1,312 lower respiratory tract infections observed in 1,010 patients were diagnosed as HRSV infections . Repeated HRSV infections occurred in 208 of the 1,010 patients . Analysis of the patients with repeated infections revealed that children were often infected multiple times even within a single short epidemic . Some patients were re-infected with strains having the same or virtually identical N gene sequences . In patients infected more than 4 times , cloning analysis revealed more frequent dual infections with both subgroups ( 23.8 % ) . The HRSV-A subgroup caused subsequent homologous infections more frequently than did HRSV-B ; furthermore , HRSV-A infections provided no protection from a second homologous infection . In contrast , HRSV-B infections offered significant protection against a second homologous infection . Statistical analysis revealed alleviation of symptoms with a reduced rate of dyspnoeic attacks only in the group re-infected with homologous HRSV-A strains . Thus , this study eluci date s new clinical features of recurrent HRSV infection . J. Med . Virol 86 : 1629–1638 , 2014 Human bocavirus ( HBoV ) is a parvovirus and detected worldwide in lower respiratory tract infections ( LRTIs ) , but its pathogenic role in respiratory illness is still debatable due to high incidence of co-infection with other respiratory viruses . To determine the prevalence of HBoV infection in patients with LRTI in Shanghai and its correlation with disease severity , we performed a 3-year prospect i ve study of HBoV in healthy controls , out patients and in patients under five years of age with X-ray diagnosed LRTIs . Nasopharyngeal aspirates were tested by PCR for common respiratory viruses and by real time PCR for HBoV subtypes 1–4 . Nasopharyngeal swabs from healthy controls and serum sample s and stools from in patients were also tested for HBoV1 - 4 by real time PCR . Viral loads were determined by quantitative real time PCR in all HBoV positive sample s. HBoV1 was detected in 7.0 % of in patients , with annual rates of 5.1 % , 8.0 % and 4.8 % in 2010 , 2011 and 2012 , respectively . Respiratory syncytial virus ( RSV ) subtype A was the most frequent co-infection detected ; HBoV1 and RSVA appeared to co-circulate with similar seasonal variations . High HBoV viral loads ( > 106 copies/ml ) were significantly more frequent in in patients and out patients than in healthy controls . There was a direct correlation of high viral load with increasing disease severity in patients co-infected with HBoV1 and at least one other respiratory virus . In summary , our data suggest that HBoV1 can cause LRTIs , but symptomatic HBoV infection is only observed in the context of high viral load Background Although acute bronchitis is quite common , there is relatively limited information regarding the microorganisms that are involved in this illness . Methods We performed a prospect i ve study of acute bronchitis at 31 hospitals and clinics in Korea from July 2011 to June 2012 . Sputum specimens were collected for polymerase chain reaction ( PCR ) and culture of microorganisms . Results Of the 811 enrolled patients , 291 had acceptable sputum specimens that were included for analysis of the etiologic distribution . With multiplex PCR testing , viruses were identified in 36.1 % ( 105/291 ) , most commonly rhinovirus ( 25.8 % ) and coronavirus ( 3.8 % ) . Typical bacteria were isolated in 126/291 ( 43.3 % ) patients . Among these patients Haemophilus influenzae ( n = 39 ) and Streptococcus pneumoniae ( n = 30 ) were isolated most commonly ; atypical bacteria were identified in 44 ( 15.1 % ) patients . Bacteria-only , virus-only , and mixed infections ( bacteria plus virus ) accounted for 36.7 % ( 98/291 ) , 17.2 % ( 50/291 ) , and 18.9 % ( 55/291 ) of infections , respectively . In particular , 52.4 % of patients with viral infection had a concurrent bacterial infection , and rhinovirus was the most common virus in mixed infections ( 40/55 ) . Additionally , infections with typical bacteria were more common in patients with chronic lung disease ( p = 0.029 ) , and typical bacterial infections showed a trend towards a higher prevalence with older age ( p = 0.001 ) . Conclusions Bacteria were associated with almost half of community-acquired acute bronchitis cases . Additional studies are required to further illuminate the role of bacteria and to identify patient groups most likely to benefit from antibiotic treatment Human respiratory syncytial virus ( HRSV ) outranks other viral agents as the cause of respiratory tract diseases in children worldwide . Molecular epidemiological study of the virus provides useful information for the development of globally effective vaccine . We investigated the circulating pattern and genetic variation in the attachment glycoprotein genes of HRSV in Beijing during 5 consecutive seasons from 2007 to 2012 . Out of 19,942 tested specimens , 3,160 ( 15.8 % ) were HRSV antigen-positive . The incidence of HRSV infection in males was significantly higher than in females . Of the total 723 ( 23.1 % ) r and omly selected HRSV antigen-positive sample s , 462 ( 63.9 % ) and 239 ( 33.1 % ) sample s were identified as subgroup A and B , respectively . Subgroups A and B co-circulated in the 5 consecutive HRSV seasons , which showed a shifting mixed pattern of subgroup dominance . Complete G gene sequences were obtained from 190 HRSV-A and 72 HRSV-B by PCR for phylogenetic analysis . Although 4 new genotypes , NA3 and NA4 for HRSV-A and BA-C and CB1 for HRSV-B , were identified here , they were not predominant ; NA1 and BA9 were the prevailing HRSV-A and -B genotypes , respectively . We provide the first report of a 9 consecutive nucleotide insertion in 3 CB1 genotype strains . One Beijing strain of ON1 genotype with a 72 nucleotide insertion was found among sample s collected in February 2012 . The reversion of codon states in glycosylation sites to previous ones were found from HRSV strains in this study , suggesting an immune-escape strategy of this important virus Background Despite a high burden of respiratory syncytial virus ( RSV ) infections among children , data on demographic and clinical characteristics of RSV are scarce in low and middle income countries . This study aims to describe the viral etiologies , the demographic , epidemiological , and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections ( LRTI ) , focusing on RSV ( prevalence , seasonality , subgroups , viral load ) and its association with disease severity . Methods A prospect i ve study among children under two years of age , hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City , Vietnam , from May 2009 to December 2010 . Socio-demographic , clinical data and nasopharyngeal swabs were collected on enrolment and discharge . Multiplex real-time RT-PCR ( 13 viruses ) and quantitative RSV RT-PCR were used to identify viral pathogens , RSV load and subgroups . Results Among 632 cases , 48 % were RSV positive . RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus ( RV ) , metapneumovirus ( MPV ) , parainfluenza virus ( PIV-3 ) and were significantly more frequent in the first 6 months of life . Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV . In multivariate analysis , RV infection was significantly associated with severity while RSV infection was not . Among RSV infections , neither viral load nor viral co-infections were significantly associated with severity . Young age and having fever at admission were significantly associated with both RSV and LRTI severity . A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity . Conclusion We report etiologies , the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity Background Pregnant women and infants under 6 months are at risk of influenza-related complications . Limited information exists on their community burden of respiratory viruses . Methods and Findings This prospect i ve , observational open cohort study was conducted in Baganuur district , Ulaanbaatar , Mongolia during 2013/14 and 2014/15 influenza seasons . Influenza-like illness ( ILI ) and severe acute respiratory infection ( sARI ) were identified by follow-up calls twice a week . For those identified , influenza and respiratory syncytical virus ( RSV ) were tested by point-of-care test kits . We calculated overall and stratified ( by trimester or age group ) incidence rates ( IR ) and used Cox proportional hazard regression for risk factor analyses . Among 1260 unvaccinated pregnant women enrolled , overall IRs for ILI , sARI and influenza A were 11.8 ( 95 % confidence interval (C.I):11.2–12.4 ) , 0.1 ( 95%C.I:0.0–0.4 ) , and 1.7 ( 95%C.I:1.5–1.9 ) per 1,000person-days , respectively . One sARI case was influenza A positive . IRs and adjusted hazard ratios ( Adj . HR ) for ILI and influenza A were lowest in the third trimester . Those with co-morbidity were 1.4 times more likely to develop ILI [ Adj . HR:1.4 ( 95%C.I:1.1–1.9 ) ] . Among 1304 infants enrolled , overall ILI and sARI IRs were 15.2 ( 95%C.I:14.5–15.8 ) and 20.5 ( 95%C.I:19.7–21.3 ) per 1,000person-days , respectively . From the tested ILI ( 77.6 % ) and sARI ( 30.6 % ) cases , the overall positivity rates were 6.3 % ( influenza A ) , 1.1 % ( influenza B ) and 9.3 % ( RSV ) . Positivity rates of influenza A and RSV tend to increase with age . sARI cases were 1.4 times more likely to be male [ Adj . HR:1.4 ( 95%C.I:1.1–1.8 ) ] . Among all influenza A and RSV positive infants , 11.8 % and 68.0 % were respectively identified among sARI hospitalized cases . Conclusion We observed low overall influenza A burden in both groups , though underestimation was likely due to point-of-care tests used . For infants , RSV burden was more significant than influenza A. These findings would be useful for establishing control strategies for both viruses in Mongolia BACKGROUND Available data on the etiology of community-acquired pneumonia ( CAP ) in Australia are very limited . Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide . METHODS The Australian CAP Study ( ACAPS ) was a prospect i ve , multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens ( cultures , urinary antigen testing , serological methods , and polymerase chain reaction ) . Antibiotic agents and relevant clinical outcomes were recorded . RESULTS The etiology was identified in 404 ( 45.6 % ) of 885 episodes , with the most frequent causes being Streptococcus pneumoniae ( 14 % ) , Mycoplasma pneumoniae ( 9 % ) , and respiratory viruses ( 15 % ; influenza , picornavirus , respiratory syncytial virus , parainfluenza virus , and adenovirus ) . Antibiotic-resistant pathogens were rare : only 5.4 % of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail . Concordance with local antibiotic recommendations was high ( 82.4 % ) , with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide ( 55.8 % ) or ceftriaxone plus either doxycycline or a macrolide ( 36.8 % ) . The 30-day mortality rate was 5.6 % ( 50 of 885 episodes ) , and mechanical ventilation or vasopressor support were required in 94 episodes ( 10.6 % ) . Outcomes were not compromised by receipt of narrower-spectrum beta-lactams , and they did not differ on the basis of whether a pathogen was identified . CONCLUSIONS The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment , such as penicillin combined with doxycycline or a macrolide . Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens Abstract We conducted a prospect i ve pilot study over a 1-year period in New Caledonia in preparation for the Pneumonia Research for Child Health ( PERCH ) project . The pathogens associated with hospitalized lower respiratory infections in children were identified through the use of culture of induced sputum and blood , urinary antigen detection , polymerase chain reaction ( PCR ) on respiratory specimens , and serology on paired sera . Respiratory viruses were detected on respiratory specimens by immunofluorescence and PCR , and by serology on paired sera . Pathogens were detected in 87.9 % of the 108 hospitalized cases . Viruses represented 81.6 % of the 152 pathogens detected . Respiratory syncytial virus and rhinovirus were the most frequent , accounting for 32.2 % and 24.3 % of the pathogens identified , respectively . Only 26.3 % of 99 induced sputum specimens collected were determined to be of good quality , which may be a consequence of the collection method used BACKGROUND There are limited data on the epidemiology and viral aetiology of bronchiolitis in Central Australia and respiratory syncytial virus ( RSV ) immunoprophylaxis in an Australian population . OBJECTIVE To ( i ) determine the incidence and the viral aetiology of bronchiolitis hospitalisations and ( ii ) report on the usage of RSV immunoprophylaxis in selected high-risk infants and children in Central Australia . METHODOLOGY A retrospective review was performed of all hospital separations for bronchiolitis for a three-year period , 1998 - 2000 . Respiratory viruses in the nasopharyngeal aspirates were identified from the cases in the year 2000 . A combined retrospective chart review and prospect i ve follow up study was undertaken of all the infants and children who received RSV immunoprophylaxis at the Alice Springs Hospital , Central Australia . RESULTS Incidence of bronchiolitis hospitalisation in infants for 1998 , 1999 and 2000 were 176 , 200 and 180 per 1000 , respectively . Nine high-risk children had RSV immunoprophylaxis on a total of 46 occasions and there were two mild RSV-related illnesses in them . None had severe lower respiratory tract illness . CONCLUSION The incidence of bronchiolitis in Central Australia is extremely high . The usage of RSV immunoprophylaxis may be justified in selected high-risk children living in high endemic areas To reduce morbidity and mortality through integrated case management , a pilot study to detect respiratory viruses in patients with acute lower respiratory infections ( ALRIs ) was design ed as part of a nationwide surveillance for this disease in Korea . The study population consisted of hospitalized patients under the age of 5 years with bronchiolitis , pneumonia , croup , or acute respiratory distress syndrome . A prospect i ve 6-month study was performed . Two hundred and ninety-seven nasopharyngeal secretions were collected and multiplex reverse transcriptase polymerase chain reactions (RT-PCR)/polymerase chain reactions ( PCR ) were performed to detect respiratory viruses . If there were any positive RT-PCR/PCR results , viral cultures were proceeded for confirmation . Respiratory viruses were identified in 49.6 % of 296 patients . The detection rates were as follows : respiratory syncytial virus ( RSV ) was the most commonly detected in 52.7 % ( 87/165 ) , human metapneumovirus ( hMPV ) in 15.8 % , human corona virus ( hCoV ) in 5.5 % , adenovirus in 9.7 % , human bocavirus ( hBoV ) in 5.5 % , parainfluenza virus ( PIV ) in 3.6 % , rhinovirus ( RV ) in 4.2 % , and the influenza virus in 3 % of the patients with ALRIs . The consistent rate of positive results between RT-PCR and viral culture was 92 % ( 105/114 ) . Using our methods to detect viral causes seemed to be acceptable for the national surveillance of severe acute respiratory infections in infants and children Previously , we conducted a 3-year prospect i ve study to determine the viral causes of acute respiratory tract infections among 495 febrile pediatric out patients . We collected 495 nasopharyngeal aspirate specimens , and used both real-time PCR assays and viral culture to test each for respiratory viruses other than coronavirus . Here , we used real-time PCR to test the 495 archival specimens for four human coronavirus strains . We identified 15 coronavirus-positive specimens : eight with OC43 , 5 with NL63 , 2 with HKU1 , and none with 229E . Of the 15 children ( 5 boys ) infected with human coronavirus , the mean age was 3.5 years , and the age range was 1.1 to 5.8 years ; one child was diagnosed with lower respiratory infection ; the other 14 were diagnosed with upper respiratory infection . Of these 15 patients , none were hospitalized , 5 were infected with coronavirus alone , 8 were co-infected with another virus , and 2 were co-infected with 2 other viruses . The multi-virus infections involved 6 adenoviruses , 3 respiratory syncytial viruses , 2 parainfluenza viruses , and 1 rhinovirus . In conclusion , the burden of human coronaviruses was relatively light among this cohort of 495 pediatric out patients , and the incidence of these infections was low Background : Community-acquired pneumonia ( CAP ) is a major cause of morbidity in industrialized countries and morbidity/mortality in developing countries . In China , comprehensive studies of the etiology of CAP in children aged between 2 months and 14 years who are serious enough to require hospitalization are lacking . Previous studies have been limited in child age range , focused on fatal cases , and /or limited in etiologies sought . An underst and ing of the etiologies is needed for development of best prevention and management practice s. Objective : The aim of this study was to prospect ively determine during a 12-month period the etiology of CAP in hospitalized children in a center in Northwest China . Design / Methods : A prospect i ve 12-month study ( 2004–2005 ) of CAP cases in children who were 2 months to 14 years of age admitted to the Second Hospital of Lanzhou University , China . Testing included admission and 1-month postdischarge serum for viral and bacterial serologic analyses ( respiratory syncytial virus , influenza A and B , paraflu 1–3 , adenovirus ; Streptococcus pneumoniae , Haemophilus influenza B , Mycoplasma , and Moraxella . catarrhalis ) , blood culture , a nasopharyngeal aspirate for viral antigen testing , and a chest radiograph on admission and 1 month postdischarge . The study was funded by Lanzhou University . The study was performed in compliance with the guidelines of the institutional review board of the Second Hospital of Lanzhou University . Results : CAP was the admitting diagnosis for 29 % of all admissions during the 12-month study . Of the 884 CAP cases , 821 ( 93 % ) were enrolled and completed the study . The age range was 2 months to 14 years ; mean age was 2.3 years ; 40 % were < 1 year . The average length of stay was 9.2 days ( range , 6–20 ) but varied by age and etiology . Fourteen percent had received antibiotics before admission and 14 % had underlying illnesses ; 12 % required intensive care unit treatment and 5 died . A microbial etiology for CAP was identified in 547 ( 67 % ) ; viral 535 ( 43 % ) , bacterial 228 ( 27 % ) , mixed viral bacterial 107 ( 13 % ) , mixed viral in 1 % , and mixed bacterial in 1 % . The etiology varied by age ; respiratory syncytial virus was most common in < 1 year , S. pneumoniae and Hib 1–3 years , and Mycoplasma > 5 years . Three potentially vaccine preventable etiologies accounted for 35 % of the cases : influenza 9 % , Hib 12 % , and S. pneumonia 14 % . Conclusions : CAP is a major cause of childhood admission in China . Given the etiologic findings in this study , potentially 25 % to 35 % of cases could be prevented if seasonal influenza vaccine and conjugated H. influenza b and conjugated pneumococcal vaccines were introduced into routine practice Abstract Background The burden of respiratory syncytial virus ( RSV ) in neonates has not been clearly studied . The aims of this study were to determine the overall distribution of respiratory viruses in neonates hospitalized with acute lower respiratory tract infectiosns ( ALRI ) and to describe the clinical characteristics of RSV infections in these neonates . Methods From January 2009 through May 2010 , neonates aged < 1 month who were hospitalized with ALRI and did not have underlying disease were included in the study . Viruses were identified on multiplex reverse transcription polymerase chain reaction using nasal swab sample s. Clinical variables were evaluated between the RSV and non‐RSV infection groups . Results Of the 108 infants included in the study , 46 ( 42.6 % ) had RSV ; human rhinovirus ( 18.5 % ) , human parainfluenza virus 3 ( 7.5 % ) , and human metapneumovirus ( 3.7 % ) were the next most common infections . Codetections accounted for 8.3 % of the cases . Crowding increased the risk of RSV infection compared to the non‐RSV group ( OR , 16.5 ; P = 0.001 ) . The RSV group had a greater incidence of dyspnea ( P = 0.027 ) , pneumonia ( P < 0.001 ) , requirement for oxygen ( P < 0.001 ) , and prolonged hospitalization ( P = 0.011 ) than the non‐RSV group . Conclusions RSV was the most common viral etiology in neonates without underlying diseases who were hospitalized with ALRI . The disease severity of RSV infection was worse than that of other detected viral infections . Strict prevention strategies should be considered in overcrowded situations BACKGROUND There is limited information on respiratory syncytial virus infections among Australians , particularly those of Indigenous descent . AIM This study identifies groups of infants at risk of hospitalisation with respiratory syncytial virus-positive lower respiratory tract infection who may be targeted for prevention with palivizumab . METHODS Case control study : the case notes of 271 children with cases of respiratory syncytial virus-positive lower respiratory tract infection admitted to The Townsville Hospital were studied for risk factors . Controls were chosen r and omly from babies born in The Townsville Hospital during that period . Multiple logistic regression analysis and classification and regression tree analysis were used to identify risk factors . RESULTS Multiple logistic regression analysis identified birthweight < 2500 g , maternal parity and marital status to be independent predictors of hospitalisation with respiratory syncytial virus-positive lower respiratory tract infection . Classification and regression tree analysis identified babies born weighing < 2500 g who possessed older siblings to be at highest risk . Single mothers and smoking were additional risk factors . Indigenous babies were significantly more likely to be exposed to all of the identified risk factors . CONCLUSION Babies born weighing < 2500 g ( especially with siblings ) could be targeted for prevention . All Indigenous babies should be considered at high risk because of their exposure to multiple risk factors Background : Viruses are detected in most hospitalized children admitted for acute respiratory infections . Etiologic underst and ing is needed to improve clinical management and prevention , particularly in re source -limited tropical countries . Methods : A 3-year prospect i ve descriptive study was conducted among Cambodian children admitted to 2 provincial hospitals for acute lower respiratory tract infection . Molecular detection for 18 viral pathogens using multiplex polymerase chain reaction/reverse transcription polymerase chain reactions was performed . Results : We enrolled 1006 children less than 5 years of age of whom 423 ( 42 % ) , 428 ( 42 % ) and 155 ( 16 % ) had pneumonia , bronchiolitis and unclassified lower respiratory tract infections , respectively . Of the 551 ( 55 % ) with documented viral infection , a single virus was detected in 491 ( 89 % ) , including rhinovirus ( n = 169 ; 34 % ) , respiratory syncytial virus ( n = 167 ; 34 % ) , parainfluenza virus ( n = 40 ; 8 % ) , human metapneumovirus ( n = 39 ; 8 % ) , influenza virus ( n = 31 ; 6 % ) , bocavirus ( n = 16 ; 3 % ) , adenovirus ( n = 15 ; 3 % ) , coronavirus ( n = 9 ; 2 % ) and enterovirus ( n = 5 ; 1 % ) . Coinfections with multiple viruses were detected in 6 % ( 2 viruses detected in 59 cases ; 3 viruses detected in 1 case ) . Conclusion : Similar to other tropical countries , rhinovirus and respiratory syncytial virus were the principal viral pathogens detected among children hospitalized for lower tract respiratory infection in Cambodia INTRODUCTION Infection is a major cause of acute exacerbations of COPD ( AE COPD s ) . We aim ed to study the infectious etiology related to AE COPD . METHODS Patients admitted to an acute care hospital in Hong Kong with an AE COPD were recruited prospect ively from May 1 , 2004 , to April 30 , 2005 . Sputum sample s , nasopharyngeal aspirate ( NPA ) sample s , and paired serology specimens were collected . Spirometry was performed with patients in the stable phase 2 to 3 months after hospital discharge . RESULTS There were 643 episodes of AE COPD among 373 patients . Their mean age was 75.3 years ( SD , 7.9 years ) with 307 male patients . The mean FEV(1 ) was 40.4 % predicted ( SD , 18.7 % predicted ) , and the mean FEV(1)/FVC ratio was 58.4 % ( SD , 16.0 % ) . Among sputum sample s from the 530 episodes of AE COPD hospital admissions that were saved , 13.0 % , 6.0 % , and 5.5 % , respectively , had positive growth of Haemophilus influenzae , Pseudomonas aeruginosa , and Streptococcus pneumoniae . Among the 505 hospital admissions with patients who had NPA sample s saved , 5.7 % , 2.3 % , 0.8 % , and 0.8 % , respectively , had influenza A , respiratory syncytial virus ( RSV ) , influenza B , and parainfluenza 3 isolated from viral cultures . Paired serology test results revealed a fourfold rise in viral titers in 5.2 % , 2.2 % , and 1.4 % of patients , respectively , for influenza A , RSV , and influenza B. Very severe airflow obstruction ( stable-state spirometry ) was associated with a higher chance of a positive sputum culture ( FEV(1 ) > /= 30 % predicted , 28.2 % ; FEV(1 ) < 30 % predicted , 40.4 % ; p = 0.006 ) . CONCLUSION H influenzae and influenza A were the most common etiologic agents in patients who were hospitalized with AE COPD s. More severe airflow obstruction was associated with a higher chance of a positive sputum culture finding Background : For most febrile respiratory tract infections ( RTIs ) in children , the causative pathogen is never identified . We sought to identify the causative pathogen in individual cases of pediatric outpatient with RTIs and to determine whether particular clinical features of RTIs are associated with particular viruses . Methods : Over 3 years , we prospect ively collected nasopharyngeal aspirate specimens from individual pediatric out patients with an RTI accompanied by persistent fever ( > 3 days , ≥38.0 ° C ) and peak temperature ≥39.0 ° C . Two methods —(1 ) viral culture for respiratory viruses and ( 2 ) real-time polymerase chain reaction ( PCR ) assays identifying 9 different respiratory viruses and 2 respiratory bacteria — were used to test specimens . Results : For 495 specimens , viral culture and real-time PCR assays together identified at least 1 pathogen in 83.0 % and ≥1 viruses alone in 79.4 % . These 2 methods identified 138 children with respiratory syncytial virus , 66 with human metapneumovirus , 73 with parainfluenza viruses , 124 with adenovirus , 23 with rhinovirus , 38 with enterovirus , 11 with influenza type C virus , 15 with Mycoplasma pneumoniae and 3 with Chlamydophila pneumoniae ; the coinfection rate was 19.7 % among all infections . Among the patients with single-pathogen infections , the rate of lower RTI was 37.6 % for respiratory syncytial virus , 40.7 % for human metapneumovirus , 18.2 % for parainfluenza viruses and 2.2 % for adenovirus ( P < 0.01 ) . Conclusions : Viral culture and real-time PCR assays were used together to identify causative pathogens in 83 % of febrile outpatient children with RTI ; specific viruses were associated with particular clinical diagnoses Background : Influenza-like illness ( ILI ) among elderly people living in residential care homes ( RCHEs ) is a common cause for hospitalisation . A study was undertaken to examine the incidence , underlying aetiology , natural history and associated healthcare re source utilisation related to ILI in the RCHE population . Methods : A prospect i ve study of ILI in four RCHEs in Shatin , Hong Kong was conducted from April 2006 to March 2007 . Each RCHE was monitored daily for the occurrence of ILI and followed up until resolution of illness or death . Clinical features were recorded and sputum , nasopharyngeal aspirate , blood and urine specimens were examined for underlying aetiology . Results : 259 episodes of ILI occurred in 194 subjects , with mild peaks in winter and summer , over a sustained level throughout the year . The infectious agent was identified in 61.4 % of all episodes , comprising bacterial infection in 53.3 % and viral in 46.7 % . Multiple infections occurred in 16.2 % of subjects . The most frequent organism was Streptococcus pneumoniae , followed by respiratory syncytial virus , Pseudomonas aeruginosa , metapneumovirus and parainfluenza virus types 1 and 3 . Clinical features did not vary according to the underlying aetiology , the common presenting features being a decrease in general condition , cognitive and functional deterioration , and withholding of food in addition to fever and respiratory symptoms . Overall , mortality at 1 month/discharge was 9.7 % . Infection with methicillin-resistant Staphylococcus aureus , low body mass index and poor function predisposed to mortality . No association was observed between influenza vaccination status and underlying aetiology , clinical features or outcome . Conclusions : The clinical presentation of ILI is non-specific and is mainly due to bacterial and viral infections other than influenza in the RCHE population Background : Respiratory syncytial virus ( RSV ) is a leading cause of acute lower respiratory infection in children less than 5 years of age . The impact of non-RSV respiratory virus coinfection on the severity of RSV disease is unknown . Methods : This hospital-based prospect i ve study was conducted in Nagasaki , Japan , on all children less than 5 years of age with acute respiratory infection ( ARI ) who had undergone a rapid RSV diagnostic test between April 2009 and March 2010 . Thirteen respiratory viruses were identified from nasopharyngeal swab sample s using a multiplex polymerase chain reaction ; polymerase chain reaction – positive sample s were considered as confirmed respiratory virus infections . The cases were classified into 3 categories ( pneumonia , moderate-to-severe nonpneumonic ARI and mild ARI ) according to the findings of the chest radiograph and the hospitalization records . Results : Among 384 cases enrolled , 371 were eligible for analysis , of whom 85 ( 23 % ) were classified as pneumonia cases ; 137 ( 37 % ) as moderate-to-severe nonpneumonic ARI cases and 162 ( 40 % ) as mild ARI cases . RSV was detected in 172 cases ( 61.6 % ) , and 31 cases ( 18.0 % ) had double or triple infections with other respiratory viruses . RSV infection was more frequently observed in pneumonia cases ( odds ratio [ OR ] : 2.3 ; 95 % confidence interval [ CI ] : 1.31–3.9 ) and moderate-to-severe nonpneumonic ARI cases ( OR : 2.95 ; 95 % CI : 1.82–4.78 ) than in mild ARI cases . The association with moderate-to-severe nonpneumonic ARI cases was stronger with RSV/non-RSV respiratory virus coinfection ( adjusted OR : 4.91 ; 95 % CI : 1.9–12.7 ) than with RSV single infection ( adjusted OR : 2.77 ; 95 % CI : 1.64–4.7 ) . Conclusions : Non-RSV respiratory virus coinfection is not uncommon in RSV-infected children and may increase the severity of RSV disease Our objective was to describe respiratory disease hospitalizations among children in a community of Seoul , Republic of Korea . Discharge data ( January 1995–December 2005 ) from Guro Hospital ( Seoul , Republic of Korea ) were collected from the hospital medical records office . Respiratory virus test results ( March 2004–December 2005 ) and hospitalization charges to the National Health Insurance Corporation ( January 2002–December 2005 ) were provided by hospital laboratory and administrative departments . Variations in hospitalizations , test results and total hospitalization-associated medical charges were described by age , clinical complaint , discharge month and length of stay . Over the 11-y period , 4247 paediatric hospitalizations for lower respiratory disease occurred . Semi-annual epidemics were identified in October – December and April – May . Among a subset ( n=400 ) of patients , 48 % had respiratory syncytial virus , 16 % parainfluenza virus , 19 % influenza viruses and 17 % adenovirus infection . On admission , children had respiratory problems ( 53 % ) , fever ( 39 % ) , or other systemic problems ( 8 % ) . The median charge of a lower respiratory disease hospitalization was highest in January ( $ 1334 ) and lowest in October ( $ 1076 ) . Median hospitalization charges were highest among children 8–15 years of age compared with younger children ≤2 years and those 3–7 years of age . Respiratory disease hospitalizations among children demonstrated annual variations reflecting patterns of children with laboratory-confirmed respiratory viral infections . In the Republic of Korea , prospect i ve studies that use st and ardized laboratory testing for respiratory pathogens in children will help to estimate the total burden of viral lower respiratory tract disease Abstract Background Pneumonia is the major cause of death under 5 years . With high CAP numbers in China and growing access to PICUs , factors associated with severe CAP need to be determined to optimize care . Objective To prospect ively determine PICU CAP admission features and outcomes . Methods A 4 year prospect i ve study of CAP aged 1 month to < 14 years admitted to PICU , Children 's Hospital Affiliated to Soochow University , China . All were managed in a st and ard manner . Clinical , laboratory , and imaging findings were collected systematic ally . All received antibiotics . Results Eight hundred ten ( 7 % ) of 10,836 CAP hospital admissions needed PICU . Seven hundred seven ( 87 % ) were enrolled . PICU CAP children were young ( 76 % ≤ 12 months ) and 33 % had co‐morbid conditions ; 21 % congenital heart disease.21 % required mechanical ventilation . The average length of PICU stay was 5 days ( range , 3–27 ) . The case fatality rate was 5.8 % . Viruses were detected in 38 % , RSV 24 % ; bacteria in 23 % , Streptococcus pneumoniae 7 % , Haemophilus influenza b 4 % , Mycoplasma 11 % . On single factor analysis , PICU admission respiratory rate > 70/min , grunting/groaning , head nodding , cyanosis , and anemia were associated with respiratory failure and with fatality . On multivariate analysis only presence of congenital heart disease , Trisomy 21 and immunodeficiency correlated with fatality ; not microbe nor PICU findings . Conclusions Young age and underlying congenital heart disease were associated factors for PICU support in CAP in China . Early referral if altered sensorium , high respiratory rate , head nodding , grunting and anemia , and universal access to conjugated vaccines may decrease morbidity and mortality . Pediatr Pulmonol . 2013 ; 48:390–397 . © 2012 Wiley Periodicals , AIM To determine the rates of respiratory syncytial virus ( RSV ) infection in children under 5 years of age with recurrent wheeze or asthma and compare their clinical presentation , course and outcome with asthmatic children of the same age who did not have RSV . METHODS Children were recruited prospect ively from the emergency department of the Royal Children 's Hospital , Melbourne during peak RSV season in 1998 . Information was collected regarding past and current asthma presentations , a nasopharyngeal asprirate was taken for viral isolation and all children were review ed by telephone 1 week following presentation . RESULTS 73 children were included with a median age of 28 months . RSV was isolated from 33 ( 45 % ) of children , one child had adenovirus and in the remainder no virus was isolated . Children less than 12 months were more likely to have RSV ( 70 % ) . RSV-positive children had a longer duration of illness prior to hospital presentation than RSV-negative children but were not more likely to be admitted or to have a longer duration of ongoing symptoms . CONCLUSION A high rate of RSV infection was demonstrated in young children with recurrent wheeze or asthma during the RSV season . This information has important implication s for the control of nosocomial infection with RSV ( i.e. isolation of patients ) and in targeting another group to be included for RSV vaccine development INTRODUCTION Laboratory capacity is needed in central Viet Nam to provide early warning to public health authorities of respiratory outbreaks of importance to human health , for example the outbreak of influenza A(H1N1 ) p and emic in 2009 . Polymerase chain reaction ( PCR ) procedures established as part of a capacity-building process were used to conduct prospect i ve respiratory surveillance in a region where few previous studies have been undertaken . METHODS Between October 2008 and September 2010 , nose and throat swabs from adults and children ( approximately 20 per week ) presenting with an acute respiratory illness to the Ninh Hoa General Hospital were collected . Same-day PCR testing and result reporting for 13 respiratory viruses were carried out by locally trained scientists . RESULTS Of 2144 surveillance sample s tested , 1235 ( 57.6 % ) were positive for at least one virus . The most common were influenza A strains ( 17.9 % ) , with p and emic influenza A(H1N1 ) 2009 and seasonal H3N2 strain accounting for 52 % and 43 % of these , respectively . Other virus detections included : rhinovirus ( 12.4 % ) , enterovirus ( 8.9 % ) , influenza B ( 8.3 % ) , adenovirus ( 5.3 % ) , parainfluenza ( 4.7 % ) , respiratory syncytial virus ( RSV ) ( 3.9 % ) , human coronavirus ( 3.0 % ) and human metapneumovirus ( 0.3 % ) . The detection rate was greatest in the 0 - 5 year age group . Viral co-infections were identified in 148 ( 6.9 % ) cases . DISCUSSION The outbreak in 2009 of the influenza A(H1N1 ) p and emic strain provided a practical test of the laboratory 's p and emic plan . This study shows that the availability of appropriate equipment and molecular-based testing can contribute to important individual and public health outcomes in geographical locations susceptible to emerging infections |
11,993 | 29,022,281 | Conclusion ILP and ILI for extremity STS can be safely performed with appreciable response rates and significant limb salvage rates . | Background Isolated limb perfusion ( ILP ) and isolated limb infusion ( ILI ) have been variably used in recent years for the treatment of locally advanced or marginally resectable extremity soft tissue sarcomas ( STSs ) .
We performed a systematic review and meta- analysis of contemporary studies to further characterize treatment patterns and outcomes . | Background In a prior r and omized phase II trial comparing hyperthermic isolated limb perfusion ( HILP ) with four different doses of tumor necrosis factor alpha ( TNF-α ) , no dose effect was detected for response , but systemic toxicity was far lower with low-dose TNF-α . The objective of the present study was to confirm these data on a larger sample size of locally advanced or recurrent extremity soft tissue sarcomas with low-dose TNF-α . Methods We assessed a prospect i ve data base comprising 100 HILP ( 38–40 ° C ) with melphalan ( 10 mg/L ) and TNF-α ( 1 mg ) . The remnant tumor was resected 2 months later . Results Among 52 recurrences , 18 were in a previously irradiated field . Stages according to the American Joint Committee on Cancer classification were II ( 19 patients ) , III ( 78 patients ) , and IV ( 3 patients ) . The site/size were : 30 patients /57 mm and 70 patients /86 mm for the upper and lower limbs , respectively . Tumor grade s ( FNCLCC ) were 1 ( 23 patients ) , 2 ( 34 patients ) , and 3 ( 43 patients ) . Fifty-one patients had received systemic chemotherapy before HILP . Responses on magnetic resonance imaging were 30 % complete , 49 % partial , 9 % no change , and 12 % progression . No mortality or systemic toxicity occurred . Local toxicity ( Wieberdink ) attained grade 2 ( 16 patients ) , 3 ( 5 patients ) , and 4 ( 1 patient ) . Limbs were able to be saved in 87 % patients . Three-year overall survival and the local recurrence rate were 89 % and 18 % , respectively . Age , sex , tumor size , recurrence , uni- or multifocality , grade , preoperative chemotherapy , and a previously irradiated field were not predictive of response or local toxicity . Conclusions We confirm that 1 mg of TNF-α is as effective as the st and ard dose and results in no systemic toxicity Background Isolated limb perfusion with tumor necrosis factor alpha and melphalan ( TM-ILP ) has proven to be a successful option in treating advanced soft tissue sarcomas ( STS ) , where amputation otherwise is needed to achieve safe surgical margins . Methods From 2000 to 2009 , 54 patients with locally advanced STS , who all were c and i date s for amputation , were treated with totally 57 TM-ILP procedures and then followed prospect ively . The median follow-up time was 30 months . Median tumor size was 10 cm , and 94 % of the patients had high- grade tumors . Results The clinical overall response after TM-ILP was 71 % ( including 21 % CR ) , and 60 % of the patients underwent resection of the tumor remnant after a median of 2 months . The histopathologic response rate in the resected specimens was 76 % . Local recurrence/progress occurred in 37 % of the patients after a median of 7 months . Thirteen patients finally underwent amputation after a median of 11 months , giving a long-term limb salvage of 76 % . Conclusions TM-ILP of advanced soft tissue sarcoma of the extremities makes limb-sparing surgery possible in a high proportion of patients Isolated limb infusion ( ILI ) is a minimally invasive technique of delivering regional chemotherapy in patients with advanced melanoma or soft-tissue sarcoma of the limb . We report the final results of the first clinical trial of ILI in North America ( NCT00004250 ) . Eligible patients had recurrent melanoma or unresectable soft-tissue sarcoma of the limb . Angiographic catheters were positioned just above the knee or elbow of the extremity . General anesthesia was performed , a proximal tourniquet inflated , and a normothermic , low flow , hypoxic infusion of melphalan and dactinomycin circulated through the involved limb for 20 min . Tumor response and morbidity were assessed using st and ard criteria . Thirty-seven patients were accrued to the trial and 44 ILIs were performed ( eight patients had two ILIs ) ; one patient was not treated . Of the 32 evaluable patients , 17 ( 53 % ) had a significant response at 3 months : 25 % of patients had a complete response and 28 % of patients had a partial response . The median duration of complete response was 1 year ( 5–32 months ) . Morbidity was acceptable , with peak erythema , edema , and pain experienced at 2 weeks and considered ‘ moderate ’ in most patients . No patients developed compartment syndrome or required amputation because of ILI . ILI is well tolerated . More than half of the treated patients experienced a complete or partial response Between May 1975 and April 1981 , 43 adult patients with high- grade soft tissue sarcomas of the extremities were prospect ively r and omized to receive either amputation at or above the joint proximal to the tumor , including all involved muscle groups , or to receive a limb-sparing resection plus adjuvant radiation therapy . The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed . Both r and omization groups received postoperative chemotherapy with doxorubicin ( maximum cumulative dose 550 mg/m2 ) , cyclophosphamide , and high-dose methotrexate . Twenty-seven patients r and omized to receive limb-sparing resection and radiotherapy , and 16 received amputation ( r and omization was 2:1 ) . There were four local recurrences in the limb-sparing group and none in the amputation group ( p1 = 0.06 generalized Wilcoxon test ) . However , there were no differences in disease-free survival rates ( 71 % and 78 % at five years ; p2 = 0.75 ) or overall survival rates ( 83 % and 88 % at five years ; p2 = 0.99 ) between the limb-sparing group and the amputation treatment groups . Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection . Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins ( p1 less than 0.0001 ) even when postoperative radiotherapy was used . A simultaneous prospect i ve r and omized study of postoperative chemotherapy in 65 patients with high- grade soft-tissue sarcomas of the extremities revealed a marked advantage in patients receiving chemotherapy compared with those without chemotherapy in three-year continuous disease-free ( 92 % vs. 60 % ; p1 = 0.0008 ) and overall survival ( 95 % vs. 74 % ; p1 = 0.04 ) . Thus limb-sparing surgery , radiation therapy , and adjuvant chemotherapy appear capable of successfully treating the great majority of adult patients with soft tissue sarcomas of the extremity Background Isolated limb infusion ( ILI ) is a therapeutic option for patients with recurrent , unresectable extremity malignancies . Methods A prospect ively collected single-institution data base of patients undergoing ILI was analyzed for preoperative , intraoperative , and postoperative parameters and outcomes . Results From May 2007 to January 2012 , a total of 76 patients successfully underwent initial ILI , and 28 after either previous hyperthermic isolated limb perfusion or ILI . Seventy-nine patients ( 74 % ) had melanoma , 24 ( 22 % ) sarcoma , 3 ( 3 % ) Merkel cell , and 1 ( 1 % ) squamous cell carcinoma . There were 55 ( 72 % ) initial and 22 ( 79 % ) repeat lower extremity ( LE ) ILIs , and 21 ( 78 % ) initial and 6 ( 22 % ) repeat upper extremity ( UE ) ILIs . Serologic toxicity , measured by serum creatine kinase ( CK ) , peaked higher and later in LE ILIs , median 620 versus 124 IU/L , and postoperative day 4 versus 2 , respectively ( P < 0.05 ) . LE ILIs had a longer hospital length of stay ( LOS ) , median 6 versus 5 days ( P < 0.0001 ) . A median grade II Wieberdink regional toxicity was observed . Three-month follow-up was available in 94 ( 90 % ) . A response ( overall response rate , ORR ) was seen in 72 % of ILIs performed for melanoma and 58 % for sarcoma . No difference in response was observed between UE versus LE or between initial versus repeat ILIs . Repeat UE ILIs , however , appeared to have an improved ORR than repeat LE ILIs , 83 versus 64 % . Conclusions ILI may be successfully performed for cutaneous and soft tissue malignancies . LE ILIs have higher CK levels and slightly longer LOS . Repeat ILIs are not associated with increased toxicity and similar ORR . UE ILIs may have better ORR BACKGROUND Isolated limb perfusion ( TM-ILP ) achieves high response rates in soft tissue sarcomas ( STS ) . Some tumors show an insufficient association between radiological and pathological response . We investigated STS after TM-ILP with a primary emphasis on histologic regression patterns . METHODS In 53 patients with STS , TM-ILP with subsequent tumor resection was performed . Regression was assessed by the Salzer-Kuntschik regression scale . Microvessel density ( MVD ) of primary biopsies of 37 patients was determined by immunohistochemistry . Tumor regression was correlated with MVD of primary biopsies and other clinico-pathological parameters . RESULTS Regression presented mainly as necrosis or fibrosis/sclerosis upon histopathology . MFH , leiomyosarcoma , or clear cell sarcoma ( CCS ) responded well ; whereas liposarcomas , synovial sarcomas , or MPNST were poor responders . MFH often had abundant necrosis ; while other STS mainly presented with fibrosis/sclerosis . MVD had no influence on regression grade but modulated histologic regression patterns . Excellent regression demonstrated a trend toward an association with improved survival and local control . CONCLUSION TM-ILP yielded high response rates in STS . Regression after TM-ILP exhibits MVD-dependent histopathologic patterns and variable efficacy in different sarcoma types . Complete regression seems to be a favorable prognostic factor . A concerted consideration of histopathology and clinical findings may contribute to a better clinical assessment of regression after TM-ILP PURPOSE To determine in a r and omized prospect i ve multi-institutional trial whether the addition of tumor necrosis factor alpha ( TNF-alpha ) to a melphalan-based hyperthermic isolated limb perfusion ( HILP ) treatment would improve the complete response rate for locally advanced extremity melanoma . PATIENTS AND METHODS Patients with locally advanced extremity melanoma were r and omly assigned to receive melphalan or melphalan plus TNF-alpha during st and ard HILP . Patient r and omization was stratified according to disease/treatment status and regional nodal disease status . RESULTS The intervention was completed in 124 patients of the 133 enrolled . Grade 4 adverse events were observed in 14 ( 12 % ) of 129 patients , with three ( 4 % ) of 64 in the melphalan-alone arm and 11 ( 16 % ) of 65 in the melphalan-plus-TNF-alpha arm ( P = .0436 ) . There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm , and one disease progression-related upper extremity amputation in the melphalan-alone arm . There was no treatment-related mortality in either arm of the study . One hundred sixteen patients were assessable at 3 months postoperatively . Sixty-four percent of patients ( 36 of 58 ) in the melphalan-alone arm and 69 % of patients ( 40 of 58 ) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months , with a complete response rate of 25 % ( 14 of 58 patients ) in the melphalan-alone arm and 26 % ( 15 of 58 patients ) in the melphalan-plus-TNF-alpha arm ( P = .435 and P = .890 , respectively ) . CONCLUSION In locally advanced extremity melanoma treated with HILP , the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up , and TNF-alpha plus melphalan was associated with a higher complication rate Background Isolated limb infusion ( ILI ) is a minimally invasive technique for delivering high-dose regional chemotherapy . We report our experience with ILI for the treatment of soft tissue sarcoma ( STS ) . Methods From our prospect i ve data base , 21 patients with STS of the limb treated with ILI between 1994 and 2007 were identified . In all patients , a high-dose cytotoxic drug combination was used . Results There were 14 men , and the median age was 60 years ( range , 18–85 years ) . Eighteen patients ( 86 % ) had lower limb tumors . All patients had advanced local disease . The procedure was well tolerated . Fourteen patients ( 67 % ) received ILI before definitive surgery . The overall response rate was 90 % ( complete response [ CR ] rate 57 % , partial response rate 33 % ) . The disease-specific overall survival was 61.9 % ( median follow-up , 28 months ) . Only American Joint Committee on Cancer stage was associated with overall survival . The local recurrence rate was 42 % . CR and malignant fibrous histiocytoma tumor subtype were associated with a lower local recurrence rate . A lower initial skin temperature ( median 35.8 ° C ) was associated with a CR ( P = .033 ) . Patients who had a steep increase in intramuscular temperature during the procedure were more likely to have a CR ( P = .055 ) . Classification tree analysis identified patients with an initial PaO2 of ≥194 mmHg as being more likely to have a CR . Ultimately , the overall limb salvage rate was 76 % . Conclusion The outcomes after ILI are comparable to those achieved by conventional isolated limb perfusion . ILI is a minimally invasive alternative to isolated limb perfusion for patients with advanced STS of the extremity BACKGROUND Extensive and mutilating surgery is often required for locally advanced soft tissue sarcoma ( STS ) of the limb . As it has become apparent that amputation for STS does not improve survival rates , the interest in limb-preserving approaches has increased . Isolated limb perfusion ( ILP ) with tumor necrosis factor-alpha ( TNF ) and melphalan is successful in providing local tumor control and enables limb-preserving surgery in a majority of cases . A mature , large , single-institution experience with 217 consecutive ILPs for STS of the extremity is reported . METHODS At a prospect ively maintained data base at a tertiary referral center , 217 ILPs were performed from July 1991 to July 2003 in 197 patients with locally advanced STS of the extremity . ILPs were performed at mild hyperthermic conditions with 1 - 4 mg of TNF and 10 - 13 mg/L limb-volume melphalan ( M ) for leg and arm perfusions , respectively . RESULTS The overall response rate was 75 % . Limb salvage was achieved in 87 % of the perfused limbs . Median survival post-ILP was 57 months and prognostic factors for survival were Trojani grade of the tumor and ILP for single versus multiple STS . The procedure could be performed safely , with a perioperative mortality of 0.5 % in all patients with no age limit ( median age , 54 yrs ; range , 12 - 91 ) . Systemic and locoregional toxicity were modest and easily manageable . CONCLUSION TNF+M-based ILP can provide limb salvage in a significant percentage of patients with locally advanced STS and has therefore gained a permanent place in the multimodality treatment of STS Controversy has surrounded the role of isolated limb perfusion ( ILP ) for unresectable extremity sarcomas . However , there remains a group of sarcoma patients for whom amputation is the only potential treatment . Because systemic therapies are limited , the authors evaluated ILP in an effort to provide a limb‐salvage option OBJECTIVE The objective of the study was to achieve limb salvage in patients with locally advanced soft tissue sarcomas that can only be treated by amputation or functionally mutilating surgery by performing an isolated limb perfusion ( ILP ) with tumor necrosis factor ( TNF ) + melphalan ( M ) as induction biochemotherapy to obtain local control and make limb-sparing surgery possible . SUMMARY BACKGROUND DATA To increase the number of limb-sparing resections in the treatment of locally advanced extremity soft tissue sarcoma , preoperative radiation therapy or chemotherapy or a combination of the two often are applied . The ILP with cytostatic agents alone is another option but rarely is used because of rather poor results . The efficacy of the application of TNF in ILP markedly has changed this situation . METHODS In 8 cancer centers , 186 patients were treated over a period of almost 4.5 years . There were 107 ( 57 % ) primary and 79 ( 43 % ) recurrent sarcomas , mostly high grade ( 110 grade III ; 51 grade II ; and 25 very large , recurrent , or multiple grade I sarcomas ) . The composition of this series of patients is unusual : 42 patients ( 23 % ) had multifocal primary or multiple recurrent tumors ; median tumor size was very large ( 16 cm ) ; 25 patients ( 13 % ) had known systemic metastases at the time of the ILP . Patients underwent a 90-minute ILP at 39 to 40 C with TNF + melphalan . The first 55 patients also received interferon-tau . A delayed marginal resection of the tumor remnant was done 2 to 4 months after ILP . RESULTS A major tumor response was seen in 82 % of the patients rendering these large sarcomas resectable in most cases . Clinical response rates were : 33 complete response ( CR ) ( 18 % ) , 106 partial response ( PR ) ( 57 % ) , 42 no change ( NC ) ( 22 % ) , and 5 progressive disease ( PD ) ( 3 % ) . Final outcome was defined by clinical and pathologic response : 54 CR ( 29 % ) , 99 PR ( 53 % ) , 29 NC ( 16 % ) , and 4 PD ( 2 % ) . At a median follow-up of almost 2 years ( 22 months ; range , 6 - 58 months ) , limb salvage was achieved in 82 % . Regional toxicity was limited and systemic toxicity minimal to moderate , easily managed , with no toxic deaths . CONCLUSIONS In the setting of isolated limb perfusion , TNF is an active anticancer drug in patients . The ILP with TNF + melphalan can be performed safely in many centers and is an effective induction treatment with a high response rate that can achieve limb salvage in patients with locally advanced extremity soft tissue sarcoma PURPOSE To determine the toxicity and the therapeutic efficacy of the combination of the recombinant tumor necrosis factor alpha ( rTNF alpha ) , recombinant interferon gamma ( rIFN-gamma ) , and melphalan , we design ed a protocol using isolation limb perfusion ( ILP ) with hyperthermia for in-transit metastases of melanoma and recurrent sarcoma . The triple combination was chosen because of the reported synergistic antitumor effect of rTNF alpha with IFN-gamma and of rTNF alpha with alkylating agents . PATIENTS AND METHODS Twenty-three patients received a total of 25 ILPs with the triple combination . There were 19 females and four males with either multiple progressive in-transit melanoma metastases of the extremities ( stage IIIa or IIIab ; 19 patients ) or recurrent soft tissue sarcoma ( five ) . The rTNF alpha was injected as a bolus in the arterial line , and total dose ranged between 2 and 4 mg , under hyperthermic conditions ( 40 degrees C to 40.5 degrees C ) for 90 minutes . The rIFN-gamma was given subcutaneously ( SC ) on days -2 and -1 and in the perfusate , with rTNF alpha at the dose of 0.2 mg . Melphalan ( Alkeran ; Burroughs Wellcome Co , London , Engl and ) was administered in the perfusate at 40 micrograms/mL. RESULTS Toxicity observed during three ILPs in a pilot study with rTNF alpha included only two severe toxicities : one severe hypotension with tachycardia and transient oliguria and one moderate hypotension for 4 hours followed by severe kidney failure with complete recovery on day 29 . In all 18 ILPs performed in the triple combination protocol , the patients received continuous infusion dopamine at 3 micrograms/kg/min from the start of ILP and for 72 hours and showed only mild hypotension and transient chills and temperature . Regional toxicity attributable to rTNF alpha was minimal . There have been 11 cases with hematologic toxicity consisting of neutropenia ( one grade 4 and one grade 3 ) and neutropenia with thrombocytopenia ( one grade 4 and three grade 2 ) . Twelve patients had been previously treated with melphalan in ILP ( 11 ) or with cisplatin ( one ) . The 23 patients are assessable : there have been 21 complete responses ( CRs ; range , 4 to 29 months ; 89 % ) , two partial responses ( PRs ; range , 2 to 3 months ) , and no failures . Overall disease-free survival and survival have been 70 % and 76 % , respectively , at 12 months . In all cases , softening of the nodules was obvious within 3 days after ILP and time to definite response ranged between day 5 and 30 . CONCLUSION This preliminary analysis of a phase II study suggests that high-dose rTNF alpha can be administered with acceptable toxicity by ILP with dopamine and hyperhydration . Tumor responses can be evidence d in melanoma and sarcoma . Furthermore , combination of rTNF alpha , rIFN-gamma , and melphalan seems to achieve high efficacy with minimal toxicity , even after failure of prior therapy with melphalan alone This paper is an overview of the new response evaluation criteria in solid tumours : revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents PURPOSE In-transit disease afflicts approximately 10 % of patients with extremity melanoma ; no single treatment approach has been uniformly accepted as the most effective . We report long-term outcomes in patients with in-transit extremity melanoma who underwent isolated limb perfusion ( ILP ) in an era of increasingly accurate staging , uniform operative and treatment conditions , and regular long-term follow-up . PATIENTS AND METHODS Between May 1992 and February 2005 , 91 patients ( median age , 57 years ; 50 women , 41 men ) underwent a 90-minute hyperthermic ILP ( melphalan , 10 to 13 mg/L limb volume , tumor necrosis factor [ TNF ; n = 44 ] , or interferon [ n = 38 ] ) using uniform operative technique and intraoperative leak monitoring . Patients were prospect ively followed for response , in-field progression-free survival ( PFS ) , and overall survival ( OS ) . Parameters associated with in-field PFS and OS were analyzed by st and ard statistical methods . Results There was one operative death ( 1.1 % ) . There were 62 complete responses ( 69 % ) and 23 partial responses ( 26 % ) in 90 assessable patients . At a median potential follow-up of 11 years , median in-field PFS was 12.4 months and median OS was 47.4 months ; 5 and 10-year actuarial OS probabilities were 43 % and 34 % , respectively . Female sex and low tumor burden ( < or = 20 lesions ) were associated with prolonged in-field PFS ( male : female hazard ratio [ HR ] , 2.07 ; 95 % CI , 1.27 to 3.38 ; 21 + v < or = 20 tumors HR , 2.29 ; 95 % CI , 1.21 to 4.34 ; P < .011 for both ) . Female sex was associated with improved OS ( P = .027 ; male : female HR , 1.82 ; 95 % CI , 1.07 to 3.09 ) . CONCLUSION In appropriately selected patients , ILP has clinical benefit . The use of TNF was not associated with improved in-field PFS , while female sex was associated with better survival Abstract Background Isolated limb perfusion ( ILP ) is indicated in locally advanced melanoma and soft tissue sarcoma of the extremities . This series reports the outcome of patients undergoing ILP with melphalan and tumour necrosis factor α ( TNFα ) at a single centre . Methods All patients undergoing ILP from January 2005 to January 2015 were identified from a prospect ively maintained data base . Those undergoing ILP for in-transit melanoma ( ITM ) were grouped according to disease burden : low volume and bulky ( > 2 cm diameter ) . Results A total of 143 perfusions were attempted : 9 and 134 in the upper and lower limbs , respectively . A response was assessable in 129 patients with overall response rates for ITM and sarcoma of 81.8 and 61.1 % , respectively . No difference was found in response rates between low-volume and bulky ITM . Limb salvage rates in these cohorts were 97 and 62 % . Regional toxicity following ILP was minimal with 7 grade III ( 5.4 % ) , and 1 grade V ( 0.8 % ) reactions . Median progression-free survival was 11 months in the ITM cohort and 12 months in the sarcoma cohort . In the ITM cohort , complete responses were significantly more durable than partial responses ( p = 0.0004 ) . Median disease-specific survival was 21 months in the ITM cohort and was not reached in the sarcoma cohort . Conclusions TNFα-based ILP is safe and provides excellent palliation of ITM due to rapid progression of systemic disease . It is less effective in sarcoma due to lower initial response rates and a lower incidence of disease dissemination |
11,994 | 29,045,286 | We found that conventional nonstrain diastolic parameters predicted doxorubicin-induced systolic dysfunction . | Doxorubicin is an important cause of chemotherapy-induced cardiomyopathy .
Prior studies have found conflicting results of whether nonstrain diastolic parameters can predict doxorubicin-induced cardiotoxicity . | BACKGROUND It has been hypothesized that the extent of acute anthracycline-induced cardiotoxicity reflects the risk for late development of heart failure . The aim of this study was to examine if short-term changes in cardiac function can be detected even after low-dose adjuvant epirubicin therapy for breast cancer when using Doppler tissue imaging of longitudinal left ventricular function . METHODS Eighty consecutive women in good cardiopulmonary health scheduled to undergo adjuvant treatment for breast cancer were included . They were examined using echocardiography and Doppler tissue imaging before and after three treatment series of epirubicin ( mean cumulative dose , 273.7 ± 46.6 mg/m(2 ) ; median time interval , 9 weeks ; range , 47 - 113 days ) . RESULTS Apart from a marginal reduction in E/A ratio , none of the conventional Doppler echocardiographic or Doppler tissue imaging indices of systolic and diastolic function were affected during epirubicin treatment . CONCLUSIONS In contrast to several previous studies using tissue Doppler and conventional echocardiography , this study did not document relevant short-term effects of low-dose epirubicin treatment on heart function Objectives To identify anthracycline-induced acute ( within 1 month ) and early-onset chronic progressive ( within 1 year ) cardiotoxicity in children younger than 16 years of age with childhood malignancies at a tertiary care centre of Pakistan . Design Prospect i ve cohort study . Setting Aga Khan University , Karachi , Pakistan . Participants 110 children ( aged 1 month–16 years ) . Intervention Anthracycline ( doxorubicin and /or daunorubicin ) . Outcome measurements All children who received anthracycline as chemotherapy and three echocardiographic evaluations ( baseline , 1 month and 1 year ) between July 2010 and June 2012 were prospect ively analysed for cardiac dysfunction . Statistical analysis including systolic and diastolic functions at baseline , 1 month and 1 year was carried out by repeated measures analysis of variance . Results Mean age was 74±44 months and 75 ( 68.2 % ) were males . Acute lymphoblastic leukaemia was seen in 70 ( 64 % ) patients . Doxorubicin alone was used in 59 ( 54 % ) and combination therapy was used in 35 ( 32 % ) . A cumulative dose of anthracycline < 300 mg/m2 was used in 95 ( 86 % ) . Fifteen ( 14 % ) children developed cardiac dysfunction within a month and 28 ( 25 % ) children within a year . Of these 10/15 ( 66.6 % ) and 12/28 ( 43 % ) had isolated diastolic dysfunction , respectively , while 5/15 ( 33.3 % ) and 16/28 ( 57 % ) had combined systolic and diastolic dysfunction . Seven ( 6.4 % ) patients expired due to severe cardiac dysfunction . Eight of 59 ( 13.5 % ) children showed dose-related cardiotoxicity ( p=<0.001 ) . Cardiotoxicity was also high when the combination of doxorubicin and daunorubicin was used ( p=0.004 ) . Conclusions Incidence of anthracycline-induced cardiotoxicity is high . Long-term follow-up is essential to diagnose its late manifestations 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 AIMS The benefits from anthracycline chemotherapy are undermined by potentially life-threatening cardiotoxicity . Transthoracic echocardiography is the most commonly used method for monitoring cardiotoxicity , and centres on the measurement of left ventricular systolic function . The aim of this study was to utilize two-dimensional speckle tracking echocardiography ( 2DSTE ) at baseline and immediately after anthracycline chemotherapy to investigate whether patients with significant changes in systolic function after anthracycline therapy would also develop alterations in diastolic parameters . METHODS AND RESULTS Fifty-two women with histologically confirmed breast cancer were prospect ively recruited . Echocardiograms were performed 1 week prior to and 1 week following chemotherapy ( always before adjuvant trastuzumab or thoracic radiotherapy ) . Conventional Doppler , tissue velocity imaging ( TVI ) , and 2DSTE were used to measure diastolic function . 2DSTE measurements included longitudinal diastolic strain , early ( E-Sr ) , and late ( A-Sr ) myocardial strain rate . 2DSTE and left ventricular ejection fraction ( LVEF ) were used to measure longitudinal systolic function . Altered LV diastolic function ( including E-Sr ) was observed in the entire cohort after chemotherapy , with a differential reduction in participants with a post therapy LVEF < 55 % . Pre-chemotherapy systolic strain was found to predict reduced E-Sr post therapy ( P = 0.04 ) . Univariate predictors of E-Sr were LVEF post therapy ( P = 0.049 ) and systolic strain post-therapy ( P = 0.01 ) . In a multivariate analysis , systolic strain after chemotherapy was the strongest independent predictor ( P = 0.001 ) . CONCLUSION Altered LV diastolic function was observed immediately after the administration of therapeutic doses of anthracycline chemotherapy . Furthermore , our analysis indicates that the changes in diastolic function are associated with reduced systolic function The aim of this study was to describe the acute effects of anthracyclines on left ventricular systolic and diastolic function using different echocardiographic modalities . Thirteen children scheduled to receive anthracyclines were prospect ively studied . They underwent complete 2-dimensional and Doppler echocardiographic evaluations , including tissue Doppler imaging , before the first dose and < 2 hours after each of the first 3 doses of anthracyclines ( dose range 30 to 75 mg/m2 ) . After the first dose , increased end-diastolic wall thickness , decreased wall thickening , and a prolonged myocardial performance index were noted . Parameters of diastolic function changed significantly , with a lower mitral E wave , a decreased E/A ratio , and prolonged isovolumic relaxation time . Also , reduced longitudinal early diastolic myocardial velocity and myocardial velocity acceleration during isovolumic contraction as well as reduced peak longitudinal and radial systolic strain rate and strain were noted . All these parameters remained significantly lower after subsequent doses . After the second dose , significant changes in the shortening fraction and the ejection fraction compared with baseline became apparent . After the third dose , further deterioration in radial peak systolic strain was seen . In conclusion , low to moderate doses of anthracyclines acutely induce cardiac diastolic and systolic dysfunction BACKGROUND To determine the normal range of left ventricular ( LV ) 2- dimensional ( 2-D ) strain and vendor-specific differences , a multicenter prospect i ve 2-D strain study endorsed by the Japanese Society of Echocardiography was conducted . METHODS AND RESULTS 2-D speckle tracking analysis was performed on 817 healthy subjects ( age range , 0 - 88 years ) ; the images included 3 LV short axis and 3 apical views using an ultrasound system from 1 of the 3 different vendors ( V(1 ) , n=333 ; V(2 ) , n=330 ; V(3 ) , n=337 ) . With the 2-D speckle tracking software from each vendor , radial , circumferential and longitudinal strain were measured using an 18-segment model . Inter-vendor variability was also assessed in a subset of subjects . The feasibility for 2-D strain measurements was different among the 3 vendors ( V(1 ) , 83 % ; V(2 ) , 70 % ; V(3 ) , 88 % , P<0.01 ) . The global radial ( V(1 ) , 54.6±12.6 % ; V(2 ) , 36.3±8.2 % ; V(3 ) , 51.4±8.0 % ) , circumferential ( V(1 ) , -22.8±2.9 % ; V(2 ) , -22.2±3.2 % ; V(3 ) , -30.5±3.8 % ) , and longitudinal ( V(1 ) , -21.3±2.1 % ; V(2 ) , -18.9±2.5 % ; V(3 ) , -19.9±2.4 % ) strain measurements were significantly different for each of the vendors . Segmental strain was also different between the 3 vendors . On inter-vendor analysis , vendor agreement ranged from mild to moderate . CONCLUSIONS Reference values are provided for normal 2-D strain for 3 different ultrasound vendors . Due to a low inter-vendor agreement , 2-D strain data are not interchangeable when conducting a longitudinal follow-up or a cross-sectional assessment of LV function The study aim ed to compare diastolic and systolic dysfunctions detected by echocardiography ( ECHO ) and multigated radionuclide angiography ( MUGA ) in patients with cancer in the first 3 months after anthracycline-comprising chemotherapy . Children with leukemia and solid tumors who had anthracycline-comprising chemotherapy were enrolled in the study . ECHO and MUGA were performed in all patients before the first chemotherapy course and in the first 3 month of completing anthracycline-comprising chemotherapy . Cumulative anthracycline doses per body surface were calculated . Left ventricular systolic and diastolic functions were measured by both techniques . Twenty-one patients with a median age of 6.9 ± 3.6 years were enrolled in the study . Mean cumulative anthracycline doses were equivalent to 276 ± 83 mg/m2 doxorubicin . After anthracycline chemotherapy , cardiac dysfunction was detected in 14 and 48 % of the patients by ECHO and MUGA , respectively . All dysfunctions detected by ECHO were systolic , whereas 29 % of the patients had diastolic and 38 % of the patients had systolic dysfunction in MUGA study . Although the study group is small , MUGA seems more sensitive in detecting anthracycline-induced systolic and diastolic cardiac dysfunctions compared to ECHO BACKGROUND Assessment of left ventricular systolic function is necessary during trastuzumab-based chemotherapy because of potential cardiotoxicity . Deformation indices have been proposed as an adjunct to clinical risk factors and ejection fraction ( EF ) , but the optimal parameter and optimal cutoffs are undefined . The aim of this study was to determine the best means of early detection of subsequent reduction of EF in patients with breast cancer treated with trastuzumab . METHODS Eighty-one consecutive women ( mean age , 50 ± 11 years ) receiving trastuzumab were prospect ively studied , 37 of whom received concurrent anthracyclines . Conventional echocardiographic indices ( mitral annular systolic [ s ' ] and diastolic [ e ' ] velocities ) and myocardial deformation indices ( global longitudinal peak systolic strain [ GLS ] , global longitudinal peak systolic strain rate [ GLSR-S ] , and global longitudinal early diastolic strain rate [ GLSR-E ] ) were measured at baseline and at 6 and 12 months . Cardiotoxicity was defined as a > 10 % decline as a percentage of baseline EF in 12 months . RESULTS In the 24 patients ( 30 % ) who later developed cardiotoxicity , myocardial deformation indices decreased at 6 months ( GLS , P < .001 ; GLSR-S , P = .009 ; GLSR-E , P = .002 vs baseline ) , but e ' was unchanged . The strongest predictor of cardiotoxicity was ΔGLS ( area under the curve , 0.84 ) ; an 11 % reduction ( 95 % confidence interval , 8.3%-14.6 % ) was the optimal cutoff , with sensitivity of 65 % and specificity of 94 % . In sequential models , the clinical model ( χ(2 ) = 10.2 ) was improved by GLSR-S ( χ(2 ) = 14.7 , P = .03 ) and even more so by GLSR-E ( χ(2 ) = 18.0 , P = .005 ) or GLS ( χ(2 ) = 21.3 , P = .0008 ) . Discrimination improvement by adding GLS was confirmed by an integrated discrimination improvement of 18.6 % ( 95 % confidence interval , 8.6%-28.6 % ; P = .0003 ) . A net 29 % of the patients without events were reclassified into lower risk categories , and a net 48 % of the patients with events were reclassified into higher risk categories , result ing in a total continuous net reclassification improvement ( > 0 ) of 0.77 ( 95 % confidence interval , 0.33 - 1.22 ; P = .036 ) . CONCLUSIONS GLS is an independent early predictor of later reductions in EF , incremental to usual predictors in patients at risk for trastuzumab-induced cardiotoxicity A phase II , open , nonr and omized trial was carried out in a group of epirubicin-treated patients with cancer at different sites with the aim of detecting early pre clinical changes that are predictive of the risk for heart failure . All patients underwent conventional echocardiography , as well as tissue Doppler imaging ( TDI ) with strain ( sigma ) and strain rate ( SR ) , a very accurate technique for detecting minimal changes in cardiac left ventricular ( LV ) function . Moreover , echocardiographic changes identified during epirubicin treatment were compared with those of a series of biochemical markers of both myocardial damage and inflammation/oxidative stress . Sixteen patients ( male-to-female ratio , 3:13 ; mean age + /- st and ard deviation , 56 + /-3 years ; range , 27 - 75 years ) with histologically confirmed tumors at different sites , scheduled to be treated with an epirubicin-based chemotherapy regimen , were enrolled in the study . A significant impairment in systolic LV function was observed after 200 mg/m2 of epirubicin ; this was shown by a lower SR peak compared with baseline ( 1.82 + /- 0.57/second versus 1.45 + /- 0.44/second ) , whereas sigma remained unchanged . The following significant changes in LV diastolic function occurred only after 300 mg/m2 of epirubicin : a decrease in conventional early/late diastolic ( E/A ) velocities ( 1.16 + /- 0.31 versus 0.93 + /- 0.24 ) and a reduction in both the E(m ) wave in the basal portion of the interventricular septum ( 8.86 + /- 1.73 cm/second versus 7.51 + /- 2.30 cm/second ) and in the E(m)/A(m ) ratio ( 1.09 + /- 0.51 versus 0.83 + /- 0.51 ) , as measured using the TDI technique . No significant changes in LV ejection fraction were observed . Baseline values of brain natriuretic peptide , troponin I , myoglobin , and creatine kinase-myocardial subfraction were within the normal range and no significant changes were observed throughout the study . Levels of interleukin (IL)-6 and its soluble receptor ( sIL-6R ) and reactive oxygen species increased significantly , whereas glutathione peroxidase ( GPx ) levels decreased significantly , after 200 mg/m2 of epirubicin . Significant correlations between the reduction in the SR peak ( deltaSR ) after 200 mg/m2 of epirubicin and the increase in IL-6 and ROS and decrease in GPx were observed . The multiple regression analysis showed that the only independent predictive variable for deltaSR was ROS level . Our data show that : ( a ) subtle cardiac abnormalities may occur at epirubicin doses significantly below those known to be potentially clinical ly harmful and ( b ) the earliest myocardial impairment affects LV systolic rather than diastolic function . Early contractility impairment during epirubicin treatment was associated with high levels of ROS and markers of inflammation . The clinical meaningfulness of our findings warrants further investigations in a larger number of patients for a longer period of follow-up BACKGROUND Epirubicin is a cytotoxic drug , widely used in patients with breast cancer , but its application is limited by its cardiotoxicity . Assessment of left ventricular ( LV ) ejection fraction ( EF ) is performed to demonstrate cardiac dysfunction . Because normal EF can mask LV impairment , the aim of this study was to evaluate whether deformation and rotation assessed using speckle-tracking echocardiography represent better markers of early epirubicin-induced cardiotoxicity . METHODS Forty women with breast cancer ( mean age , 51 ± 8 years ) , scheduled to be treated with epirubicin-based chemotherapy , were prospect ively enrolled . All patients underwent conventional echocardiography , tissue velocity imaging , and speckle-tracking echocardiography to evaluate LV geometry and EF , S ' , deformation ( longitudinal , circumferential , and radial strain and strain rate ) , and rotation . Patients were reevaluated after the third and sixth cycles of epirubicin ( mean cumulative dose , 268 ± 22 g/m(2 ) ) . RESULTS After the sixth cycle of treatment , 14 patients ( 35 % ) had developed epirubicin-induced cardiotoxicity ( a decrease in EF of ≥10 % to an EF of < 55 % ; group I ) , and 26 patients ( 65 % ) did not fulfill the criteria for cardiotoxicity ( group II ) . In the entire study population , after the third cycle of epirubicin , there were reductions in diastolic and longitudinal function , but patients in group I had significantly lower S ' , longitudinal strain , and longitudinal strain rate than those in group II . Although after the third cycle of treatment , radial and circumferential deformation and rotation remained unchanged , these parameters showed significant reductions after the sixth cycle of epirubicin . A decrease in longitudinal strain after the third cycle of epirubicin was the best independent and accurate predictor of cardiotoxicity after the completion of treatment . CONCLUSIONS Assessment of myocardial longitudinal deformation detects sub clinical LV dysfunction and can predict further changes in EF and therefore can be used to monitor epirubicin-induced cardiotoxicity OBJECTIVES The purpose of this study was to evaluate the clinical relevance of anthracycline-induced cardiomyopathy ( AC-CMP ) and its response to heart failure ( HF ) therapy . BACKGROUND The natural history of AC-CMP , as well as its response to modern HF therapy , remains poorly defined . Hence , evidence -based recommendations for management of this form of cardiomyopathy are still lacking . METHODS We included in the study 201 consecutive patients with a left ventricular ejection fraction ( LVEF ) < or=45 % due to AC-CMP . Enalapril and , when possible , carvedilol were promptly initiated after detection of LVEF impairment . LVEF was measured at enrollment , every month for the first 3 months , every 3 months during the first 2 following years , and every 6 months afterward ( mean follow-up 36 + /- 27 months ) . Patients were considered responders , partial responders , or nonresponders according to complete , partial , or no recovery in LVEF , respectively . Major adverse cardiac events during follow-up were also evaluated . RESULTS Eighty-five patients ( 42 % ) were responders ; 26 patients ( 13 % ) were partial responders , and 90 patients ( 45 % ) were nonresponders . The percentage of responders progressively decreased as the time from the end of chemotherapy to the start of HF treatment increased ; no complete recovery of LVEF was observed after 6 months . Responders showed a lower rate of cumulative cardiac events than partial and nonresponders ( 5 % , 31 % , and 29 % , respectively ; p < 0.001 ) . CONCLUSIONS In cancer patients developing AC-CMP , LVEF recovery and cardiac event reduction may be achieved when cardiac dysfunction is detected early and a modern HF treatment is promptly initiated |
11,995 | 17,389,285 | CONCLUSION Several types of interventions are effective in improving medication adherence in chronic medical conditions , but few significantly affected clinical outcomes | BACKGROUND Approximately 20 % to 50 % of patients are not adherent to medical therapy .
This review was performed to summarize , categorize , and estimate the effect size ( ES ) of interventions to improve medication adherence in chronic medical conditions . | The efficacy of self-recording of blood pressure in the management of hypertension was assessed in a r and omized clinical trial involving 140 persons who had been receiving antihypertensive therapy for a year or more , but whose diastolic blood pressure had remained at 95 mm Hg or higher . To control for the increased attention implicit in self-recording , which might affect blood pressure , the patients were assigned at r and om to one of the four groups : self-recording and monthly home visits , self-recording only , monthly home visits only , and neither self-recording nor monthly home visits . This design also permitted assessment of the effect of home visits . During the 6-month experiment no significant differences were apparent between the groups in either compliance or diastolic blood pressure . However , both self-recording and monthly home visits produced a reduction in blood pressure among patients who admitted to difficulty remembering to take their pills ; a reduction was not seen among patients who said they had no such difficulty . This confirmed an earlier observation suggesting that this easily identified group of patients may be the most responsive to intervention programs OBJECTIVES to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients . DESIGN r and omized controlled trial . SUBJECTS AND SETTING S we r and omized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care . INTERVENTIONS the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient . A copy was given to the patient and to all relevant professionals and carers . This was followed by a domiciliary assessment by a community pharmacist . In the control group , patients were discharged from hospital following st and ard procedures that included a discharge letter to the general practitioner listing current medications . OUTCOMES the primary outcome was re-admission to hospital within 6 months . Secondary outcomes included the number of deaths , attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period , together with patients ' general well-being , satisfaction with the service and knowledge of and adherence to prescribed medication . RESULTS we recruited 362 patients , of whom 181 were r and omized to each group . We collected hospital and general practice data on at least 91 and 72 % of patients respectively at each follow-up point and interviewed between 43 and 90 % of the study subjects . There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months . There were no significant differences in any of the secondary outcomes . CONCLUSIONS we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes OBJECTIVE To compare patients ' adherence to therapy , expectations , satisfaction with pharmacy services , and health-related quality of life ( HRQOL ) after the provision of pharmaceutical care with those of patients who received traditional pharmacy care . DESIGN R and omized controlled cluster design . SETTING Sixteen community pharmacies in Alberta , Canada . PATIENTS AND OTHER PARTICIPANTS Ambulatory elderly ( > or = 65 years of age ) patients covered under Alberta Health & Wellness 's senior drug benefit plan and who were concurrently using three or more medications according to pharmacy profiles . INTERVENTION Pharmacies were r and omly assigned to either treatment ( intervention ) or control ( traditional pharmacy care ) groups . Patients at treatment pharmacies were recruited into the study , and pharmacists provided comprehensive pharmaceutical care services . Pharmacists at control pharmacies continued to provide traditional pharmacy care . MAIN OUTCOME MEASURES Study participants ' opinions , adherence to therapy , and scores on the Medical Outcomes Study 36-Item Short Form Health Survey ( SF-36 ) . RESULTS Compared with those of patients receiving traditional care , treatment patients ' expectations that their pharmacist would perform activities congruent with pharmaceutical care changed over the study period . Treatment patients ' satisfaction with the constructs " trust , " " evaluation and goal setting , " and " communicates with doctor " were also positively affected . HRQOL and patient adherence were not significantly affected by pharmaceutical care interventions . CONCLUSION Successful implementation of a pharmaceutical care practice model has the potential to increase patients ' satisfaction with their pharmacists ' activities and may increase patients ' expectations that pharmacists will work on their behalf to assist them with their health care needs . If pharmaceutical care affects patients ' HRQOL , instruments more specific than the SF-36 may be needed to detect the differences The effects of metoprolol ( Betaloc tablets ) in a group of 193 hypertensives were compared with the effects of a slow-release formulation ( Betaloc Durules ) in a further group of 196 patients . Patients were selected at r and om for treatment . There were no differences between the groups in terms of age , weight , sex , blood pressure , concurrent illness or concomitant therapy . Blood pressure control and apparent adverse effects were similar for both groups ; the overall withdrawal rate from each group was similar . Compliance , assessed by tablet counts , was significantly improved in the group receiving once-daily therapy . Simplification of the dosage regimen to once-daily therapy appears to improve the patient 's willingness to comply with the physician 's instructions Background : Nearly perfect compliance seems to be indispensable to obtain the maximum benefit from highly active antiretroviral therapy ( HAART ) . Interventions to ensure a high level of adherence during a relatively long‐term period of therapy are necessary . Methods : This is a prospect i ve , r and omized , two‐arm controlled study including patients starting their first‐ or second‐line HAART who were r and omized to receive psychoeducative intervention to implement adherence ( experimental group [ EG ] ) or a usual medical follow‐up ( control group [ CG ] ) . We aim ed to study the efficacy of a psychoeducative intervention to ensure long‐term adherence to HAART , its relation with the virologic efficacy of treatment , and to determine the variables related to long‐term adherence . Visits were made at weeks 0 , 4 , 24 , and 48 for data collection . Self‐reported adherence was registered at each visit and its veracity was tested by r and omized blood analyses performed without previous warning to 40 % of patients . Appropriate adherence was defined as the consumption of ≥95 % of medication prescribed . Statistical analyses were performed both by the as treated ( AT ) and the intention to treat missing = failure ( ITT ) methods . Results : In all , 116 patients were included . At week 48 , 94 % of patients in the EG versus 69 % controls achieved adherence ≥95 % ( p = .008 ) ; 89 % of patients in the EG versus 66 % controls had HIV‐1 RNA levels < 400 copies/ml ( p = .026 ) . Overall , 85 % of patients with adherence ≥95 % but only 45 % of those with adherence < 95 % had viral load ( VL ) < 400 copies/ml ( p = .008 ) . In multivariate analysis , variables significantly related to adherence were having received a psychoeducative intervention ( odds ratio [ OR ] , 6.58 ; p = .04 ) , poor effort to take medication ( OR , 5.38 ; p = .03 ) , and high self‐perceived capacity to follow the regimen ( OR , 13.76 ; p = .04 ) . Self‐reported adherence and drug plasma levels coincided in 93 % of cases . However , differences in adherence did not reach statistical significance in the ITT analysis although a clear tendency toward benefit was observed in EG . Conclusions : Specific and maintained psychoeducative interventions based on excellence on clinical practice are useful to keep high levels of adherence as well as high levels of viral suppression . There is a clear relation between high adherence levels and virologic success . Assessment of certain specific variables related to adherence may be helpful to monitor patient 's compliance in the clinical setting Effective self-management and treatment compliance is important in achieving good symptom control in asthma . The aim of this study was to determine whether asthma nurse intervention during hospital admission could increase knowledge and improve self-management and whether this would influence the number of emergency call-out visits by Genera Practitioners ( GPs ) and hospital re-admissions . Patients with acute asthma ( n=80 ) were assessed by the asthma nurse within 24 h of admission using a British Thoracic Society ( BTS ) guideline -based question naire . Main outcome measures were : know edge of inhalers , self-management plans , peak flow monitoring , recognition of worsening symptoms and appropriate emergency action , Following r and omization , half received nurse intervention during hospitalization . All received a follow-up question naire 6 weeks post-discharge and again at 6 months ( response rates 86 % and 81 % respectively ) . GPs were contacted by postal question naire after 4 months . Question naire responses indicated an increase in knowledge in the intervention group , along with an ability to identify appropriate action on worsening symptoms . Emergency GP call-outs were more frequent in the control group in the 4 months post-discharge . Hospital re-admission rates were similar in both groups . Asthma nurse intervention appeared to increase knowledge of asthma management , maintained throughout the study period , but had no significant impact on reducing re-admissions to hospital OBJECTIVE to examine the effects and feasibility of educating and empowering older people with ischaemic heart disease using trained senior lay health mentors . DESIGN r and omised controlled trial with blinded evaluation . SETTING Falkirk and District Royal Infirmary . PARTICIPANTS in patients and out patients aged 60 or over attending secondary care with a diagnosis of angina or acute myocardial infa rct ion . Three-hundred and nineteen entered and 289 completed exit assessment s. The intervention group took part in mentoring groups for 1 year , meeting monthly for 2 hours , each led by two trained lay health mentors in addition to st and ard care . MAIN OUTCOME MEASURES primary outcome measures were changes in coronary risk factors , medication usage and actual use of secondary care health services . Secondary outcomes were total and cardiovascular events ; changes in medication compliance , non-medical support requirement , health status and psychological functioning , and social inclusion . RESULTS there were significant improvements in a reported current exercise score ( mean + 0.33 , + 0.02 to + 0.52 ) , in the average time spent walking per week by 72 minutes ( + 1 to + 137 minutes ) , and in the SF36 Physical Functioning Score ( + 6.1 , + 2.4 to + 9.5 ) . There was a 1.0 % reduction in total fat ( 95 % CI -3.0 % to -0.6 % ) and a 0.6 % reduction in saturated fat ( 95 % CI -1.5 % to -0.03 % ) . The intervention group showed reduced outpatient attendance for coronary heart disease ( -0.25 appointments , -0.61 to -0.08 ) . Attendance rates were high . Socio-economic grouping did not affect participation . CONCLUSIONS Lay Health Mentoring is feasible , practical and inclusive , positively influencing diet , physical activity , and health re source utilisation in older subjects with ischaemic heart disease without causing harm OBJECTIVE This study reports 6- and 12-month follow-up for the families of adolescents with diabetes who participated in a trial of Behavioral-Family Systems Therapy ( BFST ) . RESEARCH DESIGN AND METHODS A total of 119 families of adolescents with type 1 diabetes were r and omized to 3 months of treatment with either BFST , an education and support ( ES ) group , or current therapy ( CT ) . Family relationships , adjustment to diabetes , treatment adherence , and diabetic control were assessed at baseline , after 3 months of treatment , and 6 and 12 months later . This report focuses on the latter two evaluations . RESULTS Compared with CT and ES , BFST yielded lasting improvements in parent-adolescent relationships and diabetes-specific conflict . Delayed effects on treatment adherence emerged at 6- and 12-month follow-ups . There were no immediate or delayed effects on adolescents ' adjustment to diabetes or diabetic control . CONCLUSIONS BFST yielded lasting improvement in parent-adolescent relationships and delayed improvement in treatment adherence , but it had no effect on adjustment to diabetes or diabetic control . A variety of adaptations to BFST could enhance its impact on diabetes outcomes A 24-week open-label clinical trial was conducted in 195 HIV-infected adults commonly underrepresented in research ( 35 % female , 71 % African American , 21 % Hispanic , and 20 % injection drug users [ IDUs ] ) to evaluate the effect of an HIV educational program on efficacy and adherence with a simple , compact , twice-daily triple nucleoside regimen containing a lamivudine ( 150 mg)/zidovudine ( 300 mg ) combination ( COM ) tablet plus abacavir ( ABC ) , 300 mg . At baseline , the patients ' median plasma HIV-1 RNA level was 4.18 log10 copies/mL and the median CD4 + cell count was 379 cells/mm3 . Patients were r and omized 1:1 to 4 modules of the Tools for Health and Empowerment HIV education intervention plus routine counseling ( EI + RC ; n = 96 ) or to routine counseling alone ( RC ; n = 99 ) . No differences between the EI + RC and RC treatment arms were observed with respect to the proportion of patients achieving plasma HIV-1 RNA levels < 40 copies/mL ( 60 % [ 33/55 ] vs. 55 % [ 38/69 ] ; P = 0.529 ) or < 400 copies/mL ( 80 % [ 44/55 ] vs. 80 % [ 55/69 ] ; P = 0.689 ) at week 24 ( intent-to-treat observed analysis ) , increase in median CD4 cell count above baseline at week 24 ( 78.3 vs. 104.8 cells/mm3 ; P = 0.498 ) , or mean overall adherence rates as measured by the Medication Event Monitoring System ( MEMS ) ( 70 % vs. 74 % ) . COM + ABC was generally well tolerated , and no association was observed between interruptions in treatment and the development of ABC hypersensitivity ( 5 suspected cases ) . In conclusion , in underrepresented patients , the EI used in this study did not affect the efficacy and adherence results with ABC + COM to any greater degree than did RC This article reports a r and omized controlled trial design ed to test the effects of special packaging of antihypertensive medication on compliance and blood pressure control . One hundred eighty subjects who had exhibited elevated blood pressure greater than 90 mmHg in the two years prior to the study were recruited from patients receiving care at a community hospital-based family medicine practice . After completing preenrollment interviews and blood pressure measurements , subjects were r and omly assigned to receive their antihypertensive medications either in the usual vials or in special unit dose-reminder packaging . Follow-up interviews , pill counts , and blood pressure measurements were performed at three-month intervals . There were no statistically significant differences between the control and experimental groups with regard to age , sex , race , employment , education , marital status , insurance coverage , or blood pressure regimens . Prior to the intervention , the experimental group had slightly lower diastolic blood pressure and reported better compliance than the control group . Analyses performed on 165 subjects completing the first follow-up visit revealed no significant improvements in blood pressure control or compliance for patients receiving special medication packaging . While some patients found it easy to remember to take pills packaged using this format , they also found the packages somewhat more difficult and inconvenient to use . In contrast to previously reported work , this study did not demonstrate any significant improvement in compliance with special packaging of antihypertensive medications Asthma education decreases the number of emergency visits in specific subgroups of patients with asthma . However , it remains unknown whether this improvement is related only to the use of an action plan alone or to other components of the educational intervention . A total of 126 patients consulting urgently for an acute asthma exacerbation were recruited ; 98 completed the study . The first 45 patients were assigned to Group C ( control ; usual treatment ) . Thereafter , patients were r and omized to either Group LE ( limited education ; teaching of the inhaler technique plus self- action plan given by the on call physician ) or Group SE ( same as group LE plus a structured educational program emphasizing self-capacity to manage asthma exacerbations ) . At baseline , there was no difference between groups in asthma morbidity , medication needs , or pulmonary function . After 12 mo , only Group SE showed a significant improvement in knowledge , willingness to adjust medications , quality of life scores , and peak expiratory flows . In the last 6 mo , the number of unscheduled medical visits for asthma was significantly lower in Group SE in comparison with groups C and LE ( p = 0.03 ) . The number ( % ) of patients with unscheduled medical visits also decreased significantly in Group SE compared with Groups C and LE ( p = 0.02 ) . We conclude that a structured educational intervention emphasizing self-management improves patient outcomes significantly more than a limited intervention or conventional treatment This study purported to determine the effect of pretreatment counseling upon discontinuation of 150 mg depot-medroxyprogesterone acetate ( Depo-Provera ) given for contraception . A total of 350 Mexican women participated : 175 received detailed structured pretreatment counseling about the hormonal effects of the injectable vs. routine counseling upon duration of use and efficacy of the method . Study termination rates were significantly lower in the structured counseling group than in the control group . Cumulative life table discontinuation rates were 17 % ( 30/175 ) and 43.4 % ( 76/175 ) , respectively ( p < 0.05 ) . The most common reasons for terminating DMPA were menstrual changes ( 8.6 and 32 % for counseling and control group , respectively ) . The findings suggest that pretreatment counseling on expected side effects increases the continuation rates of DMPA users 38 hypertensive Canadian steelworkers who were neither compliant with medications nor at goal diastolic blood-pressure six months after starting treatment were allocated either to a control group or to an experimental group who were taught how to measure their own blood-pressures , asked to chart their home blood-pressures and pill taking , and taught how to tailor pill taking to their daily habits and rituals ; these men were also seen fortnightly by a highschool graduate with no formal health professional training who reinforced the experimental manoeuvres and rewarded improvements in compliance and blood-pressure . Six months later , average compliance had fallen by 1.5 % in the control group but rose 21.3 % in the experimental group . Blood-pressures fell in 17 of 20 experimental patients ( to goal in 6 ) and in 10 of 18 control patients ( to goal in 2 ) The aim of the study was to assess the respective roles of the half-life of elimination of oral anticoagulants and patient education as causes of instability of anticoagulation level in patients on oral anticoagulant therapy . Patients were r and omised to receive either warfarin ( long half-life ) or acenocoumarol ( short half-life ) and either intensive or st and ard education , according to a factorial design . Instability of oral anticoagulant therapy was evaluated by the percentage of INRs and the time within the target range , and the variability between successive measurements . Compliance was assessed by means of electronic pill bottles . Eighty-six patients were included . Apart from the variability index , instability was similar between groups . Correlations between compliance and instability were observed only in the acenocoumarol group . No difference was found between the education groups . In patients starting oral anticoagulant therapy , dose determination may be the most important factor contributing to instability Summary : Fifty‐three hospital out patients with epilepsy were r and omly allocated to either a control or an intervention group . Patients in the intervention group were subjected to a combination of compliance‐improving strategies : patient counselling , a special medication container , self‐recording of medication intake and seizures , and mailed reminders to collect prescription refills and attend clinic appointments . Compliance with anticonvulsant therapy ( as measured by plasma anticonvulsant levels and prescription refill frequencies ) , and seizure frequency , were evaluated in each patient prior to intervention and 6 months afterwards . Patient compliance and clinical control improved significantly in the intervention group patients . Seizure frequency was , on average , halved following intervention . Compliance and seizure frequency were unaltered in the control group . Intervention failed to improve clinic appointment keeping . Poor compliance with drug therapy commonly confounds the treatment of epilepsy . This study shows that compliance can be improved and seizure frequency lessened by strategies that are easily incorporated into the routine management of epileptic patients OBJECTIVE A high level of adherence to antiretroviral therapy is required for complete suppression of HIV replication , immunological and clinical effectiveness . We investigated whether cognitive behaviour therapy can improve medication adherence . DESIGN Prospect i ve r and omized 1-year trial . SETTING Collaboration of HIV university outpatient clinic and psychotherapists in private practice . PARTICIPANTS 60 HIV-infected persons on stable antiretroviral combination therapy and viral load below 50 copies/ml . INTERVENTION Cognitive behaviour intervention in individual patients , in addition to st and ard of care . MAIN OUTCOME MEASURES Feasibility and acceptance of intervention ; adherence to therapy assessed using medication event monitoring system ( MEMS ) and self-report question naire ; virological failure ; psychosocial measures . RESULTS The median number of sessions for cognitive behaviour intervention per patient during the 1-year trial was 11 ( range 2 - 25 ) . At months 10 - 12 , mean adherence to therapy as assessed using MEMS was 92.8 % in the intervention and 88.9 % in the control group ( P=0.2 ) ; the proportion of patients with adherence > or = 95 % was 70 and 50.0 % ( P=0.014 ) , respectively . While there was no significant deterioration of adherence during the study in the intervention arm , adherence decreased by 8.7 % per year ( P=0.006 ) in the control arm . No differences between the intervention group and st and ard of care group were found regarding virological outcome . Compared with the control group , participants in the intervention group perceived a significant improvement of their mental health during the study period . CONCLUSIONS Cognitive behavioural support in addition to st and ard of care of HIV-infected persons is feasible in routine practice , and can improve medication adherence and mental health BACKGROUND DOTS is the control strategy for tuberculosis promoted by WHO . Pakistan is currently developing its National Tuberculosis Programme , and requires guidance on types of direct observation of treatment appropriate for the local conditions . We did a r and omised trial to assess the effectiveness of different packages for tuberculosis treatment under operational conditions in Pakistan . METHODS We enrolled 497 adults with new sputum-positive tuberculosis . 170 were assigned DOTS with direct observation of treatment by health workers ; 165 were assigned DOTS with direct observation of treatment by family members ; and 162 were assigned self-administered treatment . The trial was done at three sites that provide tuberculosis services strengthened according to WHO guidelines for the purpose s of the research , with a st and ard daily short-course drugs regimen ( 2 months of isoniazid , rifampicin , pyrazinamide , and ethambutol , followed by 6 months of isoniazid and ethambutol ) . The main outcome measures were cure , and cure or treatment completion . Analysis was by intention to treat . FINDINGS Within the strengthened tuberculosis services , the health-worker DOTS , family-member DOTS , and self-administered treatment strategies gave very similar outcomes , with cure rates of 64 % , 55 % , and 62 % , respectively , and cure or treatment-completed rates of 67 % , 62 % , and 65 % , respectively . INTERPRETATION None of the three strategies tested was shown to be superior to the others , and direct observation of treatment did not give any additional improvement in cure rates . The effectiveness of direct observation of treatment remains unclear , and further operational research is needed OBJECTIVE To determine whether a patient education programme ( PE ) would improve rates of adherence to a slow acting antirheumatic drug and to assess any subsequent effect on patient outcome . METHODS A r and omly controlled study comprising 100 patients with rheumatoid arthritis ( 49 control CG ; 51 experimental EG ) requiring D-penicillamine ( DPA ) . The same practitioner saw patients on seven occasions , for the same length of time . The EG received 7 x 30 minute one to one sessions of PE , while the CG received st and ard management . The primary measure of adherence was a pharmacological marker ( phenobarbitone ) encapsulated with the DPA assayed at monthly intervals for six months . Plasma viscosity ( PV ) , C reactive protein , articular index , morning stiffness , and pain score were used to assess outcome . RESULTS 454 blood sample s were collected and assayed and the pharmacological marker showed the EG to be significantly more adherent on more occasions than the CG ( p<0.05 ) . Patterns of adherence over time showed that at 12 weeks 86 % ( 38/44 ) of those in the EG compared with 64 % ( 29/45 ) of the CG remained adherent ( p=0.01 ) . These trends continued and by the end of the study 85 % ( 29/34 ) of the EG compared with 55 % ( 23/42 ) of the CG were taking their DPA as prescribed . Fifteen patients ( 12 from the EG ) experienced side effects requiring study withdrawal and 14 patients requested study withdrawal ( two from the EG ) . On study entry patients in the CG had significantly higher levels of PV than the EG and this remained so throughout the research . However , on completion , the health status of patients in both groups had improved significantly ( p<0.01 ) . CONCLUSIONS PE significantly increased adherence to DPA and its effects persisted over a period of six months . No additional clinical benefit was detected in the EG in comparison with the CG The efficacy , safety , and tolerability of a moderate dose , 3-drug lipid-lowering regimen were evaluated among 29 male patients with hyperlipidemia and coronary artery disease . In an initial 12-month phase , regular niacin , 500 mg qid , lovastatin , 20 mg bid , and colestipol , 10 g/bid , were given with dose adjustment for lipid targets and side effects . This was followed by 2 r and om sequence crossover phases ( 8 months each ) alternating regular niacin with a polygel controlled-release formulation of niacin for use in this regimen . Lipid , lipoprotein , apoprotein , and clinical chemistry determinations were obtained at baseline , during the initial phase , at the 2 crossover phases , and at 6 weeks after therapy . A final question naire queried specific side effects and overall preferences . Low-/high-density lipoprotein ( LDL/HDL ) changed from means of 215/46 mg/dl at baseline , to 94/59 mg/dl after run-in , to 85/52 mg/dl after 8 months of controlled-release niacin , and to 98/56 mg/dl after 8 months of regular niacin ( regular niacin vs controlled-release niacin , p < 0.005/<0.05 ) . The target of LDL < or = 100 mg/dl was achieved at 8 months by 83 % of these patients with controlled-release niacin and by 52 % with regular niacin ( p < 0.01 ) . Compliance was 95 % with controlled-release niacin versus 85 % with regular niacin ( p < 0.001 ) . The controlled-release niacin and regular niacin regimens did not differ in terms of uric acid , glucose , insulin , or asparate aminotransferase levels . Overall , 21 % of patients called the 3 drugs " very easy " and 72 % " fairly easy " to take . The controlled-release niacin-containing regimen was preferred by 21 patients and the regular niacin by 4 . In conclusion , these regimens achieve striking lipid changes among hyperlipidemic patients . Controlled release is the preferred niacin preparation in terms of LDL reduction , compliance , patient preference , and achieving the National Cholesterol Education Program guideline of LDL < or = 100 mg/dl . The 2 niacin preparations did not differ in evidence of toxicity PURPOSE We sought to evaluate the effect of automated telephone assessment and self-care education calls with nurse follow-up on the management of diabetes . SUBJECTS AND METHODS We enrolled 280 English- or Spanish-speaking adults with diabetes who were using hypoglycemic medications and who were treated in a county health care system . Patients were r and omly assigned to usual care or to receive an intervention that consisted of usual care plus bi-weekly automated assessment and self-care education calls with telephone follow-up by a nurse educator . Outcomes measured at 12 months included survey-reported self-care , perceived glycemic control , and symptoms , as well as glycosylated hemoglobin ( Hb A1c ) and serum glucose levels . RESULTS We collected follow-up data for 89 % of enrollees ( 248 patients ) . Compared with usual care patients , intervention patients reported more frequent glucose monitoring , foot inspection , and weight monitoring , and fewer problems with medication adherence ( all P -0.03 ) . Follow-up Hb A , , levels were 0.3 % lower in the intervention group ( P = 0.1 ) , and about twice as many intervention patients had Hb A1c levels within the normal range ( P = 0.04 ) . Serum glucose levels were 41 mg/dL lower among intervention patients than usual care patients ( P = 0.002 ) . Intervention patients also reported better glycemic control ( P = 0.005 ) and fewer diabetic symptoms ( P < 0.0001 ) , including fewer symptoms of hyperglycemia and hypoglycemia . CONCLUSIONS Automated calls with telephone nurse follow-up may be an effective strategy for improving self-care behavior and glycemic control , and for decreasing symptoms among vulnerable patients with diabetes OBJECTIVES To determine the effects of patient education on compliance and on health in patients with active , recent onset rheumatoid arthritis ( RA ) . METHODS A r and omised , controlled , assessor blinded , one year trial . The experimental group followed an education programme . All patients started on sulphasalazine therapy . Compliance with sulphasalazine was measured by pill counting . Compliance rates with regimens of physical exercise , endurance activities , and energy conservation were measured by question naires . Compliance with prescriptions of joint protection was scored using a test for joint protection performance . Health was measured by a Disease Activity Score ( function of erythrocyte sedimentation rate , Ritchie score , and number of swollen joints ) , C reactive protein , Dutch- AIMS scores , and M-HAQ scores , range of motion of shoulder , elbow , and knee joints . Parameters were scored at baseline and after three , six , and 12 months . RESULTS Sixty of 65 patients gave informed consent , five of them withdrew from follow up . Compliance with sulphasalazine exceeded 80 % with no differences between groups . Compliance with physical exercise ( at three months ) , energy conservation ( at three and at 12 months ) , and joint protection ( at three months ) improved significantly more in the experimental group . The improvements of health were not different in the groups . CONCLUSION Compliance with sulphasalazine among patients with active , recent onset RA is high , whether formal patient education is followed or not . Compliance with physical exercise , energy conservation , and joint protection was increased by patient education . Formal patient education did not improve health status 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 We investigated whether hospital-based specialist asthma nurses improved recognition and self-treatment of asthma episodes by patients followed up after attending accident and emergency departments ( A&E ) for asthma exacerbations . We carried out a r and omized prospect i ve controlled trial of adult asthma self-management , following a hospital outpatient nurse consultation in two outer-London District General Hospitals ( secondary care centres ) . The study included 211 adults , over 18 years old ( mean age 40 years ) who attended for asthma in two accident and emergency departments over 13 months . One hundred and eight evaluable patients were r and omized into the control group who continued with their usual medical treatment and were not offered any intervention during the study period . One hundred and three evaluable patients were r and omized into the intervention group . They were offered three 6-weekly outpatient appointments with one of two specialist asthma nurses for a structured asthma consultation , after attendance at the accident and emergency department . Following assessment of their asthma treatment and control , the nurses advised patients , through the use of self-management-plans , how to recognize and manage uncontrolled asthma and when to seek medical assistance . Medication and inhaler device type were altered if necessary The primary outcome was patient reported self-management of asthma exacerbations for 6 months . Secondary outcomes were assessed at baseline , 3 months and 6 months . These included home peak flow and symptom diaries , structured telephone question naires and audit of general practitioner records to determine utilization of services ( 6 months before and after A&E ) . Data were analysed on an intention to treat basis by multiple and logistic regression . The intervention group increased their use of inhaled topical steroids in 31/61 ( 51 % ) vs. 15/70 ( 21 % ) attacks in controls ( OR 3.91 CI 1.8 - 8.4 , P<0.001 ) and their use of rescue medication in 54/61 ( 89 % ) severe attacks vs. 53/70 ( 76 % ) controls ( OR 2.88 CI 1.1 - 7.9 , P<0.05 ) . Intervention patients had significantly higher ( mean 20.1 l min(-1 ) ; CI 0.4 - 39.7 ; P<0.05 ) and less variable PEF and significantly lower and less variable symptom scores 6 months after entry . Thirty-four percent of intervention patients vs. 42 % controls had severe attacks ( 61 and 70 respectively , OR 0.96 CI 0.7 - 1.4 ) during the 6 months . Intervention patients had fewer days off work than controls in the first 3 months ( NS ) but similar days off during the 6-month period . Intervention patients had fewer episodes away from work in the first ( 0.34 vs. 0.54 , P = 0.08 ) and the second 3 months ( 0.25 vs. 0.30 , NS ) than the controls . Over 80 % of the patients records were audited by their general practitioners ; the active group had less routine consultations with the doctor ( P = 0.03 ) and practice nurse ( P = 0.03 ) , less consultations for uncontrolled episodes ( P = 0.06 ) and less hospital visits ( NS ) than the controls . Hospital-based specialist nurses reduced asthma morbidity by improving patient self-management behaviour in acute attacks leading to reduced symptoms , improved lung function , less time off work and fewer consultations with health professionals 230 Canadian steelworkers with hypertension took part in a r and omised trial to see if compliance with antihypertensive drug regimens could be improved . For care and follow-up these men were r and omly allocated to see either their own family doctors outside working-hours or industrial physicians during work shifts ; the same men were r and omly allocated to receive or not receive an educational programme aim ed at instructing them about hypertension and its treatment . Surprisingly , the convenience of follow-up at work had no effect upon these men 's compliance with antihypertensive drug regimens . Similarly , although men receiving health education learned a lot about hypertension , they were not more likely to take their medicine The prevalence and impact of adult asthma are substantial , and poor self-management practice s , especially failures to adhere to treatment regimens , appear to be a significant problem . Desirable characteristics of an intervention program to improve self-management were identified through needs assessment and review of existing patient education re sources . A comprehensive program was developed that integrated a workbook with one-to-one counseling and adherence-enhancing strategies . A longitudinal 1-year study compared patients receiving this self-management program with " usual care " patients receiving st and ard asthma pamphlets . Patients were r and omly assigned to conditions . Baseline score and asthma severity were statistically controlled . Self-management patients had substantially better adherence than usual care patients , as well as improved functional status , at follow-up . Hospital and emergency department visits decreased in both groups but did not differ between groups This study was conducted to evaluate the effect of automated telephone patient monitoring and counseling on patient adherence to antihypertensive medications and on blood pressure control . A r and omized controlled trial was conducted in 29 greater Boston communities . The study subjects were 267 patients recruited from community sites who were > or= 60 years of age , on antihypertensive medication , with a systolic blood pressure ( SBP ) of > or= 160 mm Hg and /or a diastolic blood pressure ( DBP ) of > or= 90 mm Hg . The study compared subjects who received usual medical care with those who used a computer-controlled telephone system in addition to their usual medical care during a period of 6 months . Weekly , subjects in the telephone group reported self-measured blood pressures , knowledge and adherence to antihypertensive medication regimens , and medication side-effects . This information was sent to their physicians regularly . The main study outcome measures were change in antihypertensive medication adherence , SBP and DBP during 6 months , satisfaction of patient users , perceived utility for physicians , and cost-effectiveness . The mean age of the study population was 76.0 years ; 77 % were women ; 11 % were black . Mean antihypertensive medication adherence improved 17.7 % for telephone system users and 11.7 % for controls ( P = .03 ) . Mean DBP decreased 5.2 mm Hg in users compared to 0.8 mm Hg in controls ( P = .02 ) . Among nonadherent subjects , mean DBP decreased 6.0 mm Hg for telephone users , but increased 2.8 mm Hg for controls ( P = .01 ) . For telephone system users , mean DBP decreased more if their medication adherence improved ( P = .03 ) . The majority of telephone system users were satisfied with the system . Most physicians integrated it into their practice s. The system was cost-effective , especially for nonadherent patient users . Therefore , weekly use of an automated telephone system improved medication adherence and blood pressure control in hypertension patients . This system can be used to monitor patients with hypertension or with other chronic diseases , and is likely to improve health outcomes and reduce health services utilization and costs The objective of this study was to evaluate the effectiveness of an asthma education program on morbidity , knowledge , and compliance with inhaled corticosteroid treatment using a prospect i ve , r and omized , controlled , one-year-before/one-year-after protocol . After rigorous optimization of asthma therapy under the care of respirologists , patients were assigned to one of three groups : Group C ( control group : no formal education ) , Group P ( education and action plan based on peak-flow monitoring ) , and Group S ( education with action plan based on monitoring of asthma symptoms ) . A total of 188 subjects with moderate to severe asthma were enrolled and 149 completed the study . Asthma morbidity decreased significantly in all groups ( p = 0.001 ) . Mean values one-year-before/one-year-after in Groups C , P , and S were : unscheduled medical visits , 2.4/0.8 , 2.3/0.7 , and 1.9/ 0.7 ; hospitalizations , 0.21/0.04 , 0.24/0.04 , and 0.40/0.09 ; oral steroid treatments ; 1.3/0.5 , 1.2/0.7 , and 1.3/0.9 ; absenteeism from work/school , 9.6/5.2 , 8.8/2.2 , and 6.3/2.9 . Between-group differences did not reach statistical significance ( p > 0.05 ) . Asthma knowledge increased in both educated groups compared with the control group ( p < 0.001 ) as did short-term compliance with inhaled corticosteroids . These results confirm that treatment optimization coupled with sustained high quality care in motivated patients can lead to a significant decrease in asthma morbidity . In such clinical setting s , structured asthma education significantly improved short-term compliance with treatment and knowledge about asthma , although it could not add extra benefit with regard to morbidity . Nevertheless , this study does not refute the potential benefit of educational interventions aim ed at improving asthma-related morbidity over a longer time period or in patients with less optimal care or with high-risk factors A r and omised controlled trial , involving 112 adolescents with asthma , and a 2-year follow-up was conducted to assess the impact of an intervention programme aim ed at enhancing adherence to asthma medication . This programme had a duration of 1 year and consisted of an experimental group which received usual care from a paediatrician , but additionally attended individual and group sessions with an asthma nurse , and a control group which received usual care only . The programme aim ed at enhancing adherence by stimulating a positive attitude , increasing feelings of social support , and enhancing self-efficacy . At baseline , and after 12-month ( T1 ) and 24-month ( T2 ) follow-up , the participants filled in question naires which were based on the concepts of the ASE-model . Adherence was assessed by self-report ( range : 1 - 10 ) at the same points in time . After 12 months , 97 adolescents ( 87 % ) were available for follow-up , decreasing to 86 adolescents ( 77 % ) after 24 months . No statistically significant differences were found between the control and the experimental group , except for one . At T2 , self-reported adherence appeared to be statistically significantly higher in the experimental group . In conclusion , there seems to have been no substantial effect of the intervention programme OBJECTIVE To compare enalapril 20 mg once daily with 10 mg twice daily in terms of blood pressure reduction and patient compliance . DESIGN Cross-over study of patients r and omly assigned to a sequence of enalapril 20 mg once daily or 10 mg twice daily in three 4-week periods following a 4-week placebo run-in . SETTING General practice s in the greater Belfast and Lisburn area in Northern Irel and . PATIENTS Twenty-five hypertensive patients who had a mean diastolic blood pressure of between 90 and 110 mm Hg after receiving placebo for 4 weeks . MAIN OUTCOME MEASURES Reduction in blood pressure and estimation of patient compliance . RESULTS Patient compliance was superior on the once daily regimen . However , the twice daily regimen was associated with a greater blood pressure reduction which almost reached statistical significance at the 5 % level . CONCLUSIONS Enalapril 20 mg should be prescribed as 10 mg twice daily and measures taken to improve patient compliance BACKGROUND To determine if the intervention of individual advice improves adherence and effectiveness to highly active antiretroviral therapy . METHODS R and omized open trial . Patients treated with zidovudine + lamivudine + indinavir were assigned ( 2/1 ) to conventional care or individual advise . Individual advise consists in adaptation to treatment to patient style of live and detailed information of therapy . Adherence were estimated with structured interview and pillo counts and were considered correct when more than 90 % of prescribed drugs were taken . RESULTS Patients 170 , conventional care : 110 and IA : 60 . FOLLOW-UP 24 weeks . Baseline characteristics were similar in both groups . Correct adherence were estimated in 52.7 % of conventional care and in 76.7 % of individual advise ( p = 0.002 , relative risk : 1.45 ; CI 95 % : 1.16 - 1.82 ) . Undetectable viral load ( NASBA < 50 copies/ml ) in 54.5 % of conventional care and in 65 % of individual advise ( p = 0.18 , relative risk : 1.19 ; CI 95 % : 0.93 - 1.53 ) . Reduction of viral load in the conventional care group 1.02 + /- 0.5 log10/ml , and in the individual advise group 1.98 + /- 0.7 log10/ml . CONCLUSION The individual advice improve adherence with a tendency to improve effectiveness of highly active antiretroviral therapy CONTEXT It is not known whether patient outcomes are enhanced by effective pharmacist-patient interactions . OBJECTIVE To assess the effectiveness of a pharmaceutical care program for patients with asthma or chronic obstructive pulmonary disease ( COPD ) . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted at 36 community drugstores in Indianapolis , Ind. We enrolled 1113 participants with active COPD or asthma from July 1998 to December 1999 . Outcomes were assessed in 947 ( 85.1 % ) participants at 6 months and 898 ( 80.7 % ) at 12 months . INTERVENTIONS The pharmaceutical care program ( n = 447 ) provided pharmacists with recent patient-specific clinical data ( peak expiratory flow rates [ PEFRs ] , emergency department [ ED ] visits , hospitalizations , and medication compliance ) , training , customized patient educational material s , and re sources to facilitate program implementation . The PEFR monitoring control group ( n = 363 ) received a peak flow meter , instructions about its use , and monthly calls to elicit PEFRs . However , PEFR data were not provided to the pharmacist . Patients in the usual care group ( n = 303 ) received neither peak flow meters nor instructions in their use ; during monthly telephone interviews , PEFR rates were not elicited . Pharmacists in both control groups had a training session but received no components of the pharmaceutical care intervention . MAIN OUTCOME MEASURES Peak expiratory flow rates , breathing-related ED or hospital visits , health-related quality of life ( HRQOL ) , medication compliance , and patient satisfaction . RESULTS At 12 months , patients receiving pharmaceutical care had significantly higher peak flow rates than the usual care group ( P = .02 ) but not than PEFR monitoring controls ( P = .28 ) . There were no significant between-group differences in medication compliance or HRQOL . Asthma patients receiving pharmaceutical care had significantly more breathing-related ED or hospital visits than the usual care group ( odds ratio , 2.16 ; 95 % confidence interval , 1.76 - 2.63 ; P<.001 ) . Patients receiving pharmaceutical care were more satisfied with their pharmacist than the usual care group ( P = .03 ) and the PEFR monitoring group ( P = .001 ) and were more satisfied with their health care than the usual care group at 6 months only ( P = .01 ) . Despite ample opportunities to implement the program , pharmacists accessed patient-specific data only about half of the time and documented actions about half of the time that records were accessed . CONCLUSIONS This pharmaceutical care program increased patients ' PEFRs compared with usual care but provided little benefit compared with peak flow monitoring alone . Pharmaceutical care increased patient satisfaction but also increased the amount of breathing-related medical care sought 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 OBJECTIVE To analyse the efficacy of the intervention through a telephone call about patients ' compliance with lipaemia therapy . DESIGN Controlled , r and omised clinical trial . SETTING Ten clinics at 6 primary care centres . PARTICIPANTS 126 people diagnosed with hypercholesterolaemia according to Spanish Consensus criteria were chosen . INTERVENTION Two groups were formed . The control group ( CG ) of 63 patients , who received the doctor 's normal treatment ; and the Intervention group ( IG ) of 63 patients , who received in addition a telephone call at 2 weeks , 2 months and 4 months . MAIN MEASUREMENTS Pills were counted and cholesterol , triglycerides , HDL-C and LDL-C determined at the start , and at the third and sixth months . Percentages of patients complying ( 80%-110 % ) , the mean compliance percentage and the degree of control were compared . The reduction of absolute and relative risk ( RAR and RRR ) and the mean number of people that required an intervention in order to avoid non-compliance ( NI ) were calculated . RESULTS 115 people ( 91.26 % ) completed the survey , 56 in the IG and 59 in the CG . 77.1 % complied with the therapy ( CI , 68.4 - 85.8 ) , ( CG=64.4 % , CI , 55.3 - 73.5 ; IG=93.5 % , CI , 88.8 - 98 [ P<.001 ] ) . Mean compliance ran at 88.7 + /- 10.2 overall , at 84.4 + /- 12.8 in the CG and at 93 + /- 8.2 in the IG ( P<.001 ) . The RAR was 29.1 % , the RRR 81 % , and the NI was 3.43 patients . The patients controlled ran at 43.9 % in the IG ( CI , 34.9 - 52.9 ) and 23.1 % in the CG ( CI , 15.4 - 30.8 ) ( P<.005 ) . CONCLUSIONS The telephone intervention is an efficacious way of improving the percentage of patients complying with lipaemia treatment Adherence to combination antiretroviral therapy ( ART ) has been shown to be a determining factor in controlling viral replication , maintaining immunologic function and long-term survival in HIV-positive individuals . Little information is available on strategies to improve adherence in pediatric HIV-infected patients . We conducted a r and omized , nonblinded , pilot study to determine if a home-based nursing intervention would improve medication adherence . The study was offered to all eligible HIV-positive patients receiving care at Connecticut Children 's Medical Center 's ( CCMC ) Pediatric and Youth HIV Program . Sixty-seven percent ( 37/55 ) of the patients and their caretakers participated . We r and omized participants to either st and ard of care or the intervention trial . The intervention was design ed to improve knowledge and underst and ing of HIV infection and HIV medications and to resolve or modify barriers to adherence . Both groups completed pre- and post-intervention question naires , assessing their knowledge and underst and ing of HIV , ART , and adherence . Adherence was estimated objective ly from medication refill history and subjectively from a self-report score . We also inferred adherence from pre- to post-test plasma viral load and CD4 + T-cell percentages . The knowledge score ( p = 0.02 ) and medication refill history ( p = 0.002 ) improved significantly in the intervention group . The adherence self-report score improved , although not significantly ( p = 0.07 ) . We did not observe statistical differences in CD4 + T-cell counts or viral load between groups . We conclude that our home-based nursing intervention helped HIV-positive children and their families in better adhering to prescribed medication regimens |
11,996 | 25,034,616 | These studies have focused primarily on patients ' experiences of the injection procedure with respect to pain and anxiety .
Anticipated discomfort is often greater than actual discomfort experienced during intra-vitreal injection .
However , different stages of the treatment procedure produce varying levels of patient discomfort .
No one method of anaesthesia has consistently been shown to be more effective in reducing discomfort associated with treatment .
Common reasons underlying patient apprehension surrounding treatment include the thought of having an injection , fear of losing eyesight and fear of the unknown . | Current therapy to slow disease progression in patients with neovascular age-related macular degeneration ( AMD ) often entails intra-vitreal injection of an anti-vascular endothelial growth factor ( VEGF ) agent , that begins with a three-month loading phase of four weekly injections followed by regular monthly visits with clinician-determined re-treatment .
The effects of AMD on quality of life and visual function have been extensively reported in the literature , however , less is known about the burden imposed on patients by the arduous and often indefinite treatment schedule which habitually follows a diagnosis of wet AMD .
To date , no systematic review has been conducted of research investigating patients ' experiences of anti-VEGF treatment for AMD .
Few studies to date have investigated patients ' experiences of treatment for AMD . | PURPOSE To describe the effect of subfoveal choroidal neovascularization ( CNV ) from age-related macular degeneration ( AMD ) on health-related quality of life ( HRQOL ) of patients at enrollment in two r and omized clinical trials ; to examine the relation of visual acuity to HRQOL ; to compare HRQOL scores between participants with unilateral and bilateral CNV independent of other characteristics . DESIGN R and omized clinical trials . METHODS Two Submacular Surgery Trials ( SST ) recruited patients with AMD and either new subfoveal CNV ( Group N Trial ) or predominantly hemorrhagic CNV ( Group B Trial ) . Health-related quality of life interviews included the National Eye Institute Visual Function Question naire [ NEI-VFQ ] , the SF-36 Health Survey , and the Hospital Anxiety and Depression Scale [ HADS ] . Linear correlation and regression analyses were used to relate baseline HRQOL scores to visual acuity and bilateral disease . RESULTS Interview data were analyzed for 789 AMD patients : 454 patients in the Group N Trial and 335 patients in the Group B Trial . Participants reported poor vision-related functioning in many domains measured by the NEI-VFQ ( mean overall scores of 65 for Group N and 63 for Group B ) . Visual acuity of the better eye was strongly associated with NEI-VFQ scores but not with SF-36 or HADS scores . After adjusting for visual acuity of the better eye and other factors , bilateral cases had NEI-VFQ overall scores six points lower than unilateral cases in Group N Trial and 10 points lower than unilateral cases in the Group B Trial . CONCLUSIONS Subfoveal CNV profoundly affects vision-related quality of life . The effect is more pronounced with bilateral disease , even after controlling for visual acuity PURPOSE To assess patient perceptions concerning discomfort and changes in vision associated with intravitreal triamcinolone injections ( IVTA ) . DESIGN Prospect i ve consecutive case series . METHODS Fifty patients treated with IVTA between June 2003 and February 2005 were interviewed by telephone 10 to 12 weeks after injection . Each question was answered on a 1 to 5 scale . RESULTS There was no significant difference in reported amount of ocular discomfort pre-injection vs post-injection ( 1.0 vs 1.1 , respectively ) . Expected pain level ( 2.9 ) was higher than the actual pain level ( 1.6 ; P < .001 ) . Patients ' self-reported vision improved from 2.7 to 3.7 ( P < .001 ) . Thirty ( 60 % ) patients reported improved vision and 20 ( 40 % ) reported no change . Thirty-three ( 66 % ) patients reported more visual improvement than expected . CONCLUSIONS Patient expectation of discomfort during IVTA was greater than their actual experience ; approximately two-thirds of patients reported improved vision and about one-third reported improved functional status after injection Purpose : To determine factors associated with patients ' comfort during routine in-office intravitreal injection . Methods : Sixty patients receiving intravitreal injections over 15 months for macular edema because of diabetes , age-related macular degeneration , or retinal vein occlusion who were r and omized into 3 groups to receive 1 of 3 commonly used forms of anesthesia — TetraVisc , proparacaine HCl , or tetracaine HCl — before receiving intravitreal injection were studied . Fifteen minutes after injection , patients were asked to rate their pain from 0 ( no pain/no distress ) to 10 ( agonizing pain/unbearable distress ) using a Visual Analog Pain score survey . Self-reported pain scores were stratified by age , gender , diagnosis , injection number , substance injected , needle gauge , and visual acuity improvement . Results : Intravitreal injection was associated with low pain scores . Patients receiving tetracaine reported a statistically significant lower pain score ( 3.05 ± 2.01 ) than patients receiving proparacaine ( 3.17 ± 2.18 ) or TetraVisc ( 3.3 9± 2.26 ; P < 0.01 ) . Other important factors influencing pain score significantly ( P < 0.01 ) included improved vision from previous injection , female sex , and age > 65 years . Pain scores decreased with each consecutive injection . Conclusion : Pain associated with intravitreal injection is generally mild , and may be associated with epidemiologic and environmental factors PURPOSE To determine the quality of life ( QOL ) of patients with bilateral severe age-related macular degeneration ( AMD ) before macular translocation with 360 degrees peripheral retinectomy . DESIGN Prospect i ve , consecutive , noncomparative case series . METHODS An observational study assessed vision-related and general health QOL using the 25-item National Eye Institute Visual Function Question naire ( NEI VFQ-25 ) and the Medical Outcomes Study 12-item short form ( SF-12 ) surveys , respectively . Mean QOL scores were correlated with patient age , duration of vision loss , and visual function . Mean QOL scores in study patients were compared with mean QOL scores in groups of patients with low vision , patients with AMD of varying severity , and reference population s. MAIN OUTCOME MEASURES National Eye Institute VFQ-25 and SF-12 QOL scores . RESULTS Seventy patients with a mean age of 76.4 years were studied . Mean distance visual acuity ( VA ) was 62.4 ( Early Treatment Diabetic Retinopathy Study letters ) , mean near VA was 0.81 ( logarithm of the minimum angle of resolution ) , and mean reading speed was 74.9 words per minute . Important NEI VFQ-25 quality of vision subscales ( general vision , difficulty with distance tasks , difficulty with near tasks ) and vision-specific subscales ( dependency , role difficulties , mental health , social function limitations ) tended to correlate negatively with increasing patient age and duration of vision loss , but correlated positively with better VA and reading speed . The mean QOL scores for these important quality of vision and vision-specific subscales were significantly worse than or similar to mean scores in patients with low vision , and significantly worse than scores in patients with AMD of varying severity and a reference population . The mean SF-12 physical composite score in study patients was similar to that seen in patients with AMD of varying severity , but significantly higher than that in patients with low vision and a reference population . The SF-12 mental composite score in study patients was similar to those of all 3 comparison groups . CONCLUSIONS Patients with bilateral severe AMD have vision-related QOL similar to that of patients with low vision but significantly worse than those of patients with AMD of varying severity and persons without eye disease . This inability to perform vision-related daily tasks is not related to general health problems OBJECTIVE To examine ( 1 ) the prevalence of depressive disorders in community-dwelling adults with advanced age-related macular degeneration ( AMD ) and ( 2 ) the relationship in this population between depression , visual acuity , the number of comorbid medical conditions , disability caused by vision loss as measured by the National Eye Institute-Vision Function Question naire ( NEI-VFQ ) and the vision-specific Sickness Impact Profile ( SIPV ) , and disability caused by overall health status as measured by the Sickness Impact Profile-68 ( SIP ) . DESIGN Analysis of cross-sectional baseline data from a r and omized clinical trial . PARTICIPANTS Participants were 151 adults aged 60 and older ( mean age , 80 years ) with advanced macular degeneration whose vision was 20/60 or worse in their better eye . METHODS Subjects were interviewed using measures of depression , disability , and chronic medical conditions . Visual acuity was obtained . Nonparametric correlation analyses and linear regression analyses were performed . MAIN OUTCOME MEASURES Structured Clinical Interview for DSM-IV ( SCID-IV ) , Geriatric Depression Scale ( GDS ) , NEI-VFQ , SIPV , and SIP . RESULTS Of the participants , 32.5 % ( n = 49 ) met SCID-IV criteria for depressive disorder , twice the rate observed in previous studies of community-dwelling elderly . Over and above depression ( GDS ) , visual acuity aided in prediction of the level of vision-specific disability ( NEI-VFQ and SIPV ) . CONCLUSIONS Depressive disorder is a significant problem for the elderly afflicted with advanced macular degeneration . Further research on psychopharmacologic and psychotherapeutic interventions for depressed AMD patients is warranted to improve depression and enhance functioning . Over and above depression , visual acuity aided in predicting vision-specific disability . Treatment strategies that teach patients to cope with vision loss should be developed and evaluated Aim : To investigate the effects of an informational video on patient expectations and satisfaction with day-stay cataract surgery . Methods : 141 patients undergoing day-stay cataract surgery were r and omised into one of two video groups , explaining either what to expect from the cataract surgery or the anatomy of cataract . Patients were surveyed as to their expectations for visual outcome , anxiety , risk , and discomfort result ing from the surgery . After the operation , patients were again asked to rate their experience of anxiety , discomfort , risk , comprehension , overall satisfaction , and comparison with expectations . Results : 84 % of patients already thought they received enough or too much information . The expectations video group expected more risk and discomfort than the anatomy video group . Yet , after the surgery , the expectations video group was significantly more satisfied , understood better what was happening to them , and felt less anxious . There was no difference in the discomfort or risk actually experienced , or the expected visual outcomes . Patients with previous cataract surgery experience expected less anxiety and discomfort , and found the surgery closer to their expectations . None the less , previous cataract surgery experience did not negate the effects of the video . Conclusions : This study demonstrates that a simple , inexpensive videotape showing patients what to expect from cataract surgery results in significant increases in patient underst and ing of and satisfaction with the cataract surgery , as well as a decrease in anxiety . These effects were independent of patients ’ expected outcomes or previous experience with cataract surgery , and despite the fact that patients generally thought they had already received enough information PURPOSE To compare the anesthetic effectiveness of 3 topical agents used for intravitreal injections . DESIGN R and omized , triple-armed , double-blinded , prospect i ve , single-centered trial in patients receiving intravitreal ranibizumab for neovascular age-related macular degeneration . METHODS Patients were r and omized 1:1:1 to receive 0.5 % tetracaine hydrochloride drops and a 4 % lidocaine pledget ( n = 31 ) , 0.5 % tetracaine hydrochloride drops alone ( n = 31 ) , or 4 % cocaine ( + epinephrine 1/100,000 ) drops alone ( n = 31 ) . Patients were asked to score their pain experience using a visual analogue scale ( VAS ) immediately following and 15 minutes after their injection . The average of these scores was used as the primary outcome . The physician performing the procedure separately scored his perception of the patients ' pain using the Wong-Baker FACES scale . RESULTS Means of the averaged VAS pain score for Groups 1 , 2 , and 3 were : 19 ( 95 % confidence interval [ CI ] 12 - 26 ) , 21 ( 95 % CI 13 - 29 ) , and 21 ( 95 % CI 16 - 27 ) respectively . Mean Wong-Baker pain scores for Groups 1 , 2 , and 3 were 1.9 ( 95 % CI 1.3 - 2.6 ) , 2.1 ( 95 % CI 1.4 - 2.7 ) , and 2.3 ( 95 % CI 1.6 - 3.1 ) respectively . There was no significant difference ( P = .549 ) between groups for average VAS pain score . Similarly , there was no significant difference ( P = .790 ) for the physician-perceived pain score between groups . CONCLUSIONS There was no clinical difference in patient pain experience between the 3 anesthetic options tested . The addition of a 4 % lidocaine pledget offered no clinical advantage in pain relief compared to 0.5 % tetracaine or 4 % cocaine ( + epinephrine 1/100,000 ) drops alone Purpose : To compare the effectiveness of four different anesthetic methods for intravitreal injection . Methods : Twenty-four patients each received four intravitreal injections using each of four types of anesthesia ( proparacaine , tetracaine , lidocaine pledget , and subconjunctival injection of lidocaine ) in a prospect i ve , masked , r and omized block design . Pain was grade d by the patient on a 0 to 10 scale for both the anesthesia and the injection . Results : The average combined pain scores for both the anesthesia and the intravitreal injection were 4.4 for the lidocaine pledget , 3.5 for topical proparacaine , 3.8 for the subconjunctival lidocaine injection , and 4.1 for topical tetracaine . The differences were not significant ( P = 0.65 ) . There were also no statistical differences in the individual anesthesia or injection pain scores . Subconjunctival lidocaine injection had the most side effects . Conclusion : Topical anesthesia is an effective method for limiting pain associated with intravitreal injections |
11,997 | 15,674,892 | These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia .
H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia . | BACKGROUND Helicobacter pylori ( H pylori ) is the main cause of peptic ulcer disease .
The role of H pylori in non-ulcer dyspepsia is less clear .
OBJECTIVES To determine the effect of H pylori eradication on dyspepsia symptoms in patients with non-ulcer dyspepsia . | Antral biopsy specimens from 89 consecutive patients with nonulcer dyspepsia and erosive prepyloric changes included in a prospect i ve , r and omized , double-blind 4-wk study of the effect of an aluminum-magnesium antacid ( 120 mmol/day ) or pirenzepine ( 50 mg b.i.d . ) vs. placebo were examined histologically . Campylobacter pylori ( CP ) was found by light microscopy of silver-stained sections in 25 patients ( 28 % ) . Campylobacter pylori-positive patients were on average older than CP-negative patients ( p = 0.02 ) . There was a strong association between CP colonization and acute inflammation ( p less than 0.001 ) , both being rare in the absence of chronic inflammation . During treatment with antacids , the density of CP decreased ( p less than 0.001 ) without any improvement of the inflammatory reaction . On the contrary , the number of patients with gastritis tended to increase after antacids as compared with placebo ( p less than 0.10 ) . A separate analysis showed no symptomatic effect of the drugs . Thus , neither nonulcer dyspepsia nor erosive prepyloric changes are strongly associated with antral CP colonization or acute inflammation . Aluminum-magnesium antacids may suppress antral CP infection without healing the gastritis or relieving symptoms The aim of this study was to determine the effect of colloidal bismuth subcitrate ( De Nol ) on symptoms and gastric histology in patients with non-ulcer dyspepsia . In a single centre trial , patients with food related upper abdominal pain not caused by ulcer disease were r and omised to receive one tablet of colloidal bismuth subcitrate or matching placebo four times daily for eight weeks . Seventy three patients were entered and 51 completed the trial : 28 patients in the colloidal bismuth subcitrate group and 23 in the placebo group . Overall there was no difference between the two groups in terms of symptom relief . Among patients with histological gastritis ( n = 23 ) , however , those who took colloidal bismuth subcitrate used fewer antacid tablets ( for three of four fortnightly periods ) and were more likely to become asymptomatic ( eight of 11 v three of 12 , p less than 0.05 ) ; their gastritis was more likely to resolve ( five of 10 v 0 of 12 , p less than 0.025 ) and their gastric biopsies more likely to become negative for Helicobacter like organisms ( eight of nine v 0 of 12 , p less than 0.001 ) when compared with patients taking placebo . In contrast , patients who did not have gastritis in their index biopsies ( n = 28 ) fared similarly whether they received colloidal bismuth subcitrate or placebo . Our results indicate that the administration of colloidal bismuth subcitrate benefited non-ulcer dyspepsia patients with gastritis but had no effect on those without Duodenal biopsy specimens from 471 adults and 47 children were examined to determine the prevalence and distribution of gastric epithelium in the duodenal bulb in relation to age , gender , gastroduodenal inflammation , smoking , alcohol and consumption of nonsteroidal anti-inflammatory drugs ( NSAID ) . Gastric metaplasia was present in the anterior wall duodenal biopsy specimen in 31 % , was significantly less common in patients under 17 than in adults , and was more common in males than females . In sixty two adults who underwent multiple radial duodenal biopsy gastric metaplasia was r and omly distributed around the duodenal circumference ; sixty three per cent of the patients with gastric metaplasia found on multiple biopsy were detected by just the anterior biopsy . Gastric metaplasia was not obviously associated with alcohol , cigarette , or NSAID consumption . While the presence of gastric metaplasia was associated with adulthood , male sex , and low fasting gastric juice pH , its extent was associated with active duodenitis and Helicobacter-associated gastritis . On logistic regression , gastric metaplasia in the duodenum and gastric Helicobacter pylori were independent predictors of active duodenitis , but were not significantly associated with inactive duodenal inflammation . H pylori was observed in duodenal biopsy specimens from 32 patients , all with active duodenitis ; bacteria were present only on foci of gastric metaplasia , and were more likely to be seen when the metaplasia was extensive . It is proposed that inflammatory injury to the duodenal mucosa by H pylori may stimulate the development of further gastric metaplasia , and that the area of duodenum susceptible to colonisation with H pylori may therefore increase progressively until mucosal integrity is compromised and ulceration supervenes BACKGROUND The efficacy of anti-Helicobacter pylori treatment and cytoprotective drugs in H. pylori-positive and -negative non-ulcer dyspepsia ( NUD ) , respectively , is debatable . METHODS In a r and omized study , the efficacy of anti-H. pylori treatment versus sucralphate was tested in patients with NUD . One hundred and twelve patients with NUD , 62 positive and 50 negative for H. pylori were studied . Of 62 patients positive for H. pylori , 32 were treated with triple therapy ( colloidal bismuth subcitrate , tetracycline and metronidazole ) for 2 weeks and the remaining 30 were treated with sucralphate ( 1 g , q.i.d . ) for 4 weeks . Of 50 patients negative for H. pylori , 25 each were treated with either sucralphate ( 1 g , q.i.d . ) or ranitidine ( 150 mg , b.d . ) for 4 weeks . RESULTS In patients with NUD and H. pylori infection , triple therapy eradicated H. pylori in 88 % and was superior to sucralphate in producing symptom relief ( 81 vs 33 % , P = 0.0003 ) and histological improvement in gastritis ( 73 vs 30 % , P = 0.003 ) . In the H. pylori-negative group , sucralphate was superior to ranitidine with regard to symptom relief ( 68 vs 36 % , P = 0.04 ) and improvement in gastritis ( 44 vs 12 % , P = 0.09 ) . The symptomatic improvement persisted until 12 weeks after the start of treatment in triple therapy group only . CONCLUSIONS In patients with NUD associated with H. pylori , triple therapy was better than sucralphate in terms of symptomatic and histological improvement . However , sucralphate was superior to ranitidine in providing symptom relief in patients with H. pylori-negative NUD This r and omised double blind placebo controlled study evaluated the effectiveness of colloidal bismuth subcitrate ( CBS ) , ampicillin and their combination in the treatment of Helicobacter Pylori in non-ulcer dyspepsia ( NUD ) and assessed if elimination of this organism is associated with improvement of gastritis and the symptoms . Forty-eight NUD patients with H. pylori and histologic gastritis were r and omly allocated to one of the three regimens for 28 days . Symptoms were assessed before and after treatment . Forty-three patients completed the trial . Repeat endoscopy within 48 hours of completing treatment showed suppression of H. pylori in 6 of 7 patients ( 85.7 % ) on combined therapy and one of 8 patients ( 12.5 % ) on CBS therapy ( p = 0.0205 ) . There was no suppression of the bacteria in patients treated with ampicillin . Repeat endoscopy performed 2 weeks after completing treatment showed suppression of H. pylori in 3 of 7 patients ( 42.9 % ) on combined therapy and none in the other two groups . Patients on combined therapy who had suppression of H. pylori , 48 hours or 2 weeks after completing treatment were noted to have historical improvement of their gastritis ( p = 0.0001 and p = 0.05 respectively ) . This was also associated with improvement of symptoms in these patients This study investigated the effect of colloidal bismuth subcitrate and cimetidine on Campylobacter pylori in peptic disease . In 74 % of 135 patients with peptic disease diagnosed at endoscopy C pylori was detected before treatment . Compared with cimetidine , colloidal bismuth subcitrate significantly decreased the incidence of C pylori after six weeks of treatment ( p less than 0.001 ) . In the colloidal bismuth subcitrate group , subsequent healing of the lesion was correlated with the clearance of C pylori , unlike in the cimetidine group . C pylori was strongly associated with the presence of histological gastritis , which was decreased by colloidal bismuth subcitrate ( p less than 0.001 ) Gastritis caused byHelicobacter pylori ( HP ) is common in patients with nonulcer dyspepsia ( NUD ) , but an etiologic relationship between the histologic lesion and clinical symptoms is unproven . HP is inhibited by bismuth subsalicylate ( BSS ) , a traditional remedy for dyspeptic complaints . The aim of this study was to assess the short- and long-term effects of BSS on HP , gastritis , and symptoms in patients with NUD . One hundred twenty-six patients with NUD who were shown to be infected withH. pylori ( HP+ ) were enrolled . There was a two-week placebo run-in period to eliminate placebo responders . Fifty patients remained symptomatic and were r and omly assigned to therapy with either BSS liquid or a matching placebo . EGD , biopsy , and clinical evaluations were performed at entry , at week 5 ( end of therapy ) , at week 9 ( four weeks after therapy ) , or at time of symptomatic relapse . Twenty-seven patients received placebo and 23 patients received BSS . BSS suppressedH. pylori in 15/23 patients ( 65 % ) and eradicated it in one patient , whereas the placebo had no effect onH. pylori . Gastritis improved during therapy with BSS but relapsed by week 9 . There was no significant change in level of dyspeptic symptoms during or after treatment , although one month after the end of treatment , the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured . The study confirms that BSS given for three weeks suppresses but does not usually eradicateH. pylori . Such short-term suppression ofH. pylori heals gastritis but does not result in clinical improvement We conducted a 12-week , double-blind , r and omized , placebo-controlled trial to determine whether cimetidine ( 300 mg with meals and at bedtime ) or a convenient , liquid aluminum-magnesium antacid regimen ( 15 ml one hour after meals and at bedtime ) would expedite healing or relief of symptoms in patients with benign gastric ulcer . Of the 101 patients who completed the trial according to protocol , 32 received the antacid , 36 cimetidine , and 33 placebo . At 4 , 8 , and 12 weeks after entry , ulcers had healed in a larger percentage of patients treated with cimetidine than of those treated with placebo : 53 , 86 , and 89 per cent of the cimetidine group versus 26 , 58 , and 70 per cent of the placebo group ( P = 0.02 , 0.01 , 0.05 ) , respectively . Healing at the three intervals had occurred in 38 , 70 , and 84 per cent , respectively , of the antacid-treated patients . Neither cimetidine nor antacid was more effective than placebo in relieving symptoms . The presence or absence of symptoms during the fourth and eighth treatment weeks was a poor predictor of the presence of absence of an ulcer crater . We conclude that cimetidine significantly hastens the healing of benign gastric ulcer Non-ulcer dyspepsia ( NUD ) is a common complaint in which no systematic illness or organic proximal alimentary tract disease can be identified . The pathophysiology of NUD is probably heterogeneous . Eighty-two subjects with NUD were studied in a prospect i ve r and omized placebo-controlled study to assess the efficacy of colloidal bismuth subcitrate ( CBS ) chewable tablets at a dose of four tablets daily for 1 month . The role of Campylobacter pylori and associated histological gastritis was evaluated . Sixty-one percent of NUD patients had C. pylori in the gastric antrum compared with 25 % of age-matched controls . C. pylori was associated with acute and chronic inflammation ( P less than 0.001 ) in the antrum . C. pylori was cleared in 59 % of CBS-treated subjects compared with only 4 % placebo ( P less than 0.05 ) . Both acute and chronic inflammation improved in subjects cleared of bacteria . Clearance of C. pylori and histological improvement was associated with a significant decrease in symptoms . In C. pylori negative subjects improvement in symptoms occurred in both the placebo and active treatment groups . This study would suggest that C. pylori and associated histological gastritis may play a role in non-ulcer dyspepsia OBJECTIVES : The aim of this study was to assess the still controversial role of treatment of Helicobacter pylori ( H. pylori ) infection in patients with nonulcer dyspepsia . METHODS : We conducted a double-blind , r and omized , placebo-controlled , multicenter trial comparing the efficacy of 7 days of eradication treatment ( lansoprazole 15 mg b.i.d . , amoxicillin 1 g b.i.d . , and clarithromycin 500 mg b.i.d . ) with a control treatment ( lansoprazole 15 mg b.i.d . and placebo ) in H. pylori-infected patients with nonulcer dyspepsia . 13C breath tests were performed at baseline and during follow-up . We assessed patient symptoms , health status ( based on the SF-12 question naire ) , patient satisfaction , drug consumption , health care consultation behavior , and absenteeism related to dyspepsia over a 1-yr period . RESULTS : A total of 74 patients r and omized to eradication treatment and 70 patients r and omized to placebo were compared . The rate of eradication of H. pylori infection was 75 % in the active treatment group and 4 % in the placebo group ( p < 0.005 ) . The symptom score improved to a similar extent in the group receiving active treatment ( −4.0 ; 95 % CI = − 5.0 to −3.0 ) and placebo ( −3.6 ; 95 % CI = − 4.5 to −2.7 ) . Treatment response was not related to the severity or duration of initial symptoms or to the severity of gastritis on histology . Quality of life scores were comparable at 12 months . There was no significant difference in dyspepsia-related absenteeism or satisfaction with management of NUD . Patients receiving active treatment were more likely not to have had to use any dyspepsia treatment over the 12 months ( 60.8 % vs 44.3 % ; p = 0.047 ) . CONCLUSIONS : This study did not demonstrate any substantial benefit of curing H. pylori infection in patients with nonulcer dyspepsia . The study adds further evidence that H. pylori is not the main pathogenetic or therapeutic target in these patients OBJECTIVE To ascertain whether triple therapy alters the history of Helicobacter pylori (HP)-related nonulcer dyspepsia ( NUD ) . METHODS Forty-one young ( < 45 yr ) dyspeptic patients were confirmed to be HP-related NUD by serology , rapid urease test , and antral biopsy . Endoscopy excluded the presence of ulcer . These cases were r and omly plotted into control ( n = 21 ) and triple therapy ( n = 20 ) groups . In the former group , H2 blocker was given for 2 months and then intermittent antisecretory agents for up to 1 yr . In the latter group , 20 patients received a course of triple therapy and then were treated like the control group . The symptom scores ( range : 0 - 10 ) were collected on enrollment , and at the end of 2nd , 6th , and 12th months . Each case had serial tests of HP IgG ELISA titer on start , at weeks 2 , 4 , and 8 , at the 6th month , and at the end of the 1st yr . The second endoscopy was done in the 9th wk for eradication survey , and the third endoscopy , at the end of the 1st yr to resurvey the HP status . The histological gradings of biopsy specimens , sample d on each endoscopy , were compared . RESULTS In the triple therapy group , the rate of eradication of HP was 75 % . At he end of the 2nd month , the HP-eradicated cases of the triple therapy group improved the symptom score more significantly then the noneradicated cases ( 2.42+/-1.37 vs.4.76+/-1.58 , p < 0.001 ) . At the ends of the 6th month and 1st yr , the symptom scores of the eradicated cases improved more significantly than those of the control group ( 6th month , 0.61+/-1.18 vs. ] 2.66+/-2.06 ; 1st yr , 0.82+/-1.17 vs. ] 3.56+/-2.89 , p < 0.001 ) . The decline trend of ELISA titers occurred only in eradicated cases and became significantly evident from the 4th wk ( 0.30+/-0.15 vs. ] 0.49+/-0.07 , p < 0.05 ) and thereafter . Both acute and chronic pathological grading was improved in the triple group at the end of the 1st yr ( acute , 1.95 - 0.46 ; chronic , 1.9 - 0.92 ; p < 0,01 ) CONCLUSION Compared with control therapy at 1 yr , triple therapy showed greater symptomatic , serological , and histological improvements . Therefore , triple therapy is beneficial to symptomatic HP-related NUD Ninety-one Helicobacter pylori-positive patients with nonulcer dyspepsia were r and omized to receive either lansoprazole , amoxicillin , and clarithromycin or lansoprazole and placebo . A vali date d question naire assessed dyspeptic symptoms at baseline and at 3 , 6 , and 12 months . Endoscopies and biopsies were performed at baseline and at 3 and 12 months . There was an overall trend , although not statistically significant , for a benefit of H. pylori eradication . Of the patients in the antibiotics group , 16 of 46 ( 35 % ) had symptomatic improvement , versus 9 of 43 ( 21 % ) in the control group ( P = 0.164 ) . In a secondary analysis , it was found that of the patients without endoscopic gastric erosions , 15 of 34 ( 44 % ) in the antibiotics group and 5 of 33 ( 15 % ) of controls had symptomatic improvement ( P = 0.015 ) . Helicobacter pylori eradication did not prove to be clinical ly beneficial , although a tendency to symptomatic benefit was detected . Further studies are necessary to confirm the implication s of endoscopic gastric erosions in these patients The association of Helicobacter pylori and functional dyspepsia is not well defined . The role of H.pylori on dyspeptic symptoms is still controversial . The aim of this study is to confirm the efficacy of H. pylori eradication by two differentcommonly used treatment regimens , as well as to examinethe improvement of the dyspeptic symptoms by eradicatingH. pylori . H. pylori functional dyspepsia is prevalent in people over 60 years old . In this age groupwe treated 126 patients with bismuth plus metronidazole and amoxicillin ( group A , 67 patients ) versus omeprazoleplus amoxicillin ( group B , 59 patients ) . Results were statistically analyzed utilizing theWilcoxon signed-rank test , McNemer test and chi-squaretest ; P < 0.05 was considered significant . Two monthsafter the end of therapy we observed an eradication rate of 66.1 % in group A vs 64.3 % in group B.All treated patients showed improvement insymptomatology . Although there was no significantdifference between patients in whom H. pylori was or wasnot eradicated within the respective groups , when examiningall H. pylori-positive patients versus H.pylori-negative posttreatment patients , there was asignificant reduction ( P < 0.05 ) in all four symptomsof functional dyspepsia measured . In conclusion , we suggestthat patients treated with H. pylori-eradicatingtherapeutic regimens have an improvement in functionaldyspepsia symptoms . We shall prefer the dual therapy as compared to the triple therapy . We believethat eradicating treatment to eradicate H. pylori in theelderly patients with H. pylori -related functionaldyspepsia will reduce health care costs by reducing the number of subsequent visits In five subsequent open clinical studies , 180 patients with Helicobacter pylori (HP)-associated ulcer disease ( n = 163 ) or severe functional dyspepsia ( n = 17 ) requiring therapy were treated with either 40 mg omeprazole plus 4 x 500 mg amoxicillin suspension for 1 wk ( group I , n = 35 ) , 2 x 40 mg omeprazole plus 4 x 500 mg amoxicillin for 1 wk ( group II , n = 50 ) , 2 x 20 mg omeprazole plus 4 x 500 mg amoxicillin for 2 wk ( group III , n = 62 ) , 2 x 20 mg omeprazole ( day 1 - 14 ) and 4 x 500 mg amoxicillin ( day 8 - 14 ) ( group IV , n = 22 ) or with 2 x 20 mg omeprazole for 2 wk ( group V , n = 11 ) . The HP eradication rates determined with a biopsy urease test , microscopy of a mucosal smear , specific culture , and histology after modified GIEMSA staining in the 5th wk after discontinuation of study medication were 61.3 % in group I , 61.7 % in group II , 82.8 % in group III , 28.6 % in group IV , and 0 % in group V. Apart from clinical insignificant pharyngeal paresthesias ( n = 6 ) , nine patients ( 5.7 % ) with combined therapy complained of important side effects ( stomatitis : n = 3 , diarrhea : n = 3 , allergic exanthema : n = 3 ) that led to termination of amoxicillin treatment in four cases ( 2.5 % ) . We conclude that omeprazole-enhanced amoxicillin antibiosis is a simple and effective approach to the eradication of HP colonization BACKGROUND There is little information on the effects of Helicobacter pylori eradication in patients with a primary diagnosis of gastro-oesophageal reflux disease ( GORD ) . Our aim was to investigate the effect of H pylori eradication in this group of patients . METHODS We did a double-blind , r and omised , placebo-controlled study in 70 patients with GORD . We assigned individuals to three groups . All patients received lansoprazole 30 mg twice daily for 10 days , followed by 30 mg once daily for 8 weeks . Patients infected with H pylori received either antibiotics ( clarithromycin 500 mg and amoxicillin 1000 mg twice daily ) or placebo for the first 10 days . Controls were patients not infected with H pylori . Patients were followed up for 6 months at 2-week intervals for GORD symptoms . At the end of the study we repeated endoscopy and oesophageal and gastric 24 h-pH monitoring . FINDINGS 58 of 70 patients completed our study . At the end of the study 16 of these patients were H pylori-positive ( 14 placebo and two eradication failures ) , 13 were negative because of successful H pylori eradication , and 29 were controls . H pylori-positive patients relapsed earlier ( 54 days ) than did those in whom H pylori was eradicated ( 100 days ) ( p=0.046 ) . The H pylori-negative control group relapsed after the longest period ( 110 days ) . However , time to relapse was also affected by oesophagitis grade ( no oesophagitis 127 days , grade III or IV oesophagitis 18 days ) . When results were corrected for the affect of oesophagitis grade , H pylori-positive patients relapsed earlier ( p=0.086 ) than H pylori-eradiated patients and controls ( p=0.001 ) . INTERPRETATION H pylori infection positively affects the relapse rate of GORD . Eradication of H pylori could , therefore , help to prolong disease-free interval in patients with GORD Seventy-two patients with Helicobacter pylori-associated chronic gastritis were r and omized to a 3-week oral treatment with furazolidone 0.1 g t.i.d . or metronidazole 0.2 g t.i.d . or placebo . Endoscopy was performed before and after treatment , and biopsy specimens were taken from the antrum of the stomach for histological examination and culture of Helicobacter pylori . Disappearance rates of Helicobacter pylori in furazolidone , metronidazole and the control groups were 74 % ( 20/27 ) if considering completion of therapy , the 20/25 or 80 % , 33.3 % ( 8/24 ) and 14.3 % ( 3/21 ) respectively . There was a significant difference in the disappearance rate of Helicobacter pylori between furazolidone and metronidazole , and between furazolidone and the placebo group ( p less than 0.01 ) , but there was no such difference between metronidazole and the placebo group ( p greater than 0.05 ) . In the patients receiving furazolidone , the eradication of Helicobacter pylori was accompanied by marked improvement in both inflammatory infiltration in the gastric mucosa and symptoms . These results reasonably suggest that Helicobacter pylori may play an etiological role in the pathogenesis of chronic gastritis , and that furazolidone is effective in the treatment of Helicobacter pylori-associated chronic gastritis Fifty patients completed an investigator-blind trial comparing bismuth subsalicylate , erythromycin ethylsuccinate , and placebo matched to the bismuth salt in the treatment of gastritis associated with Campylobacter pylori . C. pylori was cleared from 14 ( 77.8 % ) of 18 patients given locally active bismuth , from one ( 6.7 % ) of 15 patients given erythromycin , and from none of 17 patients given placebo . Gastritis resolved in 13 ( 81 % ) of 16 patients treated with bismuth but in only three of 13 receiving erythromycin and in none of 16 patients given placebo . Results of endoscopic examination showed greater improvement in patients cleared of C. pylori than in those with persistent infection . Heartburn improved in 50 % of patients who received bismuth compared with 17 % of those given placebo . The success of bismuth is probably due to its local antimicrobial activity . Erythromycin may have been inactivated by the low pH in the areas colonized with C. pylori . Relapse is less frequent when a combination of bismuth and an antimicrobial agent is used ; such a combination is characterized by local and systemic activity , stability at low pH , and good penetration into gastric mucus BACKGROUND AND OBJECTIVE The Helicobacter pylori eradication in patients with functional dyspepsia has been the subject of controversy because trials come to contradictory conclusions . The objective of this trial was to evaluate the effect , compared with placebo , of the eradication treatment in patients with functional dyspepsia . PATIENTS AND METHOD R and omized double blind placebo controlled trial . We included 158 patients attended by family physicians ( Area 10 Primary Care , Health Institute of Madrid ) with functional dyspepsia and Helicobacter pylori infection detected by the ureasa test in endoscopy . An OCA ( ameprazole clarithromycin and amoxicillin group ( n = 79 ) and a placebo group ( n = 79 ) were r and omized . During 7 days , patients at the OCA group received omeprazole ( 20 mg bid ) , clarithromycin ( 500 mg bid ) and amoxicillin ( 1000 mg bid ) daily , and patients at the control group received the placebo agent twice daily . Dyspepsia improvement according to a Likert scale ( 5 steps ) , and eradication of H. pylori by 13C-urea breath test were evaluated during one year . RESULTS Both groups were homogeneous in relation to age , sex and dyspepsia degree . The average age ( st and ard deviation ) of studied patients was 41.99 ( 13.93 ) years . At one year of follow up , H. pylori was eradicated in 81.01 % ( 64/79 ) of the OCA group and 5.06 % ( 4/79 ) of the placebo group . The difference of dyspepsia improvement ( 22.78 % ; 95 % confidence interval [ CI ] , 7.62 - 37.79 ) between the OCA group ( 41.77 % ; 95 % CI , 30.77 - 53.41 ) , and the placebo group ( 18.99 % ; 95 % CI 11.03 - 29.38 ) was significant ( p = 0.0018 ) . CONCLUSION Eradication of Helicobacter pylori in patients with functional dyspepsia is more effective improving symptoms than placebo An investigator blind trial was performed comparing bismuth salicylate , erythromycin ethylsuccinate , and placebo in the treatment of Campylobacter pyloridis associated gastritis in patients without peptic ulceration . Fifty patients fulfilled the study criteria . There was a strong correlation between the presence of C pyloridis and histologically confirmed gastritis . Clearance of organisms led to improvement of the gastritis . C pyloridis was cleared from 15 patients ; of these , 13 had gastritis initially , which resolved in 12 . Conversely , gastritis resolved in only four of 32 patients not cleared of organisms ( p less than 0.0001 ) . There was significantly greater improvement in endoscopic appearances in the patients cleared of C pyloridis compared with those whose infection persisted ( p less than 0.001 ) . In the three treatment groups organisms were cleared from 14 of 18 patients receiving the locally active bismuth salicylate , only one of 15 patients receiving erythromycin ethylsuccinate , and none of 17 patients taking placebo . These findings suggest that the ideal antimicrobial for the successful eradication of C pyloridis associated gastritis should be locally active , stable at low pH , and should penetrate gastric mucus . The resolution of gastritis and improvement in endoscopic appearances associated with clearance of C pyloridis support the view that these organisms may play a part in this condition We conducted a double-blind , placebo-controlled , r and omized treatment study in Peruvian adults with antral gastritis associated with Campylobacter pylori . Patients received either 400 mg of furazolidone ( n = 14 ) , 400 mg of nitrofurantoin ( n = 24 ) , or a placebo ( n = 31 ) for 14 days . Endoscopy was carried out at baseline , 1 day after ceasing therapy , and 6 wk after the end of treatment to verify colonization by C. pylori and determine the extent of gastric inflammation . Treatment with nitrofurantoin or furazolidone markedly reduced or , in some cases , cleared C. pylori from the antrum ( p less than 0.0005 compared with placebo ) . Resolution of acute gastric inflammation , as evidence d by decreased polymorphonuclear leukocyte infiltration and regeneration of the mucus layer , paralleled the reduction in bacterial colonization ( p less than 0.005 compared with placebo ) . A high percentage of patients experienced relapse ( recolonization by C. pylori and return to pretreatment levels of gastritis ) within 6 wk after cessation of treatment . Significant relief of dyspeptic symptoms was not evident during the study Symptomatic patients ( n = 101 ) with Helicobacter pylori infection were enrolled into a double-blind , double-dummy study to assess the efficacy of lansoprazole plus amoxycillin in the treatment of H. pylori infection . Patients were r and omized to either lansoprazole 30 mg once daily ( days 0 - 28 ) together with placebo ( matched to amoxycillin ) three times a day ( days 0 - 14 ) followed by either placebo or amoxycillin 500 mg three times daily ( days 15 - 28 ) . Biopsy specimens for culture and histology were collected on days 0 and 56 or upon symptomatic relapse . Blood for serology was collected at days 0 , 56 and 168 . A [14C]-urea breath test was performed on day 168 . Eighty-one ( 80.2 % ) patients completed the 56 day assessment . Of patients treated with lansoprazole plus amoxycillin , 35.1 % ( 13/37 ) were cured of infection as assessed at day 56 ( 26.5 % on an intention-to-treat basis ) , compared with 4.8 % ( 2/42 ) of the placebo group ( 4 % on an intention-to-treat basis ) . Recrudescence/re-infection occurred in one patient upon re-evaluation at day 168 . Analysis of prognostic factors indicated that smoking and alcohol intake had little impact on the treatment outcome . Inflammation ( both acute and chronic ) improved in patients treated with lansoprazole plus amoxycillin . The relatively low efficacy of the treatment may relate to a single daily dose of lansoprazole ( 30 mg ) being prescribed , treatment with amoxycillin being commenced 2 weeks after the initiation of lansoprazole or accurate assessment of treatment efficacy ( both antral and body biopsy specimens taken ) BACKGROUND To date , it is unclear whether Helicobacter pylori infection is associated with disturbances of gastric emptying or acid secretion in patients with functional dyspepsia ( FD ) . Our aim was to investigate whether , in the long run , cure of H. pylori infection significantly influences gastric emptying of solids , acid secretion , and gastrin and pepsinogen I ( PGI ) release in patients with FD . METHODS Thirty-eight consecutive H. pylori-positive patients with FD , whose complaints were scored for severity and frequency on the basis of a vali date d symptom question naire , were initially enrolled in the study . They were r and omized to receive an eradicating regimen consisting of omeprazole plus clarithromycin and tinidazole for 1 week or full-dose ranitidine for 3 weeks . In 33 patients ( 18 H. pylori-cured and 15 with persistent infection ) basal and pentagastrin-stimulated acid secretion , fasting and meal-induced gastrin concentrations , fasting serum PGI levels , and gastric emptying of solids were determined before and 6 months after therapy . RESULTS In the 18 H. pylori-cured patients meal-induced gastrin and fasting PGI levels were significantly reduced after 6 months as compared with pretreatment values ( peak serum gastrin , 76.0 + /- 23.4 versus 111.9+/-37.4 pg/ml ; PGI , 57.1+/-23.4 versus 72.9+/-29.1 ng/ml ) , whereas they remained virtually unchanged in the 15 patients with persistent infection . In contrast , both basal and stimulated acid secretion and gastric emptying time of solids remained unmodified over time in both groups of patients . CONCLUSIONS We confirm that also in patients with functional dyspepsia H. pylori eradication in the long run significantly reduces gastrin and PGI release as a result of improvement in the underlying antral gastritis , but this is not accompanied by modifications of gastric emptying of solids or acid secretion BACKGROUND A contribution of Helicobacter pylori gastritis to the pathogenesis of non-ulcer dyspepsia ( NUD ) remains uncertain . METHODS Administration of an appropriate clinical question naire followed by endoscopy allowed us to select , among 139 out patients with dyspepsia , 87 non-ulcer dyspepsia patients with more severe and group-distinctive symptoms , 35 of whom were classified as having ulcer-like ( ULD ) . 38 as dysmotility-like ( DLD ) , and 14 as reflux-like dyspepsia ( RLD ) . Biopsy specimens were evaluated for H. pylori gastritis in accordance with the Sydney system . The 70 H. pylori-positive cases were treated with omeprazole , 20 mg twice daily , and amoxycillin , 1 g three times daily for 2 weeks . RESULTS Higher rates of H. pylori colonization were found histologically in the gastric mucosa of ULD ( 91 % ) and RLD ( 86 % ) than in that of DLD ( 68 % ) or asymptomatic ( 42 % ) patients . ULD differed from RLD patients in their higher score of antritis activity . Three and 6 months after H. pylori eradication ULD ( but not DLD ) showed significant regression of dypspetic symptoms scores . CONCLUSIONS It seems likely that H. pylori gastritis , with special reference to active antritis , is among causative factors of ULD . Its role in the pathogenesis of RLD and DLD needs further investigation BACKGROUND Prior studies have yielded conflicting results on whether or not Helicobacter pylori causes nonulcer dyspepsia . PATIENTS AND METHODS We enrolled 100 consecutive patients with nonulcer dyspepsia into a r and omized , double-blind , placebo-controlled trial . Patients with peptic ulcer disease , esophagitis , hepatobiliary disease , irritable bowel disease , or predominantly reflux-related symptoms were excluded by history and upper endoscopy . Helicobacter pylori infection was determined by biopsy and histologic examination . Serum H. pylori IgG antibodies and CagA status were determined by Western blot . Enrolled patients were r and omized to a 14-day regimen of omeprazole ( 20 mg twice daily ) and clarithromycin ( 500 mg three times daily ) or placebo . Dyspeptic symptoms were assessed by use of a visual analog scale at baseline and at 1 , 3 , 6 , and 12 months after treatment . Follow-up upper endoscopy with biopsy was performed 4 weeks after treatment . Compliance was measured by tablet counts . RESULTS At 1 year , the change in dyspeptic symptoms was -24.0 ( 95 % confidence interval , -69.0 to 21.0 ) in the omeprazole and clarithromycin group and -24.2 in the placebo group ( 95 % confidence interval , -70.0 to 21.6 ) . Furthermore , patients with persistent H. pylori infection demonstrated a greater , but not significant , improvement in symptoms ( -40 + /- 144 [ mean + /- SD ] , -65 + /- 142 , -45 + /- 138 , and -39 + /- 163 ) than those with successful eradication ( -26 + /- 126 , -26 + /- 148 , -12 + /- 126 , and -25 + /- 151 ) at months 1 , 3 , 6 , and 12 , respectively . CONCLUSION Patients with nonulcer dyspepsia should not routinely be treated for H. pylori , since it is not a cause of this condition in most patients BACKGROUND & AIMS Observational studies have suggested that Helicobacter pylori may protect against gastrointestinal reflux disease ( GERD ) , but these results could be due to bias or confounding factors . We addressed this in a prospect i ve , double blind , r and omized , controlled trial . METHODS H. pylori-positive patients with at least a 1-year history of heartburn with a normal endoscopy or grade A esophagitis were recruited . Patients were r and omized to 20 mg omeprazole , 250 mg clarithromycin , and 500 mg tinidazole twice a day for 1 week or 20 mg omeprazole twice a day and identical placebos . A second concurrently recruited control group of H. pylori-negative patients were given open label 20 mg omeprazole twice a day for 1 week . All patients received 20 mg omeprazole twice a day for the following 3 weeks and 20 mg omeprazole once daily for a further 4 weeks . Omeprazole was discontinued at 8 weeks and patients were followed up for a further 10 months . A relapse was defined as moderate or severe reflux symptoms . H. pylori eradication was determined by 13C-urea breath test . RESULTS The H. pylori-positive cases were r and omized to antibiotics ( n = 93 ) or placebo ( n = 97 ) . Relapse of GERD occurred in 83 % of each of the antibiotic , placebo , and H. pylori-negative groups during the 12-month study period . Life tables revealed no statistical difference between the 2 H. pylori-positive groups ( log rank test , P = 0.84 ) or between the 3 groups ( log rank test , P = 0.94 ) in the time to first relapse . Two patients in each group developed grade B esophagitis at 12 months . CONCLUSIONS H. pylori eradication therapy does not seem to influence relapse rates in GERD patients This study aim ed to test whether pretreatment gastric pathology in H. pylori-infected nonulcer dyspepsia ( HpNUD ) patients is relevant to and predictive of the symptomatic response after H. pylori eradication . Anti-H. pylori triple therapy was administered to 250 HpNUD patients , enrolled as the therapy group . In addition , 60 patients were enrolled as the control group , in which omeprazole was an alternatives to the triple therapy . Pretreatment gastric histology was evaluated thoroughly by the up date d Sydney system . A [ 13C ] urea breath test was also performed to evaluate the H. pylori eradication two months and 12 months later . For each patient , the baseline , month 2 , and month 12 symptom scores were assessed for the month 2 or month 12 residual symptom ratio ( RSR-2 m or RSR-12 m ) , calculated from : 100 % × month 2 or month 12 score/baseline score . Based on either RSR-2 m or RSR-12 m , patients were categorized as good response ( RSR < 50 % ) , moderate response ( 50–70 % ) , and poor response ( > 70 % ) subgroups in both therapy and control groups to define the short-term and long-term symptomatic responses . Patients with successful H. pylori eradication in the therapy group showed a higher incidence of good symptomatic response ( RSR < 50 % ) than those from the control group ( month 2 : 30.3 vs 12 % , P < 0.05 ; month 12 : 34.7 vs 17.1 % , P < 0.05 ) . Univariate and multivariate analysis disclosed that patients with a higher acute inflammation score ( AIS ) and the lowest incidence of lymphoid follicles ( LF ) at pretreatment gastric histology are predisposed to having a good symptom response after H. pylori eradication ( P < 0.05 ) . For HpNUD patients who have an AIS of more than three and an absence of LF at gastric histology , more than 85 % had good short-term ( month 2 ) and long-term ( month 12 ) symptomatic relief after H. pylori eradication . In conclusion , nearly 30 % of HpNUD patients can obtain symptomatic relief following H. pylori eradication . The pretreatment gastric histology of HpNUD can be helpful to monitor the symptomatic response after H. pylori eradication It remains controversial whether the cure of H. pylori infection improves NUD symptoms . UNLABELLED Eradication treatment leads to improvement of gastritis . There is little information of its effect on changes in the topographic distribution and regression of actual mucosal alterations in dyspeptic patients . In a previous study we provided evidence of a complex of histopathological changes in the cardia , corpus and antrum in patients with H. pylori infection and non-ulcer dyspesia . OBJECTIVE To assess the effect of eradication treatment on the development of histological changes in the lower oesophagus , in the gastric cardia , corpus and antrum in patients with non-ulcer dyspesia three and six months after treatment . METHODS AND PATIENTS 251 consecutive dyspeptic patients ( without ulcers or gastric malignity ) with H.pylori infection were investigated prospect ively . Endoscopy with eight biopsies ( antrum , corpus , cardia and lower oesophagus ) were made before , eradication treatment and three and six months after this treatment ( Pantoprazole 40 mg 1x/day , Amoxycillin 1000 2x/day , Claritromycin 500 2x/day ) . The biopsies were stained ( H+E ) and modified Giemsa to detect H. pylori . The inflammation , activity and other mucosal changess were examined semiquantitatively and evaluated according to the Sydney System . RESULTS In the cardia , corpus and antrum a significant decline of chronic inflammation was recorded as well as of the activity and H.pylori ( p<0.001 ) . Atrophy increased insignificantly in the cardia ( p>0.05 ) while in the corpus ( p<0.05 ) and antrum it declined ( p<0.001 ) . Intestinal metaplasia remained unaltered in the cardia and antrum , in the corpus it declined insignificantly . The number of patients with hyperplasia of the foveolae in the cardia increased , the increase was however not significant , contrary to the corpus ( p<0.01 ) and antrum ( p<0.05 ) , in particular between the first and second visit of the surgery . Lymphoid follicles receded significantly in the cardia ( p<0.001 ) and in the antrum ( p<0.01 ) , while they did not change in the corpus . In the corpus and antrum was a significant increase of chemical gastropathy between the second and third visit ( p<0.001 , and the same applies to haemorrhage in the oesophageal papillae ( p<0.001 ) . CONCLUSION Eradication treatment had the most marked effect on decline of the activity of inflammation and number of Helicobacter pylori . Chronic inflammation , atrophy and intestinal metaplasia persisted , although with a lower intensity , and signs of chemical gastropathy with haemorrhage in the oesophageal papillae developed A study was undertaken to determine the role of Helicobacter pylori in non-ulcer dyspepsia ( NUD ) and to determine the efficacy of colloidal bismuth subcitrate ( CBS ) in the treatment of NUD . Seventy-one patients were r and omly allocated ( double blind ) to CBS or placebo , two tablets twice daily for 4 weeks . The severity of dyspepsia was scored and endoscopies performed before and after treatment , and antral biopsy specimens were taken for bacteriologic and histologic examination . Forty patients had H. pylori infection , and all had changes of chronic active gastritis . H. pylori was cleared from 17 to 21 patients ( 81 % ) treated with CBS , whereas none of the 19 patients treated with placebo cleared the bacteria . Improvement in histology was noted in 15 of 21 patients ( 71.4 % ) treated with CBS , whereas no improvement was noted in any of the placebo controls . Thirty-one patients were negative for H. pylori . All had either normal gastric histology or minor degrees of inflammation . Seventeen of these patients received CBS , and 14 received placebo . All groups reported improvement in the symptom score ; however , the H. pylori-positive , CBS-treated group recorded a significantly higher improvement than the other groups ( p less than 0.001 ) . Relapse of H. pylori infection after initial clearance of the bacteria was high . Twelve of 16 patients evaluated relapsed 1 month after withdrawal of CBS BACKGROUND The relationship between Helicobacter pylori infection and non-ulcer dyspepsia is controversial . METHODS In a prospect i ve , long-term , double-blind study we r and omized 100 patients with non-ulcer dyspepsia and H. pylori infection to receive either of two treatment regimens : 1 ) bismuth-based triple therapy ( n = 50 ) or 2 ) bismuth + placebo ( n = 50 ) . RESULTS Triple therapy : subjects who became H. pylori-negative ( n = 42 ) showed a significant symptomatic response when interviewed at 8 weeks , 6 months , and 1 year ( P < 0.01 ) . This improvement was evident in the ' ulcer-like ' dyspepsia group at all times ( P < 0.01 ) but in the ' reflux-like ' and ' motility-like ' groups at 6 months only ( P < 0.01 ) . Those who remained H. pylori-positive showed no decrease in symptoms at 8 weeks , 6 months , and 1 year . Bismuth-placebo therapy : subjects who became H. pylori-negative ( n = 7 ) showed an improvement in symptoms at 8 weeks , 6 months , and 1 year . Those who continued to harbour the infection after treatment ( n = 42 ) showed an insignificant improvement in the motility and non-specific groups only . CONCLUSION This study shows that eradication of H. pylori results in a significant long-term reduction in symptoms of non-ulcer dyspepsia : The relationship between Helicobacter pylori infection and non‐ulcer dyspepsia is not established . Fifty-three patients with previously uninvestigated chronic dyspepsia symptoms in the absence of gastrointestinal or extra-gastrointestinal disease ( functional dyspepsia ) underwent antral and duodenal mucosal biopsies to detect the role of such samplings in the presence of normal endoscopic findings . Patients were enrolled in a r and omized , placebo-controlled , double-blind trial , receiving either eradicating treatment ( colloidal bismuth subcitrate plus metronidazole ) or placebo if they had Helicobacter pylori-associated gastritis ( 20 patients ) , or cisapride or placebo if they had normal antral mucosa ( 28 cases ) . Unsuspected celiac sprue was found in one patient . Eradicating treatment ameliorated histological gastritis ( p = 0.01 ) . However , owing to great placebo efficacy , symptom remission rates following a 1-month wash-out period in both treatment groups were no higher than that in controls . Independent of the initial r and omization , an extremely low symptom recurrence rate was observed during a drug-free follow-up study equivalent to the mean duration of symptoms before enrollment . We conclude that in functional dyspepsia , bulbar and antral biopsies are not useful in clinical management , equivalent symptom relief can be achieved in patients r and omly assigned to both drugs and placebos , and such improvement can be long lasting in the absence of any maintenance treatment . We believe the prevalence of unsuspected villous atrophy and the therapeutic role of investigation-based reassurance deserve further assessment Although the eradication of Helicobacter pylori infection benefits patients with gastric or duodenal ulcers , the value of eradicating the infection in the patients with functional dyspepsia ( FD ) remains controversial BACKGROUND / AIMS To assess whether H. pylori therapy is significantly better than control therapy in patients with functional dyspepsia , and to assess whether curing the infection relieves symptoms of dyspepsia . METHODOLOGY We prospect ively included consecutive H. pylori-positive patients in whom a gastroscopy was carried out and who were diagnosed of functional dyspepsia . At endoscopy , biopsies were obtained ( histology and rapid urease test ) , and a 13C-urea breath test was carried out . Patients were r and omly assigned to 10 days of treatment with either eradication therapy ( omeprazole , amoxicillin and clarithromycin ) or with ranitidine . No antisecretory therapy was prescribed thereafter . Breath test was repeated four weeks after completing eradication treatment . A vali date d five-point Likert scale was used to measure severity of symptoms , both at the beginning of the study and 6 and 12 months after treatment . RESULTS Fifty patients were included in the study . Sixteen patients were r and omized to ranitidine and 34 to eradication treatment . The two groups were well balanced for base-line characteristics . One patient in each treatment arm was lost to follow-up at 12 months . Differences between ranitidine and eradication groups were not demonstrated in any of the symptom comparisons , either initially or at 12 months . The rates of treatment success for each symptom were similar in both groups . H. pylori was eradicated in 76 % of the patients receiving antibiotics . Differences between groups of patients with eradication success and failure were not demonstrated in any of the symptom comparisons , either initially or at 12 months . Among the groups given eradication regimen , the rates of treatment success for each symptom were similar in the group with H. pylori eradication success and failure . CONCLUSIONS H. pylori eradication is not likely to play a major role in the treatment of symptoms in patients with functional dyspepsia We r and omly assigned 45 adult patients with Campylobacter pylori-confirmed antral gastritis to 8 days of treatment with 1 g amoxycillin suspension twice a day , or placebo , according to a double-blind study design . At the end of therapy , 91 % of patients treated with amoxycillin demonstrated clearance of the organism from the antrum , compared with 16 % in the placebo group ( p less than 0.001 ) . Active antral gastritis resolved in 68 % of patients in the amoxycillin group versus only 9 % in the placebo group ( p less than 0.001 ) . No significant difference was observed when looking at the evolution of chronic only gastritis . No significant improvement was observed in the assessment of clinical symptoms and endoscopic appearance . Reappearance of C. pylori and significant worsening of the histological score of active gastritis was observed after 2 wk in all patients . In a second study phase , 18 patients initially not cleared of their bacteria received amoxycillin single blind for 14 days . Clearance of bacteria associated with improvement or resolution of active gastritis was observed in 72 % of the cases . In this subgroup , all patients investigated after 1 month were recolonized with C. pylori and , again , had histological active gastritis . We conclude that amoxycillin is effective in treating active antral gastritis associated with C. pylori , but not in preventing relapses , which occur in all cases within 1 month after therapy In a consecutive prospect i ve series of 186 Swedish persons with the diagnosis of non-ulcer dyspepsia 71.5 % were found to have gastritis and /or bulbar duodenitis in endoscopic biopsies . Gastroduodenitis was associated with campylobacter pylori ( CP ) in 83.5 % of the cases . The double therapeutic approach using an antibiotic and a preparation containing bismuth in an uncontrolled therapeutic pilot trial result ed in improvement of the histological picture , disappearance of CP and amelioration of symptoms . It is concluded that CP-infection plays a central role in the pathogenesis of gastroduodenitis associated NUD Background : A definitive treatment for functional dyspepsia ( FD ) , and the role of Helicobacter pylori eradication on the course of this disease are controversial . Aim : To investigate the effect of a combination of acid-suppressing and prokinetic drugs or eradication therapy on the course of H. pylori-positive FD . Method : A total of 157 patients with endoscopically-proven H. pylori-positive FD and no response to 4 weeks of antacid therapy were r and omly divided into 2 groups . 84 were placed on bismuth subnitrate plus metronidazole and amoxicillin ( group A ) and 73 received ranitidine and metoclopramide for 4 weeks ( group B ) . The severity of symptoms ( 7 items ) were assessed on a 6-point categorical scale . Group B patients who failed to respond to their medication underwent eradication therapy after 3 months . All patients were followed and assessed for 9 months after the end of therapy by the same clinicians who initiated the therapy . Results : At the end of the medication period , symptom ’s score decreased significantly , and to the same extent . At 3-month follow-up moderate or complete response was achieved in 27.4 % ( group A ) and 19.2 % ( group B ) by intention-to-treat analysis . 34 patients of group B , not responding to treatment , underwent eradication therapy and followed as group A. Eradication of H. pylori was successful in 60 of 110 controlled patients ( 54 % ) . After 9-month follow-up , complete or moderate response was observed in only 30 % of 60 patients in whom H. pylori had been eradicated ( intention-to-treat analysis ) , compared to 38 % in 50 noneradicated cases ( p > 0.05 , 95 % CI : 19–43 vs. 24–52 ) . Conclusion : Eradication therapy with bismuth compound is effective as ranitidine plus metoclopramide in a subgroup of patients with FD not responding to antacid therapy . There is no difference in improvement between patients cured or not cured from H. pylori infection . This suggests that bismuth compounds were effective in FD when used in the eradication regimen . Combination therapy with acid-suppressing drugs plus prokinetic and bismuth seems to hold promise for FD In a double-blind multicentre trial to study the effect of pirenzepine in the treatment of non-ulcer dyspepsia , 104 of 128 patients , 52 in each of the study and control groups , completed the 4 weeks of the investigation . There was improvement of the endoscopic and clinical findings but no change of the degree of the mucosal inflammation or the extent of colonisation by campylobacter pylori . The mode of action of pirenzepine in patients with non-ulcer dyspepsia associated with campylobacter related gastroduodenitis remains obscure . Further studies are needed to investigate the possibility of a causal relationship between mucosal colonisation with campylobacter pylori and gastroduodenitis specially in cases of non-ulcer dyspepsia Fifty consecutive patients with non-ulcer dyspepsia and a Campylobacter associated gastritis ( CAG ) were r and omly assigned to treatment with colloidal bismuth subcitrate ( CBS ) 240 mg twice daily or placebo , according to a double blind study design . After the blind treatment an ' open ' treatment with CBS was started in both groups . Twenty six patients treated with CBS showed a significant reduction in colonisation with Campylobacter pylori and a significant improvement in the Whitehead gastritis score . No significant changes were recorded in twenty four patients treated with placebo . After an additional course of CBS no further improvement in gastritis score was noted but there was a further reduction in Campylobacter colonisation . CBS did not greatly alter subjective complaints . Subjective complaints were improved in both treatment groups except for nausea and meteorism that improved more in the CBS treated patients . This finding again questions the clinical significance of gastritis and also casts doubt on the clinical relevance of therapeutical measures aim ed at eradication of C pylori BACKGROUND It is uncertain whether treatment of Helicobacter pylori infection relieves symptoms in patients with nonulcer , or functional , dyspepsia . METHODS We conducted a double-blind , multicenter trial of patients with H. pylori infection and dyspeptic symptoms ( moderate-to-very-severe pain and discomfort centered in the upper abdomen ) . Patients were excluded if they had a history of peptic ulcer disease or gastroesophageal reflux disease and had abnormal findings on upper endoscopy . Patients were r and omly assigned to seven days of treatment with 20 mg of omeprazole twice daily , 1000 mg of amoxicillin twice daily , and 500 mg of clarithromycin twice daily or with omeprazole alone and then followed up for one year . Treatment success was defined as the absence of dyspeptic symptoms or the presence of minimal symptoms on any of the 7 days preceding the 12-month visit . RESULTS Twenty of the 348 patients were excluded after r and omization because they were not infected with H. pylori , were not treated , or had no data available . For the remaining 328 patients ( 164 in each group ) , treatment was successful for 27.4 percent of those assigned to receive omeprazole and antibiotics and 20.7 percent of those assigned to receive omeprazole alone ( P=0.17 ; absolute difference between groups , 6.7 percent ; 95 percent confidence interval , -2.6 to 16.0 ) . After 12 months , gastritis had healed in 75.0 percent of the patients in the group given omeprazole and antibiotics and in 3.0 percent of the patients in the omeprazole group ( P<0.001 ) ; the respective rates of H. pylori eradication were 79 percent and 2 percent . In the group given omeprazole and antibiotics , the rate of treatment success among patients with persistent H. pylori infection was similar to that among patients in whom the infection was eradicated ( 26 percent vs. 31 percent ) . There were no significant differences between the groups in the quality of life after treatment . CONCLUSIONS In patients with nonulcer dyspepsia , the eradication of H. pylori infection is not likely to relieve symptoms BACKGROUND The eradication of Helicobacter pylori infection is beneficial in patients with gastric or duodenal ulcers . The value of eradicating the infection in patients with dyspepsia and no evidence of ulcer disease is not known . METHODS We performed a r and omized , placebo-controlled trial comparing the efficacy of treatment for two weeks with 20 mg of omeprazole orally twice daily , 500 mg of amoxicillin three times daily ( with 500 mg of tetracycline three times daily substituted for amoxicillin in patients allergic to penicillin ) , and 400 mg of metronidazole three times daily ( 160 patients ) with that of omeprazole alone ( 158 patients ) for resolving symptoms of dyspepsia in patients with H. pylori infection but no evidence of ulcer disease on upper gastrointestinal endoscopy . Symptoms were assessed with the Glasgow Dyspepsia Severity Score , with resolution of symptoms defined as a score of 0 or 1 in the preceding six months ( maximal score , 20 ) . One year later the patients were assessed to determine the frequency of the resolution of symptoms . RESULTS One month after the completion of treatment , 132 of 150 patients ( 88 percent ) in the group assigned to received omeprazole and antibiotics had a negative test for H. pylori , as compared with 7 of 152 ( 5 percent ) in the group assigned to receive omeprazole alone . One year later , dyspepsia had resolved in 33 of 154 patients ( 21 percent ) in the group given omeprazole and antibiotics , as compared with 11 of 154 ( 7 percent ) in the group given omeprazole alone ( 95 percent confidence interval for the difference , 7 to 22 percent ; P<0.001 ) . Among the patients in the group given omeprazole and antibiotics , the symptoms resolved in 26 of the 98 patients ( 27 percent ) who had had symptoms for five years or less , as compared with 7 of the 56 patients ( 12 percent ) who had had symptoms for more than five years ( P=0.03 ) . CONCLUSIONS In patients with H. pylori infection and nonulcer , or functional , dyspepsia , treatment with omeprazole and antibiotics to eradicate the infection is more likely to resolve symptoms than treatment with omeprazole alone In a placebo controlled prospect i ve clinical trial of bismuth salicylate in helicobacter pylori associated gastritis , 52 adult patients were r and omly allocated to treatment with bismuth salicylate or placebo . Helicobacter pylori were totally cleared in 77 % patients in bismuth group but none in placebo group ( P less than 0.001 ) . Resolution of gastritis ( P less than 0.001 ) and improvement of symptoms ( P less than 0.01 ) were significantly better in patients where H. pylori infection cleared as compared to patients where the infection persisted This double blind r and omised study tested the effectiveness of colloidal bismuth subcitrate ( De-Nol ) in non-ulcer dyspepsia ( NUD ) and if any benefit is associated with clearance of Campylobacter pylori ( C pylori ) from the gastric mucosa . Sixty six patients with dyspepsic symptoms , normal abdominal ultrasound , and upper GI endoscopy , were r and omly allocated to placebo or De-Nol for eight weeks . Antral biopsies were taken for bacteriological and histological examination , and endoscopies and clinical question naires were administered before and after treatment . Fifty two patients ( 25 on De-Nol and 27 on placebo ) completed the trial . De-Nol cleared C pylori from 10 of the 12 C pylori positive patients ( 83.3 % ) , whereas placebo did not clear C pylori from any of the eight C pylori positive patients ( p less than 0.01 ) . In patients receiving De-Nol gastritis improved ( p less than 0.01 ) and symptomatic response was better ( p less than 0.001 ) compared with placebo . In the placebo group seven of the 19 C pylori negative patients became positive : this was associated with significant deterioration of symptoms , a phenomenon not seen in the De-Nol treated group BACKGROUND The relationship between Helicobacter pylori infection and interdigestive gastroduodenal motility in functional dyspepsia is still uncertain . Recent data from a large series documented that in dyspeptic patients without gastric phase III of the interdigestive migrating motor complex ( MMC ) , the prevalence of bacterial infection was significantly higher . Since most H. pylori-positive dyspeptic patients have coexisting chronic gastritis , whether or not dyspepsia per se rather than bacterial colonization or chronic inflammation of the gastric mucosa may account for the observed interdigestive motility pattern is unknown . Our aim was to compare the interdigestive gastroduodenal motility pattern and dyspeptic symptoms before and 1 month after bacterial eradication in 20 H. pylori-positive dyspeptic subjects with chronic non-atrophic gastritis and without gastric phase III of the MMC , who were r and omly allocated to receive eradication treatment ( n = 10 ) or not ( n = 10 ) . METHODS Upper GI endoscopy with duplicate biopsies in antrum and corpus , 240-min interdigestive gastroduodenal manometric recording and symptoms assessment were performed before and 1 month after the treatments ; bacterial eradication was confirmed by 13C-urea breath test . RESULTS After H. pylori eradication , neither in the incidence of antral and duodenal phase III of MMC nor in the phase II motility index values were any changes observed . Symptomatic improvement was recorded in both groups , with no significant differences between eradicated patients and controls . CONCLUSIONS In dyspeptic patients with chronic non-atrophic gastritis and without gastric phase III of MMC , H. pylori eradication influences neither the interdigestive motility pattern nor the symptoms in the short-term period This double-blind pilot study has been undertaken in order to investigate the effect of amoxicillin and pronounced suppression of gastric acid secretion on mucosal colonisation with Campylobacter pylori ( CP ) . Twenty four CP-positive patients were included in the study and assigned to 14 days of treatment in either one of the following three therapy groups : Group 1 : Omeprazole 40 mg o.m . + Amoxicillin 750 mg b.i.d ( 9 pat ) ; Group 2 : Omeprazole 40 mg o.m . ( 8 pat ) ; Group 3 : Amoxicillin 750 mg b.i.d ( 7 pat ) . Gastroscopy with biopsy for culture and histology was performed pre-entry , at cessation of therapy and four weeks later . In the group receiving omeprazole and amoxicillin in combination 5 out of 8 patients were negative for CP four weeks after stopping treatment , while in the amoxicillin and the omeprazole groups respectively one ( 1/7 ) and none ( 0/8 ) were negative . Except for one patient who was withdrawn because of severe diarrhoea , only minor adverse effects occurred OBJECTIVE --To examine the effect of eradication of Helicobacter pylori on symptoms of non-ulcer dyspepsia . DESIGN --Four week prospect i ve study . SETTING --One hospital outpatient and endoscopy department . PATIENTS --90 adults with persistent symptoms typical of non-ulcer dyspepsia but no clinical or endoscopic evidence of other peptic , biliary , pancreatic , or malignant disease ; all had histological and microbiological evidence of infection with H pylori . 83 patients completed the treatment regimen . INTERVENTION -- Colloidal bismuth subcitrate 120 mg four times a day for four weeks ( 27 patients ) ; metronidazole 400 mg and amoxycillin 500 mg each three times a day for one week ( 27 ) ; and bismuth subcitrate 120 mg four times a day for four weeks , metronidazole 400 mg three times a day for one week , plus amoxycillin 500 mg three times a day for the first week ( 29 ) . MAIN OUTCOME MEASURES --Change in symptom scores determined with question naire ; histological evidence of gastritis and microbiological evidence of presence of H pylori in biopsy specimens . RESULTS --Overall , H pylori was eradicated in 41 ( 49 % ) patients . Although gastritis scores improved significantly in only patients in whom H pylori had been eradicated ( from 1.56 to 0.61 , p less than 0.01 v from 1.83 to 1.07 , p = 0.52 ) mean symptom scores after treatment were similar in patients in whom H pylori had or had not been eradicated ( 3.0 v 2.3 , NS ) . Similarly the mean symptom score improved whether or not gastritis improved ( 2.8 v 3.1 respectively , p = 0.72 ) . The observations were similar for treatment groups analysed individually . CONCLUSION --Antral infection with the organism does not seem to have an important aetiological role in non-ulcer dyspepsia short term We have carried out a double blind placebo controlled trial to assess the effects of treatment with colloidal bismuth subcitrate in Helicobacter pylori associated non-ulcer dyspepsia . Eighty patients with dyspepsia , normal upper gastrointestinal appearances at endoscopy and H pylori associated active chronic gastritis on histology of gastric antral biopsies were included in the trial . The patients were r and omised to receive colloidal bismuth subcitrate 240 mg twice daily for four weeks or matching placebo and were reassessed four weeks after completing treatment . Twenty-six patients ( 67 % ) receiving colloidal bismuth subcitrate had normal histology or improved inflammation compared with five ( 13 % ) receiving placebo ( p less than 0.001 ) , and symptoms were absent or improved in 32 ( 82 % ) and two ( 5 % ) respectively ( p less than 0.001 ) . Serum IgG level was a marker of infection , and fell with successful treatment . Colloidal bismuth subcitrate is effective treatment for H pylori associated non-ulcer dyspepsia with improved gastric antral histological appearances and has a beneficial effect on symptoms Aim : To investigate whether curing Helicobacter pylori infection improves symptoms over the long‐term in Japanese patients with nonulcer dyspepsia and fundic atrophic gastritis BACKGROUND The relation between Helicobacter pylori infection and nonulcer dyspepsia is uncertain . We tested the hypothesis that curing the infection will relieve symptoms of dyspepsia . METHODS We r and omly assigned 170 H. pylori-infected patients with nonulcer dyspepsia to receive twice-daily treatment with 20 mg of omeprazole , 1000 mg of amoxicillin , and 500 mg of clarithromycin for 14 days and 167 such patients to receive identical-appearing placebos ; all patients were then followed through regular visits for 12 months . Symptoms were scored on diary cards for seven days before each visit . A carbon-13 urea breath test was performed at base line and repeated at 1 and 12 months , and endoscopic biopsy was performed at 12 months to determine H. pylori status . Treatment was considered successful if the patient had only mild pain or discomfort or none at all . RESULTS The rate of eradication of H. pylori infection was 90 percent in the active-treatment group and 2 percent in the placebo group at four to six weeks ( P<0.001 ) . At 12 months , there was no significant difference between groups in the rate of successful treatment ( 46 percent in the active-treatment group and 50 percent in the placebo group ; relative likelihood of success with active treatment , 0.93 ; 95 percent confidence interval , 0.73 to 1.18 ; P=0.56 ) . There was also no significant difference in the rate of successful treatment at 12 months between patients who were H. pylori-negative and those who were H. pylori-positive ( 48 percent vs. 49 percent ) . The rates of successful treatment were also similar when patients were analyzed according to the type of dyspepsia ( ulcer-like , reflux-like , or dysmotility-like ) and changes in the quality of life . There was no significant association between treatment success and histologic improvement in chronic gastritis at 12 months ( P=0.68 ) . CONCLUSIONS We found no evidence that curing H. pylori infection in patients with nonulcer dyspepsia leads to relief of symptoms BACKGROUND & AIMS We have shown previously that cure of Helicobacter pylori infection leads to the disappearance of acid-neutralizing substances . Also , patients with ulcer after cure may gain weight . The aim of this study was to investigate whether cure of the infection increases the risk of reflux esophagitis . METHODS Patients with duodenal ulcer without reflux esophagitis at the time of Helicobacter treatment were followed up prospect ively after cure of the infection ( n = 244 ) or after diagnosis of persisting infection ( n = 216 ) . All patients underwent endoscopy at 1-year intervals or when upper gastrointestinal symptoms recurred . H. pylori infection was assessed by rapid urease test and histology . RESULTS The estimated incidence of reflux esophagitis within 3 years was 25.8 % after cure of the infection and 12.9 % when the infection was ongoing ( P < 0.001 ) . Patients who developed reflux esophagitis after the cure had a more severe body gastritis before cure ( odds ratio , 5.5 ; 95 % confidence interval [ CI ] , 2.8 - 13.6 ) , gained weight more frequently after cure ( odds ratio , 3.2 ; 95 % CI , 1.2 - 9.4 ) , and were predominantly men ( odds ratio , 3.6 ; 95 % CI , 1.1 - 10.6 ) . CONCLUSIONS A considerable proportion of patients with duodenal ulcer treated for H. pylori will develop reflux esophagitis ; risk factors are male sex , severity of corpus gastritis , and weight gain BACKGROUND Colloidal bismuth subcitrate ( CBS ) causes endoscopic and histological improvement in gastritis and eradication of Helicobacter pylori in patients with non-ulcer dyspepsia ( NUD ) . The effect of sucralfate , a cytoprotective drug , on endoscopic and histologic gastritis and H pylori clearance is not clear . We studied the effect of CBS and sucralfate on these features in patients with NUD . METHODS Sixty three patients with NUD and H pylori infection were r and omized to receive one of the following for four weeks : ( i ) CBS ( 240 mg twice daily ) ( Group 1 ) ; ( ii ) placebo I , similar in size , color and shape to CBS ( Group 2 ) ; ( iii ) sucralfate ( 2.0 g twice daily ) ( Group 3 ) and ( iv ) placebo II , similar to sucralfate ( Group 4 ) . Symptoms , endoscopic and histological findings and H pylori status were assessed before and after treatment . RESULTS Similar symptomatic improvement was observed with each treatment , indicating a placebo effect . Significant endoscopic and histological improvement was observed with CBS only . CBS was better than sucralfate in inducing endoscopic and histological improvement . Clearance rate of H pylori was 46.6 % with CBS , 16.6 % with its placebo , 33.3 % with sucralfate and 13.3 % with its placebo . CONCLUSION CBS is more effective than sucralfate in inducing endoscopic and histologic healing of H pylori-related gastritis among NUD patients Aim : To determine whether pre‐treatment antibody response to Helicobacter pylori virulence factors predicts eradication success and symptom relief 12 months after triple therapy in non‐ulcer dyspepsia OBJECTIVE To determine the rate of Helicobacter pylori eradication following bismuth-based triple therapy with colloidal bismuth subcitrate , tetracycline hydrochloride and metronidazole . PATIENTS AND METHODS One hundred and eleven patients were r and omly assigned , in a two to one ratio , to colloidal bismuth subcitrate 120 mg qid plus metronidazole 250 mg qid plus tetracycline 500 mg qid ( Gastrostat ) , or matching placebo tablets and capsules for 14 days . Presence or absence of H pylori was documented by histology at entry and at least 28 days after treatment . Patients had dyspeptic symptoms with or without a history of peptic ulcer . Patients with any previous attempt(s ) at eradication of H pylori , who used bismuth , antibiotics , H2 receptor antagonists or proton pump inhibitors in the previous four weeks were excluded . RESULTS Fifty-three of 59 ( 90 % ) patients on bismuth-based treatment and only one of 35 ( 3 % ) on placebo achieved eradication by per protocol analysis . Fifty-three of 65 ( 82 % ) patients on bismuth-based treatment achieved eradication , while only two of 34 ( 5 % ) achieved eradication on placebo by intention to treat analysis . Eradication rates for bismuth-based treatment across sites ranged from 83 % to 100 % . Only two patients in the bismuth-based treatment group ( 4 % ) and one in the placebo group ( 3 % ) discontinued treatment because of adverse events . CONCLUSIONS Colloidal bismuth subcitrate plus metronidazole plus tetracycline , given in the doses studied for 14 days , is safe and highly effective against H pylori infection and would be appropriate as a first-line therapy for eradication BACKGROUND It is unclear whether normal endoscopy results in patients investigated for dyspepsia has therapeutic value . Therefore the aim of this study was to evaluate the effect of the endoscopy on quality of life and dyspeptic symptoms . METHODS One hundred ninety-six symptomatic patients ( 85 men and 111 women , mean age 42.9 years ) , who were receiving no treatment , were investigated before and 1 week after endoscopy with the use of a battery of vali date d question naires . RESULTS Before endoscopy the health-related quality of life was compromised in comparison with a normal population , but 1 week after a negative endoscopy it is increased to a level which was close to the normal range despite no major change in symptoms . Physical activity and sleep scores improved significantly after endoscopy . CONCLUSION The present results suggest that a negative endoscopy improves quality of life in the short-term in patients with dyspepsia , even though symptoms may persist |
11,998 | 19,001,882 | Beneficial effects of various exercise programs on aspects of cognition have been observed in studies among subjects with and without cognitive decline .
The majority of the studies , however , did not find any effect . | OBJECTIVE To systematic ally review the effect of physical exercise on cognition in older adults with and without cognitive decline . | OBJECTIVE We evaluated the effects of exercise on neurobehavioral function in healthy older people more than 75 years of age . DESIGN A r and omized controlled trial with 6-month follow-up was conducted . SETTING The study was performed in the rural town of Kahoku , Japan , the population of which is considered representative of the older population of Japan . PARTICIPANTS We studied 42 healthy volunteers ( 18 men and 24 women ; mean age , 79 years ( range 75 to 87 years ) ) who were r and omly assigned to one of two groups , exercise or control . INTERVENTION Subjects assigned to the exercise group were instructed to exercise for 60 minutes twice a week for 6 months . Subjects in the control group were not instructed to engage in an specific exercise regimen . MEASUREMENTS The following measurements were recorded for both groups at baseline and at 6-month follow-up : ( 1 ) Neurobehavioral function as determined by the following tests : Mini-Mental State Exam ( MMSE ) , Hasegawa Dementia Scale Revised ( HDSR ) , Visuospatial Cognitive Performance Test ( VCP-test ) , Button score , Up & Go test , and Functional Reach ; and ( 2 ) Body mass index and blood pressure . RESULTS The effects of exercise were shown in the Up & Go test , and Functional Reach ( ANOVA with repeated measures ) . CONCLUSION This study demonstrates the acceptability and effectiveness of exercise on neurobehavioral function , even in older people more than 75 years of age The goal was to determine the existence of differential effects of long-term moderate- or low-intensity exercise on selected bio-behavioral variables in 72 community-dwelling persons over 60 years of age . After screening , subjects were r and omly assigned to a moderate ( n = 39 , 60 - 70 % heart rate reserve [ HRR ] ) or low ( n = 33 , 30 - 40 % HRR ) intensity exercise protocol . Both groups exercised three times per week for 9 months and dependent measures were taken at baseline , 4.5 months and after 9 months . Repeated measures ANOVA with Tukey post hoc comparisons constituted the analysis approach . Moderate exercise showed no superiority over low-intensity exercise ; both groups improved about equally . Variables that significantly improved included : self-reported sleep ( sleep quantity and dream recall ) , mental status ( attention/concentration , short-term memory and higher cognitive functioning ) , health perceptions ( health outlook , health worry , rejection of the sick role ) , and cardiovascular fitness indicators ( submaximum stress test heart rate , maximum oxygen consumption ( VO2max ) , maximum work capacity and maximum exercise time ) . Similarity of outcomes in both groups may mean that the moderate exercise protocol was too conservative . Conversely , the findings may indicate that lower levels of exercise , which may be safer and more feasible over time , do improve fitness levels , prolong independent functioning , and promote positive perceptions of well-being in older adults 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 Abstract A r and omised controlled trial was undertaken to measure effects of exercise on : 1 . Progression of cognitive symptoms related to dementia using the Clock-Drawing Test ( Shulman et al. 1993 ) ; and 2 . Disability using the Revised Elderly Persons Disabilities Scale ( REPDS ; Fleming and Bowles 1993 ) . Data was analysed from 75 nursing home residents with dementia who were r and omly assigned to one experimental group and two control groups . Group 1 ( control ) received no intervention . Group 2 ( control ) received a social visit equivalent in duration and frequency as those undertaking the exercise program in the experimental group , Group 3 . A specifically design ed , frail aged appropriate , twelve-week exercise program was undertaken by the those in the experimental group three times per week . Each session lasted for 30 minutes . Findings from the : 1 . Clock-drawing test showed that exercise may slow the rate of progression of the cognitive symptoms related to dementia ; and 2 . REPDS showed that exercise slowed and reversed disability in some of the activities of daily living BACKGROUND The present study examined whether aerobic fitness training of older humans can increase brain volume in regions associated with age-related decline in both brain structure and cognition . METHODS Fifty-nine healthy but sedentary community-dwelling volunteers , aged 60 - 79 years , participated in the 6-month r and omized clinical trial . Half of the older adults served in the aerobic training group , the other half of the older adults participated in the toning and stretching control group . Twenty young adults served as controls for the magnetic resonance imaging ( MRI ) , and did not participate in the exercise intervention . High spatial resolution estimates of gray and white matter volume , derived from 3D spoiled gradient recalled acquisition MRI images , were collected before and after the 6-month fitness intervention . Estimates of maximal oxygen uptake ( VO2 ) were also obtained . RESULTS Significant increases in brain volume , in both gray and white matter regions , were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning ( nonaerobic ) control group . As predicted , no significant changes in either gray or white matter volume were detected for our younger participants . CONCLUSIONS These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans . Furthermore , these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults Objective : To examine the effects of aerobic exercise or vitamin B supplementation on cognitive function in older adults with mild cognitive impairment ( MCI ) . Design : R and omised placebo-controlled trial . Setting : General community . Participants : Community-dwelling adults aged 70–80 with MCI . Interventions : The 152 participants were r and omly assigned to two interventions : ( 1 ) a twice-weekly , group-based , moderate-intensity walking programme ( WP , n = 77 ) or a low-intensity placebo activity programme ( n = 75 ) for one year ; and ( 2 ) daily vitamin pill containing 5 mg folic acid , 0.4 mg vitamin B-12 , 50 mg vitamin B-6 ( FA/B12/B6 , n = 78 ) or placebo pill ( n = 74 ) for one year . Outcome measures : Cognitive function , measured with neuropsychological tests at baseline and after six and 12 months . Results : Median session attendance at the exercise programmes ( 25th–75th percentile ) was 63 % ( 2%–81 % ) and median compliance with taking pills ( 25th–75th percentile ) was 100 % ( 99%–100 % ) . Gender was an effect modifier . Intention-to-treat analysis revealed no main intervention effect for either intervention . In women in the WP , attention ( Stroop combination task ) improved by 0.3 seconds ( p = 0.04 ) and memory ( auditory verbal learning test ) by 0.04 words ( p = 0.06 ) with each percentage increase in session attendance . In men attending at least 75 % of the sessions , the WP improved memory ( β 1.5 ( 95 % CI : 0.1 to 3.0 ) words ) . Conclusion : The walking programme and /or FA/B12/B6 supplementation were not effective in improving cognition within one year . The walking programme , however , was efficacious in improving memory in men and memory and attention in women with better adherence . Trial registration : International St and ard R and omised Controlled Trial Number Register , 19227688 , http://www.controlled-trials.com/is rct Abstract : A r and omised controlled trial was conducted to determine whether a 12–month program of group exercise had beneficial effects on physiological and cognitive functioning and mood in 187 older community – dwelling women . The exercisers ( n= 94 ) and controls ( n= 93 ) were well matched in terms of the test measures and a number of health and life – style assessment s. The mean number of classes attended by the 71 exercise subjects who completed the program was 59.0 ( range 26 to 82 ) . At the end of the trial , the exercisers showed significant improvements in reaction time , strength , memory span and measures of wellbeing when compared with the controls . There was also an indication that anxiety had been reduced in the exercisers . Within the exercise group , improvements in memory span were associated with concomitant improvements in both reaction time and muscle strength . Also , within this group , initial mood measures were significantly inversely associated with improvements at retest , which suggests that the program may have normalised mood states in subjects who had high initial depression , anxiety and stress levels , rather than inducing improvements in all subjects . These findings suggest that group exercise has beneficial effects on physiological and cognitive functioning and wellbeing in older people PURPOSE The purpose of this study was to assess the impact of 24 wk of resistance training at two different intensities on cognitive functions in the elderly . METHODS Sixty-two elderly individuals were r and omly assigned to three groups : CONTROL ( N = 23 ) , experimental moderate ( EMODERATE ; N = 19 ) , and experimental high ( EHIGH ; N = 20 ) . The volunteers were assessed on physical , hemodynamic , cognitive , and mood parameters before and after the program . RESULTS On the 1 RM test ( P < 0.001 ) , the two experimental groups performed better than the CONTROL group , but they did not show differences between themselves . The EHIGH group gained more lean mass ( P = 0.05 ) than the CONTROL group and performed better on the following tests : digit span forward ( P < 0.001 ) , Corsi 's block-tapping task backward ( P = 0.001 ) , similarities ( P = 0.03 ) , Rey-Osterrieth complex figure immediate recall ( P = 0.02 ) , Toulouse-Pieron concentration test errors ( P = 0.01 ) , SF-36 ( general health ) ( P = 0.04 ) , POMS ( tension-anxiety , P = 0.04 ; depression-dejection , P = 0.03 ; and total mood disorder , P = 0.03 ) . The EMODERATE group scored higher means than the CONTROL group on digit span forward ( P < 0.001 ) , Corsi 's block-tapping task backward ( P = 0.01 ) , similarities ( P = 0.02 ) , Rey-Osterrieth complex figure immediate recall ( P = 0.02 ) , SF-36 ( general health , P = 0.005 ; vitality , P = 0.006 ) , POMS ( tension-anxiety , P = 0.001 ; depression-dejection , P = 0.006 ; anger-hostility , P = 0.006 ; fatigue-inertia , P = 0.02 ; confusion-bewilderment , P = 0.02 ; and total mood disorder , P = 0.001 ) . We also found that IGF-1 serum levels were higher in the experimental groups ( EMODERATE , P = 0.02 ; EHIGH , P < 0.001 ) . CONCLUSIONS Moderate- and high-intensity resistance exercise programs had equally beneficial effects on cognitive functioning Objective : To evaluate the effect of a musical exercise programme on mood state and cognitive function in women with dementia . Design : R and omized controlled trial . Setting : Public Psychiatric Hospital Rekem , Belgium . Patients : Twenty-five patients with dementia . Interventions : Fifteen patients attended exercise training for three months , which consisted of daily physical exercises supported by music for 30 min/session . They were compared with a group of 10 control patients , who received an equal amount of attention through daily conversation . Main measures : The effect on cognition was measured by the Mini-Mental State Examination ( MMSE ) and the Amsterdam Dementia Screening Test 6 ( ADS 6 ) . Behaviour was evaluated with the abbreviated Stockton Geriatric Rating Scale ( BOP scale ) . The assessment s were made before , after six weeks of intervention and immediately after the three-month experimental period . Results : The exercise group showed a significant improvement in cognition . This was documented by an increased MMSE mean score of 12.87 - 15.53 , and by a higher median score , rising from 10 to 14 points , on the subset ‘ fluency ’ ( ADS 6 test ) . The control group showed no significant improvement , either on the MMSE ( mean score of 10.80 -11.00 ) or on the fluency subtest of the ADS 6 ( median scores were 6.5 - 7 points ) . The effects on behavioural changes were not significant . Conclusion : The present study suggests a beneficial effect of cognition using a music-based exercise programme in a group of patients with moderate to severe dementia . Further studies are needed to confirm these findings The primary goal of the present study was to examine whether in the elderly with mild cognitive impairment ( MCI ) , the effect of physical activity measured directly following treatment , was reflected in an improvement in cognitive functioning in general or in executive functions ( EF ) in particular . Secondly , this study aim ed to compare the effectiveness of two types of intervention , with varying intensities : walking and h and /face exercises . Forty-three frail , advanced elderly subjects ( mean age : 86 ) with MCI were r and omly divided into three groups , namely , a walking group ( n = 15 ) , a group performing h and and face exercises ( n = 13 ) , and a control group ( n = 15 ) . All subjects received individual treatment for 30 minutes a day , three times a week , for a period of six weeks . A neuropsychological test battery , administered directly after cessation of treatment , assessed cognitive functioning . The results show that although a ( nearly ) significant improvement in tasks appealing to EF was observed in both the walking group and the h and /face group compared to the control group , the results should be interpreted with caution . Firm conclusions about the effectiveness of mild physical activity on EF in the oldest old can only be drawn after studies with larger number of subjects This study examined the effects of a 12-week aerobic exercise program on psychological well-being and cognitive functioning in a group of ethnically diverse older adults living in an urban community . Forty-eight older men and women ( mean age = 72 + /- 6 ) were r and omly assigned to one of three groups : an aerobic exercise training group , a social activity control group , or a waiting list group . Results indicated little change in psychological well-being and provided limited support for the association of physiological improvement with enhanced mastery and cognitive functioning OBJECTIVE To determine the short- and long-term effects of resistance training on muscle strength , psychological well-being , control-beliefs , cognitive speed and memory in normally active elderly people . METHODS 46 elderly people ( mean age 73.2 years ; 18 women and 28 men ) , were r and omly assigned to training and control groups ( n=23 each ) . Pre- and post-tests were administered 1 week before and 1 week after the 8-week training intervention . The training sessions , performed once a week , consisted of a 10 min warm-up phase and eight resistance exercises on machines . RESULTS There was a significant increase in maximum dynamic strength in the training group . This training effect was associated with a significant decrease in self-attentiveness , which is known to enhance psychological well-being . No significant changes could be observed in control-beliefs . Modest effects on cognitive functioning occurred with the training procedure : although there were no changes in cognitive speed , significant pre/post-changes could be shown in free recall and recognition in the experimental group . A post-test comparison between the experimental group and control group showed a weak effect for recognition but no significant differences in free recall . Significant long-term effects were found in the training group for muscular strength and memory performance ( free recall ) 1 year later . CONCLUSION An 8-week programme of resistance training lessens anxiety and self-attentiveness and improves muscle strength Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Objective : To examine the prevalence estimates and 5-year outcomes of various case definitions of mild cognitive impairment ( MCI ) . Methods : The authors examined 1,790 adults 65 years of age or older who completed neuropsychological and clinical assessment s in the Canadian Study of Health and Aging , a 5-year , representative , prospect i ve cohort study . Results : The most commonly used case definition of MCI yielded a population prevalence estimate of 1.03 % ( 95 % CI 0.66 to 1.40 ) . Eliminating the requirements for subjective memory complaints and intact instrumental activities of daily living ( IADL ) increased the prevalence to 3.02 % ( CI 2.40 to 3.64 ) . Five-year outcomes , including the risk of death , institutionalization , and dementia , were not distinctly different for various case definitions of MCI , but all were at increased risk of institutionalization ( RR 2.3 to 5.2 ) and dementia ( RR 9.3 to 19.7 ) . Regardless of the case definition , most people with MCI developed dementia , chiefly Alzheimer disease ( AD ) . Still , for each case definition , almost one third were considered to have no cognitive impairment after 5 years . Conclusions : Memory complaints and intact IADL may be unnecessary requirements for a case definition of MCI in population -based sample s. The MCI criteria identify people at increased risk of AD , but the potential for improvement of a substantial proportion of those with MCI needs to be acknowledged The purpose of this study was to determine the psychological , behavioral , and cognitive changes associated with up to 14 months of aerobic exercise training . For the first 4 months of the study , 101 older ( greater than 60 years ) men and women were r and omly assigned to one of three conditions : Aerobic exercise , Yoga , or a Waiting List control group . Before and following the intervention , all subjects completed a comprehensive assessment battery , including measures of mood and cognitive functioning . A semi-crossover design was employed such that , following completion of the second assessment , all subjects completed 4 months of aerobic exercise and underwent a third assessment . Subjects were given the option of participating in 6 additional months of supervised aerobic exercise ( 14 months total ) , and all subjects , regardless of their exercise status , completed a fourth assessment . Results indicated that subjects experienced a 10 - 15 % improvement in aerobic capacity . In general , there were relatively few improvements in cognitive performance associated with aerobic exercise , although subjects who maintained their exercise participation for 14 months experienced improvements in some psychiatric symptoms . However , the healthy subjects in this study were functioning at a relatively high level to begin with , and exercise training may produce greater improvements among elderly with concomitant physical or emotional impairments This r and omized controlled trial examined the effect of a 3-month exercise programme on neuropsychological function in a population of very elderly institutionalized women . Baseline neuropsychological testing was performed , and following 3 months of exercise or control intervention , subjects were retested 3 - 7 days after the completion of the study period . Apart from the Word Fluency Test , there was no significant improvement in any of the neuropsychological test scores . This study may not have shown any significant improvement in neuropsychological function because our exercise programme was too light to improve aerobic fitness , or because neuropsychological tests were repeated 3 - 7 days after exercise was completed and any acute effects of exercise may have disappeared by that time The quadriceps strength of a group of residents homes for the elderly ( mean age 83 years ) was assessed in a r and omized controlled trial of seated group exercise versus group reminiscence therapy . Fifty-five of 65 volunteers completed the 6-month study , with 4 dropouts from the exercise group , and 6 dropouts from the reminiscence group . There were no adverse effects . Average of attendance at the exercise sessions was 72 % ( range , 18 % to 98 % ) and 62 % ( range , 29 % to 100 % ) at the reminiscence sessions . The reminiscence sessions comprised group interaction and discussion prompted by the use of reminiscence aids . By the end of the study , the change observed in the exercise group was significantly different from the reminiscence group in terms of quadriceps strength ( p < 0.01 , Mann-Whitney U test ) . Both groups improved equally in their ability to climb up steps , but neither cognitive function ( Mini-Mental State Examination ) nor reaction time altered significantly 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 OBJECTIVE The purpose of this pilot was to determine whether a strength and flexibility program in frail long-term care facility ( LTC ) residents would result in improved function . DESIGN A prospect i ve , r and omized , controlled , semicrossover trial was design ed with participants assigned either to group exercise ( EX ) or recreational therapy ( C ) . In the EX group , the intervention continued for 1 year . In the C group , recreation continued for 6 months ; these controls were then crossed over to the same exercise intervention as the EX group and followed for an additional 6 months . Functional outcomes were measured at baseline and 3 , 6 , 9 , and 12 months for both groups . SETTING A LTC facility , which included both assisted living ( AL ) and nursing home ( NH ) residents . PARTICIPANTS Twenty frail residents ( 5 from NH , 15 from AL ) aged 75 to 99 years at one LTC facility . INTERVENTION After r and om group assignment , the EX group met 1 hour three times per week . An exercise physiologist and LTC staff conducted sessions which included seated range of motion ( ROM ) exercises and strength training using simple equipment such as elastic resistance b and s ( therab and s ) and soft weights . The C group met three times per week and participated in activities such as painting during the first 6 months , before crossing over to exercise . MEASUREMENTS AND METHODS Objective measures of physical and cognitive function were obtained at baseline and 3 , 6 , 9 , and 12 months using the timed get-up- and -go test ( TUG ) , Berg balance scale , physical performance test ( PPT ) , and mini-mental status exam ( MMSE ) . Because we were interested in the impact of exercise on multiple endpoints and to protect the type I error rate , a global hypothesis test was used . RESULTS There was a significant overall impact across the four measures of the exercise intervention ( P = 0.013 ) . Exercise benefit as indicated by the difference between exercise and control conditions showed exercise decreased TUG by 18 seconds , which represents an effect size ( in st and ard deviation units ) of 0.50 , increased PPT scores by 1.3 , with effect size = 0.40 , increased Berg scores by 4.8 , with effect size of 0.32 , and increased MMSE by 3.1 , with effect size = 0.54 . Except for the Berg , 90 % confidence intervals on these exercise effects excluded 0 . CONCLUSION Frail elderly in a LTC facility were able to participate and benefit from a strength training program . The program was delivered with low-cost equipment by an exercise physiologist and LTC staff . The advantage of such a program is that it provides recreational and therapeutic benefits Elderly subjects diagnosed with mild cognitive impairment ( MCI ) are becoming the target of intervention trials . The criteria used for MCI are principally issued from prospect i ve clinical studies , although longitudinal population -based studies having identified several cognitive predictors of dementia can be of great contribution in the definition of these criteria . This study was conducted to explore the external validity of MCI criteria issued from a longitudinal population -based study , and subsequently to identify the best predictors of the short-term conversion to Alzheimer ’s disease 2 years after the MCI diagnosis . Ninety elderly volunteers with memory complaint diagnosed with MCI on the basis of their functional and neuropsychological performances were followed up within 2 years . The potential predictors of the conversion to dementia collected at baseline included age , gender , educational level , size of temporal lobe , apolipoprotein E genotype and a series of neuropsychological measures ( Mac Nair Scale , Mini-Mental State Examination , Benton Visual Retention Test , Isaacs Set Test , Digit Symbol Substitution Task , Letter Cancellation Task , digit span tasks and finger-tapping test ) . Within the 2 years , 29 subjects ( 32.2 % ) presented a conversion to dementia . The risk of conversion to dementia was associated with age and size of temporal lobe but not with gender , education , or apolipoprotein E4 genotype . Several neuropsychological measures were associated with the risk of conversion to dementia , but in a logistic regression performed with the significant variables found in the univariate analysis , only the Letter Cancellation Test was shown to be an independent predictor . In conclusion , the quite elevated conversion rates obtained show the usefulness , when defining MCI criteria , of considering not only memory impairment but also impairment in other cognitive areas , as well as mild impairment on higher-order activities of daily living . Among the variables considered , the Letter Cancellation Test proved to be a major predictor of short-term conversion to dementia Previous studies concerning psychological benefits of exercise among the elderly has focused predominantly on the effects of aerobic exercise . In the present study , psychological and behavioral adaptations in response to 12-weeks of strength training were examined in medically healthy but sedentary 42 older adults ( mean age = 68 years ) . The purpose of this study was to evaluate the effects of high and low intensity resistance training intensity on a ) muscular fitness , b ) psychological affect , and c ) neurocognitive functioning . Subjects were r and omly assigned to high intensity/low volume ( EXH : 2 sets of 8 to 10 repetitions for 75 to 85 % of 1 RM ) , low intensity/high volume ( EXL : 2 sets of 14 to 16 repetitions for 55 to 65 % of 1 RM ) , or no exercise control programs . Prior to and following the 12-week program , subjects underwent comprehensive physiological and psychological evaluations . Physiological assessment included measurements of blood pressure , heart rate , arm and leg muscle strength , body composition , and oxygen consumption ( VO2max ) . Psychological measures included evaluations of mood , anxiety , and physical self-efficacy as well as cognitive functioning . The results of this study indicated that both high and low intensity strength programs were associated with marked improvements in physiological fitness and psychological functioning . Specifically , subjects in the strength training programs increased overall muscle strength by 38.6 % and reduced percent body fat by 3.0 % . Favorable psychological changes in the strength-trained subjects included improvements in positive and negative mood , trait anxiety , and perceived confidence for physical capability . The treatment effects of neurocognitive functioning were not significant . In summary , this study demonstrated that participation in 12-weeks of high or low intensity strength training can improve overall physical fitness , mood , and physical self-efficacy in older adults while cognitive functioning remains constant Wound-care journals contain abundant reports of trials , but not all report a satisfactory methodology . Systematic review s of wound-care trials have highlighted many areas for improvement , and the National Institute for Clinical Excellence ( NICE ) guidelines recommend that primary research in the field of pressure ulcer prevention should adhere more closely to current method ological st and ards in terms of conduct and reporting . The CONSORT tool was developed to help achieve these improvements in the design and reporting of r and omised controlled trials ( RCTs ) The effects of aerobic exercise training in a sample of 85 older adults were investigated . Ss were assigned r and omly to either an aerobic exercise group , a nonaerobic exercise ( yoga ) group , or a waiting-list control group . Following 16 weeks of the group-specific protocol , all of the older Ss received 16 weeks of aerobic exercise training . The older adults demonstrated a significant increase in aerobic capacity ( cardiorespiratory fitness ) . Performance on reaction-time tests of attention and memory retrieval was slower for the older adults than for a comparison group of 24 young adults , and there was no improvement in the older adults ' performance on these tests as a function of aerobic exercise training . Results suggest that exercise-related changes in older adults ' cognitive performance are due either to extended periods of training or to cohort differences between physically active and sedentary individuals The authors examined whether resistance training has an effect on working memory span . Participants included 210 community-residing older adults with at least one disability from the Strong for Life program , a r and omized controlled trial that examined the effects of home-based resistance exercise . Memory was assessed with the WAIS backward digit span at baseline and 3 and 6 months into the intervention . Although there were no differences between the experimental treatment and control groups in average levels of memory change , within the treatment group change in resistance level during the intervention was a significant predictor of memory change , controlling for age , education , sex , and disability level . The results suggest that strength training can benefit memory among older adults , especially when using higher resistance levels Background : Falls are a major cause of morbidity in old age . A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective . This study set out to examine the preventability of falls in older people living in institutional care . Objective : To evaluate the effectiveness of falls risk factor assessment /modification and seated balance exercise training in reducing falls among elderly people living in residential care . Methods : 133 residents with a mean age of 84± ( SD ) 6.8 years were allocated at r and om by home to receive either a 6-month falls risk factor assessment /modification and seated balance exercise training programme ( n = 77 ) or 6 months of reminiscence therapy ( n = 56 ) . The risk factors targeted were postural hypotension , polypharmacy , visual acuity , and ambient lighting levels . Falls risk factor assessment s and recommendation for modifications were performed at baseline in the intervention group and assessment s repeated at 6 months . Functional reach , reaction time , timed up- and - go , grip strength , spinal flexibility , and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a ‘ blind ’ observer . Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period . Results : Only 90 of 133 ( 67.7 % ) residents completed the 6-month intervention period , and 84 ( 63.2 % ) completed the 7- to 12-month falls-monitoring follow-up period . Both prevalence of postural hypotension ( p = 0.0005 ) and poor visual acuity ( p = 0.04 ) were reduced in the intervention group . There was no difference between the groups in the number of falls sustained , the risk of falling [ odds ratio 0.45 ( 95 % CI 0.19–1.14 ) ] , or in the risk of recurrent falling [ odds ratio 1.07 ( 95 % CI 0.40–2.97 ) ] . No significant differences were found between the groups with regard to change in other outcome measures . Conclusions : The high drop-out rate reduced the power of this study to detect any effect of the interventions used . It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed st and ing . Further research is required to identify effective fall prevention strategies for elderly people in residential setting Background and aims : The aim of the study was to assess the effect of structured strength and balance training on cognitive function in frail , geriatric , long-term care facility residents , aged 75 years or older , and additionally to evaluate the influence of training on various functional , physical and psychological parameters . Methods : Participants were r and omly assigned to a training group or a control group . Physical training was performed three times a week for ten weeks in the training group . Muscle function was assessed by manual examination on a scale of 0–5 . Cognitive function was tested with the Mini Mental State Examination ( MMSE ) . In addition , scores for activities of daily living , mobility and depression were assessed . Results : 30 subjects with a mean age of 86.8 years completed the study . After 10 weeks of intervention in the training group , muscle strength increased from a mean of 3.75 to 4.44 points ( p<0.001 ) and the mean MMSE score increased from 20.9 to 23.9 points ( p=0.023 ) . In the training group , the change in the MMSE score correlated significantly with change in muscle function , with a Pearson correlation coefficient of 0.750 ( p=0.002 ) . An increase in mean BMI from 23.8 to 25.0 kg/m2 ( p=0.013 ) was also found in the training group , but no significant changes in scores for activities of daily living , mobility or depression . Compared with the control group , the change in the mean scores over the ten-week training period was significantly higher for the trained group with regard to muscle scores , BMI and lean body mass , but not for MMSE scores . Conclusions : Our findings reinforce the recommendation that structured strength and balance training should be implemented in long-term care facilities . Besides the well-known benefits of physical training , our findings showed that an improvement in cognitive function may also be possible The age-related decline in physical working capacity , cognitive performance , and psychological well-being can presumably be modified by regular physical exercise . The present study comprises 20 men and 20 women with a mean age of 66 years . Half of the participants were r and omly assigned to an exercise group , the remaining half to a control group . The members of the exercise group exercised individually through regular walking ( three times a week ) during a period of three months . The control group performed instead a series of mental tasks with the same regularity . Results showed significant differences in favor of the exercise group on complex tasks at the post-test , whereas only minor differences were found on simple tasks . Mood improvements were uniform , regardless of exercise involvement . The latter can be taken to indicate that exercise is not the most important factor , instead social context and regular contacts with other people may be equally important for elderly individuals |
11,999 | 25,539,250 | Additional high- quality evidence is required to determine the relative efficacy of ultrasound-guided needle lavage in the management of calcific tendinitis of the rotator cuff | OBJECTIVE The purpose of this study was to conduct a systematic review of the efficacy of ultrasound-guided needle lavage in treating calcific tendinitis . | We carried out a prospect i ve , r and omised controlled trial on two groups of 40 patients with painful calcific tendonitis and a mean age of 48.4 years ( 32.5 to 67.3 ) . All were to undergo arthroscopic removal of the calcific deposit within six months after r and omisation . The 40 patients in group I received ultrasound-guided needling followed by high-energy shock-wave therapy and the 40 in group II had shock-wave therapy alone . In both groups one treatment consisting of 2500 impulses of shock waves with an energy flux density of 0.36 mJ/mm(2 ) was applied . The clinical and radiological outcome was assessed using the 100-point Constant shoulder scoring system and st and ardised radiographs . The mean follow-up was 4.1 months and no patient was lost to follow-up . Both groups had significant improvement in their Constant shoulder score . Radiographs showed disappearance of the calcific deposit in 60.0 % of the shoulders in group I and in 32.5 % of group II ( p < 0.05 ) . Significantly better clinical and radiological results were obtained in group I than in group II . Arthroscopic removal of the deposit was avoided in 32 patients of group I and in 22 of group II . No severe side-effects were recorded . Ultrasound-guided needling in combination with high-energy shock-wave therapy is more effective than shock-wave therapy alone in patients with symptomatic calcific tendonitis , giving significantly higher rates of elimination of the calcium deposits , better clinical results and reduction in the need for surgery PURPOSE To evaluate clinical response to treatment of calcified tendinitis of the shoulder by using a modified percutaneous ultrasonography (US)-guided fine-needle technique . MATERIAL S AND METHODS Thirty shoulders of 30 consecutive patients ( 23 women , seven men ; mean age , 47.4 years ) with chronic shoulder pain ( average duration , 43.1 months ) refractory to medical treatment were treated percutaneously by using a fine needle and US guidance . Patients were prospect ively evaluated by using a shoulder pain and disability index consisting of 13 items and divided into two subcategories : pain and disability . The patient completed the question naire before the procedure and during the follow-up visit approximately 1 month later . A diagnostic US examination was also performed at that time . RESULTS There was a statistically significant improvement in the shoulder pain and disability index total score ( 27.0 % ) and the pain ( 30.5 % ) and disability ( 23.9 % ) scores . According to the index , these results indicate a significant clinical response . CONCLUSION This modified US-guided fine-needle technique for calcified tendinitis of the shoulder appears to be an effective therapy and was less aggressive than previously described percutaneous techniques PURPOSE To compare short- and long-term outcomes of patients with rotator cuff calcific tendonitis who did and did not undergo ultrasonographically (US)-guided percutaneous treatment . MATERIAL S AND METHODS Institutional review board approval and informed patient consent were obtained . Of patients referred for US-guided treatment of rotator cuff calcific tendonitis , 219 ( 86 men , 133 women ; mean age , 40.3 years + /- 10.9 [ st and ard deviation ] ) were treated ; 68 ( 31 men , 37 women ; mean age , 40.2 years + /- 11.3 ) patients refused treatment and served as control subjects . After local anesthesia was induced , two 16-gauge needles were inserted into the calcific deposit . Saline solution was injected through one needle , and the dissolved calcium was extracted through the other needle . Shoulder joint function was assessed by using Constant scores , and pain was assessed by using visual analogue scale ( VAS ) scores . Mann-Whitney U and chi(2 ) tests were performed . RESULTS At baseline , no significant difference in age or sex distribution , Constant score , or VAS score was detected between treated and nontreated ( control ) patients . Compared with control subjects , treated patients reported a significant decrease in symptoms at 1 month ( mean Constant score , 73.2 + /- 6.2 vs 57.5 + /- 3.9 ; mean VAS score , 4.8 + /- 0.6 vs 9.1 + /- 0.5 ) , 3 months ( mean Constant score , 90.2 + /- 2.6 vs 62.6 + /- 7.2 ; mean VAS score , 3.3 + /- 0.4 vs 7.3 + /- 1.8 ) , and 1 year ( mean Constant score , 91.7 + /- 3.1 vs 78.4 + /- 9.5 ; mean VAS score , 2.7 + /- 0.5 vs 4.5 + /- 0.9 ) ( P < .001 ) . Symptom scores were not significantly different between the groups at 5 years ( mean Constant score , 90.9 + /- 3.6 vs 90.5 + /- 4.8 ; mean VAS score , 2.6 + /- 0.5 vs 2.8 + /- 0.7 ) ( P > or= .795 ) and 10 years ( mean Constant score , 91.8 + /- 5.0 vs 91.3 + /- 9.6 ; mean VAS score , 2.5 + /- 0.6 vs 2.7 + /- 0.6 ) ( P > or= .413 ) . CONCLUSION US-guided percutaneous treatment facilitated prompt shoulder function recovery and pain relief . Treated patients had better outcomes than did nontreated patients at 1 year . However , 5 and 10 years after the procedure , the nontreated group reported outcomes similar to those of the treated group OBJECTIVE The purpose of our study was to evaluate the short- and long-term effectiveness of sonographically guided percutaneous needle aspiration and lavage in calcific tendinitis of the shoulder and to study the progress of calcifications and symptoms in the first year after treatment . MATERIAL S AND METHODS Symptoms and radiologic findings after percutaneous aspiration of calcific tendinitis were prospect ively evaluated in the short and the long term using a shoulder pain and disability index , evaluation of shoulder motion , and a survey of the self-perception by the patients regarding the progress of their disease . RESULTS Sixty-seven consecutive shoulders were treated . A significant improvement was seen in shoulder motion , pain , and disability in the short term and in the long term ( p < 0.0001 ) . One year after treatment , 91 % of shoulders had substantially or completely improved , 64 % had perfect motion , and calcifications on radiography had resolved completely or nearly completely in 89 % . A transitory recurrence was observed approximately 15 weeks after treatment in 44.3 % of shoulders that improved . CONCLUSION Percutaneous needle aspiration and lavage is effective in the short term and in the long term in calcific tendinitis of the shoulder , with results similar to or better than those published for other techniques , and it is only slightly invasive and painful . Progress after treatment may include a transitory period of recurrence of the pain OBJECTIVE To define prognostic factors in chronically symptomatic patients with calcific tendinitis of the shoulder . METHODS We evaluated 420 patients ( 488 shoulders ) in the context of a prospect i ve cohort study . Epidemiologic data were assessed . The radiographic and sonographic appearance of the calcific deposits was classified . The mean period of nonoperative therapy was 4.4 years ( range 0.5 - 13.7 years ) . After referral to our institution , st and ardized nonoperative therapy was continued for a minimum of 3 months . Failure of nonoperative therapy was defined as the persistence of symptomatic calcific tendinitis of the shoulder after a minimum of 6 months . Prognostic factors ( determined at P < 0.05 by chi-square test ) were analyzed by logistic regression . RESULTS Of the 420 patients , 269 ( 64 % ) were women , 151 ( 36 % ) were men . The mean age of the patients was 51.3 years ( range 28 - 84 years ) . Occurrence of calcific tendinitis of the shoulder was unilateral in 84 % and bilateral in 16 % . Gärtner type I calcific deposits were found in 37 % , type II in 32 % , and type III in 31 % . Failure of nonoperative therapy was observed in 114 patients ( 27 % ) . Negative prognostic factors were bilateral occurrence of calcific tendinitis of the shoulder , localization to the anterior portion of the acromion , medial ( subacromial ) extension , and high volume of the calcific deposit . Positive prognostic factors were a Gärtner type III deposit and a lack of sonographic sound extinction of the calcific deposit . CONCLUSION Our findings demonstrate the existence of prognostic factors in the nonoperative treatment of chronic symptomatic calcific tendinitis of the shoulder . Guidelines for optimal treatment can be implemented according to these factors to avoid a long-term symptomatic disease course PURPOSE To determine whether saline temperature influences procedure performance and outcome in patients undergoing ultrasonography (US)-guided lavage for the treatment of rotator cuff calcific tendinitis ( RCCT ) . MATERIAL S AND METHODS This study was approved by the institutional review board , and informed consent was obtained from all patients . From December 2009 to May 2011 , 462 patients ( 191 men and 271 women ; mean age , 39.7 years ) with painful RCCT diagnosed at US were prospect ively enrolled and r and omized into two groups . Operators subjectively classified calcifications as hard , soft , or fluid according to their appearance at US . US-guided percutaneous treatment of RCCT ( local anesthesia , double-needle lavage , intrabursal steroid injection ) was performed with warm saline ( 42 ° C , 107 ° F ) in 229 patients and with room-temperature saline in 233 . Operators and patients were not blinded to saline temperature . The ease of calcium dissolution was subjectively scored ( easy=1 , intermediate=2 , difficult=3 ) . Procedure duration was recorded . Patient discomfort was assessed by using a visual analog scale ( VAS ) . The occurrence of postprocedure bursitis was recorded . Statistical analyses were performed with Mann-Whitney U , χ2 , and analysis of variance tests . RESULTS Procedure duration was significantly shorter ( P<.001 ) in patients treated with warm saline ( mean , 576 seconds±121 ) than in those treated with room-temperature saline ( mean , 777 seconds±151 ) . Calcium dissolution was significantly easier in patients treated with warm saline ( median score , 1 ) than in those treated with room-temperature saline ( median score , 2 ) . Subgroup analysis according to calcification appearance at US showed a significant difference between groups for both soft ( P=.003 ) and hard ( P<.001 ) calcifications . No overall significant differences were found for VAS score ( warm saline group : baseline=8.9±0.6 , 1 month=4.7±0.6 , 2 months=4.0±0.7 , 3 months=3.4±0.4 , 1 year=3.0±0.7 ; room-temperature saline group : baseline=9.2±0.4 , 1 month=4.5±0.7 , 2 months=4.1±0.9 , 3 months=3.1±0.7 , 1 year=3.2±0.8 ; P=.491 ) . Postprocedural bursitis was observed in eight patients in the warm saline group and 20 in the room-temperature saline group ( P<.022 ) . CONCLUSION In the treatment of RCCT , warm saline appears to reduce procedure duration and improve calcification dissolution while reducing the frequency of postprocedural bursitis HYPOTHESIS Needle lavage is frequently performed before consideration of surgical removal in shoulders with calcific tendinitis because this may avoid surgery . However , its role in nonoperative treatment has not been fully investigated in terms of clinical and radiographic response . We hypothesized that needle decompression and subacromial steroid injection would show good clinical results in chronic calcific tendinitis patients . MATERIAL S AND METHODS Thirty-five shoulders in 30 consecutive patients with painful calcific tendinitis were treated by ultrasound-guided needle decompression and subacromial corticosteroid injection . Patients were prospect ively evaluated using American Shoulder and Elbow Surgeons ( ASES ) and Constant scores at 1 , 3 , and 6 months after the intervention . Size and morphology of the calcific deposits were compared with those in baseline radiographs at each visit . RESULTS At 6 months after the index procedure , 25 shoulders ( 71.4 % ) showed ASES and Constant score improvements from 48.0 and 53.7 to 84.6 and 87.9 , respectively ( P < .01 ) . Ten shoulders ( 28.6 % ) showed no symptom relief at the last follow-up . In shoulders with pain improvement , the mean size of calcific deposits reduced from 13.6 to 5.6 mm ( P < .01 ) , and in shoulders with no pain improvement or that underwent operation , mean size was 13.1 mm at initial visits and 12.7 mm at final visits ( P = .75 ) . DISCUSSION Shoulders showing little evidence of deposit size reduction at 6 months after needle decompression are less likely to achieve symptomatic improvement and may be considered as c and i date s for surgical removal . CONCLUSION Needle decompression with subacromial steroid injection is effective in 71.4 % of calcific tendinitis within 6 months . The size of calcific deposits in patients that achieved symptom relief was reduced |
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