Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study Steroids in duchenne muscular dystrophy — Deflazacort trial Deflazacort vs. prednisone in Duchenne muscular dystrophy: trends of an ongoing study Deflazacort in Duchenne dystrophy: study of long-term effect. A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group. A comparison of daily and alternate-day prednisone therapy in the treatment of Duchenne muscular dystrophy. Duchenne dystrophy Whole-body vibration training in children with Duchenne muscular dystrophy and spinal muscular atrophy. Six-minute walk test versus two-minute walk test in children with Duchenne muscular dystrophy: Is more time more information? Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. Can we rely on the best trial? A comparison of individual trials and systematic reviews Clinical trial in Duchenne dystrophy. I. The design of the protocol. Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial Cognitive and Psychological Profile of Males With Becker Muscular Dystrophy Intrarater reliability of manual muscle test (Medical Research Council scale) grades in Duchenne's muscular dystrophy. Clinical trials in Duchenne dystrophy. Standardization and reliability of evaluation procedures. Systemic administration of PRO051 in Duchenne's muscular dystrophy. Caries-preventive effect of glass ionomer and resin-based fissure sealants on permanent teeth: An update of systematic review evidence Balancing the strengths of systematic and narrative reviews. “Effectiveness of interventions in reducing pain and maintaining physical activity in children and adolescents with calcaneal apophysitis (Sever’s disease): a systematic review” How to write an evidence-based clinical review article.
Objective : We aim ed to perform an observational study of age at loss of independent ambulation ( LoA  ) and side-effect profiles associated with different glucocorticoid corticosteroid ( GC ) regimens in Duchenne muscular dystrophy ( DMD ) . Methods : We studied 340 participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study ( CINRG-DNHS ) . LoA was defined as continuous wheelchair use . Effects of prednisone or prednisolone (PRED)/deflazacort ( DFZ ) , administration frequency , and dose were analyzed by time-varying Cox regression . Side-effect frequencies were compared using χ2 test . Results : Participants treated ≥1 year while ambulatory ( n = 252/340 ) showed a 3-year median delay in LoA ( p < 0.001 ) . Fourteen different regimens were observed . Nondaily treatment was common for PRED ( 37 % ) and rare for DFZ ( 3 % ) . DFZ was associated with later LoA than PRED ( hazard ratio 0.294 ± 0.053 vs 0.490 ± 0.08 , p = 0.003 ; 2-year difference in median LoA with daily administration , p < 0.001 ) . Average dose was lower for daily PRED ( 0.56 mg/kg/d , 75 % of recommended ) than daily DFZ ( 0.75 mg/kg/d , 83 % of recommended , p < 0.001 ) . DFZ showed higher frequencies of growth delay ( p < 0.001 ) , cushingoid appearance ( p = 0.002 ) , and cataracts ( p < 0.001 ) , but not weight gain . Conclusions : Use of DFZ was associated with later LoA and increased frequency of side effects . Differences in st and ards of care and dosing complicate interpretation of this finding , but stratification by PRED/DFZ might be considered in clinical trials . This study emphasizes the necessity of a r and omized , blinded trial of GC regimens in DMD . Classification of evidence : This study provides Class IV evidence that GCs are effective in delaying LoA in patients with DMD We conducted a double blind controlled trial in 28 Duchenne muscular dystrophy ( DMD ) patients with Deflazacort ( DF ) , an oxazoline derivative of prednisolone which reduces its side-effects . Myometric muscle strength measurements , Scott Score and timed tests showed statistically significant improvement for the treated group ( P less than 0.05 ) . Side-effects after 9 months of treatment included mild cushingoid appearance in four patients ( 28 % ) and moderate in only one ( 7 % ) , increased appetite in seven ( 50 % ) , increased body hair in four ( 28 % ) , irritability and hyperactivity in three ( 21 % ) . Increased body weight was not prominent and was controlled with dietary measures . No patient had to be withdrawn from medication . More research and long-term follow-up are needed in order to establish the mechanism of improvement and the consequences of long-term steroid administration in DMD . In this regard DF appears as an alternative to prednisone preserving its benefits but with fewer side-effects Several studies have demonstrated the slowing effect of corticosteroids on the decline of muscle strength in Duchenne muscular dystrophy ( DMD ) .  Deflazacort ( DFC ) is supposed to have fewer side effects than prednisone ( PRED ) . An ongoing double blind multicenter study is comparing the effects and side effects of deflazacort ( 0.9 mg/kg/day ) and prednisone ( 0.75 mg/kg/day ) in DMD . This interim report includes data for 67 boys between age 5 years and loss of ambulation . Besides the common clinical and laboratory data for chronic corticoid treatment , motor performance has been tested . Interim results , 3 - 15 months after starting the medication , show some scattering but no grouping of data for all the functions tested : timed motor functions , sum of the strength of 20 muscles according to a 10-point scale on manual testing , weight gain , osteocalcin and alkaline phosphatase . Only the changes in CK activity after 3 months medication might reflect two equal groups without any correlation with the initial activity or with other parameters . On average , there was no clear-cut loss of muscle strength or performance . Except for in 4 patients , who were excluded due to unacceptable weight gain and /or loss of ambulation  , there were no side effects considered to be serious . The results suggest that ( i ) DFC and PRED in equal anti-inflammatory dosage are similarly or equally efficient in slowing down the decline of muscle strength in DMD ; ( ii ) benefits outweigh the side effects . This allows the study to continue as design ed A r and omized double-blind controlled trial of deflazacort was conducted in 28 Duchenne muscular dystrophy patients either treated with deflazacort 2.0 mg/kg alternate-day therapy or placebo .  The deflazacort group showed significant improvement in climbing stairs ( P < 0.01 ) , in rising from a chair , Gower 's maneuver , and walking ( P < 0.0025 ) after 6 months of treatment . After 1 year , all the above changes remained significantly improved and the MRC index was significantly better ( P < 0.05 ) in the treated group . After 2 years , a significant change was found in the MRC index : higher scores in walking , chair rising ( P < 0.02 ) , and grade and time of Gower 's maneuver ( P < 0.05 ) were found . The mean time for loss of ambulation for the treated group after we started the trial was 33.2 + /- 9 months ; for the placebo group it was 20.5 + /- 11 months ( deflazacort vs. placebo group , P < 0.05 ) [ corrected ] . Our treated patients lost their ambulation at a median age of 11.8 years vs. 10.5 years in the placebo group . Side effects were mild , consisting of moderate weight gain and slight behavioral changes We r and omized 18 Duchenne muscular dystrophy ( DMD ) boys whose age ranged from 5.2 to 14.6 years ( mean , 7.3 years ) for treatment with either deflazacort ( 0.9 mg/kg/day ) or prednisone ( 0.75 mg/kg/day ) on the basis of age and functional score at the onset of treatment . We followed the patients every 3 months for 1 year , evaluating four limb muscles with the Medical Research Council scale and performance of four functions ( walking , climbing stairs , Gowers ' maneuver , and rising from a chair ) . Side effects were monitored by a question naire and by routine blood examination , and weight and height were recorded at each visit . At 12 months , the effect of both steroids was examined by comparing the status of the treated patients with another group of untreated DMD patients that served as natural history control . The two steroids were equally effective in improving motor function and functional performances . At 9 months , the average weight increase with respect to baseline value was 5 % ( 2 kg ) in the deflazacort group but 18 % in the prednisone group ( P < 0 . 005 ) , and the change remained significant after 12 months ( P < 0.05 ) . Other minor but nonsignificant side effects were observed . Steroid treatment with deflazacort appears to cause fewer side effects than with prednisone , particularly weight gain , which could be important to maximize motor performances BACKGROUND Glucocorticoid treatment is recommended as a st and ard of care in Duchenne muscular dystrophy ; however , few studies have assessed the long-term benefits of this treatment . We examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in patients with Duchenne muscular dystrophy . METHODS For this prospect i ve cohort study , we enrolled male patients aged 2 - 28 years with Duchenne muscular dystrophy at 20 centres in nine countries . Patients were followed up for 10 years . We compared no glucocorticoid treatment or cumulative treatment duration of less than 1 month versus treatment of 1 year or longer with regard to progression of nine disease-related and clinical ly meaningful mobility and upper limb milestones . We used Kaplan-Meier analyses to compare glucocorticoid treatment groups for time to st and from supine of 5 s or longer and 10 s or longer , and loss of st and from supine , four-stair climb , ambulation , full overhead reach , h and -to-mouth function , and h and function . Risk of death was also assessed . This study is registered with Clinical Trials.gov , number NCT00468832 . FINDINGS 440 patients were enrolled during two recruitment periods ( 2006 - 09 and 2012 - 16 ) . Time to all disease progression milestone events was significantly longer in patients treated with glucocorticoids for 1 year or longer than in patients treated for less than 1 month or never treated ( log-rank p<0·0001 ) . Glucocorticoid treatment for 1 year or longer was associated with increased median age at loss of mobility milestones by 2·1 - 4·4 years and upper limb milestones by 2·8 - 8·0 years compared with treatment for less than 1 month . Deflazacort was associated with increased median age at loss of three milestones by 2·1 - 2·7 years in comparison with prednisone or prednisolone ( log-rank p<0·012 ) . 45 patients died during the 10-year follow-up . 39 ( 87 % ) of these deaths were attributable to Duchenne-related causes in patients with known duration of glucocorticoids usage . 28 ( 9 % ) deaths occurred in 311 patients treated with glucocorticoids for 1 year or longer compared with 11 ( 19 % ) deaths in 58 patients with no history of glucocorticoid use ( odds ratio 0·47 , 95 % CI 0·22 - 1·00 ; p=0·0501 ) . INTERPRETATION In patients with Duchenne muscular dystrophy , glucocorticoid treatment is associated with reduced risk of losing clinical ly meaningful mobility and upper limb disease progression milestones across the lifespan as well as reduced risk of death . FUNDING US Department of Education/National Institute on Disability and Rehabilitation Research ; US Department of Defense ; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases ; and Parent Project Muscular Dystrophy A r and omized , controlled trial of daily prednisone was conducted in 99 boys ( aged 5 to 15 years ) with Duchenne dystrophy to define the time course of improvement and the dose response to treatment . Prednisone at 0.3 mg/kg ( n = 33 ) , prednisone at 0.75 mg/kg ( n = 34 ) , and placebo ( n = 32 ) were administered for 6 months . Patients were examined using manual muscle and myometry testing , timed functional testing , pulmonary function testing , and laboratory measurements at 10 days , 1 month , 2 months , 3 months , and 6 months of treatment . Boys treated with prednisone had stronger average muscle strength scores , than did boys treated with placebo as early as 10 days after starting therapy . At the 3-month visit , the boys in the group given 0.75 mg/kg of prednisone were significantly stronger than those in the group given 0.3 mg/kg of prednisone , indicating a dose response . At 6 months , significant side effects occurred in the group treated with 0.75 mg/kg of prednisone , including weight gain , cushingoid appearance , and excessive hari growth . Only weight gain was observed in the group taking prednisone at a dose of 0.3 mg/kg . Importantly , no side effects were evident at 10 days or 1 month of treatment , despite improvement in muscle strength and function . We conclude that prednisone produces a rapid increase in muscle strength in patients with Duchenne dystrophy and that this improvement is maximal at a prednisone dosage of 0.75 mg/kg or less We previously reported the results of a r and omized , double-blind 6-month trial of prednisone therapy in which 102 boys aged 5 to 15 years with Duchenne muscular dystrophy received daily doses of 1.5 and 0.75 mg/kg per day and were compared with those receiving placebo . The strength and function in both prednisone-treated groups improved equally and were significantly better than in the placebo group . To compare alternate-day and daily dosing of prednisone with respect to benefits and adverse side effects , the placebo group was started on alternate-day prednisone therapy , and the treatment group regimens were changed to equivalent doses of alternate-day prednisone without breaking the double-blind nature . At the end of 6 months , the group that was changed from daily to alternate-day therapy had declined in strength back to levels observed 12 months previously , at the start of daily therapy . The group in which alternate-day therapy was started showed a significant improvement in strength at 3 months , similar in magnitude to the response of boys treated with daily therapy . However , their strength declined significantly in the subsequent 3 months compared with boys who received daily therapy . The frequency of side effects was not significantly different for alternate-day therapy compared with daily therapy . We conclude that alternate-day prednisone therapy effectively increases strength but does not sustain the improvement to the same extent as daily therapy or mitigate side effects Prednisone has been shown to improve strength in Duchenne dystrophy .  Azathioprine often benefits corticosteroid-responsive diseases and can reduce the dose of prednisone needed . The present study reports a r and omized , controlled trial of prednisone and azathioprine design ed to assess the longer-term effects of prednisone and to determine whether azathioprine alone , or in combination with prednisone , improves strength .  Ninety-nine boys ( aged five to 15 years ) with Duchenne dystrophy were r and omized to one of three groups : ( I ) placebo ; ( II ) prednisone 0.3 mg/kg/d ; or ( III ) prednisone 0.75 mg/kg/d . After 6 months , azathioprine 2 to 2.5 mg/kg/d was added in groups I and II and placebo added in group III . The study showed that the beneficial effect of prednisone ( 0.75 mg/kg/d ) is maintained for at least 18 months and is associated with a 36 % increase in muscle mass . There was weight gain , growth retardation , and other side effects .  Azathioprine did not have a beneficial effect . This study suggests that prednisone 's beneficial effect is not due to immunosuppression INTRODUCTION Whole-body-vibration training is used to improve muscle strength and function and might therefore constitute a potential supportive therapy for neuromuscular diseases . OBJECTIVE To evaluate safety of whole-body vibration training in ambulatory children with Duchenne muscular dystrophy ( DMD ) and spinal muscular atrophy ( SMA ) . METHODS 14 children with DMD and 8 with SMA underwent an 8-week vibration training programme on a Galileo MedM at home ( 3 × 3 min twice a day , 5 days a week ) . Primary outcome was safety of the training , assessed clinical ly and by measuring serum creatine kinase levels . Secondary outcome was efficacy as measured by changes in time function tests , muscle strength and angular degree of dorsiflexion of the ankles . RESULTS All children showed good clinical tolerance . In boys with DMD , creatine kinase increased by 56 % after the first day of training and returned to baseline after 8 weeks of continuous whole-body vibration training . No changes in laboratory parameters were observed in children with SMA . Secondary outcomes showed mild , but not significant , improvements with the exception of the distance walked in the 6-min walking test in children with SMA , which rose from 371.3 m to 402.8 m ( p < 0.01 ) . INTERPRETATION Whole-body vibration training is clinical ly well tolerated in children with DMD and SMA . The relevance of the temporary increase in creatine kinase in DMD during the first days of training is unclear , but it is not related to clinical symptoms or deterioration BACKGROUND / PURPOSE The six minute walk test is a widely accepted primary outcome parameter in most studies in Duchenne muscular dystrophy ( DMD ) . To compare information obtained by the six minute walk distance ( 6MWD ) test and the two minute walk distance ( 2MWD ) in patients with DMD , a cohort of 13 voluntary DMD boys did a repeated six minute walking test . METHODS Patients had to be ambulatory with a physical disability according to Levels 1 - 3 on the Vignos-Scale for lower extremity . Measurements were taken at one minute intervals . Reliability was measured by intraclass correlation . RESULTS Test-retest reliability for 6MWD and 2MWD in two different age classes was very good for both subgroups . Test-retest-reliability was lower in patients with more advanced disability in both tests . Walking speed remained completely stable from time points 1 - 6 minutes in the whole study patient collective , which indicates that physical exhaustion is not reached after six minutes even in more disabled patients . CONCLUSION Thus the 6MWD in DMD patients does not give additional information as compared to a 2MWD We performed a r and omized , double-blind , controlled six-month trial of prednisone in 103 boys with Duchenne 's muscular dystrophy ( age , 5 to 15 years ) . The patients were assigned to one of three regimens : prednisone , 0.75 mg per kilogram of body weight per day ( n = 33 ) ; prednisone , 1.5 mg per kilogram per day ( n = 34 ) ; or placebo ( n = 36 ) . The groups were initially comparable in all measures of muscle function . Both prednisone groups had significant improvement of similar degree in the summary scores of muscle strength and function . Improvement began as early as one month and peaked by three months . At six months the high-dose prednisone group , as compared with the placebo group , had improvement in the time needed to rise from a supine to a st and ing position ( 3.4 vs. 6.2 seconds ) , to walk 9 m ( 7.0 vs. 9.7 seconds ) , and to climb four stairs ( 4.0 vs. 7.1 seconds ) , in lifting a weight ( 2.1 vs. 1.2 kg ) , and in forced vital capacity ( 1.7 vs. 1.5 liters ) ( P less than 0.001 for all comparisons ) . There was an increase in urinary creatinine excretion ( 261 vs. 190 mg per 24 hours ) , which suggested an increase in total muscle mass . However , the prednisone-treated patients who had required long-leg braces ( n = 5 ) or wheelchairs ( n = 11 ) continued to require them . The most frequent side effects were weight gain , cushingoid appearance , and excessive hair growth . We conclude from this six-month study that prednisone improves the strength and function of patients with Duchenne 's muscular dystrophy . However , further research is required to identify the mechanisms responsible for these improvements and to determine whether prolonged treatment with corticosteroids may be warranted despite their side effects Background The ideal evidence to answer a question about the effectiveness of treatment is a systematic review . However , for many clinical questions a systematic review will not be available , or may not be up to date . One option could be to use the evidence from an individual trial to answer the question ? Methods We assessed how often ( a ) the estimated effect and ( b ) the p-value in the most precise single trial in a meta- analysis agreed with the whole meta- analysis . For a r and om sample of 200 completed Cochrane Review s ( January , 2005 ) we identified a primary outcome and extracted : the number of trials , the statistical weight of the most precise trial , the estimate and confidence interval for both the highest weighted trial and the meta- analysis overall . We calculated the p-value for the most precise trial and meta- analysis . Results Of 200 review s , only 132 provided a meta- analysis of 2 or more trials , with a further 35 effect estimates based on single trials . The average number of trials was 7.3 , with the most precise trial contributing , on average , 51 % of the statistical weight to the summary estimate from the whole meta- analysis . The estimates of effect from the most precise trial and the overall meta-analyses were highly correlated ( rank correlation of 0.90).There was an 81 % agreement in statistical conclusions . Results from the most precise trial were statistically significant in 60 of the 167 evaluable review s , with 55 of the corresponding systematic review s also being statistically significant . The five discrepant results were not strikingly different with respect to their estimates of effect , but showed considerable statistical heterogeneity between trials in these meta-analyses . However , among the 101 cases in which the most precise trial was not statistically significant , the corresponding meta-analyses yielded 31 statistically significant results . Conclusions Single most precise trials provided similar estimates of effects to those of the meta-analyses to which they contributed , and statistically significant results are generally in agreement . However , " negative " results were less reliable , as may be expected from single underpowered trials . For systematic review ers we suggest that : ( 1 ) key trial(s ) in a review deserve greater attention ( 2 ) systematic review ers should check agreement of the most precise trial and the meta analysis . For clinicians using trials we suggest that when a meta- analysis is not available , a focus on the most precise trial is reasonable provided it is adequately powered Therapeutic trials in muscular dystrophy have often been inconclusive . A protocol has been design ed which selects patients with Duchenne muscular dystrophy and permits accurate measurement of their status . An integral part of the protocol is a system for checking on the consistency of the data obtained using a computer program BACKGROUND Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy . Based on pre clinical and phase 2 evidence , we assessed the efficacy and safety of idebenone in young patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids . METHODS In a multicentre phase 3 trial in Belgium , Germany , the Netherl and s , Switzerl and , France , Sweden , Austria , Italy , Spain , and the USA , patients ( age 10 - 18 years old ) with Duchenne muscular dystrophy were r and omly assigned in a one-to-one ratio with a central interactive web response system with a permuted block design with four patients per block to receive idebenone ( 300 mg three times a day ) or matching placebo orally for 52 weeks . Study personnel and patients were masked to treatment assignment . The primary endpoint was change in peak expiratory flow ( PEF ) as percentage predicted ( PEF%p ) from baseline to week 52 , measured with spirometry . Analysis was by intention to treat ( ITT ) and a modified ITT ( mITT ) , which was prospect ively defined to exclude patients with at least 20 % difference in the yearly change in PEF%p , measured with hospital-based and weekly home-based spirometry . This study is registered with Clinical Trials.gov , number NCT01027884 . FINDINGS 31 patients in the idebenone group and 33 in the placebo group comprised the ITT population , and 30 and 27 comprised the mITT population . Idebenone significantly attenuated the fall in PEF%p from baseline to week 52 in the mITT ( -3·05%p [ 95 % CI -7·08 to 0·97 ] , p=0·134 , vs placebo -9·01%p [ -13·18 to -4·84 ] , p=0·0001 ; difference 5·96%p [ 0·16 to 11·76 ] , p=0·044 ) and ITT population s ( -2·57%p [ -6·68 to 1·54 ] , p=0·215 , vs -8·84%p [ -12·73 to -4·95 ] , p<0·0001 ; difference 6·27%p [ 0·61 to 11·93 ] , p=0·031 ) . Idebenone also had a significant effect on PEF ( L/min ) , weekly home-based PEF , FVC , and FEV1 . The effect of idebenone on respiratory function outcomes was similar between patients with previous corticosteroid use and steroid-naive patients . Treatment with idebenone was safe and well tolerated with adverse event rates were similar in both groups . Nasopharyngitis and headache were the most common adverse events ( idebenone , eight [ 25 % ] and six [ 19 % ] of 32 patients ; placebo , nine [ 26 % ] and seven [ 21 % ] of 34 patients ) . Transient and mild diarrhoea was more common in the idebenone group than in the placebo group ( eight [ 25 % ] vs four [ 12 % ] patients ) . INTERPRETATION Idebenone reduced the loss of respiratory function and represents a new treatment option for patients with Duchenne muscular dystrophy . FUNDING Santhera Pharmaceuticals Duchenne and Becker muscular dystrophy are allelic X-linked disorders causing progressive muscle weakness in males . Duchenne muscular dystrophy is caused by absence of dystrophin in muscle and brain ; boys with Duchenne muscular dystrophy have a static cognitive impairment with mean Full Scale IQ approximately 1 st and ard deviation below the mean . Less is known of the cognitive profile of males with Becker muscular dystrophy , which is associated with variable alterations in the amount or size of the dystrophin protein . The aim of this study was to describe the cognitive and psychological profile of males with Becker muscular dystrophy . This was a prospect i ve cohort study . Clinical data collected included age at diagnosis and assessment , socioeconomic status , serum creatine kinase level , and site of gene deletion/mutation ( by exon number ) . The following psychological tests were used to assess general intellectual functioning , academic achievement , incidence and nature of behavioral problems : The Wechsler Intelligence Scales , The Wide Range Achievement Test — Revised , The Developmental Test of Visual-Motor Integration , The Child Behavior Checklist , and The Conner 's Parent Rating Scale .  Twenty-four males were enrolled . The Wechsler Full Scale IQ was normally distributed with a mean of 95.6 ( SD 23.3 ) , which did not differ significantly from the population mean . The frequency of learning difficulties for reading was 21 % , for spelling was 32 % , and for arithmetic was 26 % , significantly higher than the frequency in the general population . The frequency of total behavioral problems in the clinical range was 67 % , and the frequency of autism was 8.3 % . Patients with Becker muscular dystrophy demonstrate a less homogeneous cognitive phenotype than that seen in Duchenne muscular dystrophy . Males with Becker muscular dystrophy have a high incidence of learning difficulties . Autism and behavioral and attention problems are also more common in Becker muscular dystrophy than in the general population The purpose of this study was to document the intrarater reliability of manual muscle test ( MMT ) grade s in assessing muscle strength in patients with Duchenne 's muscular dystrophy ( DMD ) . Subjects were 102 boys , aged 5 to 15 years , who were participating in a double-blind , multicenter trial to document the effects of prednisone on muscle strength in patients with DMD . Four physical therapists participated in the study . Two identical ( duplicate ) evaluations were performed within 5 days of each other by the same examiner initially and after 6 and 12 months of treatment . A total of 18 muscle groups were tested on each patient , 16 of them bilaterally , using a modification of the Medical Research Council scale . Reliability of muscle strength grade s obtained for individual muscle groups and of individual muscle strength grade s was analyzed using Cohen 's weighted Kappa . The reliability of grade s for individual muscle groups ranged from .65 to .93 , with the proximal muscles having the higher reliability values . The reliability of individual muscle strength grade s ranged from .80 to .99 , with those in the gravity-eliminated range scoring the highest . We conclude the MMT grade s are reliable for assessing muscle strength in boys with DMD when consecutive evaluations are performed by the same physical therapist A multiclinic , collaborative study has been design ed to assess the natural progression and efficacy of treatment of Duchenne muscular dystrophy . This article describes the protocol for the evaluation technique and the method used to establish within ( intraobserver ) and between ( interobserver ) reliability of the protocol evaluation procedures .  St and ardized patient evaluations  were used , and consistency of evaluation was monitored by a computer . The reliability of the measures was analyzed 1 ) within observers by comparing the results of each of the first three tests done by each evaluator for all patients and 2 ) between observers by comparing , at multicenter group meetings , the results of each of the four evaluators ' tests of the same patient . We have demonstrated reliability for an evaluation method that will provide an objective foundation on which to cl aim a drug or therapeutic procedure does or does not have an effect in treating Duchenne muscular dystrophy BACKGROUND Local intramuscular administration of the antisense oligonucleotide PRO051 in patients with Duchenne 's muscular dystrophy with relevant mutations was previously reported to induce the skipping of exon 51 during pre-messenger RNA splicing of the dystrophin gene and to facilitate new dystrophin expression in muscle-fiber membranes . The present phase 1 - 2a study aim ed to assess the safety , pharmacokinetics , and molecular and clinical effects of systemically administered PRO051 . METHODS We administered weekly abdominal subcutaneous injections of PRO051 for 5 weeks in 12 patients , with each of four possible doses ( 0.5 , 2.0 , 4.0 , and 6.0 mg per kilogram of body weight ) given to 3 patients . Changes in RNA splicing and protein levels in the tibialis anterior muscle were assessed at two time points . All patients subsequently entered a 12-week open-label extension phase , during which they all received PRO051 at a dose of 6.0 mg per kilogram per week . Safety , pharmacokinetics , serum creatine kinase levels , and muscle strength and function were assessed . RESULTS The most common adverse events were irritation at the administration site and , during the extension phase , mild and variable proteinuria and increased urinary α(1)-microglobulin levels ; there were no serious adverse events . The mean terminal half-life of PRO051 in the circulation was 29 days . PRO051 induced detectable , specific exon-51 skipping at doses of 2.0 mg or more per kilogram . New dystrophin expression was observed between approximately 60 % and 100 % of muscle fibers in 10 of the 12 patients , as measured on post-treatment biopsy , which increased in a dose-dependent manner to up to 15.6 % of the expression in healthy muscle . After the 12-week extension phase , there was a mean ( ±SD ) improvement of 35.2±28.7 m ( from the baseline of 384±121 m ) on the 6-minute walk test . CONCLUSIONS Systemically administered PRO051 showed dose-dependent molecular efficacy in patients with Duchenne 's muscular dystrophy , with a modest improvement in the 6-minute walk test after 12 weeks of extended treatment . ( Funded by Prosensa Therapeutics ; Netherl and s National Trial Register number , NTR1241 . ) Background This article constitutes a partial up date of the original systematic review evidence by Yengopal et al. from 15 January 2008 ( published in the Journal of Oral Science in 2009 ) with primary focus on research quality in regard to bias risk in trials . Its aim is to up date the existing systematic review evidence from the English literature as to whether caries occurrence on pits and fissures of teeth sealed with either GIC or resin is the same . Methods In addition to the 12 trials included during the original systematic review , 5 new trials were identified during the data base search ( up to 26 August 2010 ) and 2 further trials were included from a h and search and reference check . Of these , 3 trials were excluded and 16 were accepted for data extraction and quality assessment . The quality of accepted trials was assessed , using up date d quality criteria , and the risk of bias was investigated in more depth than previously reported . In addition , the focus of quantitative synthesis was shifted to single data sets that were extracted from the accepted trials . Results Twenty-six dichotomous and 4 continuous data sets were extracted . Meta- analysis and cumulative meta- analysis were used in combining clinical ly homogenous data sets . The overall outcome of the computed data sets suggest no difference between the caries-preventive effects of GIC- and resin-based fissure sealants . Conclusions This overall outcome is in agreement with the conclusions of the original systematic review . Although the findings of the trials identified in this up date may be considered to be less affected by attrition- and publication bias , their risk of selection - and detection-/performance bias is high . Thus , verification of the currently available results requires further high quality r and omised control trials The m and ate of Human Reproduction Up date involves several roles : ( i ) to provide a synthesis of evidence that can aid scientists and clinicians in their daily work ; ( ii ) to help reproductive specialists underst and concepts from related disciplines ; and ( iii ) to summarize current knowledge generated by basic science as the foundation of future scientific and clinical advancement . Given that review and synthesis are central to good scientific and clinical practice , and that a grasp of the current state of knowledge is a prerequisite to design ing new studies , it is pertinent to ask which review s are most likely to fulfil the needs of readers . A related question concerns whether systematic review s meet the needs of all review topics and all readers . Summarizing evidence or knowledge is a difficult problem in reproductive medicine , as in other branches of science and medical care ( Eddy et al. , 1992 ) . For each question there may be multiple studies that use different design s and inclusion criteria . For clinical questions , the interventions , outcomes and measures of effect may vary : the effect measures in treatment studies include odds ratios , relative risks and absolute differences . For scientific questions , the experimental species , models and design s may differ . Moreover , it is always uncertain whether all of the relevant evidence has been evaluated . Even when the search has been exhaustive , there are no simple guides on how to interpret conflicting results and whether to accept apparently outlying studies . The choices that the review er makes to address the variable conditions and uncertainties may be conservative , strict and exclusive , or liberal , open and inclusive . The decisions made by the review er may not be consistent throughout and these choices may or may not satisfy the reader who seeks out the review to address a clinical or research question . Faced with uncertainty and doubt , readers nonetheless must form an impression of the evidence and synthesize the state of knowledge in order to address the clinical or research question that stimulated their interest in the review . We argue that the reader is better served when the choices made in the review , regardless of whether they are strict or open , should be explicit , transparent , clearly stated and reproducible by interested readers . This list of objectives for review s is more easily satisfied by systematic review s , which use explicit methods to method ically search , critically appraise and synthesize the available literature on a specific issue . The question or issue need not be clinical : indeed , the concept evolved primarily in psychology studies ( Light and Pillemer , 1984 ) . The systematic review attempts to reduce review er bias through the use of objective , reproducible criteria to select relevant individual publications and assess their validity . A systematic review may include a meta- analysis or statistical summary of the individual study results : the aggregate of effects from several studies yields an average treatment effect that is more precise than the individual study results ( Schlesselman and Collins , 2003 ) . Thus , the systematic review involves explicit , transparent methods which are clearly stated , and reproducible by others . Whether a systematic review of r and omized controlled trials adheres to the guidelines can easily be evaluated by means of a widely used checklist ( the QUORUM statement ) ( Moher et al. , 1999 ) . The strengths of the systematic review include the narrow focus of the question , the comprehensive search for evidence , the criterion-based selection of relevant evidence , the rigorous appraisal of validity , the objective or quantitative summary , and the evidence -based inferences ( Cook et al. , 1997 ) . For some review topics , however , the strengths of the systematic review may turn into weaknesses . The primary problem is that the narrow focus and prescribed methods of the systematic review do not allow for comprehensive coverage . For example , the historical review is an irreplaceable means of tracing the development of a scientific principle or clinical concept , but the narrative thread could be lost in the strict rules of systematic review . As other examples , it would be burdensome to apply systematic methods to a survey on  aneuploidy and fertility in the aging female or to an assessment of mouse knockout models and polycystic ovarian phenotype . Such topics would require the wider scope of a traditional narrative review , in Human Reproduction Up date , Vol.11 , No.2 pp . 103–104 , 2005 doi:10.1093/humupd/dmh058 Advance Access publication December 23 , Background Calcaneal apophysitis , also commonly known as sever ’s disease , is a condition seen in children usually aged between 8–15 years . Conservative therapies , such as taping , heel lifts and orthotic intervention are accepted management practice s for calcaneal apophysitis , though there is very little high quality research examining the efficacy of such treatment modalities . Previous narrative literature review s and opinion pieces provide some evidence for the use of heel raises or orthoses . The aim of this manuscript was to complete a systemic review on the treatment options for calcaneal apophysitis as measured by pain reduction and maintenance of physical activity . Methods A search strategy completed by two review ers examined nine data bases from inception to May 2012 . Search terms included heel pain , children , adolescent , calcaneal apophysitis , sever ’s disease , treatment , and management ( full text publications , human studies ) . Systematic review s , r and omised control trials , case series , and case studies were included . The reference lists of the selected articles were also examined . The methodology , quality and risk of bias was examined and assessed using the PEDro scale . Results Nine articles were retrieved including three clinical trials involving r and omisation , two case series , two retrospective case review s , and two case reports . Effect size calculations and a meta analysis were unable to be completed due to the limited data reported within the literature . Numerous treatment options were reported throughout the literature , though few were examined against a control or alternate treatment option in well- design ed trials . The limited evidence indicated that orthoses provided greater short-term pain relief than heel raises . Health practitioners should view these results with caution , as there were apparent method ological problems with the employed study design and limited follow-up of participants . Conclusion There is limited evidence to support the use of heel raises and orthoses for children who have heel pain related to calcaneal apophysitis . Further research is needed to generate higher quality evidence with larger sample sizes , and vali date d measures of pain and function to establish effective treatment approaches for children with calcaneal apophysitis Traditional clinical review articles , also known as up date s , differ from systematic review s and meta-analyses . Up date s selectively review the medical literature while discussing a topic broadly . Non-quantitative systematic review s comprehensively examine the medical literature , seeking to identify and synthesize all relevant information to formulate the best approach to diagnosis or treatment . Meta-analyses ( quantitative systematic review s ) seek to answer a focused clinical question , using rigorous statistical analysis of pooled research studies . This article presents guidelines for writing an evidence -based clinical review article for American Family Physician . First , the topic should be of common interest and relevance to family practice . Include a table of the continuing medical education objectives of the review . State how the literature search was done and include several sources of evidence -based review s , such as the Cochrane Collaboration , BMJ 's Clinical Evidence , or the InfoRetriever Web site . Where possible , use evidence based on clinical outcomes relating to morbidity , mortality , or quality of life , and studies of primary care population s. In articles su bmi tted to American Family Physician , rate the level of evidence for key recommendations according to the following scale : level A ( r and omized controlled trial [ RCT ] , meta- analysis ) ; level B ( other evidence ) ; level C ( consensus/expert opinion ) . Finally , provide a table of key summary points
Conclusions Examining individual studies it appears that DFZ improves strength and functional outcomes compared to placebo , but it remains unclear if it has a benefit over prednisone on similar outcomes .
Two trials found that DFZ causes less weight gain than prednisone
Background To complete a systematic review and meta- analysis based on the clinical question : Is Deflazacort ( DFZ ) , a prednisolone derivative , an effective therapy for improving strength , with acceptable side effects , in children with Duchenne Dystrophy ( DD ) ?