***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: For the early career research er or PhD student about to have a leading role in a clinical trial , it would be a tremendous help to have a ‘ How to ’ guide , consisting of advice and key literature to help the research er move successfully along the initial trial pathway from research question to protocol completion . While the ideal trial team should include experienced trialists , who participate in the preparatory research meetings , this support is not always available . The PREPARE Trial guide is intended to assist the early career research er in this situation , but not replace an experienced trial team and regular research meetings . The guide may also serve as preparation for research meetings , or part of curricula for courses on research methodology , to be used by experienced PhD supervisor , trialist or lecturer . Evidence from r and omised controlled trials ( RCTs ) is often wasted1 2 ( for a collection of papers relating to this issue , please see http:// research waste.net/ ) . Many trials are not published , and hence the results are not reported , which is indeed a waste . There are many reasons for this waste , but we believe that at least some trials are discontinued because of poor trial planning . Similarly , many completed and published trials suffer from fundamental flaws or poor conduct due to lack of preparation and careful planning . Some flaws in the conception or planning phase prior to the finalised trial protocol and registration are difficult to rectify once the trial starts . For example , patients may decline participation if the study involves delaying or withholding treatment , or if the experimental condition is deemed unfeasible by patients . This can be avoided , for example , by involving patients in the planning of the trial or by conducting pilot or feasibility studies prior to the full-scale trial . In many cases , the planning of a trial is as least as important as Context Some guidelines recommend splinting for symptomatic treatment of base-of-thumb osteoarthritis . Contribution In this r and omized trial , nighttime splinting had no effect compared with usual care after 1 month , but it clinical ly significantly reduced patients ' pain and disability after 12 months . Caution The study was not blinded , and the splints were custom-made . Implication Nighttime splinting is an effective treatment of base-of-thumb osteoarthritis . The Editors Base-of-thumb osteoarthritis ( BTOA ) is a relatively common condition affecting middle-age and older persons ( 1 ) . Base-of-thumb osteoarthritis induces pain and closure of the first web , which in turn causes an alteration of the thumbindex pinch and , therefore , limitation in h and function ( 1 ) . The consequences of BTOA have been specifically evaluated and compared with osteoarthritis of digits 2 to 5 of the interphalangeal joints ( 2 ) . Substantial pain and similar pain and disability levels were observed in both osteoarthritis locations , and results suggested that h and osteoarthritis ( base of thumb or interphalangeal joints ) is as cumbersome as a rheumatoid arthritis of the h and for some people ( 3 , 4 ) . Few treatments have been specifically assessed in BTOA . The European League Against Rheumatism recently proposed 11 evidence -based recommendations for the management of h and osteoarthritis ( 5 ) . Among these , 3 specifically concern BTOA : intra-articular corticosteroid injections for painful flares , surgery when conservative treatments have failed , and splints to prevent or correct lateral angulation and flexion deformity . However , no r and omized trials with placebo or nonsplint comparison have been done to support this recommendation . Two small ( 26 and 21 participants each ) head-to-head , r and omized , controlled trials ( RCTs ) found better pain relief with a full splint ( covering the thumb base and wrist ) than with a half splint ( covering only the thumb base ) ( 6 , 7 ) . However , these studies did not examine the effect on disability or closure of the first web . More recently , a small RCT compared 2 splints and exercise regimens and found no short-term differences ( 8) . The conclusions of the European League Against Rheumatism st and ing committee on splints for BTOA was that apart from expert opinion , placebo-controlled or nonsplint-controlled research evidence [ is ] required ( 5 ) . We conducted an RCT to assess the efficacy of splinting for BTOA on pain at 1 month . Secondary objectives were to assess the efficacy of splinting for BTOA  on pain and disability at 12 months and safety and adherence with splinting for BTOA . Methods Design We conducted a 12-month , open-label , parallel-group , multicenter RCT in 2 tertiary care hospitals ( Cochin Hospital and Lariboisire Hospital , Paris , France ) after method ological and reporting guidelines ( 9 , 10 ) . Participants We screened all patients who consulted with physicians ( mostly rheumatologists ) for disabling BTOA during outpatient visits at tertiary care hospitals or at private practice s for inclusion in the trial and invited them to participate . Inclusion criteria were pain at the base of the thumb 30 mm or greater on a visual analogue scale ( VAS ) ( range , 0 to 100 mm ) , age 45 to 75 years , radiographic evidence of at least 2 of 4 radiographic items ( osteophytes , joint space narrowing , subchondral bone sclerosis , or subchondral cysts ) , and at least 1 of 2 clinical items ( trapeziometacarpal joint enlargement or closure of the first web ) at the trapeziometacarpal joint . Other h and joints could be affected . Exclusion criteria were posttraumatic osteoarthritis , crystal arthritis , inflammatory arthritis , neurologic disorder involving the upper limb , h and or wrist trauma within the past 2 months , previous h and surgery , collagen diseases ( the Dupuytren syndrome , the Marfan syndrome , or the EhlersDanlos syndrome ) , h and or wrist infiltration within 2 months , skin disease interfering with wearing the splint , having already worn a splint for BTOA ( that is , splinting had been previously proposed ) , having bilateral BTOA with no predominant symptomatic side , psychiatric disorder needing treatment adaptation in the past 3 months , inability to speak or write French , and pregnancy . Ethics Approval The local ethics committee approved the study protocol , and all patients gave written informed consent to participate . Intervention Patients were r and omly assigned to receive a custom-made neoprene splint to be worn at night or to usual care . The splint was a rigid rest orthosis recommended for use only at night . It covered the base of the thumb and the thenar eminence but not the wrist ( Figure 1 ) . Splints were made by 3 trained occupational therapists , who adjusted the splint for each patient so that the first web could be opened and the thumb placed in opposition with the first long finger . Patients were encouraged to contact the occupational therapist if they felt that the splint needed adjustment , pain increased while wearing the splint , or they had adverse effects ( such as skin erosion ) . Figure 1 . Dorsal view ( top ) and palmar view ( bottom ) of a custom-made neoprene splint for base-of-thumb osteoarthritis . Because no treatment can be considered the gold st and ard in this situation , patients in the control and intervention groups received usual care at the discretion of their physician ( general practitioner or rheumatologist ) . We decided not to use a placebo because , to our knowledge , no placebo for splinting has achieved successful blinding of patients , as recommended ( 11 ) . Furthermore , use of a placebo could underestimate the treatment effect ( 12 ) . R and omization and Allocation Concealment We r and omly assigned patients who met the inclusion criteria and agreed to participate . The r and omization process was central ized at the coordinating office ( Clinical Research Unit , Cochin Hospital ) , which had no involvement in enrollment , follow-up , or assessment of participants . A statistician made a computer-generated r and omization list ( with a block size of 6 and stratified by center ) at the coordinating office . Once the screening process was complete , the investigator sent a fax to the coordinating office . The coordinating office r and omly assigned the patient to a treatment and faxed the investigator the allocated treatment . Patients r and omly assigned to wear the custom-made neoprene splint were sent information on an appointment time to meet with 1 of the 3 trained occupational therapists to adjust the splint within 1 week after inclusion . Outcome Measures Our primary outcome was change in pain level assessed on a VAS ( 0 to 100 mm ) from baseline to 1 month . Secondary outcomes were change in measures of h and disability at 1 month , as well as change in pain level and measures of disability at 12 months . Two independent , trained physicians of physical medicine and rehabilitation ( who were not involved in patients ' treatment ) assessed several clinical and radiographic ( structural ) variables at enrollment ( baseline ) and at 1 , 6 , and 12 months . Clinical Variables We assessed several clinical variables at each visit . We assessed pain during the previous 48 hours ( VAS , 0 to 100 mm ) . A clinical ly relevant success at the individual level was defined by the following improvement thresholds : greater than 10 , 15 , and 20 mm on a 0- to 100-mm VAS for pain ( 13 ) . H and disability was assessed by using the Cochin H and Functional Scale score ( 0 = low level of disability ; 90 = high level of disability ) ( 3 , 4 , 14 ) . We also assessed patient global perceived disability ( VAS , 0 to 100 mm ) and patient global assessment ( semiquantitative scale of 6 points : worse , the same , weakly improved , fairly improved , much improved , or totally improved ) at 1 , 6 , and 12 months . We considered patients who responded at least fairly as having improved . We assessed pinch strength by using an electronic dynamometer ( Amplifier HDM , Socit Biometrics France , Parc Club Orsay Universit , Orsay , France ) ( 15 , 16 ) . We tested  pinch strength  3 times ( 1 minute apart ) and recorded the highest value , and we also assessed  pain during pinch ( VAS , 0 to 100 mm ) . Thumb mobility , evaluated by the Kap and ji index thumb opposition ( 0 to 10 for each side ) and counter-opposition subscales ( 0 to 4 for each side ) ( 0 = impossible to do ) , was also assessed ( 1719 ) . Closure of the first web ( at baseline and 12 months ) was examined . A photograph of both h and s was taken with the patient sitting on a chair , palms of the h and s and wrists resting on a table in front . We asked patients to put the thumb in maximal abduction ( Figure 2 ) . One physician calculated the angle between the line measured along the medial side of the thumb after the axis of the first and second phalanges and the line measured along the lateral side of the index after the axis of the first and second phalanges by using a goniometer . We assessed intrarater reliability on the 40 first measures as good , with an intraclass correlation coefficient of 0.96 . Figure 2 . First web closure and measurement of maximal abduction . Top . Example of a closure of the first web in base-of-thumb osteoarthritis . Bottom . Measurement of the angle in maximal abduction . The angle between the line measured along the medial side of the thumb after the axis of the first and second phalanges and the line measured along the lateral side of the index after the axis of the first and second phalanges was calculated by using a goniometer . Radiographic Variables Patients had st and ardized radiography of the h and at baseline and 12 months . Images of both h and s , palm down , were taken on the same film . To obtain optimal positioning , we asked patients to sit in front of the radiography table and rest their palms comfortably on the table . One experienced reader ( blinded to treatment allocation and any order of patients undergoing radiography ) assessed the radiographs . We blinded films for date s and names , and baseline and follow-up films were mixed . We assessed radiographic evidence of progression of 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 Fregni F , Imamura M , Chien HF , Lew HL , Boggio P , Kaptchuk TJ , Riberto M , Hsing WT , Battistella LR , Furlan A : Challenges and recommendations for placebo controls in r and omized trials in physical and rehabilitation medicine : A report of the International Placebo Symposium Working Group . Compared with other specialties , the field of physical and rehabilitation medicine has not received the deserved recognition from clinicians and research ers in the scientific community . One of the reasons is the lack of sound evidence to support the traditional physical and rehabilitation medicine treatments . The best way to change this disadvantage is through a well conducted clinical research , such as st and ard placebo- or sham-controlled r and omized clinical trials . Therefore , having placebo groups in clinical trials is essential to improve the level of evidence -based practice in physical and re 
    Output:
    
No significant effect was found at short-term or for different types of splints .
No studies reported HR-QoL. CONCLUSIONS Splinting demonstrated a moderate to large effect for pain and small to moderate effect for function in the medium-term but not in the short term .