***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: Purpose This study aims to assess and compare the value of FDG PET with combined 111In-labeled leukocyte/99mTc-sulfur colloid bone marrow ( WBC/BM ) imaging for diagnosing infection in hip and knee prostheses . Methods In this prospect i ve study , patients with painful hip or knee arthroplasty , who were scheduled to undergo clinical and diagnostic evaluation for prosthesis revision , were included . They have been studied by using FDG PET and WBC/BM scan . This study was institutional review board approved and Health Insurance Portability and Accountability Act compliant . All patients provided written informed consent . Results A total of 134 hip and 87 knee prostheses , suspected of being either infected or noninfectious loosening , were evaluated . All 221 prostheses underwent FDG PET , whereas both  WBC/BM imaging and FDG PET  were performed in 88 prostheses . The initial analysis of data from the WBC/BM images demonstrated somewhat suboptimal results compared with those of FDG PET scans on 88 patients . In addition , some patients were not willing to undergo both procedures and therefore participate in this study . Therefore , a decision was made to eliminate WBC/BM imaging from the procedures for the remainder of this research study . This decision was reached partly because of the significant radiation dose delivered from labeled WBC and safety issues related to preparing these labeled cells . Final diagnosis was based on microbiological examinations of the surgical specimens in 125 prostheses and joint aspirations combined with the clinical follow-up of 6 months or more in 86 prostheses . The sensitivity , specificity , positive predictive value , and negative predictive value of FDG PET  in hip prostheses were 81.8 % , 93.1 % , 79.4 % , and 94.0 % , respectively , and in knee prostheses were 94.7 % , 88.2 % , 69.2 % , and 98.4 % , respectively . The sensitivity , specificity , positive predictive value , and negative predictive value of WBC/BM imaging in hip prostheses were 38.5 % , 95.7 % , 71.4 % , and 84.6 % , respectively , and in knee prostheses were 33.3 % , 88.5 % , 25.0 % , and 92.0 % , respectively . In those cases that underwent both FDG PET and WBC/BM imaging , there was a trend ( P = 0.0625 ) toward a higher sensitivity for FDG PET in hip prostheses , whereas other comparisons did not show any significant differences between the 2 imaging modalities . Conclusions Based on this study , the diagnostic performance of FDG PET scan in detecting infection in painful hip and knee prostheses is optimal for routine clinical application . Considering the complexity and costs of WBC/BM imaging and related safety issues associated with this preparation , FDG PET seems to be an appropriate alternative for assessing these patients In r and omized controlled trials as well as in observational studies , research ers are often interested in effects of treatment or exposure in different subgroups , i.e. effect modification [ 1 , 2 ] . There are several methods to assess effect modification and the debate on which method is best is still ongoing [ 2–5 ] . In this article we focus on an invalid method to assess effect modification , which is often used in articles in health sciences journals [ 6 ] , namely concluding that there is no effect modification if the confidence intervals of the subgroups are overlapping [ 7–9 ] . When assessing effect modification by looking at overlap of the 95 % confidence intervals in subgroups , a type 1 error probability of 0.05 is often mistakenly assumed . In other words , if the confidence intervals are overlapping , the difference in effect estimates between the two subgroups is judged to be statistically insignificant . By using mathematical derivation , we calculated that the chance of finding non-overlapping 95 % confidence intervals under the null hypothesis is 0.0056 if the variance of both effect estimates is equal and the effect estimates are independent ( see Supplemental material for derivation of this probability ) . If the variance of the effect estimates is not equal , the chance of finding non-overlapping 95 % confidence intervals can be calculated by taking into account ρ , i.e. the ratio between the st and ard deviations in the subgroups , σ2/σ1 ( Supplementary material , formula ( 3 ) ) . Figure . 1 shows the relation between ρ and the type 1 error probability if the effect estimates are independent . If the effect estimates are not independent , the correlation coefficient between the effect estimates can also be accounted for ( Supplementary material , formula ( 3 ) ) . Fig. 1 Relation between ρ , which is the ratio of σ2 and σ1 , and the probability of non-overlapping confidence intervals under the null hypothesis ( type 1 error ) To arrive at a type 1 error probability of 0.05 , 83.4 % confidence intervals should be calculated around the effect estimates in subgroups if the variance is equal and the effect estimates are independent ( see Supplementary material for derivation of this percentage ) . If the variance is not equal , ρ should be taken into account ( Supplementary material , formula ( 11 ) ) . Figure . 2 shows the relation between ρ and the level of the confidence interval . If the effect estimates are not independent , the correlation coefficient should be taken into account ( Supplementary material , formula ( 11 ) ) . Adapting the level of the confidence interval can be especially useful for graphical presentations , for example in meta-analyses [ 10 ] . However , it is necessary to explicitly and clearly state which percentage confidence interval is calculated and its meaning should be thoroughly explained to the reader . Many readers will still interpret this ‘ new ’ confidence interval as if it were a 95 % confidence interval , because this percentage is so commonly used . To prevent such confusion , other methods to assess effect modification could be used , such as calculating a 95 % confidence interval around the difference in effect estimates [ 8 ] . Fig. 2 Relation between ρ , which is the ratio of σ2 and σ1 , and the percentage confidence intervals to be calculated to arrive at a type 1 error probability of 0.05 The assumption used in the formulas presented in the appendices is that the effect estimators in the subgroups are normally distributed . Assuming that epidemiologic effect measures , such as the odds ratio , risk ratio , hazard ratio and risk difference , follow a normal distribution , the methods presented can also be used for these epidemiologic measures . Note that the assumption for normality is generally unreasonable in small sample s , but a satisfactory approximation in large sample Aim To analyse the role played by bone scintigraphy in the diagnosis of infected joint prostheses . Methods The study included 77 patients , aged 32–77 years , in whom infection of a joint prosthesis ( 48 hip , 29 knee ) was suspected . In all patients the following examinations were performed consecutively : a two-phase 99mTc methylene diphosphonate ( 99mTc-MDP ) bone scan , a 99mTc hexamethylproplyene amine oxime ( 99mTc-HMPAO ) labelled white blood cell ( WBC ) scan , and a 99mTc microcolloid bone marrow ( BM ) scan . The minimum interval between examinations was 48 h. The diagnoses were based on data obtained from bacteriological cultures . Results The bone scan was positive in all patients and 28 of them had an infection ( sensitivity 100 % , specificity 0 % ) . The  WBC scan was positive in 61 patients but only 27 had an infection . The WBC scan was negative in 16 patients , and the possibility of infection was discarded in 15 of these cases ( sensitivity 96 % , specificity 30 % ) . The results of the bone marrow scan were not compatible with those of the WBC scan  ( suggestive of infection ) in 27 patients : 26 of them had prosthesis infection . The results of both examinations were compatible in the other 34 patients and the possibility of infection was discarded in 33 of these patients ( sensitivity 92.8 % , specificity 98 % ) . The addition of a BM scan to a WBC scan decreased the sensitivity from 96 % to 92.8 % but increased specificity from 30 % to 98 % . The addition of a bone scan to this dual combination did not alter the results . Conclusions When infection of a prosthesis is suspected the diagnostic procedure should start with a WBC scan followed , if positive , by a BM scan . This procedure reduces the cost , the time required for a diagnosis , and the dose of radiation received by the patient Background Synovial fluid biomarkers have demonstrated diagnostic accuracy surpassing the currently used diagnostic tests for periprosthetic joint infection ( PJI ) . Questions / purpose sThe purpose of this study is to directly compare the sensitivity and specificity of the synovial fluid α-defensin immunoassay to the leukocyte esterase ( LE ) colorimetric test strip . Methods Synovial fluid was collected from 46 patients meeting the inclusion criteria of this prospect i ve diagnostic study . Synovial fluid sample s were tested with both a novel synovial-fluid-optimized immunoassay for α-defensin and the LE colorimetric test strip . The Musculoskeletal Infection Society ( MSIS ) definition was used to classify 23 periprosthetic infections and 23 aseptic failures ; this classification was used as the st and ard against which the two diagnostic tests were compared . Results The synovial fluid α-defensin immunoassay correctly predicted the MSIS classification of all patients in the study , demonstrating a sensitivity and specificity of 100 % for the diagnosis of PJI . The α-defensin assay could be read for all sample s , including those with blood in the synovial fluid . The leukocyte esterase test strip could not be interpreted in eight of 46 sample s ( 17 % ) as a result of blood interference . Analysis of the LE strips that could be interpreted yielded a sensitivity of 69 % and a specificity of 100 % . Conclusions The synovial fluid α-defensin immunoassay outperformed the LE colorimetric test strip in this study and provided reliable results even when the LE test strip failed as a result of blood interference . The simple analytic results provided by the α-defensin immunoassay , compared with the more complex and interpretive nature of both the MSIS criteria and LE colorimetric test strip , make it a highly attractive diagnostic tool . Level of Evidence Level II , diagnostic study . See Guidelines for Authors for a complete description of levels of evidence Objective To evaluate clinical efficacy of a dual-time acquisition protocol consisting of early 4 h and delayed 20–24 h imaging with anti-granulocyte scintigraphy ( LeukoScan ) in the diagnosis of infection in painful total knee arthroplasty ( TKA ) . Material s and methods Seventy-eight consecutive patients with TKA ( 12 bilateral ) were prospect ively enrolled in the study from August 2004 to July 2005 . All the patients had clinical and biochemical suspicious of infection , except for the 12 patients with bilateral painless prosthesis who had no signs and symptoms of loosening and /or infection and were considered as controls . TKA prostheses had been implanted 4 months to 9.5 years before our studies . Forty-three patients were on antibiotic therapy  at the moment of scintigraphic examination , and treatment was not discontinued . All patients underwent LeukoScan examination by performing both early 4 h and delayed 20–24 h imaging . In addition to planar imaging SPECT was performed in 18 cases . A decrease in radiotracer uptake from early to delayed LeukoScan imaging was interpreted as an unspecific finding ( negative for infection ) , while an increasing uptake was interpreted as a positive finding for the presence of infection . Three-phase 99mTc-MDP bone scan was also routinely performed by st and ard technique . Sensitivity and specificity of early and delayed LeukoScan imaging were calculated . Results Sensitivity for early and delayed imaging were 92.7 % , while specificity was 78.4 % for early imaging and 100 % for delayed imaging approach . SPECT imaging did not add any significant information as regard to specificity in our experience . Eight false positive early scans were correctly diagnosed as negative at delayed imaging . Three false negative results were recorded . Sensitivity and specificity were similar when patients were on or off antibiotic therapy . Imaging was negative in all 12 controls . Conclusions Our results , based on a large group of patients , suggest that delayed LeukoScan imaging is important in identifying false positive results detect at early imaging . Thus , a dual-time , 4 h early and 20–24 h delayed LeukoScan imaging approach should be recommended to increase the diagnostic accuracy of the scintigraphy , with the exception of patients with a negative early LeukoScan examination , in whom the acquisition of delayed imaging appears unnecessary . In our experience , concomitant antibiotic therapy did not influence the diagnostic value of LeukoScan UNLABELLED The objectives of this study were to investigate (18)F-FDG imaging , using a coincidence detection system , for diagnosing prosthetic joint infection and to compare it with combined (111)In-labeled leukocyte/(99m)Tc-sulfur colloid marrow imaging in patients with failed lower extremity joint replacements . METHODS Fifty-nine patients --with painful , failed , lower extremity joint prostheses , 40 hip and 19 knee -- who underwent (18)F-FDG , labeled leukocyte , and bone marrow imaging , and had histopathologic and microbiologic confirmation of the final diagnosis , formed the basis of this investigation . (18)F-FDG images were interpreted as positive for infection using 4 different criteria : criterion 1 : any periprost 
    Output:
    
Conclusions Based on current evidence , antigranulocyte scintigraphy and combined leukocyte and bone marrow scintigraphy appear to be highly specific imaging modalities in confirming periprosthetic knee infection .
Bone scintigraphy was a highly sensitive imaging technique but lacks the specificity needed to differentiate among various conditions that cause painful knee prostheses .
FDG-PET may not be the preferred imaging modality because it is more expensive and not more effective in confirming periprosthetic knee infection .