Only controlled blocks are capable of confirming the zygapophysial joints (ZJ) as the pain generator in LBP patients. However, previous workers have found that a cluster of clinical signs ("Revel's criteria"), may be valuable in predicting the results of an initial screening ZJ block. It was suggested that these clinical findings are unsuitable for diagnosis, but may be of value in selecting patients for diagnostic blocks of the lumbar ZJ's. To constitute evidence in favour of a clinical management strategy, these results need confirmation. This study evaluates the utility of 'Revel's criteria' as a screening tool for selection of chronic low back pain patients for controlled ZJ diagnostic blocks.This study utilized a prospective blinded concurrent reference standard related validity design. Consecutive chronic LBP patients completed pain drawings, psychosocial distress and disability questionnaires, received a clinical examination and lumbar zygapophysial blocks. Two reference standards were evaluated simultaneously: 1. 75% reduction of pain on a visual analogue scale (replication of previous work), and 2. abolition of the dominant or primary pain. Using "Revel's criteria" as predictors, logistic regression analyses were used to test the model. Estimates of sensitivity, specificity, predictive values and likelihood ratios for selected variables were calculated for the two proposed clinical strategies.Earlier results were not replicated. Sensitivity of "Revel's criteria" was low sensitivity (<17%), and specificity high (approximately 90%). Absence of pain with cough or sneeze just reached significance (p = 0.05) within one model."Revel's criteria" are unsuitable as a clinical screening test to select chronic LBP patients for initial ZJ blocks. However, the criteria may have use in identifying a small subset (11%) of patients likely to respond to the initial block (specificity 93%). It is estimated that 15 – 40% of chronic low back pain patients have pain arising from the lumbar zygapophysial joints (ZJ). PreviouBecause prognosis for acute low back is good, invasive and expensive and invasive diagnostic testing cannot be justified. However, persistent disabling pain needs more intensive investigation in order to determine appropriate management strategies. Back pain of ZJ origin may be treated using intra-articular steroid injection,10., or The current study objectives were to estimate the predictive value of the two clinical strategies of Revel et al (1998), using similar measurement parameters (75% reduction in pain VAS after ZJ block), and apply alternative analytic methods to explore any potential utility of the variables used.This study utilized a prospective, blinded, concurrent, reference standard-related validity design with intra-articular ZJ or medial branch blocks as the reference standard against which clinical variables were compared. Local Institutional Review Board approval was granted at the beginning of the study. A 75% or more reduction in pain following ZJ block on pain VAS was designated as reference standard A, the same standard used by Revel et al (1998). Based on pain drawings and patient self-report, complete abolition of the patient's primary or dominant pain was designated as reference standard B. Dominant pain location was acquired by pain drawing and direct questioning, and documented prior to clinical examination and diagnostic injection in a prospective manner. Post injection dominant pain location was acquired by reference to pain drawings and direct questioning also.Patients with low back pain with or without lower extremity symptoms, referred to a private radiology practice in New Orleans, USA specializing in the diagnosis of spinal pain, were invited to participate in the study. Patients receiving ZJ blocks were either referred specifically for that procedure or had the procedure included in their radiology examination based on pre-injection clinical evaluation by the injectionist (CA). Between May 2001 and October 2002, physical therapists attended the clinic in blocks that ranged from 4 to 8 weeks (ML) and examined patients. Normal scheduling was not affected by the presence of the visiting therapists, so patients were consecutive during these periods. All patients had undergone imaging studies prior to referral from a variety of medical and paramedical practitioners. Some were self-referred.Patients were excluded from the study if they were unwilling to participate, were too frail to tolerate a physical examination, or were deemed by any member of the clinic team to be unable to comprehend the study procedure. Prior to the formal clinical examination, clinic staff recorded basic demographic and medical data.100 mm visual analog scales (VAS) scales for current, best and worst pain. A current pain VAS was repeated after the clinical examination and following ZJ blocks. The 23-point Roland-Morris Disability Questionnaire  was compHistory taking and a structured physical examination were carried out by a physical therapist with 30 years of clinical experience as a manipulative therapist (ML). Some patients were examined by a physical therapist with 17 years experience (SBY). The clinical examination occupied 30 to 60 minutes and included many tests besides those necessary for the current analysis, as part of a larger project. Inconclusive findings or incomplete examinations were documented. The physical examination included a visual assessment of range of motion, recording anatomical location of dominant pain, nerve tension tests, key muscle strength tests, tendon reflex tests, light touch sensitivity, a McKenzie styled ePrior to ZJ blocks, the radiologist reviewed case notes and imaging studies, and conducted a physical examination that guided the type of diagnostic procedure to be employed and the target structures. Intra-articular ZJ joint injection or MBB using standard technique was carrPhysical therapists conducting the clinical examination were blinded to the results of previous imaging studies and diagnostic injections, the Roland, Zung and MSPQ questionnaires. The injectionist was blinded to the results of the physical therapy examination and diagnostic conclusions.Basic statistical values for demographic variables and regression analyses were calculated using statistics software (Minitab version 13.31 © Minitab Inc 2000). Differences between included and excluded patients were evaluated with the student's t, chi square, and Kruskal-Wallis tests where appropriate. Significance for differences was set at p < 0.05.Calculations of sensitivity, specificity, predictive values and likelihood ratios with 95% confidence intervals were performed using Confidence Interval Analysis software © Bryant T.N. 2000.Initial ZJ blocks were carried out on 151 chronic low back pain patients. Thirty-four patients were excluded from analysis as they received another intervention in the same procedure session and did not return for differentiating and confirmatory blocks. One case was excluded through incomplete data on Revel's criteria. Following ZJ block, 27 of 116 patients satisfied reference standard A. Data required for determination of Reference standard B were missing for five of the 116 cases. Eighteen of these 111 patients satisfied reference standard B. Table In specifically evaluating Revel's criteria against reference standard A, logistic regression failed to achieve significance as a model . Two variables; "absence of pain with coughing and sneezing" and "no exacerbation of pain rising from flexion", showed a trend towards significance as predictors within the model (p = 0.07).Using Revel's criteria within a logistic regression with reference standard B as the response variable, a strong trend towards significance was reached . One component variable (age over 65) individually reached significance within the model: . In the whole sample 12.5% were aged over 65 years whereas of the 19 positive responders six were over 65 years (31.6%).The same patients satisfied both strategies of Revel et al. Estimated sensitivity, specificity, predictive values and positive likelihood ratios for both strategies of Revel et al are presented in Table Of the 27 patients satisfying reference standard A, 13 (48%) returned for confirmatory ZJ blocks. Three of these reported 75% or more reduction in pain following the confirmatory block. None of the three patients with confirmed ZJ pain satisfied Revel's criteria.The current data produces results that are in stark contrast to those of Revel et al (1998) with sensitivity low and specificity high. However, 'no pain with cough and sneeze' and 'no exacerbation of pain rising from flexion' approached statistical significance in relation to a 75% reduction pain after ZJ block (reference standard A). These variables are in line with Revel's results. Age over 65 is associated with reference standard B (abolition of primary pain). Likelihood ratios for the criteria are lower in the current data also. Some of the differences in results may be explained by a number of factors:1. Revel et al's study was a placebo controlled design whereas we did not routinely utilize a similar or equivalent control.2. The patients in Revel et al's sample were older (mean 58 versus 43 years), and had a shorter duration of symptoms (mean 78 versus 160 weeks).3. It is also possible that the high level of standardization when acquiring the criteria data in the current study, and the prospective methodology might have contributed to the differences in results.Following anaesthetic blocks, patients frequently state that the pain prompting consultation is abolished, yet a post-procedure pain VAS still registers more than 0/100. In this study reference standard B was evaluated as an alternative to the usual standard, so that pain in areas above the lumbar spine or pain directly attributable to the needle insertion site do not result in inappropriate post procedure VAS scores. In the interests of developing more precise instruments documenting results of diagnostic blocks, we propose that in future studies, the VAS scale should specifically refer to the primary pain complaint for which the diagnostic block is undertaken.Based on the current data, Revel's criteria are not suitable as a screening test to select patients suitable or unsuitable for an initial screening ZJ block. Such a screening device should have high sensitivity to ensure that most patients likely to respond are included in the initial diagnostic block. Our study suggests that, at best, Revel's criteria, might identify a small subset (11%) of patients likely to respond to a screening block (specificity 93%).Neither strategy utilizing Revel's criteria is suitable as a clinical screening device for selection of chronic LBP patients for initial diagnostic ZJ blocks. In contrast to Revel's findings, the current data demonstrated low sensitivity and high specificity for these clinical criteria. The high specificity of the criteria reported in this study relates to a single uncontrolled screening block. Consequently these criteria can not considered diagnostic of painful lumbar ZJ. Only placebo controlled or double ZJ blocks are able to diagnose this source of low back pain.The author(s) declare that they have no competing interests.ML conceived the design of the study, examined all but 10 patients, carried out data analysis and prepared the manuscriptBÖ assisted in project design and manuscript preparationCNA assisted in project design, provided facilities and conducted fluoroscopically guided injectionsBMcD carried out data analysis and assisted in manuscript preparation.All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Uncertainty regarding comorbid illness, and ability to tolerate aggressive therapy has led to minimal enrollment of elderly cancer patients into clinical trials and often substandard treatment. Increasingly, comorbid illness scales have proven useful in identifying subgroups of elderly patients who are more likely to tolerate and benefit from aggressive therapy. Unfortunately, the use of such scales has yet to be widely integrated into either clinical practice or clinical trials research.This article reviews evidence for the validity of the Charlson Comorbidity Index (CCI) in oncology and provides a Microsoft Excel (MS Excel) Macro for the rapid and accurate calculation of CCI score. The interaction of comorbidity and malignant disease and the validation of the Charlson Index in oncology are discussed.The CCI score is based on one year mortality data from internal medicine patients admitted to an inpatient setting and is the most widely used comorbidity index in oncology. An MS Excel Macro file was constructed for calculating the CCI score using Microsoft Visual Basic. The Macro is provided for download and dissemination.The CCI has been widely used and validated throughout the oncology literature and has demonstrated utility for most major cancers. The MS Excel CCI Macro provides a rapid method for calculating CCI score with or without age adjustments. The calculator removes difficulty in score calculation as a limitation for integration of the CCI into clinical research. The simple nature of the MS Excel CCI Macro and the CCI itself makes it ideal for integration into emerging electronic medical records systems.The increasing elderly population and concurrent increase in oncologic disease has made understanding the interaction between age and comorbid illness on life expectancy increasingly important. The MS Excel CCI Macro provides a means of increasing the use of the CCI scale in clinical research with the ultimate goal of improving determination of optimal treatments for elderly cancer patients. Comorbid illness plays an essential, but poorly defined, role in the diagnosis and management of malignant disease. Increasingly, the importance of measuring comorbidity in consistent and quantifiable ways is being recognized. This movement has stemmed in part from a growing consensus that comorbidity confounds the results of clinical trials and limits the generalization of results to older and sicker patients ,2. For vWhile multiple comorbidity indices are available, each with unique advantages and disadvantages, no single index has emerged as clearly superior to the others. In fact, we have noted that a distinct trade-off between prognostic utility and ease of use exists. We believe that a scoring system that maximizes ease of use while maintaining prognostic validity represents the optimal balance required for use in clinical research. In addition, a scoring system that can be easily integrated into an electronic medical record will further promote the widespread use of comorbidity data. We have, therefore, chosen to explore the use of the Charlson Comorbidity Index (CCI) as the prototypical comorbidity index in our department. The primary aim of this article, therefore, is to provide an electronic Charlson Comorbidity Index Scoring program and explain its development and use. In an effort to provide the reader with the context in which the electronic application was developed and should be used, the interaction of comorbidity and malignant disease and the validation of the Charlson Index in oncology are discussed. For more detailed reviews of the comorbidity indices outlined in this article, the authors refer readers to three systematic reviews of comorbid illness scoring systems by Extermann and de Groot -4.In the 1960's, Feinstein initially reported the prognostic importance of patient-related characteristics, such as symptomatology and concurrent illness, in his analyses of differences between actual survival outcomes and those predicted by TNM-based staging among lung cancer patients . In receHall, et al, for example, evaluated the effect of comorbidity on survival among head and neck cancer patients, concluding that 16% of mortality at 3 years and 18% at 5 years was attributable to comorbid illness alone, with non-cancer causes of death exceeding cancer-related causes of death after 7.5 years [Comorbidity has also demonstrated marked predictive power for survival and treatment allocation among prostate cancer patients. A Netherlands cancer registry study, for example, identified comorbidity as the single most important prognostic factor for 3-year survival, with hazard ratios of 2.0 (95% CI = 1.0–4.3) for a single comorbid illness and 7.2 (95% CI = 3.1–16.6) for 2 or more comorbid conditions, and trends toward fewer radical prostatectomies among men with higher degrees of comorbidity . Total cAlthough the preceding examples are not intended to provide a comprehensive review of the influence of comorbidity on survival and treatment-related complications in oncology, they provide a clear demonstration of the effect. In addition, the themes of increasing comorbidity with age and the influence of comorbidity on outcomes and treatment decision-making are illustrated. With these interactions in mind, the investigation of comorbidity has become an area of increasing interest in our department. In particular, we have begun focusing on the use of comorbidity indices and their application in clinical research. For a variety of reasons, which will be explained in forthcoming sections of this work, we have focused on the Charlson Comorbidity Index as the prototypical index on which to base this research.The Charlson Index was developed in 1987 based on 1-year mortality data from internal medicine patients admitted to a single New York Hospital and was initially validated within a cohort of breast cancer patients. The index encompasses 19 medical conditions weighted 1–6 with total scores ranging from 0–37. In the development phase of the index, mortality for each disease was converted to a relative risk of death within 12 months. A weight was then assigned to each condition based on the relative risk (RR); for example, RR <1.2 = weight 0, RR ≥ 1.2<1.5 = weight 1, RR ≥ 1.5<2.5 = weight 2, RR ≥ 2.5<3.5 = weight 3, and for 2 conditions (metastatic solid tumor and AIDS) = weight 6.From the weighted conditions, a sum score can be tallied to yield the total comorbidity score. The CCI can be further adapted to account for increasing age. In the validation phase of the CCI, age was also found to be an independent risk factor for death from a comorbid condition. As a result, relative risk was calculated to increase by 2.4 for each additional decade of life. In the same cohort, the relative risk of death for each 1-point increase in CCI score was 2.3. To account for the effects of increasing age, one point can be added to the CCI score for each decade of life over the age of 50 .Reviews of the CCI suggests it has good reliability, excellent correlation with mortality and progression-free survival outcomes, and is easily modifiable, particularly to account for the effect of age. The CCI's basic limitations include preservation of data only for the 19 conditions listed in the index, the exclusion of non-malignant hematologic disease, such as anemia, and reduced predictive ability for outcomes < 6-months. The CCI is praised for its ease of use, short rating time, extractability from other indices, and widespread use ,3.Statistical criteria for the assessment of the validity of a test include content validity, criterion validity, construct validity, and reliability . AlthougIn a review of validity among comorbidity indices, de Groot, et al, systemically identified articles referring to comorbidity between 1966 and 2000. They compared the Charlson Index with the Cumulative Illness Rating Scale (CIRS), Kaplan-Feinstein Index (KFI), and Index of Coexistent Disease (ICED) and identified correlation coefficients of > 0.40, "good" test-retest reliability and "moderate to good" inter-rater reliability for the CCI [A similar review by Extermann suggests the Charlson Index possesses excellent validity and reliability for use in clinical research in oncology. Extermann also reported exceptional predictive validity, correlating the CCI with outcomes involving mortality risk from weeks to years, postoperative complications, length of hospital stay, discharge to nursing home, and progression-free survival among cancer patients. Additionally, inter-rater reliability, by various measures, was reported at 0.74 among a cohort of older general oncology patients and 0.945 within a group of elderly breast cancer patients. Test-retest reliability was also good, ranging from 0.92 among surgical patients and 0.86 among the previously mentioned group of elderly oncology patients. Although Extermann urges some caution based on the tendency of the CCI to result in comorbidity scores that are sometimes lower than those observed with other indices, she concludes that the CCI is easy to use and "highly suitable for vast cohort studies but may under-detect significant problems resulting in non-lethal endpoints" [2 = 163, p < 0.0001), with CCI scores of 0, 1, 2, and 3 predicting 10-year survival rates of 93%, 73%, 52%, and 45%, respectively. In the original manuscript, Charlson, et al, cautioned that their index should be considered preliminary and that it required validation in larger populations [The Charlson Index has demonstrated excellent predictive validity for a variety of clinical outcomes as well as numerous malignancies. As discussed previously, the CCI was developed using a prospective analysis of 1-year mortality rates among internal medicine patients and then validated within a population of 588 breast cancer patients. In the validation phase of Charlson's original study, increasing CCI scores were significantly correlated with increased 10-year mortality within a breast cancer cohort , and increased risk of cancer death (RR = 2.35) for patients with advanced (≥ 2) CCI scores. The CCI compared similarly to the KFI with respect to frequency of advanced comorbidity (30% for CCI and 32% for KFI) and prognostic power . However, the CCI was more applicable to the study population than the KFI, with the KFI successfully applied to only 80% of the study population compared with 100% application of the CCI .Fowler, et al, also examined the validity of the Charlson index in a cohort of men with prostate cancer treated with EBRT or RP. After adjusting for age, a direct relationship between actuarial survival and CCI score (p = 0.00001) was found for all patients. Among individuals with CCI scores of 0, 5 and 10-year survival rates were 86% and 66% compared with 40% and 9% for patients with CCI scores of 3 to 5. Relative mortality risk, based on CCI scores of 0, 1, 2, and 3–5, increased from 1 to 1.7, 2.6, and 5.7, respectively .Additional studies among prostate cancer patients have compared the CCI, KFI, and ICED. Albertsen, et al, for example, found each of the three comorbidity indices had similar power to predict survival (p < 0.001 for each), with the addition of any of the three indices to Gleason score improving predictive power for survival over Gleason score alone . We alsoThe Charlson Index has also been validated as a prognostic indicator for survival in lung cancer cohorts. Firat, et al, recently explored the prognostic importance of comorbidity among patients undergoing surgical resection or definitive EBRT for clinical NSCLC. Within the combined group, both CIRS-G scores ≥ 4 (p < 0.001) and Charlson score ≥ 2 (p = 0.004) emerged as significant prognostic indicators of reduced overall survival. Examination of the surgical and EBRT groups separately also demonstrated higher CIRS-G and Charlson scores within the EBRT group as compared with the surgical group .The effect of comorbidity on complication rates among lung cancer patients has also been investigated. Brim, et al, for example, identified gender, CCI score 3–4, COPD, and prior tumor within the last 5 years as predictors for major complications . Charlson scores of 3–4 maintained statistical significance after multivariate regression  .CCI scores have also demonstrated prognostic value, both in terms of postoperative complications and survival among colon cancer patients. Rieker, et al, found raw CCI scores reached 0–2, 3–4, and ≥ 5 in 66%, 25%, and 8% of patients, respectively. With respect to survival, CCI score >2 emerged as a poor prognostic indicator for overall survival for all stages . Subgroup analysis of stage III and IV patients revealed reduced cancer-specific survival among patients with CCI score >2 (log rank p <0.005). CCI scores > 2 were also correlated with receipt of blood transfusion , postoperative complications , and ICU stay > 2 days  .Taken together, this series of papers represents a diverse and relatively large experience with the Charlson Index. In each report, CCI scores consistently correlate with disease specific survival, overall survival, or treatment-related complications, confirming its predictive validity.The CCI Calculator provided with this manuscript is based on the original index proposed by Charlson, et al, and is available in the section: supplementary material/table 1/appendix 1 [see Presented as a simple Microsoft Excel tool, it can be easily extended or integrated with other systems that can import Microsoft Excel data, or imported as a flat file. The Calculator functions well with both MS Windows and Macintosh operating systems running any Microsoft Excel version with Macro capabilities and is free to all users of Biomed Central Cancer. There are no restrictions concerning the use of the calculator software. A running CCI score can be calculated by selecting the conditions and age groups within the file. The calculator can be used with or without age modification as proposed by Charlson, et al . It is iTo use the calculator, the user must select "enable macros" when prompted to do so as the file opens. To calculate a CCI score, any of the applicable conditions can be selected. All selected conditions will then be displayed in a lighter shade within the table. Corrections can be made by deselecting conditions, which then removes their weighted value from the score. The CCI score can then be totaled, or an age-modified score can be determined by selecting any one of the applicable "Age by Decade" groups. Scores totaled without age modification will appear in the "Age Unadjusted CCI Score" total and no value will appear in the "Age Adjusted Score" total. Scores totaled by selecting an age group without selecting a comorbidity will result in no value for either total and the user will be prompted to "Reset & Select Condition." To reset the program, the "Reset CCI Calculator" button can be selected. The calculator can be further modified as needed by changing entries in the "Data Sheet" area of the workbook which is hidden in the read-only version of the calculator, but can be unhidden by selecting "Format," then "Sheet," followed by "Unhide" from the Excel menu. The "Data Sheet" can then be selected and will be viewable. To modify the original Macro, users can contact the authors and the password will be provided on a case-by-case basis.The extensive validation of the CCI as a powerful predictor of clinical outcome combined with its simplicity and widespread use in oncology have led to the adoption of the Charlson Index as the prototypical comorbidity index in our department. In addition to validity, our criteria for the use of a comorbidity index focus on simplicity in design, consistency in scoring, and ease of use. It is our contention that many of the commonly used comorbidity indices, such as the ICED, CIRS, and KFI have failed to achieve widespread use because they remain complicated, cumbersome to use, and poorly accessible for use in clinical research. Given the adaptability of the CCI for the inclusion of additional variables, such as age, the CCI also demonstrates marked potential for modification into cancer specific comorbidity indices. We have, therefore, developed a Charlson Comorbidity Calculator based on a Microscoft Excel File to improve the collection of comorbidity data in our department.) also require training courses for effective use [Comorbid illness has demonstrated increasing importance as a prognostic factor for survival and treatment-related outcomes in oncology. It confounds the results of clinical trials because the lack of a standardized measurement has resulted in the failure to adjust for comorbidity in statistical analysis of outcomes data ,2. It altive use . By contThe use of comorbidity data in clinical research is at an important crossroads, with necessity of its use becoming imperative as electronic capabilities for its assessment become more feasible. As the US population gets older, the use of comorbidity data in clinical trials will only increase in relevance. Current estimates indicate that the elderly will comprise 20% of the population by the year 2030 . StudiesFurthermore, evidence to suggest that comorbidity and performance status represent independent prognostic factors is accumulating. Extermann, et al, for example, examined the relationship between comorbidity and performance status. Both Charlson and CIRS-G were found to have little or no correlation with ECOG performance status, activities of daily living (ADL), or instrumental activities of daily living (IADL). More recently, Repetto, et al, found that among 269 elderly cancer patients with a reported ECOG performance score of <2, 13% had 2 or more comorbidities, 9.3% had ADL limitations, and 37.7% had IADL limitations. Although a statistical correlation between ECOG performance status, number of comorbidities, and comprehensive geriatric assessment was identified in univariate analysis, only comorbidity, ADL limitation and IADL limitation maintained statistical significance in multivariate analysis. Firat, et al also found CIRS-G and Karnofsy performace status to be independent predictors of outcome in their analysis of prognostic factors in 112 patients enrolled on 4 RTOG trials of stage III lung cancer [Without widespread integration of comorbidity data into clinical research, an increasing number of elderly patients, and their physicians, will be left with treatment recommendations and outcomes data that lack relevance for their age and level of comorbidity.Concurrently, electronic medical records (EMR) and data collection systems are becoming increasingly common and easy to use, with EMR use among European countries approaching 60% to 90% . The EMRTo our knowledge, this is the first electronic data collection system offered for the Charlson Comorbidity Index. The simplicity of the index itself, coupled with the simplicity of MS Excel and the Visual Basic programming language, have resulted in a robust electronic CCI calculator that functions well across both Windows and Macintosh platforms. The latest version of the calculator, which is provided with this manuscript, has performed without error consistently on the first (WH), second (RR) and third (SN) authors' Windows-based PCs.The major limitations of the CCI calculator lie in the limitations known to comorbidity indices and to the index itself. These include lack of understanding as to the relative importance of various individual conditions on mortality, treatment-related complications and quality of life. Furthermore, failure to include some conditions with particular relevance to cancer patients, such as non-malignant hematopoietic disorders and thromboembolic disorders, as well as uncertainty as to whether a few specific diseases or the overall disease burden is more important for prognosis, remain important considerations limiting use of the CCI ,3. AdditDespite its limitations, the general oncology literature supports the use of CCI as a prognostic variable in clinical research. It should be emphasized that the CCI is not meant to replace clinical experience and its use in clinical decision-making should be considered investigational. With additional research, CCI methodological limitations can be addressed and the index modified to improve upon its utility. In an effort to improve our understanding of the CCI and identify areas of the index in need of improvement, we are currently investigating the effect of score thresholds on treatment decision-making among prostate cancer experts. We believe that dissemination of the MS Excel CCI Macro will lead to increased use of the CCI for clinical research purposes as well as modification of the CCI to increase its validity and clinical utility. Ultimately, we hope that the comorbidity indices, such as the CCI, will see widespread use in clinical research and eventual integration into EMRs as a result of these efforts.The Charlson Comorbidity Index has demonstrated excellent predictive validity in numerous cancer-related outcome studies. It has met the criteria for statistical validity as outlined by several authors. In our opinion, the CCI represents the optimal balance between ease of use and prognostic ability. Its simplicity in design also makes its adaptation to include additional variables extremely feasible. We have, therefore, adopted the CCI as an acceptable comorbidity measurement tool in our department and created a Microsoft Excel Macro to facilitate its correct and uniform use in clinical research.Project name: Charlson Comorbidity Calculator• Project home page: None• Operating system(s): Windows or Macintosh OS• Programming language: Visual Basic• Other requirements: Microsoft Excel (macro enabled)• License: None• Any restrictions to use by non-academics: None• CCI: Charlson Comorbidity Index• ICED: Index of Co-Existent Disease• KFI: Kaplan-Feinstein Index• CIRS: Cumulative Illness Rating Scale• RR: Relative Risk• EMR: Electronic Medical Record• CDSS: Computer-Based Decision Support Services• The author(s) declare that they have no competing interests.WH, SN, AJ, and SV carried out the literature review, assembly and editing of the manuscript. RR created the CCI calculator. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:A Microsoft Excel  is included with this manuscript and can be found in supplementary material/table 1/appedix 1. A detailed description of the creation of the file and instructions for its use are included in the implementation section of this manuscript. To Calculate a Charlson Comorbidity Index score using the calculator double click on the CCI-Calc.xls icon or open the file from MS Excel. You must select "enable macros" when prompted to do so by the MS Excel macro warning pop-up window. A CCI score can then be calculated by selecting the conditions and age groups within the file. Selected conditions will appear in the table as a lighter shade than deselected conditions. As comorbidities are selected a running total of the score will be calculated. Scores totaled without age modification will appear in the "Age Unadjusted CCI Score" total and no value will appear in the "Age Adjusted Score" total. A selected condition can be deselected by clicking on once on the button for that condition. A score may be calculated without selecting an age category, however Scores totaled by selecting an age group without selecting a comorbidity will result in no value for either total and the user will be prompted to "Reset & Select Condition." Once finished with a calculation, the calculator can be reset by selecting the green "Reset CCI Calculator" button. The file is presented in a password protected format so that no changes can be made to the categories and weighting as proposed in the original Charlson Comorbidity Index.Click here for file


Until recently the most accepted technique of doing root canal treatment stresses multiple visit procedure. Most schools also concentrated upon teaching the multi-visit concept. However, it has now been reported that the procedure of single visit treatment is advocated by at least 70% of schools in all geographical areas. It was therefore the aims of the present study to find the incidence of post-obturation flare-ups following single and multiple visit endodontic treatment procedures, and to establish the relationship between pre-operative and post-obturation pain in patients referred for endodontic therapy in a Nigerian teaching Hospital.st, 7th and 30th day. The presence or absence of pain, or the appropriate degree of pain was recorded for each recall visits and the interval between visits. The compiled data were analysed using chi-square where applicable. P level ≤ 0.05 was taken as significant.Data collected included pulp vitality status, the presence or absence of pre-operative, inter-appointment and post-obturation pain. Pain was recorded as none, slight, or moderate/severe. Flare-ups were defined as either patient's report of pain not controlled with over the counter medication or as increasing swelling. The patients were recalled at three specific post-obturation periods, 1Ten endodontic flare-ups (8.1%) were recorded in the multiple visit group compared to 19 (18.3%) flare-ups for the single visit group, P = 0.02. For both single and multiple visit procedures, there were statistically significant correlations between pre-operative and post-obturation pain (P = 0.002 and P = 0.0004 respectively). Teeth with vital pulps reported the lowest frequency of post-obturation pain (48.8%), while those with nonvital pulps were found to have the highest frequency of post-obturation pain (50.3%), P = 0.9.The present study reported higher incidences of post-obturation pain and flare-ups following the single visit procedures. However, single visit endodontic therapy has been shown to be a safe and effective alternative to multiple visit treatment, especially in communities where patients default after the first appointment at which pain is relieved. Until recently the most accepted technique of doing endodontic treatment stresses multiple visit procedures. Most schools also concentrated upon teaching the multi-visit concept. However, it has now been reported that the procedure of single visit treatment is advocated by at least 70% of schools in all geographical areas .Some of the problems of root canal treatment are post-obturation pain, inter-appointment pain and swelling. Although these in most cases do not last long, but could be a source of embarrassment to the dentist and annoying for the patient, more so if the tooth was symptomless before the commencement of treatment. Literature review revealed varied opinions on the incidence and severity of post-obturation pain. Some authors reported slightly more post-obturation pain following single visit than with multiple visit procedures ,3. Otherst, 7th, and 30th post-obturation days, and to compare these results with those reported in previous studies.Endodontic treatment in Nigeria is carried out in the department of restorative dentistry of the four dental schools and in few private dental clinics located in major cities, health centres and general hospitals. Previous report revealed that few cases of root canal treatment were undertaken and that root canal treatment was completed in multiple visits, specifically three visits for about half the teeth treated . ReasonsConsenting patients referred to the department of Restorative Dentistry for root canal therapy within a period of twelve months were randomly assigned for either single visit or multiple visit procedures. For the multiple visit procedures, Patients that defaulted after the first appointment (incomplete treatment) were excluded from the study. For each tooth treated, the clinical factors and conditions existing before, during and after the completion of treatment were recorded. This data included pulp vitality status, the presence or absence of pre-operative pain, post-obturation flare-ups and degree of post-obturation pain. For patients requiring root canal treatment on more than one tooth, the treatment of each tooth was separated by a period of at least four weeks to allow for proper evaluation. The pulp vitality was determined by an electric pulp tester  in combination with the presence of pulpal haemorrhage.st, 7th and 30th day. At each post-obturation recall visit, the patients were interviewed to determine whether or not there were symptoms at the present visit and whether or not there had been symptoms during the interval between the present visit and the previous one. The presence or absence of pain, or the appropriate degree of pain was recorded for each recall visit and the interval between visits. Pain was recorded as none, slight, or moderate/severe. Slight pain was defined as any discomfort no mater how brief in duration that did not require medication and that did not impair masticatory function in any way. Moderate/severe pain was defined as pain requiring medication or other palliative treatment. Impairment of masticatory function (discomfort in chewing) was recorded as moderate/severe pain. Endodontic flare-ups were defined as either patient's report of pain not controlled with over the counter medication and or increasing swelling.The patients were recalled at three specific post-obturation periods, the 1The root canals were obturated with multiple gutta-percha cones and a zinc oxide-eugenol based sealer, using the lateral condensation technique. The compiled data were analysed using chi-square where applicable. P level ≤ 0.05 was taken as significant.st post-obturation day, of these 107 were completed in single visit and 136 were completed in multiple visit. Eighty-six (86) had vital pulps and 157 had nonvital pulp canal contents. Two hundred and twenty seven (227) reported for check-up on the 7th post-obturation day, of these 104 was completed in single visit and 123 completed in multiple visit. Two hundred and twenty two reported for check-up on the 30th post-obturation day, 102 completed in single visit and 120 in multiple visit.Two hundred and eighty three (283) teeth in 255 patients were treated in all, given a ratio of 1.11 teeth per patient. Of these 56 were excluded from the study due to non-availability of patients at post-obturation recall visit. These exclusions were randomly distributed between treatment groups, with no differential loss to follow-up . The treatment groups were fairly comparable, with similar distribution of tooth types between treatment groups, Table 2 = 9.04, p = 0.002). For the multiple visit procedures, 88 teeth presented with pre-operative pain out of which 55 (62.5%) reported post-obturation pain. 48 teeth had no pre-operative pain out of which 6 (12.5%) had post-obturation pain . These show that for both single and multiple visit procedures, there were statistically significant correlations between pre-operative and post-obturation pain , that is patients presenting with pain not controlled by over the counter medication and or increasing swelling, were recorded in the multiple visit group compared to 19 18.3%) flare-ups for the single visit group. This shows a significant difference , Table % flare-uTeeth with vital pulps reported the lowest frequency of pain 48.8%), while those with nonvital pulps were found to have the highest frequency of pain (50.3%), Table 8.8%, whist and 7th days respectively 35.5% and 16.3% were higher than those in the multiple visit group 30.2% and 9.8%. Chi square test indicated no statistically significant differences  whose pulps were non-vital.Many authorities in the field of endodontics advice against the completion of root canal treatment in single visit in order to prevent post-obturation pain, especially in cases presenting with pre-operative pain ,12.In the present study more flare ups occurred in the single visit group (18.3%) than in the multiple visit group (8.1%), showing a disadvantage for single visit treatment at a 95% confidence level, Table . This isPrevious studies have shown that there is a strong positive correlation between pre-operative and post-obturation pain ,14,15. Tth day in both groups, these present a strong indication that practitioners should not overreact to early post-obturation symptoms by immediately initiating endodontic retreatment procedures or extraction of the involved tooth. Apart from the reported higher incidence of flare-ups in the single visit group, the post-obturation pain experienced by the patients in both groups compares favourably well with each other. Therefore the higher incidence should not be taken as condemnation for the single visit endodontic therapy, it should however stress the fact that a thorough understanding of the basic endodontic principles is important in considering each case on an individual basis before making a decision as to whether or not it can be completed in one visit [Despite the high percentages of post-obturation pain reported on the first post-obturation day in both groups Table , seven dne visit . As it iThe present study reported higher incidences of post-obturation pain and flare-ups following the single visit procedures. However, single visit endodontic therapy has been shown to be a safe and effective alternative to multiple visit treatment, especially in communities where patients default after the first appointment at which pain is relieved.The author(s) declare that they have no competing interests.AOO conceived of the study, participated in its design, performed the statistics, and participated in the final write-up of the manuscript. CIU participated in the design, collected the data, drafted the initial manuscript, and participated in the final write-up of the manuscript.The pre-publication history for this paper can be accessed here:


Complex Regional Pain Syndrome type one (CRPS I) or formerly Reflex Sympathetic Dystrophy (RSD) is a disabling syndrome, in which a painful limb is accompanied by varying symptoms. Neuropathic pain is a prominent feature of CRPS I, and is often refractory to treatment. Since gabapentin is an anticonvulsant with a proven analgesic effect in various neuropathic pain syndromes, we sought to study the efficacy of the anticonvulsant gabapentin as treatment for pain in patients with CRPS I.We did a randomized double blind placebo controlled crossover study with two three-weeks treatment periods with gabapentin and placebo separated by a two-weeks washout period. Patients started at random with gabapentin or placebo, which was administered in identical capsules three times daily. We included 58 patients with CRPS type 1.Patients reported significant pain relief in favor of gabapentin in the first period. Therapy effect in the second period was less; finally resulting in no significant effect combining results of both periods. The CRPS patients had sensory deficits at baseline. We found that this sensory deficit was significantly reversed in gabapentin users in comparison to placebo users.Gabapentin had a mild effect on pain in CRPS I. It significantly reduced the sensory deficit in the affected limb. A subpopulation of CRPS patients may benefit from gabapentin. Spontaneous recovery does occur and several therapies have been described, but for some patients CRPS I is a chronic disabling disease. Neuropayndromes -15. Anecyndromes ,8,16-27.This study complied with the Declaration of Helsinki regarding investigations in humans after approval of the protocol by the Institutional Review Board of the University Hospital Maastricht, the Netherlands. Patients were recruited from a database with patients who, in recent years, had been diagnosed with complex regional pain syndrome type I in our hospital. All patients had been treated in our pain management and research center  and had received sympathetic blocks, mannitoSince our patient population consisted of chronic CRPS I patients with a multiple years' duration of pain complaints refractory to various treatments, we assumed that their pain complaints would be more or less stable. We therefore undertook a double blind, randomized crossover study. Randomization of patients took place after baseline measurements and written informed consent. The assignment scheme was generated by our hospital pharmacy from a table of random numbers. The closed envelopes containing the assignments were prenumbered and kept at the pharmacy. The first treatment group received gabapentin, followed by a washout period and placebo treatment. The second treatment group received placebo treatment, which was followed by a washout period and gabapentin treatment. Each medication period lasted three weeks separated by the two-weeks washout period. Medication was stocked and delivered to the patient at the hospital pharmacy. Both the gabapentin capsules and the identical placebo capsules were delivered immediately before the start of the two medication periods. Left over medication was recollected and counted.The gabapentin (GBP) dose was slowly increased to reduce adverse side effects:600 mg's GBP AN once a day on day 1–2600 mg's GBP b.i.d. on day 3–4600 mg's GBP t.i.d on day 5–21Placebo dose was identically titrated. Patients were allowed to take their usual analgesics and were told preferably not to change the usual dose.The patients were reevaluated at the hospital three weeks (T1), five weeks (T2) and eight weeks (T3) after randomization. During the trial, the patient noted her/his pain rate of the past 24 hr (VAS) and the use of additional analgesics in a diary. During each hospital visit the following assessments were done:1. Global perceived effect (GPE) on pain indicating: worst ever; much worse; somewhat worse; not improved/not worse; somewhat improved; much improved and best ever. GPE on function was scored on an analogous scale.2. Neuropathic pain scale (NPS), a 10 item qualitative evaluation of neuropathic pain.3. Sensibility through Von Frey monofilament skin application each on 9 areas corresponding to cutaneous nerve branches and dermatomes of either both hands or both feet. Stimulu4. Mechanic allodynia test with brush strokes and static pressure with the finger tip, on 9 ar5. Edema, discoloration, and changed skin temperature were scored after physical examination on a three point scale indicating no, some or overt presence of each sign, the latter two signs in comparison to the healthy or healthiest limb. Physical examination in CRPS is well comparable to instrumental evaluation of signs with volumeter, infrared thermometer and goniometer.90-R)[6. Impairment and disability tests: Symptom Checklist-90-Revised (SCL-90-R), Brief P90-R), adaptedA blinded independent investigator (STvdB) did sensibility, allodynia and range of motion tests (see above). A physician (AvdV), who examined each patient, did all the other measurements throughout the trial. Patient, investigator and physician were unaware of the treatment received. We tested blinding by questioning physician and participants after each medication period.The statistical analysis of VAS-scores was determined per patient using estimating medication and period effect through linear regression analyses. Possible relationship of patient characteristics and outcome was tested by Pearson R's test. Mann-Whitney analyses were used for monofilament sensitivity on log-transformed data. Three point scales and seven point scales were dichotomized and like the SCL-90-R, NPS and CRPS-Brief Inventory questionnaires intra-individual paired tested . Student t-tests and regression analysis were used to test treatment effect, which is calculated in crossover studies as ((AT1-AT0)-(AT3-AT2))/2+((BT3-BT2))-BT1-BT0)/2, where A represents data of placebo starters and B data of gabapentin starters both before  and after  treatments. BlindinAfter randomization 58 patients were enrolled, with a mean age of 44.0 range 24–75) resulting in 29 patients in the gabapentin-placebo arm and 29 patients in the placebo-gabapentin arm; 49 patients completed the gabapentin period, 50 patients the placebo period, 46 patients completed both periods and were used for further within-patient paired analysis Fig. . Twelve 4–75 resuAfter each medication period both patient and physician were asked about their ideas concerning study medication in the past period. The treating physician guessed the used medication correctly more often after both phases than can be explained by coincidence (p = 0.000). Blinding for patients was sufficient in the first phase, but not anymore after the second phase (p = 0.2 versus p = 0.000).Comparing gabapentin and placebo users in terms of pain relief, there was a significant pain relief in favor of gabapentin in the first period. Therapy effect in the second period was less, finally resulting in no significant effect combining results of both periods. There was an unexpected increase of pain level above baseline in the washout period for both the gabapentin starters and placebo starters Figure .Global perceived pain relief as measured by the seven-point scale showed a significant effect for gabapentin, and also more pronounced in the first period. This measurement also found a significant effect in the second period, with an effect being defined as a patient scoring 'much improvement'. Statistical analysis of global perceived effect showed significant more treatment effect (p = 0.002) with 43 % versus 17 % reported pain relief respectively during gabapentin compared to placebo treatment. 13 % of patients reported aggravation of pain during gabapentin vs. 9 % during placebo treatment . This difference was found in patients with upper and lower extremity CRPS, but was still significant in the subgroup of lower extremity CRPS (p = 0.011) as seen in table Mechanical allodynia to static and dynamic stimuli (soft touch and brush) was measured by a mean of 11-point scales (range 0–10) of 9 areas of the hand/feet corresponding to cutaneous nerve branches. We found no effect of gabapentin on allodynia in comparison to placebo.No difference was found on the parameters edema, discoloration, range of motion of wrist/ankle and fingers/toes between placebo and GBP. 10 patients out of 45 improved in relative skin temperature during placebo use compared to 18 patients out of 45 in gabapentin, which is two sided tested not significantly different .The reported function improvement was, with 10 positive responders during GBP versus 7 positive responders during placebo, not significantly different (N = 46) between the two treatments. The SCL-90 showed no significantly better scores during gabapentin treatment. CRPS-BI showed improvement of sleep between placebo treatment and gabapentin treatment., but this effect disappeared after Bonferroni-Holm correction.Dizziness, somnolence and lethargy were significantly more often reported during gabapentin use than during placebo. Before washout 95 % of patients (n = 21) reported side effects during gabapentin use versus 58 % in placebo treatment (n = 14). After washout this was respectively 63% (n = 15) in GBP and 32% (n = 7) in placebo use. For more details on side effects see table 6. Since a high incidence of side effects can produce a stronger placebo effect, we analyzed the possible correlation between side effects and pain relief. There was a small relation between perceived side effects and pain relief in placebo users in period 2 , but, whether in period 1 or period 2, no relationship was found during the use of gabapentin .To evaluate gabapentin treatment as a treatment for pain in CRPS, we conducted a placebo-controlled crossover study. We conclude from our trial that overall, gabapentin did not relieve pain as compared to placebo on pain visual analogue scores, our primary outcome measure. Gabapentin relieved pain in a subgroup of patients and gave a significant global perceived pain relief. The effect was mild and there was no patient in which gabapentin completely eliminated pain. Moreover, the frequency of side effects as dizziness, somnolence and lethargy was higher during gabapentin treatment than with placebo. These side effects probably also account for the relative lack of blinding we observed in our study. This does not mean that the study was biased: our population was chronic CRPS patients who all had undergone numerous unsuccessful treatments, and clearly wanted the drug to work. Any possible bias would therefore have been positive towards gabapentin.Although we did not find a significant pain reducing effect when analyzing the complete trial, we did find a significant effect in the first half of the trial. In fact, the difference in outcome between the two trial halves is striking. There was a reverse carry-over effect resulting in increasing pain above baseline after the washout period for both gabapentin and placebo starters. The increase of pain intensity above baseline level in the second period (before the start of placebo treatment) cannot be explained pharmacologically. Gabapentin has no known biological dependency or tolerance mechanism. It can be a period effect, although this would more likely result in a regression to the middle instead of increasing pain. Perhaps this is a reversed placebo effect in which the expectation and/or the actual perception of not receiving gabapentin anymore might increase pain intensity. Kemler and de Vet found that treatment allocation in a trial could influence pain intensity in CRPS. The decWe found a decreased sensory deficit in gabapentin users compared to placebo users. We did not expect this, but found in the literature several cases in which gabapentin decreased the area of hypesthesia in neuropathic pain syndromes. This haGabapentin had a mild effect on pain in patients CRPS I. It significantly reduced the sensory deficit in the affected limb. A subpopulation of CRPS patients may benefit from gabapentin, but then for each individual patient the benefit has to be weighed against the frequently occurring side effects.Parke-Davis (now a Warner-Lambert/Pfizer division) supplied gabapentin and matching placebo capsules for this trial. Drs. Van de Vusse and Weber have received financial support from Parke-Davis to attend one congress. Parke-Davis has had no role in the writing of this manuscriptAvdV initiated the trial and wrote, with WEJW and AHFK, the protocol. The study and its data management was done by AvdV and SS-vdB. AHFK did the statistical analyses. AvdV wrote the first draft of the manuscript, which was finished in its final form by WEJW.The pre-publication history for this paper can be accessed here:


Low back pain is a common disorder in western industrialised countries and the type of treatments for low back pain vary considerably.In a randomised controlled trial the cost-effectiveness and cost-utility of an intensive group training protocol versus physiotherapy guideline care for sub-acute and chronic low back pain patients is evaluated. Patients with back pain for longer than 6 weeks who are referred to physiotherapy care by their general practitioner or medical specialist are included in the study. The intensive group training protocol combines exercise therapy with principles of behavioural therapy ("graded activity") and back school. This training protocol is compared to physiotherapy care according to the recently published Low Back Pain Guidelines of the Royal Dutch College for Physiotherapy. Primary outcome measures are general improvement, pain intensity, functional status, work absenteeism and quality of life. The direct and indirect costs will be assessed using cost diaries. Patients will complete questionnaires at baseline and 6, 13, 26 and 52 weeks after randomisation.No trials are yet available that have evaluated the effect of an intensive group training protocol including behavioural principles and back school in a primary physiotherapy care setting and no data on cost-effectiveness and cost-utility are available. Low back pain is a very common complaint with major social and economical consequences. In a recent cross-sectional study the annual prevalence of low back pain in the general Dutch population was estimated at 44% . The couEvidence-based physiotherapy for sub-acute and chronic low back pain patients consists of adequate information and an active approach, including behavioural principles. As physiotherapists have not yet put these principles into practice -7 two imThe study is a randomised controlled trial (RCT). Alongside the trial a full economic evaluation will be conducted. The Medical Ethics Committee of VU University Medical Centre has approved the study design, protocols and informed consent procedures.The trial will be conducted in a primary physiotherapy care setting in Amsterdam and its surroundings. Eighty-five physiotherapists will participate in the trial; 40 physiotherapists are trained to provide the intensive group training protocol and 45 physiotherapist are instructed to provide usual physiotherapy care according to the Low Back Pain Guidelines of the Royal Dutch College for Physiotherapy (KNGF).Patients with non-specific low back pain referred to one of the participating physiotherapists by their general practitioner are eligible for participation in the trial. Patients are included if the current episode of low back pain lasts more than 6 weeks and if the complaints show no tendency to decrease, meaning that the patient has not increased his activities in the last three weeks. Furthermore, patients have to be between the age of 18 and 65 years old, live or work in Amsterdam and have a health insurance with one insurance company (Agis). This health insurance company covers about 80 to 90 percent of the Amsterdam population and is the only company that reimburses the intensive group training protocol. Patients are excluded from the study if 1) they have specific low back pain, attributable to e.g. infection, tumour, osteoporosis, rheumatoid arthritis, fracture, inflammatory process, radicular syndrome or cauda equina syndrome; 2) their general practitioner or medical specialist advised them not to perform physically straining activities; 3) they are pregnant; 4) they have pelvic pain/instability; 5) they are dealing with a lawsuit related to either their low back pain or related to their disability for work. Patients are recruited by participating physiotherapists. If patients are interested in participating in the trial, they receive written information about the trial and their name and phone number is given to a research assistant. The research assistant calls the patient two days later and explains the aim and implications of the study. If the patient agrees to participate, an appointment is made at a local research centre. At the local research centre a research physiotherapist checks again if the patients meets the eligibility criteria. Patients who meet the criteria and agree to participate in the trial must sign an informed consent form. Patients are asked to complete baseline questionnaires and the research physiotherapist will conduct baseline assessment of physiologic outcome measures.In accordance with the CONSORT statement, information on number of recruited and eligible patients and reasons for exclusions or refusal to participate will be registered for all recruited patients by the participating physiotherapists and the research physiotherapist.Patients are randomly assigned to either the intensive group training protocol or physiotherapy guideline care. Randomisation is stratified for duration of complaints to ensure a sufficient number of sub-acute and chronic patients in each treatment group. To avoid inconvenience for the patients, seven local research centres are set up in different parts of the city. For each research centre two randomisation lists are prepared and permuted blocks of 4 patients are made to ensure equal distribution of patients for each research centre. An independent statistician generated the randomisation lists, using series of random numbers. The principle investigator (NvdR), who is not involved in the selection of patients, prepared the opaque, sealed envelopes, guaranteeing concealed randomisation. At the local research centre the administrative assistant hands the next envelope to the patient who then opens the envelope. The administrative assistant then checks the envelope and informs the participating physiotherapist about the treatment allocation.Both the research physiotherapists and the principle investigator remain blinded for the allocation of treatment. Patients cannot be blinded for the interventions. As a consequence most outcome measures, consisting of self-report questionnaires are not blinded either. All physical outcome measures are blindly assessed by the research physiotherapist as we ask the patients not to reveal information about their treatment to the research physiotherapists. Participating physiotherapists can not be blinded for treatment allocation, but they are not involved in the assessment of outcome measurements.Patients who are assigned to physiotherapy guideline care are treated according to the recently published Low Back Pain Guidelines of the Royal Dutch College for Physiotherapy (KNGF) . The guiThe intensive group training protocol combines exercise therapy with principles of back school and behavioural therapy. Back school principles include group lessons with adequate information on causes of low back pain, factors influencing low back pain, advice on physical activity and dealing with a relapse. Operant conditioning and graded activity as components of behavioural therapy are included in the protocol. Baseline measurements, goal setting and time-contingency are the main elements of the intervention. The purpose of the protocol is to improve activities and participation in work or other social activities, instead of focussing on pain or anatomical impairments. The patient has an active role and is responsible for the results of the therapy. The physiotherapist has the role of coach and focuses on the achieved improvement instead of the remaining complaints . Active The protocol has a total duration of 30 weeks and consists of three phases: the starting phase, the treatment phase and the generalisation phase. It concerns 10 individual sessions of 30 minutes per session and 20 group sessions of 1,5 hours per session. During the first phase of three weeks, six individual sessions are planned for patient history and physical examination, providing information on the treatment, determining baseline level of functional capacity and signing a treatment contract. During the treatment phase the group sessions have a frequency of twice a week for eight weeks. Every patient has his own gradually increasing exercise program, with an operant-conditioning behavioural approach based on the baseline level of functional capacity. The treatment phase gradually changes into the generalisation phase in which patients learn to apply everything they have learned in the treatment phase to their own daily situation. Therefore the frequency of the sessions decrease in the last four weeks; patients are encouraged to exercise more at home and to choose a physical activity they will continue after treatment has finished. Two individual sessions are planned for evaluation during the twelve week training period and two additional individual sessions are planned three weeks and three months after the group sessions have finished.The exercise program consists of:1. warming-up and cooling down2. aerobic exercises on a rowing machine, stationary bike or treadmill3. muscle strengthening exercises of the lower back, abdomen and buttocks4. exercises that specifically apply to the patient's situation5. home exercisesThe exercises mentioned at point 4. are determined by a Patient Main Complaint Form . During For training, the physiotherapists will receive instruction on the background and content of the protocol, and will be trained to include behavioural principles in the physiotherapeutic management of low back pain at two meetings of six hours each. In groups of 7–8 physiotherapists discussions and role playing are supervised by one expert trainer with extensive experience in behavioural principles. Four months after the last meeting 2 follow up sessions of 4 hours are organised to discuss practical problems and practice difficult situations with the trainers. The principal investigator (NvdR) will regularly visit the group sessions at the physical therapy practices to monitor the conduct of the intensive group training protocol. For each participating patient the physiotherapist is asked to complete a registration form containing the treatment goals, content of the different sessions and evaluation of the protocol.The intensive group training protocol is a standardised approach consisting of 30 treatment sessions. As the physiotherapy guideline care is not a protocol, the number of sessions will vary per patient. In daily practice the average number of treatment sessions is 9 and the average duration of treatment is 6 weeks [During the intervention period, co-interventions are discouraged. However, co-interventions will be reported and evaluated. Compliance to the intensive group training protocol is assessed by registering the number of treatment sessions that patients attend. The content of treatment and number of treatment sessions received by the physiotherapy guideline care group will be registered.In 1998 a proposal for standardised use of outcome measurement in low back pain studies was published . An inte1. The functional status is assessed with the Roland Morris Disability Questionnaire . The que2. General improvement is measured on a 6 point scale ranging from "much worse" to "completely recovered".3. An 11-point numerical rating scale is used for determining pain intensity, ranging from 0 "no pain" to 10 "very severe pain" .4. Work absenteeism is measured with the Short Form Health and Labour Questionnaire ,16. This5. The EuroQol instrument is administered to assess the patient's general health status. The questionnaire describes the general health status in 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression . Because6. The Tampa scale for kinesiophobia is developed as a measure of fear of movement/(re)injury by Miller et al. . The que7. Cognitive and behavioural pain coping strategies are assessed using the Pain Coping Inventory . This qu8. Self-efficacy beliefs are measured using the Pain Self-Efficacy Questionnaire . With th9. For measuring patient satisfaction four items (out of 17 items) of the Patient Satisfaction Scale of Cherkin et al.  are combThe physical measurements will be performed at several local research centres. Therefore all physical tests must be easy to administer en practical. To minimize patient burden the tests should take as little time as possible en should not be too strenuous for the patient.10. Anthropometric measurements will be done for interpretation of the physical outcome measures. Body weight, body height and skin fold measures are assessed. Skin fold thickness of biceps, triceps, subscapular and suprailiac will be assessed with a Harpenden skin fold calliper. The skin fold-thickness equation developed by Durnin and Womersley will be used to determine body fat mass .11. Aerobic capacity will be assessed with the Chester Step Test ,29. This12. The isometric endurance of the back muscles is evaluated with the test according to Ito . The pat13. The fingertop-to-floor distance is measured to determine the flexibility of the spine . StandinAt baseline, data of various prognostic measures will be collected to evaluate if randomisation successfully resulted in two prognostically comparable groups and to be able to adjust for baseline differences in the analysis, if necessary.1. Data on individual factors such as age, gender, level of daily activity and preference for one of the treatment groups will be gathered by the administrative assistant.2. Characteristics of low back pain: duration and severity of the current episode and number of previous episodes will be assessed by the research physiotherapists.The aim of the economic evaluation will be to determine and compare all back pain related costs of patients receiving the intensive group training protocol or physiotherapy guideline care. The costs will be related to the effects of the interventions. Cost effectiveness will be conducted from a societal perspective. Direct health care costs, including the costs for physiotherapy, additional visits to other health care providers, prescription medication, professional home-care and hospitalisation and direct non-healthcare costs such as out-of-pocket expenses, costs for paid and unpaid help and travel expenses will be included. Also data on indirect costs of loss of production due to back pain will be estimated for both paid and unpaid labour. Direct and indirect costs will be evaluated with cost diaries that patients keep during the whole time they participate in the trial . The genPatients will be asked to complete questionnaires at baseline and 6, 13, 26 and 52 weeks after randomisation. Physical measurements will be performed at baseline, 13 and 52 weeks after randomisation. Table To be able to detect a clinically relevant difference in pain intensity  with a We expect a drop-out rate of 10% at most. Drop-out rates of similar RCT's on neck pain and tennis elbow conducted at our institute were less than 3%. Therefore, to get complete data sets of 120 patients with sub-acute and 120 patients with chronic low back pain, 280 patients will be recruited, 140 sub-acute and 140 chronic low back pain patients. 85 Participating physiotherapists will be asked to recruit 5 patients; the recruitment period will be of 12 months duration.Intention-to-treat analyses will be conducted for all patients participating in both groups. A generalised linear mixed model will be applied to evaluate differences between groups over a period of 52 weeks. Subgroup analyses will be performed for duration of back pain: sub-acute (6–12 weeks) versus chronic (>12 weeks), for severity of complaints at baseline, for age, and for the psychosocial characteristics somatisation, fear avoidance, catastrophising and self efficacy.Bootstrapping will be used for pair-wise comparison of the mean differences in direct health care, direct non-health care, total direct, indirect and total costs between the intervention groups. Confidence intervals will be obtained by bias corrected and accelerated (Bca) bootstrapping using 2000 replications . Cost-efThe intensive group training protocol includes interventions, such as exercise therapy, behavioural treatment and back school, that have recently been proven to be effective in patients with low back pain. The graded activity intervention is considered the be a form of behavioural treatment and earlier studies have proven the effectiveness of this intervention for workers who are sick-listed due to low back pain ,37. The In the Netherlands, the national physiotherapy guidelines for low back pain consist of general recommendations regarding diagnostic and therapeutic management of low back pain while the intensive group training protocol prescribes the frequency, intensity and duration of the exercise therapy, the content of informative group lessons and graded activity in detail. The intensive group training protocol is expected to be more effective, because it is a detailed protocol and because it combines principles of exercise therapy back school and behavioural therapy, which have recently been proven to be effective for this patient population in systematic Cochrane reviews -40.Although the general practitioner, and if applicable the occupational physician, will be informed about the treatment and progress of the patient, the intervention is mono-disciplinary. A multidisciplinary intervention in a primary care setting has major practical implications and would increase the costs of the intervention considerably. The intensive group training protocol itself probably generates higher costs than physiotherapy guideline care but we expect reduction in health care utilization and productivity losses in the long term, compensating for the increase in treatment cost. This trial will provide physiotherapists with more knowledge and experience in behavioural treatment for low back pain patients and may increase the efficiency of physiotherapeutic care for this complex and expensive patient group. If the intensive group training protocol appears to be more cost-effective than physiotherapy guideline care, a future update of the national physiotherapy guideline will include more specific recommendations in line with this protocol. In that case the protocol will be implemented throughout the Netherlands.KNGF = Royal Dutch College for PhysiotherapyBca bootstrapping = bias corrected and accelerated bootstrappingThe author(s) declare that they have no competing interests.NvdR is responsible for the data collection and drafted the manuscript. MWvT, JMB, WvM and HCWdV were involved in developing the original idea for funding and were co-applicants on the successful funding proposal. WKF and ACO both will contribute to data collection and processing. All authors participated in development of research protocols and in the design of the study. All authors read and corrected draft versions of the manuscript.The pre-publication history for this paper can be accessed here:


Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial.Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse.Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%).A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up. Chronic, non-cancer pain, defined as pain of greater than 3 months duration, is a common, important health issue. The prevalence of chronic pain ranges from 20% to 60% . The preThe optimal approach to treating chronic pain is controversial -13. The In large part, uncertainty about how to best manage patients with chronic pain stems from a lack of research in this area . The limChronic pain management is complex. Like other chronic diseases, chronic pain is multi-faceted, and it is attended by its own set of comorbidities. It is complicated by substantial psychological and functional impairment in the forms of depression, disability, and loss of livelihood -30. It iGeneralists, even if well-versed in the biopsychosocial model of disease, often feel unprepared to manage chronic pain. They may lack the training in using certain pharmacological regimens, such as combining chronic opioids with psychiatric and pain modulating agents ,32. TheyWe developed a disease management program to improve the management of chronic pain in opioid-treated patients attending an academic general medicine practice. Traditional models of office-based care focus on diagnonsis and acute management of medical problems in the context of a single provider-patient relationship. In contrast, disease management emphasizes: (1.) The use of multi-disciplinary teams providing integrated care; (2.) Evidence-based algorithms; (3.) Interval visits to monitor response to therapy; and (4.) Information systems that permit tracking of outcomes and adjustment of therapy -39. We aIn designing the program, we reviewed existing research, contacted experts, and conducted informal assessments of the main barriers to effective pain management in our practice . BarrierPatients were eligible if they had pain of greater than 3 months duration and were either taking or considering opioid therapy. Attending and resident physicians were encouraged to refer patients if they were having difficulty managing their pain or if they suspected misuse of opioid medications. We publicized the program through educational conferences with residents and attendings and through informal communication within our practice.After obtaining informed consent, a research assistant administered a comprehensive baseline assessment to gather socio-demographic data and review the medical history with an emphasis on the medical management of pain. Validated measures of pain, disability and psychological status were included. Using an 11 point scale, the Brief Pain Inventory (BPI) asked patients to rate their pain at the time of the interview and at its worst, least, and average over the past month ,43. The Patients were managed by a multi-disciplinary team consisting of the patient's primary care physician, a clinical pharmacist, a program assistant with training in health behavior, and a psychiatrist with sub-specialization in pain management who saw patients with the team one half-day per week. One nurse was dedicated to checking-in study patients and obtaining urine specimens. At entry, all patients signed a Medication Contract (Appendix A)  and provThe clinical pharmacist or psychiatrist modified or titrated a patient's pain medications in consultation with the primary care physician. During titration of medications, patients returned at one month intervals. Medical management adhered to published guidelines and expert opinion on the management of chronic, non-cancer pain ,52-54. T• Longer-acting opioids  were initiated in patients who had been receiving short-acting agents that were only partially effective.• Short-acting, potent opioids  were prescribed for breakthrough pain.• Longer-acting opioids were titrated at interval visits.• Less costly, generic medications (e.g. methadone and long-acting morphine) were preferred over proprietary products of equal or lesser efficacy .• Tricyclic anti-depressants, gabapentin, and other agents were used adjunctively, especially for neuropathic pain.To address psychiatric comorbidity, patients with depression and other complex psychiatric conditions (e.g. psychotic depression and bipolar disorder with substance misuse) received psychiatric evaluation. Depression was diagnosed based on clinical interview and CESD score. In addition, primary care physicians could request psychiatric consultation on patients who had unaddressed psychiatric problems. The clinical pharmacist, psychiatrist and primary care physicians used CESD scores to guide treatment of patients scoring in the depressed range. The program, however, did not employ a strict protocol for depression treatment.As defined in our medication agreement with participants, we prospectively monitored substance misuse through clinical history, review of medications, communication with pharmacies and providers, and urine toxicological screening (UTS). Medications were documented in the electronic medical record and our program database. Discrepencies and inconsistencies were discussed with the patient's primary provider. We contacted a patient's pharmacy to verify procurement of medications, and, if substance misuse was suspected, we contacted additional pharmacies to ascertain whether or not a patient was receiving opioids from multiple sources. A UTS was obtained at each visit and was correlated with the patient's reported history of medication use. In collaboration with our institution's toxicologist, results of the UTS were verified using the appropriate confirmatory assays. For example, the presence or absence of "opiates" on the UTS was confirmed using gas chromatography. In addition, all positive results for amphetamines were confirmed with gas chromatography due to the possibility of assay interference from other medications ,51.We defined serious substance misuse prospectively as any of the following: 1. Cocaine or amphetamines detected on UTS; 2. Procurement of opioids from more than one provider on a regular basis ("doctor collecting"); 3. Diversion of opioids; 4. UTS negative on at least two occasions for prescribed opioids in the context of a reported history that the patient was taking the medication as prescribed (We considered repeatedly "negative" urines as an indicator of possible diversion.); 5. UTS positive on at least two occasions for opioids not prescribed by our practice (an inappropriate or inconsistent urine). A positive cannabinoid finding on UTS was not defined as serious substance misuse for the purposes of our study, but we counseled patients to refrain from marijuana use.Patients were advised at entry into our program (and in the Medication Contract) that serious violations of the contract would result in discontinuation of opioids. Past instances of serious misuse were not subject to sanction. We constituted a formal practice-wide committee to evaluate and respond to suspected misuse. It consisted of the practice director, two attending physicians, a clinical pharmacist, two resident physicians, and a nurse. The committee deliberated through secure email and considered the violations defined above. Patients committing serious substance misuse were offered referral to substance abuse experts at our institution. In most cases, opioid therapy would be reconsidered in 6 months if the patient participated in substance abuse counseling (The practice policy addressing substance misuse is included as Appendix B.).At 3 month follow-up, a research assistant reassessed each patient's clinical status. Pain, disability, and mood scores were re-measured using the instruments previously described. The research assistant was not blinded to study participation status.Descriptive statistics are reported as means and percents. Paired t-tests were used to compare changes in pain, disability and depression scores from baseline to 3 month follow-up. McNemar's test was used to measure differences in proportions of patients receiving treatment for depression at 0 and 3 months. We also compared changes in pain scores based on changes in opioid dose. All analyses were performed using Stata 7.0 .The research protocol was approved by the University of North Carolina School of Medicine Committee on the Protection of the Rights of Human Subjects. The funding sources had no role in the collection or interpretation of the results.Between December 2002 and May 2003, 85 patients agreed to participate in the study. Table The average age of patients was 51 years, 60% were male, and 78% were white, most (83%) had an income less than $20,000 per year and 65% were disabled. Forty-four percent had a history of illicit substance use . All patients had pain of at least 3 months duration and 90% had pain for greater than 1 year. At baseline 93% were receiving opioids. At 3 month follow up, 97% were receiving opioids.Table Table At 3 month follow up, BPI pain scores improved by 12% to 15%, and all reductions were statistically significant. The mean depression score improved from 24.0 to 18.0 (p < 0.001), and the proportion of patients scoring in the depression range decreased from 79% to 54% (p = 0.003). We did not correct for multiple comparisons because of the exploratory nature of our analyses.Some authors have demonstrated that the conventional cutoffs for the CESD  may lack specificity in patients with chronic pain and have proposed a CESD threshold of 27 for diagnosing depression in this population . Using tThe mean daily opioid dose in milligram equivalents of morphine increased from 72 mg per day to 91 mg per day . Forty-eight percent of patients had their opioid dose increased over 3 months. In these patients, the mean opioid equivalent increased from 53 mg to 105 mg per day. No clear relationship emerged between opioid dosing and improvements in pain, disability, and depression scores, after adjusting for baseline pain, disability and depression (Table Twenty-seven patients 32%) committed some form of serious substance misuse Table .. Althou% committWe found that a multi-disciplinary, primary care-based, disease management program can improve pain, depression and disability scores in opioid-treated patients with chronic pain in a 3 month uncontrolled trial. The improvements across all outcomes support an improved quality of life resulting from the intervention. These improvements were obtained using an approach that balanced the potential benefits and adverse effects of opioids.We hyothesize that these improvements resulted from the combined effects of systematizing pain management and treating depression. Improvements appear independent of opioid dosing. The clinical significance of the 12% to 15% improvement in pain scores is unclear. Uncontrolled trials in specialty pain clinics have reported a 20% to 25% reduction in pain scores . Some reThe improvement in depression scores was clinically important and may reflect combined effects of intensification of pharmacological management for depression and pain and the systematization of care. Although the reciprocal relationship between pain and depression has been established in previous studies, the effect that treating one condition has on the other has not been well-assessed . One recTo our knowledge, this is the first study to prospectively examine the effects of multi-discplinary pain management on the outcomes of pain, disability, depression, and substance misuse in an academic primary care practice caring for a wide range of patients. Previous studies conducted in a military clinic and a heWe documented a high prevalence of substance misuse (32%). We did not assess addiction per se. The prevalence of substance misuse and addiction in patients receiving chronic opioids is unclear and depends on the populaton under study. Some authors have asserted that addiction and substance misuse are uncommon consequences of opioid use for pain. One widely cited reference estimated the prevalence of addiction at approximately 4 in 10,000 treated patients . Others ® and other prescription drugs among teens and young adults  CIS NOTE."The pre-publication history for this paper can be accessed here: