The International Classification of Functioning, Disability and Health, (ICF) provides a unified, international standardized framework for describing and classifying health and health-related functioning and disability. Based on an ICF core sets the Functional Barometer, (FB), was developed for assessments of perceived pain-related problems with functions, activity and quality-of-life by patients suffering from long-term pain. The aim was to evaluate the construct validity, and to compare the assessments of a patient’s problems from the perspectives of the patient and of the examining professional when using the validated FB and corresponding ICF-classification form, respectively.Patients with long-term pain for more than 3 months that visited one of four pain clinics during specified time periods of data collections were eligible. The self-report Balanced Inventory for Spinal disorders was used for validation of the FB. Correspondingly to the validated FB an ICF-classification form for professional’s assessment was developed. The data sets for these inter-scale and the patient-professional comparisons were collected adjacent to the clinical examination. By the statistical method used for evaluation of the pairs of ordinal data presence of systematic disagreement was identified and measured separately from additional individual variations.The validation process resulted in a revised FB(2.0) that meets the requirements of good construct and content validity. The professionals’ ICF-classifications of the patients’ problems disagreed with the patients’ assessments on the FB(2.0); the percentage agreements ranged from 18% to 51%. The main reason was that the practitioners systematically underestimated the patients’ levels of problems but the different professionals contributed also to a large individual variability (noise) in assessment.This study presents an ICF-based validated self-report questionnaire, The FB, to be used for identifying and describing pain-related problems with current functioning, activities and quality-of-life as perceived by patients suffering from long-term pain. The strong evidences of underestimation of the patients’ problems and the variability in the professionals’ ICF-classifications demonstrated the importance of describing the patient’s problems both from the patient’s and the professional’s perspective beneficial for the patient’s rehabilitation. Pain is a subjective perception that is linked to various co-morbidities and mental disorders -3. MuscuThe multi-dimensional characteristics of perceived pain is evident by the diversity of operational definitions of pain and pain-related disability ranging from assessments on one or more rating scales with a discrete number of ordered alternatives or on visual analogue scales to electrical pain threshold assessments . Visual International comparisons would be facilitated by questionnaires referring to the World Health Organization’s International Classification of Functioning, Disability and Health, (ICF) . The ICFOn the other hand in the context of the measurement process for development of questionnaires that we use in this paper, the ICF has a hierarchical structure of well-defined variables and sub-variables. The first level category, an ICF chapter, is often called dimension, especially in multi-dimensional questionnaires. Each of the variables can be operationally defined to being measured by an item, for example a question suitable for the specific implementation of the ICF ,21. AsseContent comparison studies have shown that health-related quality-of-life instruments can be mapped to the ICF, and Chieza and Stucki  considerThe ICF categories/variables can be used as building blocks for creating ICF based core sets addressing different implementations. These core sets can be the starting point for development of clinical or self-report questionnaires for estimating various aspects of functioning in specified studies. ICF core sets have for example been developed in acute medicine , in physMany ICF variables are suitable for expert’s assessments and of patient-oriented instruments for clinical practice. Rauch et al.  describeWith the Swedish version of the WHO Guidelines and the ICF core sets for chronic widespread pain as base a self-report questionnaire for patients suffering from long-term pain conditions, the Functional Barometer (FB) was developed. Correspondingly an ICF-classification form for assessment of the patient’s problems from the professional’s perspective based on clinical examination was composed ,27,29. TTo our knowledge this is the first time ICF core sets have been used for comparing the assessments of a patient’s functioning state from the patient’s and a professional’s perspectives. The use of standardized ICF assessments by the same problem scales  provide additional aspects of the patient’s functioning and an opportunity to describe possible differences in estimation and perception between patients and professionals. The statistical approach used in this study makes it possible to evaluate such differences in assessments and explain the observed disagreement in terms of systematic and individual disagreements, respectively. Presence of systematic disagreement refers to the group of professionals and patients which is important information that could have an impact on the rehabilitation plan for the patients ,30-32.Quality control of questionnaires, item scales and assessments involves the three components: validity, reliability and responsiveness, each having sub-concepts referring to specific contexts, types of studies and applications. Quality control is an ongoing process ,33. EvalIn this study, the assessments on the original version of the Functional Barometer (1.0) were compared with assessments on corresponding items of the Balanced Inventory for Spinal Disorders (BIS) , which iThe aim of this paper is firstly to evaluate the construct validity and to present a validated Functional Barometer. Secondly, to investigate the agreement between the patients’ self-rated problems on the validated FB and the professionals’ ICF-classification of corresponding problems of the patient.no, slight, moderate, major, and total problems.The Functional Barometer, FB1.0) was developed by the author (JRN) to meet the need for a self-report questionnaire for assessments of perceived pain-related problems by patients suffering from long-term pain condition that was experienced in discussion with patients and professionals in pain management, general medicine and occupational health. Relevant ICF categories/variables of the components body function and structure, and activities and participation were identified from the ICF core sets for chronic widespread pain in accordance with the Swedish version of the ICF Checklist ,27,29. T.0 was deCorrespondingly an ICF-classification form for assessment of the patient’s problems from the professional’s perspective was constructed.not at all, negligible, moderate, quite a bit, and very much. This means that the two questionnaires have somewhat different operational definitions of the variables of interest, but could be used in similar applications.The BIS is a validated multi-dimensional questionnaire with 18 items for assessments of perceived level of pain, the level of limitations in pain-related body functions/activities and in quality-of-life . All iteSince the FB is addressed to patients with long-term pain when visiting different clinical settings and professionals a variety of patients and professionals were included. Our study design by consecutively inviting all patients with long-term pain for more than 3 months that visit a pain clinic in central Sweden during a specified time period reflects the reality in which the FB will be used. Statistical simulation studies and experiences gained from clinical studies of inter-scale and inter-rater comparisons have shown that a set of 20 paired data will provide enough power for identifying and measure evidence of systematic disagreement and individual variations between assessments . HoweverData for the evaluation of construct validity of the FB(1.0) regarding the operational definitions of the items and the order consistency between the assessments on the FB(1.0) and the BIS were collected between autumn 2010 and spring 2011. After informed consent, 89 patients who visited one the four pain clinics involved in this part of the study filled out the FB(1.0) and the BIS questionnaires in the waiting room before the medical examination by a professional.Data for the patient-observer comparisons between the assessments on the revised validated FB(2.0) were collected between December 2011 and February 2012. The 41 patients who visited the pain clinic involved during this period and consented to participate after information filled out the FB(2.0) before the medical examination. Eleven multi modal team professionals, well experienced on the ICF-classification procedure ,29 were The study was conducted in accordance with the Helsinki Declaration and approved by the Regional Ethical Review Board in Uppsala (2010/350 and 2011/381).1;Q3) and bar charts were used to describe item response profiles of the group, when applicable. The frequency distribution of pairs is shown by a square contingency table, the agreement diagonal being oriented from lower left to upper right corner [Assessments on rating scales generate ordinal data, which means that the values represent only an ordered categorical level and not a numerical value in a mathematical sense, even when the assessments are numerically coded. Therefore statistical methods applicable to data from scale assessments differ from the traditional methods for quantitative data, especially when dealing with paired data -43. The t corner ,30,31,35Both the inter-scale and the patient-observer comparisons were investigated by a non-parametric statistical method for paired ordinal data that makes it possible to identify and measure systematic disagreement separately from disagreement caused by individual variations. These two sources of an observed disagreement provide different information of the quality of data, since systematic disagreement refers to the group, and individual variations are related to individual pairs of assessments.The evaluation of the construct validity refers to the level of order-consistency between the FB(1.0) items and the corresponding or similar items in the BIS. This is a much stronger requirement of validity than is the measure of association between the assessments expressed as the Spearman rank-order correlation coefficient, which is also calculated . A high  on the problem scale is disordered the pair  but both pairs agree in ordering with the pair . The RV is a rank-based variance measure of this variability. Possible values range between 0 and 1, but with five response categories, the maximum possible RV is 0.61 which is the RV when the pairs of data are uniformly distributed to all cells of the contingency table [The designed heterogeneity in the groups of patients and observers is one of the sources of individual variations; uncertainty in interpretation of items another. Lack of understanding of a patient’s problem could also be an important factor of disagreement in patient-observer comparisons ,32. The cy table .The evaluation of the patient-observer agreement refers to the paired assessments of the problems self-rated by the patients on the validated FB(2.0) and by the observers on the ICF-classification form. Presence of systematic disagreement, bias, between them was measured by the RP. A positive RP value indicates that patients more frequently assess higher levels of problems on the FB(2.0) than do the observers on the ICF-classification form than vice versa. Individual variability was expressed by the D and the RV. The measures of RP, RV and the corresponding 95% confidence intervals (CI) were calculated by a free software program ,46.1 42; Q3 58) years. The Spearman rank-order correlation coefficient of the relationship between the assessments on items of function and activity of the FB(1.0) and on similar items on the BIS ranged from 0.40 to 0.84, Table The evaluation of construct validity was based on assessments on the FB(1.0) and the BIS made by 58 females and 31 males aged between 18 and 75 years; Md 48Q1 4; Q3 58 yordinary housework and on the BIS item of pain-related limitations in indoor activities is shown in Figure The frequency distribution of the pairs of data from the assessments on the FB1.0) item of perceived pain-related problem with .0 item os, 0.73 and 0.61, respectively. The significant negative RP-values indicates that the these walking activities in the group of patients would be assessed to higher rather than lower levels of problems on the FB(1.0) when compared with the levels of limitations in walking ability on the BIS. The small RV- and D-values indicate slight additional individual variations.Corresponding set of measures hold for the variables of walking and walking up- and downstairs. The relationships between the perceived limitations on the BIS and the perceived problems with these variables on the FB(1.0) were confirmed by the rThe comparisons between the assessments of pain-related problems with quality-of-life variables on the FB(1.0) and corresponding assessments on the BIS show that the group of patients perceived lower levels of problem than of limitation effects according to the significant positive RP-values, Table pain just now were major  problem. Correspondingly major  problem with pain during the last week, total  problem with worst pain, and moderate  problem with mildest pain respectively.The perceived problems with pain were measured by four items with different response profiles. The median and quartiles of the level problem with The result of the validation study of the FB(1.0) mainly concerned the verbal description of the items and the order consistency in the inter-item comparisons to similar variables of the BIS, and resulted in a major reformulation of the items to clarify that they referred to the patient’s own problem to perform an activity without help. The fitness of the formulation of variables to the ICF variables was also improved. Hence, the operational definitions of the variables of the revised Functional Barometer meet the requirements of good construct and content validity.Do you have problems making your bed because of your pain?The validated FB(2.0) consists of 29 items which verbally describes the problem to be measured, for example: no, slight, moderate, major, and total problems. The variables of body function activity/participation are measured by 12 specified items and one open question asking for “another activity that brings you problems because of your pain”. Perceived problems with quality-of-life variables and with pain are measured by 12 and four items respectively. The item variables and the corresponding ICF codes are seen in Tables The problem scale categories are: 1 36; Q3 58) years. The origin of the pain varied but the majority of the patients suffered from pain from the musculoskeletal system, such as fibromyalgia, low back pain and localized pain.The patient-observer comparison of the FB(2.0) and the ICF assessments involved 25 females and 16 males aged between 24 and 76 years; median 46,  items The observers’ ICF-classifications of the patients’ problems disagreed with the patients’ assessments on the FB(2.0), the median percentage agreement was 32%, (Range 18% to 51%), see Table no or slight problems while these patients’ assessed no, slight, moderate and major problems.The paired assessments of problems with ordinary housework (ICF d640) and with lifting and carrying things (ICF d430) had similar levels of agreement, PA, 29% and 28%, respectively, but the reasons for disagreements differ. In the assessments of patients’ problem with ordinary housework the observers systematically used lower categories than did the patients, RP -0.27, Figure no, total problems) and  assessed by two different observers contributed with 34% to the RV-value, Figure In the assessments of lifting and carrying the heterogeneity among observers, RV 0.40, was the main reason for disagreement. The disagreeing pairs  and the worst pain the RP-values range between –0.25 and –0.65. The 95% confidence intervals of these significant negative RP-values are strong evidences that the observers’ ICF-classifications of problems in a relevant population of patients more likely will be lower than the self-rated levels of problems on the FB(2.0) than the opposite.The aim of this study was to evaluate the Functional Barometer as being an ICF-based self-report valid questionnaire for assessments of perceived pain-related problems with functions, activity and quality-of-life by patients suffering from long-term pain. The content and construct validity studied refer to the operational definition of the item variables and will be generally valid and independent of the application. Our study resulted in a revised FB(2.0) with valid properties.http://www.funktionsbarometern.se. When translated to other languages the translation validity must be considered. Concepts of reliability are study specific. The test-retest reliability, also called the intra-rater reliability, must be evaluated when introducing a questionnaire to an empirical study in order to establish the stability of assessments [As mentioned, quality control of questionnaires and of data from scale assessments is an ongoing process and most of the three components: validity, reliability and responsiveness refer to specific contexts, types of studies and/or types of applications and target populations . The Funessments ,47,48. Iessments ,49-51.We have used a statistical method that takes account of the non-metric properties of ordered categorical data. Such data have become very common in studies because of the increased interest in qualitative variables and probably also because of the WHO recommendation of quality-of-life assessments in research and clinical practice. The statistical method used  is the oThe designed heterogeneity in the groups of patients and observers was one expected source of individual variability in this study, possible uncertainty interpretation of items another. The paired assessments on the FB(1.0) and the BIS showed that the main reason for the observed disagreement was the systematic disagreement because of different operational definitions of the items and not the heterogeneity in patients. The observed disagreements in the assessments on the FB(1.0) vs the BIS, referring to exercise vs leisure activities Table , and to Previous inter-observer clinical studies have shown systematic disagreement in assessments out of different levels of skills or perspectives, findings that motivated the design of this study. In a study on children with juvenile chronic arthritis the parent systematically overestimated the child’s pain compared with the child’s assessment on a four-point verbal descriptive scale . In anotIn accordance with the WHO Guideline and the suggested use of the ICF framework and core sets for obtaining an integrated deeper understanding of the patient’s problems and need, the self-report FB and the corresponding ICF-classification form for professional’s assessments were developed ,22,27,29Having the study specific concepts of quality control of questionnaires in mind, the Functional Barometer is a valid ICF-based self-report questionnaire that could be used for different purposes regarding assessments of current functioning, activities and follow-up assessments after treatment or rehabilitation. Our results clearly demonstrated the need of the self-report FB(2.0) for assessment of the level of pain-related problems, since the patient’s perspective will provide important complementary information benefiting treatment and rehabilitation.The authors declare that they have no competing of interests.JRN developed the FB and drafted parts of the manuscript. ES carried out the study designs, the statistical evaluations, participated in the operational definitions of the final version of FB-items, and drafted the manuscript. Both authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/14/187/prepub


Plantar fasciopathy is a common cause of foot pain, accounting for 11 to 15 % of all foot symptoms requiring professional care in adults. Although many patients have complete resolution of symptoms within 12 months, many patients wish to reduce this period as much as possible. Orthotic devices are a frequently applied option of treatment in daily practice, despite a lack of evidence on the effectiveness. Therefore, the objective is to study the (cost)-effectiveness of custom made insoles by a podiatrist, compared to placebo insoles and usual care in patients with plantar fasciopathy in general practice and sports medicine clinics.This study is a multi-center three-armed participant and assessor-blinded randomized controlled trial with 6-months follow-up. Patients with plantar fasciopathy, with a minimum duration of complaints of 2 weeks and aged between 18 and 65, who visit their general practitioner or sport physician are eligible for inclusion. A total of 185 patients will be randomized into three parallel groups. One group will receive usual care by the general practitioner or sports physician alone, one group will be referred to a podiatrist and will receive a custom made insole, and one group will be referred to a podiatrist and will receive a placebo insole. The primary outcome will be the change from baseline to 12 weeks follow-up in pain severity at rest and during activity on a 0–10 numerical rating scale (NRS). Secondary outcomes include foot function (according to the Foot Function Index) at 6, 12 and 26 weeks, recovery (7-point Likert) at 6, 12 and 26 weeks, pain at rest and during activity (NRS) at 6 and 26 weeks and cost-effectiveness of the intervention at 26-weeks. Measurements will take place at baseline and at, 2, 4, 6, 12 and 26 weeks of follow-up.The treatment of plantar fasciopathy is a challenge for health care professionals. Orthotic devices are frequently applied, despite a lack of evidence of the effectiveness on patient reported outcome. The results of this randomized controlled trial will improve the evidence base for treating this troublesome condition in daily practice.NTR5346. Date of registration: August 5th 2015.Dutch Trial Registration: Plantar fasciopathy is a common cause of foot pain in both primary and secondary care. Plantar fasciopathy was formerly known as plantar fasciitis in literature. It typically affects middle aged or older women 40–60 years), with being overweight as a risk factor –3. Besid0 years, The etiology of plantar fasciopathy is poorly understood and is probably multifactorial , 8. HistPlantar fasciopathy is characterized by pain over the anteromedial aspect of the inferior heel and the pain tends to increase after periods of inactivity or during weight bearing activities. The diagnosis can be made primarily based on symptoms and physical examination . PatientThe most commonly prescribed treatments include footwear modification, taping, stretching exercises, anti-inflammatory agents, Extra Corporal shock wave therapy (ESWT) and cortisone injections , 12. RevIt has therefore been suggested that treatment options should be offered to the patient in sequence, either based on objective patient criteria or based on the preference of the patient . DiffereOrthotic insoles (custom made by a podiatrist) and prefabricated insoles belong to the most researched biomechanical treatments of plantar fasciopathy , 19, 22.To our knowledge there is no literature available on the cost-effectiveness of orthotic insoles for the treatment of plantar fasciopathy.Given the favorability of treatment of plantar fasciopathy with insoles, the high estimated costs involved due to the custom-made nature and the insufficient evidence for this intervention, there is a need to conduct a high quality randomized controlled trial investigating the effectiveness of orthotic insoles on pain, function and recovery in patients with plantar fasciopathy.The primary objective of our study is to examine the effectiveness of custom made insoles by a podiatrist, compared to placebo insoles and compared to usual care in general practice and sports medicine alone in patients with plantar fasciopathy in terms of pain.The secondary objective of our study is to examine the cost-effectiveness of custom made insoles by a podiatrist, compared to usual care in patients with plantar fasciopathy.th version, October 2013 [The STAP-study is a multi-center three-armed armed participant and assessor-blinded randomized controlled trial with 6-months follow-up. STAP is an acronym for: Soles as Treatment Against Pain in feet. The reporting of the study protocol will follow CONSORT guidelines . The stuber 2013 . The MedPatients with plantar fasciopathy, characterized as pain at the medial hind foot, presenting themselves to a GP or sports physician, aged between 18 and 65 years and a minimal pain duration of 2 weeks are eligible for participation.Participants will be excluded if they have recurrent complaints of plantar fasciopathy for more than 2 years, complaints caused by trauma, earlier treatment for plantar fasciopathy by a podiatrist or treatment with orthotics, suspected (by the GP or sports physician) (osteo)arthritis in the subtalar or talonavicular joint, suspected tarsal tunnel syndrome, suspected stress fractures, infections or tumors in the painful foot or presence of systemic diseases . Patients who have no sufficient understanding of the Dutch language will also be excluded, since they will not be able to complete the questionnaires.Based on the RCT of Landorf et al. (2006)  –pain scRecruitment of patients will take place in two different settings. All eligible patients who consult a participating GP or sports physician for plantar fasciopathy will be considered for participation (prospective recruitment). On average a GP will see 8 new patients each year. It is estimated that 30 % of these patients will be willing to participate. Therefore, a total of 47 participating GP’s will be necessary to include 185 patients within two years’ time. We aim for a minimum of 50 participating GP’s or sports physicians.All potentially eligible patients will be invited to participate in the study and will receive comprehensive information about the study. Patients that are willing to participate will fill in a reply card with their contact details and send it to the research team. The research team will then contact the interested patients and inform them further about the study and check the inclusion and exclusion criteria. If a patient is willing to participate in the study and meets all inclusion criteria and none of the exclusion criteria, he or she will sign the informed consent form and send it to the research team. The baseline questionnaire will subsequently be send to all participating patients by email. After completing the baseline questionnaire all patients will be randomized into one of the three study groups.After providing informed consent and baseline measurement, randomization will be performed by an independent person with the use of a computer generated randomization list using block randomization with random block sizes between 3 and 10. This sequence is kept hidden from all involved researchers. It can be expected, that patients referred by a GP and patients referred by a sports physician are different in terms of BMI and activity level. These have both been described as possible risk factors for plantar fasciopathy and therefore might influence treatment response . For thin = 47) randomized to the usual care group will receive an information booklet with general information on plantar fasciopathy. This information booklet will contain information on the use of pain medication and possible stretching and strength exercises  that arn = 69) and the placebo insole group (n = 69) will a be referred to a podiatrist. All patients that are referred to a podiatrist will additionally receive the information booklet identical to the usual care group as described above. The first appointment with the podiatrist will take place as soon as possible after randomization (preferably within 1 week). All patients referred to a podiatrist will receive a standardized intake with identical procedures. These procedures have been discussed and agreed upon with the participating podiatrists in a consensus meeting. If a podiatrist could not attend they were given elaborate explanation and the opportunity to give input during a telephone conference.Patients randomized to the custom made insole group . Secondary outcome measures include foot function as measured by the Foot Function Index at 6, 12 and 26 weeks follow-up, perceived recovery measured on a 7-point Likert scale  at 6, 12 and 26 weeks follow-up, pain at rest and during activity at 6 and 26 weeks follow-up and cost-effectiveness of the intervention at 26-weeks follow-up.During a 6 month follow-up the participating patients will be asked to complete a total of six questionnaires. At baseline, at 2 weeks, at 4 weeks, at 6 weeks, at 12 weeks and at 26 weeks of follow-up. The participants will receive an e-mail that contains a secured hyperlink to the questionnaire, using the survey application Lime Survey. Phone calls and reminder emails will be used to minimize loss to follow-up and missing data.The baseline questionnaire will include questions on demographics , duration of pain, work activity , sports activities  , 31, genThe 2, 4 and 6 week questionnaires will include questions on recovery on a 7-point Likert scale , pain atDifferences between the intervention groups will be analyzed following the intention-to-treat principle. Linear regression techniques for repeated measurements will be used to compare pain severity between the intervention group and control groups, which take the correlation of multiple measurements within one patient into account. A Bonferroni correction will be performed for the secondary comparisons to the usual care group. The analysis will be adjusted for potential confounders .Recovery, pain scores and function will be analyzed using regression techniques for repeated measures using generalized mixed models.Mean direct, indirect and total costs will be estimated and compared between the three study groups. Because costs will not be normally distributed, 95 % confidence intervals for the differences in mean costs will be obtained by bias corrected and accelerated bootstrapping (2000 replications). Differences in costs and differences in recovery will be included in a cost-effectiveness ratio, which estimates the additional costs to completely recover one patient.Confidence intervals for the cost-effectiveness ratio will be calculated with bootstrapping, using the bias-corrected percentile method with 5000 replications. An incremental cost-effectiveness ratio will be estimated of the incremental costs to recover one patient. Uncertainty of this ratio will be evaluated by presenting a cost-effectiveness plane and sensitivity analyses will be performed to check the robustness of the results. An acceptability curve will also be presented.Pre-defined subgroup analysis will be performed in patients with a long (>12 months) and short (<12 months) duration of the complaints at baseline, in patients with a low, moderate or high total activity score derived from the SQUASH questionnaire (in tertiles), in patients recruited in general practice and by sports physicians and in patients where the podiatrist agrees with the indication for orthotic insoles and in patients where the podiatrist does not.In order to explore the effectiveness of custom-made insoles, we will compare the insole to a placebo insole. One earlier study found similar effects on pain and function at both short and long-term follow-up between placebo insoles and custom made podiatric insoles . Since bIt has also been acknowledged that the placebo effect plays a role in clinical trials using orthotic devices and that the development of a placebo intervention in these trials is a difficult task . For theWe expect to find a larger difference between the custom made insole group and the usual care group, compared to the custom made and placebo insole groups, since patients allocated to the usual care group are likely to have a different attitude towards their treatment. It is worthwhile to study these differences since this provides information on the treatment with custom made podiatric insoles compared to other strategies used in daily practice and on the possible placebo effect involved with treatment with insoles. This knowledge will improve the insight into the treatment of plantar fasciopathy as it is currently given in clinical practice.We will include patients from both general practice and sport medicine clinics. Previous studies have suggested possible subgroups of patients, which might be represented by the two different recruitment settings. For example, patients recruited in general practice are more likely to be middle-aged with perhaps higher mean BMI’s, whereas patients recruited by sports physicians are probably more physically active compared to those in general practice. By performing a stratified randomization for type of referral we will be able to analyze the possible difference in effectiveness of insoles in subgroup analysis.Our sample size calculation is based on the data from Landorf et al.  This triThe strength of this study is that we will perform a trial in which we will compare custom made insoles, a preferred treatment in patients with plantar fasciopathy, to a placebo treatment and usual care. The results will contribute to clinical decision making in primary health care when it comes to plantar fasciopathy and will additionally provide information on the cost-effectiveness of podiatric care including orthotic insoles.


Breast cancer represents a major public health problem, being the highest incidence neoplasia in females in Romania. The most important step in the treatment of this neoplasia is the surgical procedure; the biggest problem associated with this form of treatment in these patients is pain-related. Pain is a complex symptom with an impact on quality of life and psychology of cancer patient and can only be monitored verbally and subjectively. Consequently, the purpose of our work is to identify some biochemical parameters involved in the events cascade associated with inflammation and pain in breast cancer female patients, monitored in dynamics of anesthesia and surgical procedure. Measurements of lipid peroxides, ceruloplasmin and immune circulating complexes in mentioned dynamics have been performed. The recorded values are in concordance with the inflammatory processes and pain intensity, thus we can allege that these measurements can complete the pain-associated clinical picture in female breast cancer patients. A major factor in order to obtain favorable results in breast cancer is represented by an early diagnosis and a proper therapeutic management. The treatment decision is based on the following: stage, axillary nodes status, tumor biology, histopathological and immunohistochemical characteristics and includes the surgical procedure as an important stage [2]. This is associated with pain specific episodes.Breast cancer represents a major public health problem, being the highest incidence neoplasia in female sex in Romania [3]. Definitions of pain try to cover the big diversity of aspects of this symptom, from the simple explanation as pure physiological phenomenon, until the usual multidimensional type image. Pain is an individual experience that includes physical and psychosocial aspects and is always subjective. There are many classification modalities, that reflect the multidimensional aspect of pain sensation, but until now, there has been no universal description system [4]. These classifications have been elaborated in relation to the following:Pain is frequent in cancer patients and remains one of their most important suffering aspects, besides the multiple analgesic therapy methods. Pain is a complex symptom with an impact on quality of life and psychology of the cancer patient . The progress of cancer disease often reclaims an increase of the analgesic doses and the opioid tolerance expresses itself like a decrease in the duration or disappearance of analgesia. An adequate treatment of secondary opioid effects is of capital importance because these represent a barrier in front of an effective analgesia obtaining. For a proper approach of this pain treatment and to objectively evaluate the intensity of its physical manifestations, in this paper we proposed to correlate pain intensity with some biochemical parameters involved in female breast cancer patients, monitored during the dynamic of anesthesia and surgical procedure.Clinical expression of pain can be influenced by multiple factors, for this reason, pain treatment needs a complex approach of the patient like a person. Pain treatment is a dynamic process, which needs frequent reevaluations in order to verify the efficiency of the therapy and to facilitate the doses adjustment . MDA from the serum sample is a weak, unstable, acid, very reactive, that reacts with TBA (thiobarbituric acid) on boiling, in tricloractic acid environment. The red product resulted has a maximum of absorption at 532 nm. The absorption of colored product by the precipitate is prevented by adding hydrochloric acid, and the turbidity produced by lecithin is removed with organic solvents (CHCl3 or n-butanol).Although lipid peroxidation of biological samples can be evaluated by different physical and chemical methods, based on MDA measurement  formed by endoperoxides cracking during the last step of polyunsaturated fatty acids oxidation, being the simplest and largest scale utilized in present .Ceruloplasmin (CP) is an acute phase protein with an intermediary response in comparison with other acute phase proteins, whose level increases 2-3 times in inflammations, pregnancy, traumatic lesions and surgical procedures. Serum ceruloplasmin level is useful as a clinical indicator in Wilson disease. Every CP molecule contains 6 or 7 copper atoms and 90-95% of serum copper can be found in this form .Ceruloplasmin is a light-blue-colored protein with oxidative activity on the polyamines, polyphenols and inorganic ferrous ions (Fe 2+). The main biological substratum is Fe 2+, ceruloplasmin having a maximum affinity for this. Catalytic oxidation of Fe 2+ or complexes containing Fe 2+ is named ferroxidase activity. Several methods for the determination of ceruloplasmin ferroxidase activity are described. Ravin method that consists in the reaction of p-phenylenediamine in acetic acid - acetate buffer was used . CIC increasing conducts to an increase of thrombocytes and erythrocytes aggregation. In addition, because of complement system activation, inflammatory reactions may appear, that determine leucocytes stimulation, macrophages activation with consecutive alteration at tissular level. This complement activation can elicit a series of potentially destructive events, like cell lysis, anaphylatoxins production, leucocitaria stimulation and macrophages activation. The majority of the tissular lesions are induced by immune complexes fixation at cell membranes level [11]. Although CIC detection is not specific for one condition, CIC testing can provide interest information about the pathology, disease course and prognosis. CIC presence is an indicator about the exceeded immune defense or autoimmune conflict that conducts to the necessity of performing some complementary tests to clarify the diagnosis. Highly persistent concentrations of CIC may indicate an active chronic disease, while CIC concentration normalization indicates the treatment success [12].Immune circulating complexes are protein aggregates formed by the binding of antigens with antibodies. They are continuously forming as a result of the immune response. Because they are fast destroyed in the blood circulation, these immune complexes (CIC) are not detected in serum or they are detected in very small quantities. CIC detection is possible in some conditions in which there exists a high immune complex concentration that exceeds phagocytes clearance [13].We determined CIC by modified Haskova method. Normal values are between 1-50 µmoli/ ml. The test is useful for monitoring the diseases with immune complexes , as well as monitoring some neoplasias evolution [14]. Recent studies have shown that COX-2 and oncoprotein p53 are fundamental markers of angiogenic process. Associated with p21ras oncogene, the promoting effect of polyunsaturated n-6 fatty acids in experimental carcinogenesis of mammary gland can be explained [15]. These polyunsaturated fatty acids are spread in cell membranes, where they are exposed to lipid peroxidation reaction. The most frequent acid is the arachidonic acid. This acid is also present in membranes as a compound of phosphatidylinositol, phosphatidylserine, triacylglycerols (from adipose tissue) and cholesterol esters . Therefore, the first step of biosynthesis consists of releasing the arachidonic acid from cell membranes that take place under the action of phospholipase A2. This enzyme, compound of cell membranes, must be activated under the action of some immunological stimuli like phagocytosis, antibodies, immune complexes, bacterial endotoxins, and limphokines [16]. As phospholipases A2 type I is tightly related to the membranes, being stimulated by Ca2+, at physiological pH, that of type II, cytoplasmatic, is inhibited by the calcium ions and it has an optimal pH at acid values. Arachidonic acid can also be released by the thrombin from thrombocytes and by the contracting of the aortic factor in the lungs, etc. The most interesting are the apparently contradictory actions that can be understood and explained in the context of inflammatory process. Cox-2 is the prevailing isoform of cyclooxygenases, present at the inflammation spot and which produce prostaglandins that cause swelling and pain. In situations when the release of protective prostaglandins by Cox-1 was lost, Cox-2 induction can compensate and reduce the inflammatory response. Therefore, Cox-2 is anti-inflammatory in the case of cell proliferation [17]. Cox-2 is related to inflammatory cell and tissue types and is believed to be the target enzyme for nonsteroidal drugs anti-inflammatory activity. This way, the relation between inflammation and lipid peroxidation is unquestionable and we succeeded to prove, by these determinations, the pain intensity produced by inflammation and lipid peroxidation in investigated patients.The results are presented in the following figures. We registered an increase of the lipid peroxides level with a maximum peak at 48 hours after the surgical procedure, the curve profile showing an increase of values until 7 days post-operatory. These data are in accordance with the VAS pain scale. From a biochemical point of view, data confirm mechanisms that are based on malignization and pain occurrence. In case of cell modification induced by malignization, eicosanoides, especially those PGE2-type are induced by the angiogenesis basic regulators, β-TGF, endothelin-1 [18]. Ceruloplasmin has a peroxidase activity, oxidizing Fe2+ to Fe3+ and facilitating transferrin loading. The importance of this peroxidase activity of ceruloplasmin has been studied in patients with aceruloplasminemia, who had a mutation of the gene that codifies the protein. These patients have a low iron level, a high ferritin level and increasing of iron storage in brain and liver, causing diabetes, degenerative retinopathy and neurological disorder. The injection of ceruloplasmin increases the serum iron level [19]. Conversely, the iron oxidation catalyzed by the ceruloplasmin does not generate free radicals. Like an acute phase protein, ceruloplasmin can be a marker of inflammatory reaction and of pain. In investigated patients, the values presented in Fig. 2 show an increase of ceruloplasmin level and of its activity during the dynamic of pain-inducing surgical treatment, values that remain in plateau for almost 7 days post-operatory, when the registered decrease is associated with a diminishing of the pain. It can be stated that this parameter biochemically reflects the verbally registered value in investigated patients.Copper ions are powerful catalysers of free radicals lesions. They convert H2O2 to OH-, decomposing lipid peroxides; catalyze auto oxidative reactions, especially of ascorbate, DNA oxidation and LDL peroxidation. The median copper content of an adult is 80 mg in total. Copper is absorbed from the diet in the duodenum, in chelated form with amino acids or small peptides. Absorbed copper enters the blood, links to the albumins and is transported to the liver, where it is incorporated into a protein - ceruloplasmin. This is secreted in the plasma, as the excess of copper is secreted in the bile. Ceruloplasmin cedes the copper to the cells after the fixation on the membranous receptors. The human body contains 200-400 mg/ l of ceruloplasmin, which includes 90% of the total plasmatic copper, the rest of plasmatic copper being bound to albumin, histidine and small peptides . The big, insoluble complexes, formed in excess are fast removed from blood and phagocytized by the monocyte-macrophage system. On the other side, the intermediary size immune complexes formed in the excessive presence of some antigens remain in solution and they can be stored, delivering the values registered at 7 days post-operatory. Immune circulating complexes pathogenicity consists of their capacity to elicit a series of phenomena resulting in basal membranes alteration and cell proliferation [21]. The registered values are in concordance with the intensity of inflammatory processes and with the pain, thus, it can be affirmed that these determinations can also complete the clinical pain-associated picture in breast cancer female patients.The registered values are in normal limits, the explanation being the pathogenicity and the manner of sedimentation on and in the membranes, which depends on the quantitative and qualitative aspects of them: the quantity of Atg-Atb complexes, the size of the complexes; the molecular configuration, antibody affinity for the antigen, electrical charge and solubility . Days or even weeks are necessary for the recovery of physiological states from the perioperatory period. Any patient who presents a preoperatory pathology and must bear an elective surgical procedure, will pass these three physiopathological statuses under other doctors’ supervision: the internist or the oncologist in the perioperatory period, anesthesiologist and surgeon in the intra- and post-operatory period.The perioperatory management of patients with cancer disease can be a challenge, a science and an art. The multiple problems, directly related to the presence of the tumor but also to the antineoplastic treatments sequentially performed before and after the surgical procedure, induce the raising of morbidity and mortality risk during the perioperatory period. This period implies the passing of patients exposed to surgical treatment through three different physiological statuses: one preoperatory physiologic status, than the anesthetic intra-operatory and the post-operatory status, after that they should successfully return to the status anterior to the operation [23].Oncological patients care exemplifies this concept of perioperatory medicine, combining knowledge and technical abilities of the anesthesiologist, radio/ chemotherapeutics oncologists and surgeons [The perioperative medicine of the oncological patient needs the ability of integrating in a unitary vision the different problems of a patient generated by the presence of cancer disease, the performed treatments, but also the other associated non-malignant diseases, which add to the anesthetic risk.


Thumb CMCJ arthritis is a commonly encountered condition. A wide variety of surgical interventions are advocated to those who failed conservative measures. They include ligament reconstruction, osteotomy, resection arthroplasty, suspension arthroplasty, arthrodesis, prosthetic replacement, joint denervation and etc. They are tailored to different radiographic stages of disease, patient’s demand and expectations. However, it is well known that there is a poor correlation between severity of degenerative disease and clinical symptomatology. It is not uncommon to encounter patients having Eaton stage IV CMCJ1 arthritis with minimal symptoms.What determines the magnitude of patient’s symptoms and functional disability with thumb CMCJ arthritis? Is it the degree of degenerative synovitis, severity of inflammation, mechanical instability, mechanical bone pain, or individual’s thumb biomechanics? And, what determines the surgical outcomes in each operation. In fact, the results of the above surgical interventions are variable and sometimes unpredictable. Is there a role of less invasive operation while giving a reliable outcome?Arthroscopic synovectomy, debridement, with minimal bone work, of thumb CMCJ & STTJ arthritis, is a minimal invasive procedure, with both diagnostic and therapeutic role. It gives an excellent visualisation of the joint, including the joint capsule, cartilage, ligament, degree of synovitis, and etc. It allows the detection of any intra-articular changes long before they would be noted through routine radiographs, and enables earlier treatments in those patients. It provides better judgement of management decision according to the intra-articular pathology. Most important of all, it is a viable option to relieve patient’s symptoms.From 2002 to 2013, 76 thumb CMCJ arthroscopic debridement and synovectomy were performed in 65 patients. There were 51 females. The average age was 56. The dominant hand was affected in 38 thumbs. All failed conservative measures for more than 6 months. The follow-up duration was 59 months on average. There were 38 thumbs of Eaton & Littler Stage II disease, 36 Stage III, one stage I and one stage IV. Most of them were operated under portal site local anaesthesia except two were under intravenous local anaesthesia and one was under forearm intravenous regional anaesthesia.The average duration of operation was 68 minutes. 49 of them were classified as Badia’s Stage III arthroscopic changes, 23 Stage II, and 4 Stage I. Synovectomy and debridement of frayed joint capsule and radio-frequency ablation were done in all thumbs. Loose bodies were removed in 25 thumbs. Thermal shrinkage was done in 30 thumbs with intact, non-frayed ligaments. Limited bone work was done. Bone surface was smoothened and prominent osteophytes were removed in 12 thumbs. For those who received thermal shrinkage, they were immobilised in a cast for 4 weeks.In an average follow up of 59 months, 69 cases experienced pain relief after the operation, occurring on average of 3 months after the surgery. The visual analogue pain score decreased from a mean 8.3/10 to 2.7/10. 20 patients had excellent final outcome in which pain relieved for >90% and lasted till the end of the follow-up. 14 had good results in which pain was relieved for >70% and lasted till the end of the follow-up. 24 had fair results in which pain was relieved for >70% and lasted for >1year or pain was relieved <=70% but was not a nuisance.The grip strength was 88.3% of the contralateral side, whereas pinch power was 81.7%. The average Kapandji index was 8. DASH score averaged at 26.5. No complications was encountered. 7 patients requested the same operation on the contralateral thumb. 3 patients requested repeating the operation on the same thumb as pain relief lasted for 1-3 years. The overall patient satisfaction rate was 77%.However, 7 cases never experienced pain relief after the operation. 18 patients had pain reappearing to the pre-operative level subsequently undergoing open surgeries at an average of 14 months (5 months to 4 years) after the arthroscopy.Statistical analysis revealed that patient’s age, gender, duration of symptoms, MCPJ hyper-extendibility, radiological staging, size of the impinging osteophytes, cartilage status, loose body removal and post-operative radiological progression did not correlate with the outcome after arthroscopic debridement and synovectomy. Better outcomes were seen in those who had smoothening of the bone surface and prominent osteophytes removal, thermal shrinkage procedure, and post-operative immobilisation.Removal of synovitis and frayed capsule might eliminate one of the source of pain. Debridement and the use of radio-frequency could be a kind of joint denervation to abolish pain transmission. Thermal shrinkage, postoperative immobilisation and postoperative joint fibrosis promoted stabilisation of the CMCJ. Limited bone work might help to promote bone bleeding and release of mesenchymal cells to the joint. We did arthroscopic partial trapeziectomy under portal site local anaesthesia on other occasions. Those patients did not anticipate pain during bone burring. Bare bone surface may not be the source of pain. We advocate limited bone work, without hemi-trapeziectomy, in order to preserve the hard subchondral bone, which may be helpful in sharing the load across the CMCJ.Arthroscopic synovectomy, debridement, with minimal bone work in thumb CMCJ and STTJ arthritis, is a “buy time surgery” helping patients to endure the painful period of osteoarthritis, until the joint is partially stabilised naturally, the joint biomechanics are adjusted and adapted to the daily activities. It may also be a definitive procedure to alleviate symptoms. We regard this as the first line of surgical treatment in all stages of arthritis at the thumb CMCJ and STTJ.


Pain is an often underestimated and neglected symptom in amyotrophic lateral sclerosis (ALS).In a cross-sectional survey, 46 patients with ALS, 46 age- and gender matched population-based controls, and 23 diseased controls with myotonic dystrophy type 2 (DM2) were screened for occurrence, type, distribution, and treatment of pain and cramps. Data were collected with the use of the short form brief pain inventory (BPI).P < 0.05). More ALS patients than controls reported moderate to severe pain (42% vs. 20%). Pain in ALS patients interfered significantly more with daily activities than in controls , especially enjoyment of life (5.0 vs. 1.0) and mood (3.0 vs. 1.0). There was no correlation between the duration of the disease and the severity of pain. Movement-induced cramps were reported in 63% of ALS patients, mostly in the distal extremities. There was no difference in the duration of ALS disease between patients reporting cramps and those who did not.Pain was reported in 78% of ALS patients,79% of DM2 patients, and 54% of controls (Our study showed that pain was a relatively frequent symptom which had an important impact on the quality of life. Pain that requires treatment can occur at every stage of ALS. The progressive loss of upper and lower motor neurons in amyotrophic lateral sclerosis (ALS) causes a rapidly advancing paresis and atrophy of skeletal muscles which is occasionally combined with spasticity. Pain has been considered relatively rarely in ALS, in particular in the early stages of the disease. It has been suggested that the intensity of pain increases with disease duration and decreasing functional status  and to correlate it with disease duration and severity parameters. We also analyzed the prevalence, site, and treatment of cramps and spasticity.n = 4). All consecutive patients were seen by author F.H. at the Outpatient Clinic for ALS and Motoneuron Diseases, Department of Neurology, Martin-Luther-University, Halle (Germany) between March 2013 and September 2013 and were asked to fill out the questionnaires during a visit to the clinics for follow-up. All patients were on riluzole and received physiotherapy in regular intervals, for example, once weekly. The study was approved by the local ethics committee of the Martin-Luther University Halle. All participants provided written informed consent.Patients were eligible if they fulfilled the criteria of probable and definitive ALS according to the revised El Escorial criteria  were asked to fill out the short form of the BPI only.The short form of the BPI is a self-administered 9-item questionnaire that was used to assess the presence and severity of current pain (pain within the previous 24 h) and its interference with daily activities. Pain was rated from 0 (no pain) to 10 (pain as bad as you can imagine). Four questions asked patients to rate the worst, least, and average pain experienced in the previous 24 h, and also to rate current pain. The average of these four answers was used to produce a pain severity score (PSS). The recall bias of the BPI is minimal. Finally, the BPI assesses the sites of pain and its treatment  was used to score activities of daily living. A lower score means lower functional abilities . A significance level of 0.05 was used. All analyses were performed using SPSS for Windows .Descriptive statistics were used to summarize all variables for the patient and control groups. To assess differences in demographic characteristics and differences in the prevalence, severity, interference, and treatment of pain between patients and population-based controls, we used the Chi-squared trend test for discrete data, or the Mann–Whitney We invited 55 ALS patients to participate in the survey, 46 of whom took part. The response rate was 84%. The demographic and clinical profiles are listed in Table A history of diabetes had 5/46 ALS patients, 11/23 DM2 patients, and 4/46 population-based controls.n = 36) reported having pain, against 54% of controls (n = 25); P = 0.027). These figures obtained with the BPI short-form refer to the prevalence of pain in the last 24 h.Seventy-eight percent of the 46 patients (P = 0.08).Table P = 0.01). Pain interfered especially with patients' enjoyment of life (score of 5) and mood (score of 4), followed by mild interference with general activities, walking ability, and sleep (score of 3). Relationships with other people were the least affected (score of 1.5). For each of the seven domains of daily life, the interference scores were significantly worse in ALS patients than in controls, except for interference with sleep and the general activity.At 3.0 (range 0.75–6.75), ALS patients' median Pain Interference Score (PIS) differed significantly from that of controls (PIS 1.2 (range 0.75–5.25); FigureControls reported pain frequently in the back (45%) and in joints (50%), but rarely in the extremities (10% of controls). There was no significant difference in the painful affection of neck, shoulder, elbow, hip, knee, and ankles between ALS patients, DM2 patients, and controls.Figuren = 17) reported receiving treatment for it (Table n = 11). Four controls used medication only, four used physical therapy only, and three took a combination of both.Forty-seven percent of ALS patients with pain n = 7 reporter = 0.15). Those patients with none or mild pain in the PSS (score 0–3) had a similar disease duration compared to patients with moderate or severe pain in the PSS (score 4–10) .There was no correlation between the duration of the disease and the severity of pain .There was a weak negative correlation Sixty-three percent of the 46 ALS patients reported having cramps Table . Thirty-Twenty-eight percent of the controls reported having cramps occasionally Fig.G. CrampsThere was no difference in the duration of ALS disease between (A) patients reporting cramps and those who did not, and (B) patients reporting to take drugs for cramps and those who did not (data not shown).P = 0.4). Fifteen of 31 patient (49%) with none or mild pain in the PSS (score 0–3), and 12 of 15 patients (80%) with moderate to severe pain (PSS score 4–10) reported to experience cramps. Ten out of 15 patients reporting none or mild pain took medication for cramps and 2 out of 12 patients reporting moderate to severe pain (Table The ALS-FRS-R in patients reporting cramps (score 38.5) was nonsignificantly higher compared to those reporting no cramps . Six percent required treatment either with baclofen or tolperisone.On neurological examination, spasticity was present in 11% of the 46 patients with ALS  in ALS patients as compared to controls. However, consistent with Chiò et al. , pain waAmong patients with different neuromuscular disorders, patients with ALS reported the greatest pain interference in the BPI  required specific pain treatment, it is noteworthy that 13% were treated with opioids or opiates. In other case series the percentage of patients receiving therapy for pain was even higher , the absence of a formal evaluation of depression and quality of life, and the lack of a standardized and validated questionnaire to assess cramps in ALS patients.Our study showed that pain was a relatively frequent symptom which had an important impact on the quality of life. Pain that requires treatment can occur at every stage of ALS. Treatment for pain should be recognized as an important aspect of palliative care in ALS. In the absence of any evidence from randomized controlled trials, the treatment of pain should follow the recommendations of the WHO Analgetic Ladder WHO . However


The treatment of low back pain is very challenging due to the recurrent nature of the problem. It is believed that traditional Malay massage helps to relieve such back pain but there is a lack of scientific evidence to support both the practice of traditional Malay massage and the mechanism by which it exerts its effect. The aim of this study is to investigate the immediate effect of traditional Malay massage on the pain scale, substance P, inflammatory mediators, and functional outcomes among low back pain patients.A non-blinded, randomised controlled trial will be conducted. A total of sixty-six patients who fulfil the inclusion criteria will be recruited. The participants will be randomly allocated into intervention  and control (relaxation position) groups. Blood and saliva samples will be collected before and immediately after intervention. All collected samples will be analysed. The primary outcomes are the changes in the level of substance P in both saliva and blood samples between both groups. The secondary outcomes include the levels of inflammatory mediators , the pain intensity as measured by a visual analogous scale and functional outcomes using the Roland-Morris Disability Questionnaire.Massage is a type of physical therapy that has been proven to be potentially capable of reducing unpleasant pain sensations by a complex sensory response and chemical mediators such as substance P and various inflammatory mediators. Previous studies conducted using Thai, Swedish, or other forms of massage therapies, have showed inconsistent findings on substance P levels pre and post the interventions. Each massage genre varies in terms of massage and joint mobilization points, as well as the lumbar spinous process. Traditional Malay massage, known locally as “Urut Melayu”, involves soft-tissue manipulation of the whole body applied using the hands and fingers. This massage technique combines both deep muscular tissue massage and spiritual rituals. This trial is expected to give rise to new knowledge underlying the mechanisms for pain and inflammation relief that are activated by traditional Malay massage.ACTRN12615000537550.Australian New Zealand Clinical Trials  It has been reported that approximately 40–60 % Malaysians suffer from low back pain (LBP) . A recen2+ and K+currents at the cellular level .2 and 29.9 kg/m2. The patients will be excluded if they suffer from identified health problems such as nerve involvement or compression, spinal disorders , neurological deficit , and infectious diseases . Smokers and those experiencing menstruation, pregnancy or febrile convulsion during the study will also be excluded. LBP patients who are taking medication containing analgesics or steroids, and those who have sought treatment for LBP in the past two weeks will also be excluded.LBP patients who fulfil the inclusion criteria, will be screened by a Physiotherapist and Orthopaedic specialist and will be invited to participate in this study. Inclusion criteria will be as follows: has experienced an episode of LBP of more than four weeks’ duration with a score on the visual analogue scale (VAS) of at least 4, is aged between 20 and 40 years old and has a body mass index (BMI) of between 18.5 kg/mAn explanatory statement will be given to those deemed to be eligible to participate, and written informed consent will be obtained before the commencement of the study. Consenting participants will then be randomly assigned into the two groups as described above.The patients in the TMM group will be treated by one certified practitioner of TMM, with the treatment being applied for 30 min in one session only on the area of pain in the lower back. The practitioner will follow the protocol of TMM that has been provided for and approved by the Ministry of Health, Malaysia . The masThe primary outcome measure for this study is the difference in the level of SP in blood and saliva samples pre- and post-intervention. All samples will be analysed at the Collaborative Drug Discovery Research (CDDR) Laboratory, Faculty of Pharmacy, UiTM Puncak Alam Campus.The secondary outcome measures include the levels of inflammatory mediators  in both blood and saliva samples . Other sBoth blood and saliva samples will be collected and centrifuged  to eliminate debris and cellular matter. Then, the Human Substance P EIA kit  will be used to determine the level of SP. Other inflammatory mediators, such as TNF-α , IL-1β , IL-6 (BMS213/2TEN), IL-8 , IL-10 , monocyte chemotactic protein-1(MCP-1)  and the soluble form of the intercellular adhesion molecule (sICAM-1) , will be tested individually in both blood and saliva samples using a human Elisa kit  software 3.1.2 version . The dift-test will be used to measure the differences pre- and post-intervention within and between groups for every outcome measure. A p-value of less than 0.05 will be used to show that the result is statistically significant.Data from participants will be entered into a computerised database and analysed using SPSS software version 20.0. The mean, standard deviation and range will be calculated for each variable. Data will be checked for a normal distribution in terms of skewness and kurtosis, normality test, univariate outliers and missing data. Data will be presented in table and line graphs. The paired angin), which if left untreated can turn into mucus  and finally solid lumps . These effects could relieve and control back pain [This study is designed to investigate how SP and inflammatory mediators might contribute to the pain reduction and inflammation relief apparently offered by TMM. Generally, therapeutic massage involves the manipulation of the soft tissue of the whole body area in a way that contributes to health improvements, including relaxation, improved sleep and specific physical benefits, such as relief of muscular aches and pain . Gentle ack pain , 28.This is the first ever study conducted to quantify the pain and inflammatory mediators present before and after TMM. It must be noted, however, that MacKawan et al.  have preIn Malaysia, TMM is one of the most popular alternative treatments. Thus, the present project, will be the first to provide new knowledge on the immediate effects of TMM on pain and inflammation relief, in the context of investigating the underlying mechanism of relief by reductions in SP. In addition, the control group in this study will be given a relaxation technique rather than a treatment that might show the same effect as massage therapy. Furthermore, other inflammatory mediators will also be measured to show their involvement in the pain and inflammation process among LBP patients. The difference in the response towards treatment among the patients could also lead to genomic related studies investigating the effect of SP in terms of human genetic. Since the current scientific evidence is limited, this experimental study can provide the necessary evidence to prescribe TMM as an alternative or additional complementary treatment for LBP.


Pancreatic cancer is a malignant neoplasm with a high mortality rate, often associated with a delayed diagnosis, the early occurrence of metastasis and an overall, poor response to chemotherapy and radiotherapy. Pain management in pancreatic cancer consists mainly of pharmacological treatment according to the WHO analgesic ladder. Surgical treatment for pain relief, such as splanchnicectomy, is considered amongst the final step of pain management. It has been proven that splanchnicectomy is a safe procedure with a small percentage of complications, nevertheless, it is often used as a last resort, which can significantly decrease its effectiveness. Performance of thoracoscopic splanchnicectomy along the first step of the analgesic ladder may lead to long-lasting protection against the presence and severity of pain.A prospective, open label, 1:1 randomized, controlled trial, conducted at a single institution to determine the effectiveness of invasive treatment of pain via splanchnicectomy, in patients with advanced pancreatic cancer. The size of tested group will consist of 26 participants in each arm of the trial, to evaluate the level of pain relief and its impact on quality of life. To evaluate the influence on patients’ rate of overall survival, a sample size of 105 patients is necessary, in each trial arm. Assessments will not only include the usage of analgesic pharmacotherapy throughout the course of disease, and overall patient survival, but also subjective pain perception at rest, in movement, and after meals (measured by NRS score questionnaire), the patient’s quality of life (measured using the QLQ-C30 and FACIT questionnaires), and any pain-related suffering (measured with the PRISM projection test). The primary endpoint will consist of pain intensity. Questionnaires will be obtained upon the initial visit, the day of surgery, the day after surgery, as well as during long-term follow-up visits, held every two weeks thereafter.Earlier implementation of invasive treatment, such as thoracoscopic splanchnicectomy, can provide a higher efficacy of pain management, prevent deterioration in the patient’s quality of life, and lengthen their overall survival.NCT02424279. Date of registration January 2, 2015.ClinicalTrials.gov identifier:  Difficulties in the treatment of pancreatic cancer are frequently connected to the fact that the diagnosis is often made in the late stages of the disease. Total resection of the lesion is the treatment of choice, but is possible only in less than 20 % of cases . The couOne of the available methods for the treatment of pain associated with pancreatic cancer, is thoracoscopic splanchnicectomy. It has been proven that splanchnicectomy is a safe procedure, with only a small amount of complications , 6, neveThe use of invasive treatment, such as thoracoscopic splanchnicectomy, as part of the first step of the analgesic ladder, can lead to long-lasting protection against the presence and severity of pain, help maintain a satisfactory quality of life despite disease progression, or may even extend the patient’s total survival time due to a reduction in the use and thus decrease in the adverse side effects of analgesic pharmacotherapy, such as the immunosuppressive effect of opioids and common post-prandial ailments leading to decreased nutrient intake.This trial is a prospective, open label, 1:1 randomized, controlled trial, conducted at a single institution. The aim of this study is to determine the effectiveness of invasive treatment of pain via splanchnicectomy, in patients with advanced pancreatic cancer. Assessments will not only include the usage of analgesic pharmacotherapy throughout the course of disease, and overall patient survival, but also subjective pain perception at rest, in movement, and after meals (measured by NRS score questionnaire), the patient’s quality of life (measured using the QLQ-C30 and FACIT questionnaires) , 9, and A flow diagram of the trial is depicted in Fig. The final protocol was approved by the independent ethics committee of the Medical University of Gdansk . Informed consent will be obtained from the patient in both oral and written form prior to inclusion in the clinical trial.Patients of both sexes with unresectable pancreatic cancer  will be considered for inclusion in the study. All tumors of the pancreas will be confirmed histologically. Patients after prior surgical treatment of pancreatic cancer with radical intent will also be allowed to join the study. Patients will be enrolled in the study despite their incidence of pain symptoms and/or the intensity of pain therapy used, according to the WHO analgesic ladder steps 1, 2, or 3.In Poland, according to the National Cancer Registry, about 3,000 patients are diagnosed with pancreatic cancer each year. In our Clinic, we treat about 50 patients per year with this type of carcinoma. We assume that a time period of 24 months will be sufficient enough to enroll a statistically significant group of patients in our trial.Patients with diagnosed pancreatic cancer: both non-operative tumor  and/or after prior surgical treatment.Age over 18 years.Signed informed consent to participate in the study.Age under 18 years.Intellectual inadequacy to complete necessary questionnaires.Coexistence of a disease or disease state in which there is significant chronic pain, which has been identified before the onset of pancreatic cancer.The setting of the study is the Department of General, Endocrine and Transplantation Surgery within the Medical University of Gdansk, Poland.http://www.randomizer.org/). The first group will be offered the invasive treatment of pain with splanchnicectomy through a thoracoscopic approach, while the second group will be offered non-invasive conservative treatment, with the most appropriate available non-invasive pain control (NIPC). At each stage of the clinical trial, patients will be able to convert from the non-invasive intervention group to that of the group with invasive treatment (splanchnicectomy). However, these patients will then be excluded from participation in the clinical trial.Prior to participation in the trial, patients determined as potential candidates will be informed about the purpose of the study and its implementation. In addition, each person will receive detailed information about the trial in writing. Patients will be allowed to review the methodology of the project and discuss any possible questions with their doctor, before they decide to take part in the trial. During their initial visit at the Clinic, participants will again go over the principles of the study. Upon agreement of both the doctor and patient for inclusion in the clinical trial, the patient must then state their intent to enroll in the study, both verbally and with a written consent form. If the patient is currently taking any analgesic pharmacotherapy, a grade according to the WHO analgesic ladder will be assigned to them . PatientEach patient in the invasive intervention group will undergo a thoracoscopic splanchnicectomy. Prior to surgery, all electrolyte disturbances and fluid balance are corrected. A 1000 mg dose of Cefazolin is given as a single dose, thirty minutes prior to surgical incision as antibiotic prophylaxis. The surgery is performed under general anesthesia with endotracheal ventilation. The patient is placed in the flank thoracotomy position, with the initial procedure done on the patient’s left side. The skin and subcutaneous tissue is anesthetized locally with the injection of 0.5 % Bupivacine and then, by the use of two 5 mm ports, access to the left pleural cavity is obtained after lung collapse. Block of T6, T7, and T8 intercostal nerves is performed. The pleural cavity is insufflated with carbon dioxide and maintained at 8 mmHg throughout the procedure. The greater splanchnic nerve is identified at its origin in the sympathetic trunk, then isolated along with its lateral branches to the level of diaphragm and resected. Additional splanchnic nerves may be incised or excised if they are found connected to the greater splanchnic nerve. A pleural drain is inserted for a short period of time during desufflation, and is then removed. The incision points of the ports are closed with single sutures placed on the skin. The same procedure is performed on the patient’s right side. There is no histopathological examination of the excised tissue. Patients are given routine postoperative pain management. The procedure is recorded for future assessment. Patients are allowed to leave the hospital and return home on the first postoperative day.Bilateral thoracoscopic splanchnicectomy has been shown to be a safe and effective procedure with a minimal mortality rate. It ensures precise visualisation of the splachnic nerves endoscopically without the need for a thoracotomy, which minimises blood loss during the procedure. Among the complications that can occur after this procedure, intercostal neuralgia is the most common, and occurs in about 25 % of cases. Less than 2 % of patients can suffer from other complications such as pulmonary atelectasis, chylothorax and orthostatic hypotension.Patients in the non-invasive, conservative treatment group are treated with the most appropriate available non-invasive pain control (NIPC). The therapy is conducted according to WHO and IASP  guidelines. Pharmacotherapy is administered in accordance with the WHO analgesic ladder. The first step medications include non-opioid analgesics: paracetamol, ibuprofen, diclofenac, indometacine, and naproxen. In the second step, drugs from first step are still used, along with mild opioids such as codeine, and tramadol. Finally, the third step includes drugs from second step as well as strong opioids: morphine, fentanyl, oxycodon, and pethidine. Oral or percutaneous administration is the preferred route of administration as opposed to intravenous, subcutaneous or intramuscular administration. The analgesics are given in time-contingent basis. The patient is transferred to next step of the pain management ladder if their pain is stronger than a 6 in the NRS scale and/or if it continues for more than 5 days.Measurements of pain score  will beAfter the initiation of treatment for both the invasive and non-invasive groups, the severity of pain will be measured in each group at two-week intervals during the patient’s follow-up visits in the clinic, or at the patient’s home, if there constitutes a physical or organization impediment to the patient’s abilities to participate in follow-up care. These visits will continue indefinitely, or until the patient’s death. All the measurement points are shown in Table Pain intensity (NRS score questionnaire).Pain impact on quality of life (QLQ-C30 and FACIT questionnaire).Perception of the illness, suffering (PRISM questionnaire).Total need of analgesics.Total lifespan, overall survival time.The effectiveness of splanchnicectomy performed on early stages of pancreatic cancer.Postoperative complications.Analyzing the power of the study, we estimate that a test group of 26 participants in each arm of the trial will be required to be able to evaluate the level of pain relief and its impact on quality of life. To evaluate the influence on the patients’ rate of overall survive, a sample size of 105 patients is necessary, in each trial arm.t test and Mann–Whitney test. Parametric variables will be analyzed using ANOVA and non-parametric variables will be analyzed with chi-square test. Statistical analysis will be performed using Statistica 11 PL licensed to the Medical University of Gdansk, in Poland. Results will be considered statistically significant for p < 0.05. An interim analysis will be performed after 52 patients have been randomized and treated.Continuous data will be presented as the mean ± standard deviation and the range. Continuous variables will be compared between the two groups using an unpaired-sample student Pancreatic cancer is a malignant neoplasm with a high mortality rate, often associated with a delayed diagnosis, the early occurrence of metastasis and an overall, poor response to chemotherapy and radiotherapy , 14. A mPancreatic cancer is a disease associated with severe chronic pain that leads to a dramatic worsening of the patient’s quality of life . Upon inThe main basis for the treatment of chronic pain in pancreatic cancer is the WHO analgesic ladder, which is divided into three stages of intensity, depending on the pharmacotherapy used by the patient . The medThe fourth stage of the analgesic ladder proposes surgical treatment for the management of pain. It is possible to interrupt the conduction of pain impulses along the pain tract at the level of the celiac plexus (celiac plexus block) or splanchnic nerves (splanchnicectomy) .However, present surgical methods such as celiac plexus block or thoracoscopic splanchnicectomy are considered to be reserved only for cases refractory to pharmacological analgesic treatment up to the third level of the analgesic ladder . It has


Background ContextControversy remains over the use of provocative discography in conjunction with computed tomography (CT) to locate symptomatic intervertebral discs in patients with chronic, low back pain (LBP). The current study explores the relationship between discogenic pain and disc morphology using discography and CT, respectively, and investigates the efficacy of this combined method in identifying surgical candidates for lumbar fusion by evaluating outcomes.Methods43 consecutive patients between 2006 and 2013 who presented with refractory low back pain and underwent discography and CT were enrolled in the study. For this study, "refractory LBP" was defined as pain symptoms that persisted or worsened after 6 months of non-operative treatments. Concordant pain was defined as discography-provoked LBP of similar character and location with an intensity of ≥ 8/10. Fusion candidates demonstrated positive-level discography and concordant annular tears on CT at no more than two contiguous levels, and at least one negative control disc with intact annulus. Surgical outcomes were statistically analyzed using Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Short Form-36 (SF-36) for back-related pain and disability preoperatively, and 2 weeks, 3, 6, 12, and 24 months postoperatively.ResultsAnnular tears were found in 87 discs. Concordant pain was reported by 9 (20.9%) patients at L3-L4, 21 (50.0%) at L4-L5, and 34 (82.9%) at L5-S1; pain occurred significantly more often in discs with annular tears than those without (p<0.001). Painless discs were independent of annulus status (p=0.90). 18 (42%) of the original 43 patients underwent lumbar fusion at L3-L4 (n=1(6%)), L4-L5 (n=6 (33%)), L5-S1 (n=5 (28%)), and two-level L4-S1 (n=6 (33%)) via a minimally invasive transforaminal lumbar interbody fusion (MITLIF) approach with the aim to replace the nucleus pulposus with bone graft material. Median follow-up time was 18 months (range: 12–78 months). VAS, ODI, and SF-36 scores demonstrated significant improvements at 10 out of 12 postoperative time points compared with preoperative baseline.ConclusionsLumbar discography with post-discography CT can be an effective method to evaluate patients with discogenic back pain refractory to non-operative treatments. Those patients with one- or two-level high concordant pain scores with associated annular tears and negative control disc represent good surgical candidates for lumbar interbody spinal fusion. Over two-thirds of individuals experience chronic low back pain (LBP) in their lifetime . Some ofA number of factors adversely affect the cellular metabolism of the intervertebral disc, including cigarette smoking, atherosclerosis of segmental arteries, and sudden or sustained weight overload . A commoProvocative discography is a useful technique that complements CT by differentiating anatomically abnormal discs that generate pain from those that do not -11. Disc43 consecutive patients (23 (53%) men, 20 (47%) women, mean age 51.8±11.2) who presented with refractory low-back pain were included in the study. For this study "refractory" patients were defined as those whose pain symptoms persisted or worsened after a minimum of 6 months of non-operative treatments, including but not limited to analgesics, physical therapy, lifestyle modifications, and steroid injections. Comorbidities are summarized in Table For clinical consistency, discography was performed on all patients by the same physician (H.C.T.). All lumbar fusion surgeries were carried out by the senior author (M.J.P.).The benefits and risks of discography were thoroughly discussed with the patient prior to signing informed consent. Sterile fields were created using standard practices for surgical procedures. Fluoroscopy was used to identify the targeted vertebral interspaces and the bony landmarks of the planned, left-sided posterolateral approach. The skin, subcutaneous tissue, and muscle in line with the planned approach were anesthetized with 1% Lidocaine to the posterior portion of the superior articular process. Under fluoroscopy, a 22G or 23G 6" needle was inserted and directed into the central nucleus of each IVD. In this study, the most commonly examined levels were L3-L4, L4-L5, and L5-S1. Next, the testing phase began with 9cc Omnipaque  mixed with 1cc clindamycin 150mg/cc injected separately into each of the tested IVDs in a random manner. The patient maintained constant communication with the examiner during the test. The patient was not informed of which level was being injected during questions about pain response. Injection volume, pain response, and concordance were recorded. Throughout the procedure, the patient was awake and alert. The patient was able to voluntarily move bilateral legs, feet, and toes upon command following the procedure. All procedures were performed by author H.C.T.Concordant pain was defined as provoked, low-back pain of similar character, location, and intensity. For this study, intensity threshold for concordance was set at ≥8/10 on a 10-point scale. Subsequent CT evaluation was performed at each injected level. Radial trans-annular tears that allowed extravasation of radio-opaque dye from the intervertebral disc were considered positive morphological findings. Discs with contained dye within the nucleus pulposus were considered negative. Candidates for interbody arthrodesis satisfied all of the following criteria:1. Demonstrated concordant pain on discography, with annular tears at the same level(s) on post-discography CT.2. Pain with annular tears was found at one or two, but not three or more, contiguous intervertebral levels.3. At least one level of negative control disc (negative discography and negative CT) existed.The decision-making algorithm is illustrated in Figure Lumbar interbody fusion was achieved via a minimally invasive transforaminal approach previously described . Other oThe Student’s t-test was used to comparatively analyze the difference between dye injection volumes in painful discs versus non-painful discs, and to evaluate changes in VAS, ODI, and SF-36 scores from preoperative baseline. The chi-square test was used to evaluate the relationship between annular tears and concordant pain. Statistical significance was defined as p<0.05. All statistical analyses were performed with Microsoft Excel software .A total of 129 intervertebral levels were examined with 126 discs at risk and the remaining 3 previously fused. Disc levels that exhibited concordant pain were L5-S1 (80.5%), L4-L5 (50.0%), and L3-L4 (20.9%). Annular tears were found in 30 (88.2%) patients who reported concordant pain at L5-S1, 18 (85.7%) at L4-L5, and 6 (60.0%) at L3-L4. These results are summarized in Table The volume of injected dye was significantly higher in patients with concordant pain  than those without  (p<0.05). The volume of injected dye was also significantly higher in patients with annular tears  than those without  (p<0.001).Concordant pain occurred significantly more often in discs with annular tears than those without (p<0.001). Painless discs were independent of annulus status (p=0.90) . Both physical and mental components of SF-36 significantly improved from preoperative baseline at the same time points (p<0.05), except for mental component at 2 weeks and physical component at 6 months with discernable improvements that did not reach statistical significance. Overall, good to excellent outcomes  were achieved in 14 (78%) patients. The remaining 4 patients are accounted for in the discussion.Provocative discography with subsequent CT provided basis for lumbar fusion in low-back-pain patients with an etiology of annular damage. In this study, concordant pain occurred significantly more often in discs with annular tears than those without. Non-painful discs occurred equally frequently in both groups, independent of annular status. These results mirror those previously published -11. ContOur data provided a rationale for fusion. Because we found a positive association between pain generation and annular disruption, we believed that arthrodesis of pathomorphological levels would be instrumental in pain relief. The use of post-discography CT was advantageous because of its superior resolution to visualize dye leakage compared with fluoroscopy alone . Discs tThe subjective nature of reported pain is an important confounding factor that may create false positives in discography. Patients with psychometric abnormalities are known to have an exaggerated pain response upon stimulation -20. IndeIt is worth noting that provocative discography is not devoid of issues. It was recently found that discography was more likely than control to be associated with advancement of degenerative disc disease over a 10-year period . The curTo date, there has not been a single, large-scaled, well-designed study that provides unequivocal evidence for or against the use of discography in conjunction with post-discography CT in providing scientific basis for surgical intervention. This is primarily due to the difficulty to control for subjective pain, the issue with sample size, the challenge of long-term follow-up, and perhaps most importantly the lack of a gold standard against which the current diagnostic protocol is compared. These limitations also apply to the current study. In addition, because no control was available for data analysis, it was impossible to conclude if surgical patients performed better than nonsurgical patients based on our criteria, or vice versa. Nonetheless, our data do suggest that discography with imaging is a useful tool that reliably generates significantly positive outcomes. While the ultimate etiology of discogenic pain remains elusive, it is important to factor into surgical decision making both the clinical and morphological manifestations; discography divulges the former and CT the latter. Although reliance on either one alone does not result in desirable outcome, a combination of both is one of the best currently available tools to identify painful degenerative discs.There was a significant association between concordant discogenic pain and annular tears as determined by discography and CT, respectively. Patients who received surgical management based on both positive discography and positive annular tears experienced symptomatic and functional improvements. This study suggests that, in the absence of a “gold standard”, discography in juxtaposition with CT remains a useful diagnostic tool in locating the generator of low back pain. Future research may focus on controlled prospective studies with larger sample size to examine the validity of this method.