Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain.We were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room.p value less than 0.05 was considered as significant.For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A In recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups.Intraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief. Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect -4. The eIn order to evaluate the effectiveness of intraoperative paracetamol administration in the management of postoperative pain and morphine consumption, a standardized anesthesia protocol without long-acting opioid is necessary. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain.Therefore, the present study was designed to evaluate the effect of intraoperative administration of propacetamol during remifentanil-based anesthesia on postoperative pain in patients undergoing reduction mammoplasty.After approval by the Local Ethical Committee and written informed consent, 36 consecutive female patients who underwent elective reduction mammoplasty were included. Exclusion criteria were the preoperative use of analgesic drugs; a body mass index ≥ 35, an American Society of Anesthesiology physical status ≥ 3 and sensitivity to paracetamol. Pain evaluation using a Simplified Numerical Pain Scale (SNPS) was explained to the patients during the preoperative anesthetic visit and the day before surgery. A standardized surgical technique was used for all patients.-1 was given orally 12 h and 2 h before anesthesia as premedication. Before induction of anesthesia, patients were randomly allocated to either Placebo group or Propacetamol group. Randomization was based on computer-generated codes maintained in sequentially numbered, opaque envelopes. The preparation of the propacetamol or saline infusion was done by a nurse who was not in charge of the patient. The anesthetist, the patient and the nurse's staff caring for the patients in the recovery room were unaware of the treatment group. In both groups, anesthesia was induced with propofol 2.5 mg.kg-1 followed by a slow bolus (1 min) of remifentanil 1 mcg.kg-1. Tracheal intubation was facilitated by atracurium 0.5 mg.kg-1. Anesthesia was maintained with remifentanil 0.1 mcg.kg-1.min-1 and isoflurane  with nitrous oxide (N2O) in 50% oxygen. Remifentanil infusion rate was increased or decreased by 0.05 mcg.kg.min-1 in order to maintain an arterial systolic pressure of 20% more or less than the baseline value. One hour before the end of surgery, which corresponded to the beginning of the skin closure, patients received either propacetamol 2 g in 50 cc saline (Propacetamol group) or 50 cc saline alone (Placebo group) infused over 10 min. At the end of surgery, administration of isoflurane and N2O were withdrawn and the patient was transferred in the recovery room. The anaesthetist, the patient and the nurse's staff caring for the patients in the recovery room were unaware of the treatment group. Remifentanil infusion was interrupted when the patient arrived in recovery room. Tracheal extubation was performed within a few minutes after remifentanil discontinuation. Clinical monitoring included heart rate, blood pressure, pulse oxymetry, respiratory rate, and sedation score .Hydroxyzine 2 mg.kgFrom the time of extubation, pain was evaluated on using a SNPS  and intravenous 2 mg morphine was administered on request every 5 min until pain relief (SNPS<4). When pain relief was reached, SNPS was subsequently evaluated every 15 min. Morphine was interrupted when the sedation score went up to 1, systemic arterial pressure < 80 mmHg or respiratory rate less than 8/min. During the data collection period, intravenous morphine titration was further administered if SNPS was up to 4. Patients did not receive antiemetic prophylaxis. If post-operative nausea and vomiting (PONV) occurred, metoclopramide 10 mg and ondansetron 4 mg if necessary were intravenously administered.Patients fulfilling Aldrete criteria  were disMorphine requirement, pain and sedation scores were measured every 5 min until pain relief was obtained. When SNPS was below 4 during 15 min, parameters were subsequently recorded every 15 min. Morphine side effects  and need for supplemental medications  were also recorded.The total dose of morphine in recovery room was the primary end point. Pain scores after extubation and one hour after tracheal extubation, delay for morphine requirement, delay for pain relief and incidence of morphine side effects were recorded.p value less than 0.05 was considered as significant. Anticipating a standard deviation of 2.49 [Data are expressed as mean (± standard deviation) for quantitative variables normally distributed, or otherwise as median (25th – 75th percentiles) when data were not normally distributed, and as percentage for categorical variables. Data were analyzed using Statview 5.0 software . For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A  of 2.49 , it was Thirty-six patients were included during a 12 months period: 19 in Propacetamol group and 17 in Placebo group  and 4 patients had vomiting , no other side effects were observed. In one patient receiving placebo, morphine titration was interrupted because of nausea and vomiting.This study shows that propacetamol administered one hour before end of surgery reduced the morphine dose given over the first four postoperative hours and shortened the elapsed time to obtain a SNPS under 4 in patients undergoing elective reduction mammoplasty. In our study, surgical technique and anesthetic protocol were similar in both groups. Remifentanil was the only analgesic used during anesthesia period and was interrupted before morphine administration. Thus, the beneficial effect on postoperative pain observed is clearly linked to intraoperative administration of propacetamol.In a recent study , VerchèrOur results are apparently at variance with those of other previous studies. Paracetamol given rectally immediately after induction of anesthesia  or at th-1) pain score and analgesic demand were significantly reduced in the early postoperative period [Cobby and colleagues observed a morphine sparing effect when paracetamol 1.3 g was administered rectally at the end of hysterectomy . One expe period .The presently observed incidence of postoperative nausea and vomiting was of 25% and was similar to that of a previous study . DespitePropacetamol was administered at the beginning of skin closure, which corresponds to one hour before the end of surgery. This delay may be insufficient to achieve pain control immediately after tracheal extubation, as the peak effect of intravenous propacetamol was shown to occur only two hours after its administration . NeverthIn summary, intraoperative propacetamol administration in women undergoing reduction mammoplasty improved significantly early postoperative pain in recovery room, and should be recommended for postoperative pain management.The pre-publication history for this paper can be accessed here:


The Steno hypothesis states that changes in basement membrane anionic charge leads to diabetic microvascular complications. In diabetic nephropathy, loss of basement membrane glycosaminoglycans and the association between glomerular basement membrane heparan sulphate and proteinuria has been documented. A correlation between erythrocyte surface and the glomerular capillary wall charges has also been observed.The aim of this study is to evaluate the relationship between retinopathy and erythrocyte anionic charge and urinary glycosaminoglycan excretion in type 2 diabetic patients.49 subjects  with type 2 diabetes with proliferative retinopathy (n = 13), nonproliferative retinopathy (n = 13) and without retinopathy (n = 23) were included in the study. 38 healthy subjects were selected as control group . Erythrocyte anionic charge (EAC) was determined by the binding of the cationic dye, alcian blue. Urinary glycosaminoglycan and microalbumin excretion were measured.6 RBC, 312 ± 30 ng alcian blue/106 RBC for diabetic and control groups respectively, p < 0.001). We did not observe an association between urinary GAG and microalbumin excretion and diabetic retinopathy. EAC is found to be negatively corralated with microalbuminuria in all groups.EAC was significantly decreased in diabetic patients with retinopathy (255 ± 30 ng alcian blue/10We conclude that type 2 diabetic patients with low erythrocyte anionic charge are associated with diabetic retinopathy. Reduction of negative charge of basement membranes may indicate general changes in microvasculature rather than retinopathy. More prospective and large studies needs to clarify the role of glycosaminoglycans on progression of retinopathy in type 2 diabetic patients. PrevErythrocyte anionic charge by itself is unlikely to be important in the pathogenesis of diabetic retinopathy but reduced RBC alcian blue binding was found to be associated with the loss of glomerular basement membrane anionic charges in diabetic rats and patients . ChangesSeveral authors have questioned the validity of the alcian blue binding assay. The major objections concern the incomplete alcian blue dissolution in PBS buffer and its tendency to precipitate with time ,23. We pDiabetic retinopathy is characterized by gradually progressive alterations in the retinal microvasculature leading to vascular hyperpermeability, capillary occlusion and ultimately neovascularization. Thickening of the retinal microvascular basement membrane and loss of anionic content are well documented morphological features of diabetic retinopathy ,21,24. TGlycosaminoglycan primarily heparan sulfate has been implicated in permeability properties of basement membrane of glomerular basement membrane as well as the retinal basement membrane . Kahaly Systemic treatment of IDDM patients with proteinuria with danaparoid sodium, a glycosaminoglycan, not only reduced proteinuria, but also decreased the number of hard exudates in the retina . StudiesIn this study we found that urinary GAG excretion is increased in diabetic patients than healthy controls, but there was no difference in GAG excretion between nonproliferative and proliferative retinopathy patients. We couldn't find a correlation between GAG excretion and EAC but we found a correlation between albumin excretion and EAC. Although our working hypothesis is that the reduction in anionic charge in basement membranes may be due to an abnormal GAG metabolism, we couldn't confirm it with this study.Our study did not directly address the pathophysiology of diabetic retinopathy but a reduction in erythrocyte charge perhaps connected with the properties of retinal basement membrane.Several reports suggest that elevated serum sialic acid levels in type 1 and type 2 diabetic patients indicate microvascular damage ,33. In oWe conclude that type 2 diabetic patients with low erythrocyte anionic charge are associated with diabetic retinopathy. Reduction of negative charge of basement membranes may indicate general changes in microvasculature rather than retinopathy. More prospective and large studies needs to clarify the role of glycosaminoglycans on progression of retinopathy in type 2 diabetic patients.BMI: Body mass indexEAC: Erythrocyte anionic chargeGAG: GlycosaminoglycanPBS: Phosphate buffered salineRBC: ErythrocytesGAG : Urinary glycosaminoglycanUThe authors declare that they have no competing interests.YB : Evaluated laboratory parameters. Designed the study. Wrote the paper.HD: Diagnosed outpatients according to American Diabetes Association criteria.MA: Examined ocular fundus after dilation of the pupils and classified according to the severity of retinopathy.DY: Performed the analysis of the data with a PC compatible Instat-II programme. Improved the manuscript.The pre-publication history for this paper can be accessed here:


Personal Digital Assistants (PDAS) are rapidly becoming popular tools in the assistance of managing hospitalized patients, but little is known about how often expert recommendations are available for the treatment of infectious diseases in hospitalized patients.To determine how often PDAs could provide expert recommendations for the management of infectious diseases in patients admitted to a general medicine teaching service.Prospective observational cohort studyInternal medicine resident teaching service at an urban hospital in Dayton, Ohio212 patients (out of 883 patients screened) were identified with possible infectious etiologies as the cause for admission to the hospital.Patients were screened prospectively from July 2002 until October 2002 for infectious conditions as the cause of their admissions. 5 PDA programs were assessed in October 2002 to see if treatment recommendations were available for managing these patients. The programs were then reassessed in January 2004 to evaluate how the latest editions of the software would perform under the same context as the previous year.PDAs provided treatment recommendations in at least one of the programs for 100% of the patients admitted over the 4 month period in the 2004 evaluation. Each of the programs reviewed improved from 2002 to 2004, with five of the six programs offering treatment recommendations for over 90% of patients in the study.Current PDA software provides expert recommendations for a great majority of general internal medicine patients presenting to the hospital with infectious conditions. PDAs  are becoming widely used in medicine. A survey done by the America College of Physician predicted that 67% of physicians would be using PDAs by the end of 2002 . These dOne medical specialty which has focused on PDA's application in medicine is infectious diseases . There aMiami Valley Hospital is an 827 bed secondary and tertiary referral center, in Dayton, Ohio. It is an urban hospital that averages over three-thousand patient admissions per month. The internal medicine resident teaching service consists of two teams, each team with 2 senior residents and 2 interns who are supervised by an attending physician. There is a senior resident and intern on call in the hospital at all times. Patients were eligible to be admitted to resident's service if they were established within the Medical-Surgical Health Center of Miami Valley Hospital, if they were uninsured or if they had insurance but were without a local physician (a.k.a. private unattached patients). The general medicine teaching service averages approximately eight admissions per twenty-four hour period.Mandell, Douglass and Bennett's Principles and Practice of Infectious Disease (PPID) (8) (Table The patients were screened prospectively over a four month period (July 2002 through October 2002). The admitting senior resident prospectively recorded the chief complaint and initial differential diagnosis for each patient. One of us (SDB), as the chief resident during these months, gathered the data during morning report. Patients were considered appropriate for the study if they had a leading diagnosis or active alternatives that suggested an infectious disease at the time of admission. Cases selected were then assigned categories based on the "major clinical syndromes" from 8) Table . Syndrom (SG) [ (JHABx) [) (5MID) [) (5MCC) [) (PMID) [) (QID) [A Sony Clie T615C  was the device used to access the software, but all programs evaluated were also available in the Pocket PC format . Five PDA programs were initially searched to determine if expert recommendations were available. Software was chosen based on its availability to both the Palm OS and the Pocket PC and at the time of the initial software evaluation were the primary infectious disease programs available (since 2002 numerous other titles have been released to address infectious diseases). The PDA programs included: Sanford's Guide to Antimicrobial Therapy  (SG) , John's ) (5MID) , 5-Minut) (5MCC) , and Poc) (PMID) . The ini[) (QID)  was alsoA minimum of three attempts were used to locate conditions within each program. Searching was done using either the disease name or clinical problem that had led to the patient's admission. Synonyms were used when appropriate to increase the possibility of locating a condition within each program . Programs that were organized according to organ system  were searched within the appropriate organ system, while programs that listed diagnoses alphabetically were searched accordingly. Expert recommendations were considered to be present and thus counted as a positive if the software had treatment recommendations present, whether related to antibiotic decision or "supportive care."In order to determine the change in software capabilities over a 14 month period, the same patient data set was used to assess software programs in January of 2004. A comparison of the programs was then performed comparing the availability of expert recommendations.The data was collected by a single physician (SDB) and then validated independently by a second physician (TEH). The data was analyzed using descriptive statistics with simple frequencies and the confidence intervals were calculated according to standard formulas.Over the four month period, from July through October of 2002, there were 883 patients admitted to the resident service, of whom 212 had syndromes that were suspected on admission to be infectious in etiology (202 of which could be assigned to the pre-defined categories)  familiar with both the PDA and the aforementioned software looking for management recommendations. This usually included antibiotic recommendations and occasionally recommendations regarding further evaluation. The possibility that we did not find recommendations which were indeed available seems unlikely because of the previously mentioned points as well as a systematic approach using multiple synonyms. Furthermore, the data was independently reviewed by a second physician and no inconsistencies were identified.A third potential limitation is that of reproducibility. Since searching was done by an experienced user, searching errors would be more likely with less experienced user(s). Many of the programs require persistent use to learn the nuances and style of the programs and how to best access information. Therefore, in order for others to duplicate our results, users will need to develop some profiency with the software and be willing to perform searches using multiple synonyms.Lastly, our study may have limits to its applicability. Our patients were admitted to an inpatient general internal medicine teaching service at an urban hospital in the United States. These data probably apply to similar inpatient services elsewhere within North America, but may not apply to either other specialty services  or hospitals in other parts of the world.While the limitations mentioned above apply to this study, they can also be expanded to include limitations in the software. No physician can access a software program for the first time and be expected to take full advantage of the recommendations available. It takes time and effort to maximize the clinical utility that is available on the PDA, which unfortunately, many clinicians do not accomplish. This paper was focused on treatment recommendations and did not evaluate the ability of the individual programs to assist with diagnosis. The diagnostic data and information other than treatment recommendations varies from program to program. This could be a topic for future research or may be available in other formats such as software reviews in PDA magazines.This study demonstrates that these infectious disease programs have improved over time table . The reaDespite these potential limitations, our data suggests that PDAs provide expert recommendations for the majority of infectious clinical conditions encountered in practice by non-infectious disease general physicians. Since a majority of patients admitted to the hospital receive care from clinicians who are not specialists in infectious diseases, PDA's have the potential to have an impact on the quality of initial care by guiding not only the choice of antibiotics but also diagnostic testing and when to involve infectious disease specialists. Further research is needed to examine the efficiency of use; evidence supporting the recommendations, and the clinical impact of the use of these resources.


Breast pain and tenderness affects 70% of women at some time. These symptoms have been attributed to stretching of the nerves with increase in breast size, but tissue mechanisms are poorly understood.Eighteen patients (n = 12 breast reduction and n = 6 breast reconstruction) were recruited and assessed for breast pain by clinical questionnaire. Breast skin biopsies from each patient were examined using immunohistological methods with specific antibodies to the capsaicin receptor TRPV1, related vanilloid thermoreceptors TRPV3 and TRPV4, and nerve growth factor (NGF).TRPV1-positive intra-epidermal nerve fibres were significantly increased in patients with breast pain and tenderness . Nerve Growth Factor, which up-regulates TRPV1 and induces nerve sprouting, was present basal keratinocytes: some breast pain specimens also showed NGF staining in supra-basal keratinocytes. TRPV4-immunoreactive fibres were present in sub-epidermis but not significantly changed in painful breast tissue. Both TRPV3 and TRPV4 were significantly increased in keratinocytes in breast pain tissues; TRPV3, median [range] – no pain group, n = 6, 0.75 [0–2]; pain group, n = 11, 2 [8; p = 0.Increased TRPV1 intra-epidermal nerve fibres could represent collateral sprouts, or re-innervation following nerve stretch and damage by polymodal nociceptors. Selective TRPV1-blockers may provide new therapy in breast pain. The role of TRPV3 and TRPV4 changes in keratinocytes deserve further study. Breast pain is a common problem, which can affect up to 70% of women . Breast The mechanisms of breast pain in the majority of women are not well understood at the cellular or molecular level. We hypothesized a relationship between clinical breast pain, nerve growth factor (NGF) and its regulated ion channels or receptors expressed by nociceptor fibres. Estrogens upregulate NGF receptor mRNA in sensory neurons , and enhEighteen patients were recruited  at Chelsea and Westminster, Charing Cross, Ravenscourt Park Hospitals in London and Broomfield Hospital in Essex were recruited. Breast reduction patients had no previous surgery. The breast reconstruction patients had Latissimus dorsi flap reconstructions after previous mastectomies, and had implants. Patients below 18 years or above 70 years, with any local skin inflammation, infection or cancerous skin changes were excluded. The Research Ethics Committee of Hammersmith Hospitals Trust and Mid Essex Hospitals Trust gave ethical permission for the study. Informed consent was obtained prior to the clinical examination and questionnaire administration.Age, parity, height, weight and menstrual data were collected. Details of current surgery, any previous breast surgery and breast disease were also recorded. A questionnaire which included questions on breast and period pain was administered, a diagram to indicate painful and tender areas and the 78 pain descriptors from the McGill Pain Questionnaire  were proFull thickness skin biopsies were collected from each patient along the incision line of about 2 mm depth. Samples were coded, frozen on site and stored at -70°C. The skin samples were mounted in embedding medium . Frozen tissue sections (10 μm) were collected onto poly-L-lysine-coated (Sigma Poole Dorset UK) glass slides and post-fixed in freshly prepared, 4% w/v paraformaldehyde in phosphate buffered saline . After washing in PBS, endogenous peroxidase was blocked by incubation with 0.3% w/v hydrogen peroxide in methanol. After a further wash in PBS the tissue sections were incubated overnight with affinity purified antibodies to TRPV1 , TRPV3 , TRPV4 , recombinant human NGF  or marker of large and some small calibre nerve fibres . Methodological controls included omission of primary antibodies, or their replacement with pre-immune serum. Specificity of antibodies has been described in previous publications ,20. SiteA non-parametric, two tailed test (Mann Whitney U) was used. Commercially available statistical software was used to perform the test (Prism 3™).Pain Rating Indices (PRI) and Visual Analogue Scores (VAS) were used to group patients with (n = 10) and without (n = 8) breast pain: pain group; PRI -Median (range) 12 (4–30); Mean (SEM) 13.44(3.07) and VAS – Median (range) 5(3.7–6.7); Mean (SEM) 5.14(0.31)]; in patients without breast pain, PRI and VAS were zero. Only 2 patients reported thermal pain descriptors , while most reported ache and tenderness. The numbers of breast reduction and reconstruction patients with pain were 7 out of 12 and 3 out of 6 respectively, and all reported pain of duration greater than 6 months. The presence (n = 8) or absence (n = 10) of dysmenorrhoea was also recorded. There was no association between breast pain and the presence of dysmenorrhoea.TRPV1-immunoreactive fibres were present mainly in the sub-epidermis in normal (pain free) skin Fig. . In breaTRPV3 immunoreactivity was detected in basal keratinocytes and occasional suprabasal cells throughout the epidermis. Quantification of immunostaining showed a significant (*P = 0.011) increase with breast pain  and the expression of the capsaicin receptor 1 (TRPV1) in nociceptor fibres, as these are key molecules in pain and hypersensitivity. Our finding, that TRPV1-positive intra-epidermal fibres were significantly increased in patients with breast pain and tenderness, is both novel and important. The increased and abnormal "clusters" of intra-epidermal fibres were shown in patients who had no previous breast surgery, and no known episodes of mastitis. Hence this may be a surrogate marker for "idiopathic" or macromastia related breast pain in some patients. Studies are in progress to correlate changes in TRPV1 nerve fibres with quantitative sensory perception thresholds.The cause of the increased intra-epidermal fibres is not known. Given the trend to thinning of the epidermis, normally associated with denervation , in the Our recent studies have demonstrated increased TRPV1-immunoreactive nerve fibres in inflammatory bowel disease , and in Little is known of the roles of TRPV3 and TRPV4 in human pain pathophysiology and keratinocyte function. While we have previously demonstrated TRPV3 in human sensory neurons , no TRPVBreast pain and tenderness appears to be associated with abnormal intra-epidermal innervation. This may reflect re-innervation of skin following nerve stretch damage, and/or collateral sprouting. While further studies are necessary to establish functional links between the TRPV1, TRPV3 and TRPV4 immunohistological changes and breast pain, our findings indicate a path for increasing understanding and treatment of breast pain.TRPV = transient receptor potential vanilloid; NGF = Nerve Growth Factor; VAS = Visual Analogue Score; PRI = Pain Rating IndexThe author(s) declare that they have no competing interests.PG and EW recruited patients, collected biopsies and participated in immunohistology studies. PF participated in immunohistology and coordination of the study. AH participated in design of the study and recruitment of patients. JD, GS and CB provided antibodies and helped draft the manuscript. PA conceived the original study, its design and coordination, and helped with the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The Shoulder Pain and Disability Index (SPADI) is a self-report measure developed to evaluate patients with shoulder pathology. While some validation has been conducted, broader analyses are indicated. This study determined aspects of cross-sectional and longitudinal validity of the SPADI.Community volunteers (n = 129) who self-identified as having shoulder pain were enrolled. Patients were examined by a physical therapist using a standardized assessment process to insure that their pain was musculoskeletal in nature. This included examination of pain reported during active and passive shoulder motion as reported on a visual analogue pain scale. Patients completed the SPADI, the Coping Strategies Questionnaire (CSQ) and the Sickness Impact Profile (SIP) at a baseline assessment and again 3 and 6 months later. Factor analysis with varimax rotation was used to assess subscale structure. Expectations regarding convergent and divergent subscales of CSQ and SIP were determined a priori and analysed using Pearson correlations. Constructed hypotheses that patients with a specific diagnosis or on pain medication would demonstrate higher SPADI scores were tested. Correlations between the observed changes recorded across different instruments were used to assess longitudinal validity.The internal consistencies of the SPADI subscales were high (α > 0.92). Factor analysis with varimax rotation indicated that the majority of items fell into 2 factors that represent pain and disability. Two difficult functional items tended to align with pain items. Higher pain and disability was correlated to passive or negative coping strategies, i.e., praying/hoping, catastrophizing on the CSQ. The correlations between subscales of the SPADI and SIP were low with divergent subscales and low to moderate with convergent subscales. Correlations, r > 0.60, were observed between the SPADI and pain reported on a VAS pain scale during active and passive movement. The two constructed validity hypotheses (on diagnosis and use of pain medications) were both supported (p < 0.01). The SPADI demonstrated significant changes over time, but these were poorly correlated to the SIP or CSQ suggesting that these scales measure different parameters.The SPADI is a valid measure to assess pain and disability in community-based patients reporting shoulder pain due to musculoskeletal pathology. The shoulder pain and disability index (SPADI)  is a selA second group of investigators conducted a larger validation study in 1995 . This stSupport for validity in these initial situations encouraged others to use the SPADI in clinical practice and research. Additional studies were conducted to examine the validity of the SPADI either in isolation or in comparison to other shoulder instruments -14 Thes. All havThe SPADI is only one of many joint-specific self-report forms that focuses on the shoulder. Previous narrative reviews have reflected this spectrum . More reParticipants were 129 community volunteers who self-identified in response to newspaper ads or clinic posters recruiting patients having shoulder pain. All participants completed a screening examination that included self-report measures and physical assessment by a physical therapist. Subjects who were unable to read or write in English were excluded from the study. Subjects were participating in a larger study examining behavioural measures of pain.The study was approved by the McMaster University Research Ethics Board.All patients were examined using a standardized physical examination to insure the pain was attributable to musculoskeletal dysfunction. This assessment included joint irritability, which was assessed by having the patient rate on a VAS pain scale, the extent of pain with active and passive shoulder movement . For this study, these scores were averaged.All subjects completed the numeric version of the SPADI Figure  1]. The. The1]. The CSQ  is a 44-The SIP -21 has 1Most subjects had some form of physical therapy for their shoulder problem, i.e., 82% for the total population. See Table All data analyses were conducted using SPSS 13.0. The distributions of our scores, skewness and kurtosis suggested data were normally distributed. Internal consistency was determined using Cronbach's alpha. Validity was evaluated by conducting three types of validation analyses: factor, construct and longitudinal. Factor analyses with and without varimax rotation were used to evaluate the factor structure of the SPADI. Cross-sectional construct validity analyses were performed separately at each of the 3 time-points. Longitudinal validity was determined across the 3 assessment points by correlating changes observed on different instruments.Convergent and divergent validity were determined by comparing correlations with SPADI scores across related aspects of pain behaviour (CSQ) and the general health scale (SIP) using Pearson r correlations. SPADI scores were also correlated to joint irritability scores. The clinical significance of correlations is debatable, as a variety of benchmarks have been described. We described the association of different constructs using correlations and rated the effect size of these as defined by Cohen where the effect sizes for correlation coefficients are: r ≈ 0.10 is small effect with negligible practical importance, r ≈ 0.30 is a medium effect with moderate practical importance and r ≈ 0.50 is a large effect of crucial practical importance .Construct validity was evaluated by testing two hypotheses. The first hypothesis was that subjects with diagnosed shoulder problems would have more severe pathology, and therefore more pain and disability than those who complained of shoulder pain, but did not have a specific diagnosis. The second hypothesis was participants who were taking pain medication for their shoulder problem would have higher SPADI scores. These hypotheses were tested using a generalized linear model (ANOVA), which evaluated the changes across the repeated factor (time) and between the two hypothesis-groups (medication or diagnosis hypotheses tested). Finally, longitudinal validity was evaluated by correlating changes on the SPADI to changes in pain subscales on the SIP that were expected to be affected by shoulder pain, i.e., home maintenance and physical health.Patient characteristics are in Table This study provides additional support for the use of the SPADI as a measure of pain and disability in patients with shoulder pain. Despite the availability of outcome measures specific to upper extremity it has been shown that the rates of utilization of self-report measures are low in clinical practice . Brevityoverhead reaching and carrying heavy objects tended to load with pain in 2/3 of the evaluations. This may reflect that these higher demand activities are most painful for patients with shoulder problems. In one case, a pain item that included a functional component (reaching) loaded with disability items. Others have questioned the extent to which functional items are independent from pain items on the WOMAC's assessment of lower extremity musculoskeletal problems, particularly when items ask about pain during a functional task [Some of the current findings substantiate the results of previous validation. For example, Roach  originalnal task ,27. Our Previous studies have compared SPADI scores to shoulder motion and found that patients with better movement had less pain and disability . We haveOther studies have correlated the SPADI with instruments measuring function , pain or general health (SF-36). Our results are in general agreement with others who have reported that upper extremity instruments, including the SPADI are moderately related to physical subscales of the SIP ,28,29. OThis study adds to previous validation studies in that a novel scale that addresses pain coping behaviour was included. This provides broader support for the SPADI and new information on the relationships between different aspects of pain coping and pain reporting on the SPADI. We were able to determine that negative or passive coping strategies were associated with higher levels of reported disability at each cross-sectional analysis. Previous research has illustrated the importance of pain catastrophizing as a determinant of self-reported pain or disability in other musculoskeletal problems -41. OtheThis study validates the SPADI for usage in patients presenting at the primary care level with shoulder pain. Our study did not determine the specific diagnosis, although a physical therapist confirmed it was of a musculoskeletal nature. Therefore, it was impossible to determine which patients had resolution of their problem, preventing traditional responsiveness analyses. A further limitation is that we did not compare the SPADI to competing shoulder instruments. Despite these limitations, this study indicates that the SPADI detects change over time in excess of that reported on the SIP and that the extent of this change fits with constructed hypotheses. This supports the validity of the SPADI as a measure of shoulder pain and disability. This study also highlights that patients with different responses to pain may report pain and disability differently confirming the importance of serial measurements when assessing the response to interventions and suggesting that further study on this phenomena and how it relates to treatment response is warranted. Given the number of shoulder instruments reported in the literature, head-to-head comparisons determining the ability of different scales to detect treatment responses in different clinical situations are needed.This study provides additional support for the validity of the SPADI in clinical evaluation of shoulder pain and disability in that it discriminates between levels of pain and disability in a community-based sample. It provides new information suggesting that negative pain coping strategies are associated with greater self-reported pain and disability. Future studies should focus on comparing competing measures to encourage greater uniformity or comparability across future clinical outcomes studies.The author(s) declare that they have no competing interests.PS and KP formed the original study team that obtained the ethics approval and obtained grant funding for a study on facial recognition of pain. JM consulted on shoulder scales during grant development and worked with PS to develop the research questions around instrument validation. PS coordinated data collection/management. JM conducted statistical analyses and drafted the manuscript. All authors approved the final study protocol, contributed to interpretation of the study results and participated in revisions of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:Supplementary Tables 1–3 On Reliability, Validity and Responsiveness of SPADI reported in previous studies (word file with tables).Click here for file


The Brief Pain Inventory (BPI) is recommended as a pain measurement tool by the Expert Working Group of the European Association of Palliative Care. The BPI is designed to assess both pain severity and interference with functions caused by pain. The purpose of this study was to investigate if pain interference items are influenced by other factors than pain.We asked adult cancer patients to complete the original and a revised BPI on two study days. In the original version of the BPI the patients were asked how, during the last 24 hours, pain has interfered with functions. In the revised BPI this question was changed to how, during the last 24 hours, these functions are affected in general. Heath related quality of life was assessed at both study days applying the European Organization for Research and Treatment of Cancer quality of life questionnaire.Forty-eight of the 55 included patients completed both assessments. The BPI pain intensities scores and the health related quality of life scores were similar at the two study days. Except for mood this study observed no significant distinctions between the patients' BPI interference items scores in the original (pain influence on function) and the revised BPI . Seventeen patients reported higher influence from pain on functions than the total influence on function from all causes.We observed similar scores in the original BPI interference scores (pain influence on function) compared with the revised BPI interference scores . This finding might imply that the BPI interference scale measures are partly responded to as more of a global interference measure. Pain is a one of the major distressing symptoms experienced by patients with a malignant disease. To monitor the efficacy of pain treatments it is important to have valid methods for pain measurements. Such pain assessments should be easily completed and communicated. It is generally recognised that pain measurement should use methods based on patients' self-report. Numeric scales are easy to understand and easy to score and have for these reasons been endorsed for use in both in cancer clinical trials and trials of chronic non-malignant pain ,2.Cleeland and colleagues developed the Brief Pain Inventory (BPI), a questionnaire designed to assess both pain severity and the interference from pain on seven areas of daily life . The BPIWe included 55 in-patients at the Department of Oncology at St. Olavs Hospital, a 400-bed tertiary university hospital. Patients, who had an established diagnosis of cancer and who were at least 18 years of age, were eligible. Patients with cognitive failure, with planned hospitalisation less than 4 days or with scheduled surgery in the study-period were not included. All patients were naive to the BPI questionnaire.Demographic data were collected from the patients' hospital records. We registered age, gender, malignant diagnosis, date for diagnosis, anticancer treatment (former and ongoing) and all medications on both observations. The patients' functional status was assessed using the Karnofsky score .To provide information regarding health related quality of life (HRQOL) we used the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire . It has The first part of the BPI measures pain severity using four different 11-point numeric scales anchored by 0 representing "no pain" and 10 being "pain as bad as you can imagine". Patients are instructed to rate their pain now and worst for the last 24 hours, least for the last 24 hours and average pain. The second part of the BPI measures how pain interferes with general activity, mood, walking, normal work, relationships with others, sleep and enjoyment of life. Similar to pain severity each functional item is ranked on an 11-point numeric scale, where 0 represents "Does not interfere" and 10 denotes "completely interferes". The sum of the scores of the pain intensity items represents the summed pain intensity score and the sum of the scores on the pain interference items represent the summed interference score. Because BPI has no validated method for handling missing values the summed scores were not calculated for patients with missing values.This study compared the original BPI with a revised version. In the original BPI the patients are asked to "Circle the one number that describes how, during the last 24 hours, pain has interfered with your general activity, mood, walking ability, normal work, relations with other people, sleep or enjoyment of life". In the revised BPI, designed for this study, this question was changed to "Circle the one number that describes how, during the last 24 hours, these functions are disturbed". In both versions of the BPI this question was written in bold letters. The numeric rate scale (0–10) and the anchor descriptive statements were identical in the original and in the revised BPI.The participants were asked to complete the BPI  and the EORCT QLQ-C30 on both study days. The sequence of the BPI questionnaires was randomised and an equal number of the patients received the original and the revised version of the BPI at the first study day fig. . In ordeThe Regional Committee for Medical Research Ethics, Health region IV, Norway, approved the study, and all patients gave their oral and written informed consent before inclusion into the study.within for use in this sample size calculation we used a SDwithin of 1.2. Thus, we assumed that half of the variation is due to within subjects variation and half of the variation is due to between subjects variation. For paired observations, significance level of 0.05, power of 0.90 and two-sided tests the appropriate sample size was 27 paired observations [In the sample size calculation for the study we used a clinical difference of interest of two points on the 11-point numeric rate scale . The poprvations . AllowinStatistical comparisons between the trial days were performed using paired Student t-test for continuous data and Wilcoxon-test for categorical variables.The statistical software SPSS version 11.02 for Windows was used throughout the analyses.We approached 65 patients who met the criteria for inclusion in the study. Ten patients refused to participate in the study. Of the 55 patients who were included into the study seven patients did not answer the second scheduled administration of the questionnaires .The patient sample consisted of 24 males and 31 females, with a mean age of 66  years. The most prevalent diagnoses were breast cancer (31%), colorectal cancer (18%), malignant lymphoma (11%) and lung cancer (9%). Sixty percent of the patients had confirmed cancer metastases. The Karnofsky score ranged from 30 to 100, with a mean score of 82. Twenty-four patients had received anticancer treatment prior to inclusion , whereas 23 of the patients received anticancer treatment during the survey .Sixteen percent of the patients received regular scheduled analgesics , whereas 24 percent of the patients used analgesics when needed.We observed no statistical significant differences between the trial days in the EORTC QLQ-C30 pain scores Table . The patSeven of the completed BPI questionnaires had one or two missing items. As shown in Table We observed similar scores in the original BPI interference scores (pain influence on function) compared with the revised BPI interference scores . This finding suggests that it is difficult for patients to interpret the contribution from pain on functional limitations. This finding was further emphasized by that 17 patients reported a higher summed interference scores from pain interference on functions than the total summed interference on functions from all causes This observation means that some patients interpret the influence from pain on function as higher than the total reduction of function, a result that demonstrates an inability for these patients to decipher the specific influence from pain on function. The finding in this study also is in accordance in previous studies showing that pain interference scores are in general higher in patients with decreased all over functional performance ,7.In our study only about 40 % of the patients received analgesics and the pain ratings were generally low. These observations show that the majority of patients included in this study did not suffer from severe pain. Despite the reports of low intensities of pain several patients reported that pain influenced functions. This finding of pain interference in patients without any major pain further demonstrates the inability to deline pain influence on functions from functional limitations related to other causes. However, because of low pain intensities the observations in this study can not be generalized to patients with severe cancer pain. Furthermore, the patients in this study had in general a high level of function. Thus, a study including patients with more pain and more complex symptoms burden is indicated in order to study the BPI measure of influence on function on pain in patients with more advanced cancer disease. Furthermore, new studies should investigate if BPI validity changes in studies including patients with non-malignant chronic pain.In studies comparing two different versions of a questionnaire it is critical to choose an ideal time interval between the paired observations. A short time interval gives a risk for recall bias, while a long interval is associated with a risk for that change in scores are associated with fluctuations in the patients symptoms intensities and not related to differences in the questionnaires. In previous studies on test/retest properties of questionnaires the time intervals between assessments have ranged from 2 to 14 days . We chooThe ratings of pain in the BPI precede the interferences scales. Therefore, it could be argued that pain may be the referent point for the patients' judgment about interference. Also it may be argued that in the context of the BPI pain intensity items, the patients may rate pain related interference in both versions of the questionnaire. However, for the aim of this study, to study the pain interference items of the BPI, the questionnaire has to be administered in the exact form as it is used in clinical studies. To omit the pain items and hereby doing a major change in the BPI design, would render the study invalid with respect to investigating the psychometric properties of the BPI questionnaire. If the interference items included in the BPI would perform different if not preceded by the pain items is not studied.This study does not answer why patients have difficulties with reporting the specific influence from pain on functions. One potential explanation is that reduced cognitive function decreases the patients' ability to analyze and report the differential influence from different causes on functional ability. For patients included into this study, however, the cognitive function assessed by the EORTC QLQ-C30 cognitive score was comparable to the cognitive function reported in the general Norwegian population . There aThis study observed similar scores in the original BPI interference scores (pain influence on function) compared with the revised BPI interference scores . This finding might imply that cancer patients' ability to interpret the contribution from pain to loss of function is limited.The author(s) declare that they have no competing interests.GS, MB, SK and PK all participated in the design of the study, data analyses and drafted the manuscript. PK conceived the study and performed the statistical analyses. All authors have approved the final manuscript.The pre-publication history for this paper can be accessed here:


Patellofemoral complaints are frequently seen in younger and active patients. Clinical strategy is usually based on decreasing provoking activities as sports and demanding knee activities during work and leisure and reassuring the patient on the presumed good outcome.Exercise therapy is also often prescribed although evidence on effectiveness is lacking.The objective of this article is to present the design of a randomized clinical trial that examines the outcome of exercise therapy supervised by a physical therapist versus a clinically accepted "wait and see" approach (information and advice about the complaints only).The research will address to both effectiveness and cost effectiveness of supervised exercise therapy in patients with patellofemoral pain syndrome (PFPS).136 patients (adolescents and young adults) with patellofemoral pain syndrome are recruited in general practices and sport medicine centers. They will be randomly allocated receiving either 3 months of exercise therapy  and incorporates direct medical costs and productivity costsThis study has been designed after reviewing the literature on exercise therapy for patellofemoral pain syndrome. It was concluded that to merit the effect of exercise therapy a trial based on correct methodological concept needed to be executed.The PEX study is a randomized clinical trial where exercise therapy is compared to usual care. This trial started in April 2005 and will finish in June 2007. The first results will be available around December 2007. Patellofemoral pain syndrome (PFPS) is a common complaint in adolescents and younger adults. Though exact epidemiological data do not exist, 5–6 six new cases per year in Dutch GP-practices may be expected . The symPFPS frequently becomes a chronic problem, forcing the patient to stop sports and other similar activities . The lonClinical guidelines of the Dutch College of General Practitioners  advise GEvidence for the effectiveness of conservative therapies for PFPS is scarcely available . ExercisWe found limited evidence that exercise was beneficial, though the quality of the trials was such that further research was recommended to confirm this conclusion . RecentlBecause physicians, especially the GP and sports physician, frequently are confronted with patients with PFPS, but by lack of evidence are unable to apply the most (cost)effective treatment, a randomized intervention study is highly indicated. The 'wait and see' policy advocated in the guidelines should be compared to the more active approach of exercise therapy under supervision of a physical therapist, in order to assess (cost)effectiveness of both approaches.The trial will target patients (adolescents and young adults) presenting in general practice and sports clinics with the symptoms of PFPS and no history of previous active treatment with exercises.In this article we will present the detailed protocol of the trial.This trial started April 2005 and patients will be included until June 2006.This study is a randomized clinical trial to study short-term and long-term (cost) effectiveness of exercise therapy in combination with advice and information on the background of PFPS compared to advice and information on the background of PFPS only ("wait and see")The study design Figure  was apprPatients eligible for this trial are adolescents and young adults in the age of 14 to 40 years consulting the GP or sports physician for PFPS lasting longer than two months but not longer than 2 years. Recruitment will take place in "HONEUR" practices  and in 4 sports medical centers in Rotterdam, Leidschendam, Breda and Gorinchem.The recruitment period is planned from April 2005 until June 2006.Inclusion criteria are the following diagnostic criteria;Presence of at least 3 symptoms of the following: pain when walking stairs, pain when squatting, pain when running, pain when cycling, pain when sitting with knees flexed for a prolonged period of time, grinding of the patella, positive physical tests .The exclusion criteria are: knee osteoarthrosis/arthritis, previous knee injury or knee operations, patellar tendinopathy, M. Osgood Schlatter, or other defined pathological conditions of the knee.Sample size is based on studies included in our systematic review . In a siThe interventions that will be compared in this trial are:A) Exercise therapy for a period of 6 weeks, provided by a physical therapist according to a standardized protocol drawn up according to present international expert opinion and modified by local participating physical therapists into a practical protocol which is feasible in daily practice. The program consists of static and dynamic muscular exercises for quadriceps muscles, balance exercises and flexibility exercises. Patients are directed to practice 7 times a week during 20 minutes.Instructions concerning the exercises will be noted on the "workout book" Figure  which haPatients will receive standardized information about the background and prognosis of PFPS on a specially designed leaflet. After the period of 6 weeks patients will be advised to keep up the exercises at home for the following 6 weeks.B) The control group will receive the standardized information and advice. This advice consists of the information usually given by GPs, according to the guidelines: information about the background of the condition and its good prognosis, advice to refrain from all (sports-) activities that provoke pain, and to find alternatives to keep in shape.An information leaflet for the patients has been compiled to contribute to the standardization for both groups.During the one year follow-up other interventions like the use of ice applications, bandages or braces, or consumption of oral analgesics (NSAIDs or paracetamol) indicated by pain severity are allowed for both groups. Information about these co-interventions will be collected after 6 weeks and every 3 months and during one year follow-up and will be used in the cost-effectiveness analysis.After recruitment through the participating GP's and sport physicians the patient is finally accepted in the study after written informed consent and reassessment of the inclusion and exclusion criteria.Following this informed consent and baseline assessments, patients are allocated to the intervention or control group using a blinded and computer based randomization list.The randomization table will be stratified for the setting  and for age (14–18 versus 19–40). Patient are informed about the treatment allocation and subsequently the patients in the exercise group receive their treatment from a physical therapist in a predetermined centre, whereas patients in the control group will not receive this intervention.Primary outcome measures are: perceived recovery  and a nuBaseline and follow-up questionnaires at 6 weeks and 3 and 12 months will be filled out by the patients themselves. Quality of life, direct costs and productivity costs and compliance to the interventions will be measured after 6 weeks and every 3 months during one year also by self report.All analyses will take place after the trial has finished, no intermediate analyses will be performed.To evaluate the effectiveness of supervised exercise therapy in patients with PFPS differences in clinical outcome measures between intervention and control group will be analyzed on the basis of intention to treat. Additionally, analysis per protocol will be conducted. Dichotomous outcomes at three and 12 months follow-up will be analyzed using logistic regression techniques and continuous outcomes with linear regression techniques. Of the primary outcomes perceived recovery will be dichotomized to recovered  or not recovered (slightly-strongly worsened). Other primary outcome measurements will be analyzed as continuous variablesAnalyses will be adjusted for baseline values and for co-interventions and possible prognostic factors in case the effect estimate changes with more than 10% when including these variables in the model.Additionally the overall one year dichotomous outcomes will be analyzed using GEE  , continuResearch question 2 "What is the cost-effectiveness of supervised exercise therapy in patients with PFPS...." is the basis for the economic evaluation.In the economic evaluation  both the costs and the consequences of both treatment options are compared and incremental costs and incremental health effects the latter  is estimated.The economic evaluation is performed alongside the randomized clinical trial. Patients will complete questionnaires for costs and quality of life after 6 weeks and every 3 months. Only if the difference in health between the treatment arms appears not to be stable over time, an additional modeling study using a Markov model will be performed. Statistical methods are used to describe uncertainty in costs and effects estimates based on patient data. A 95% confidence interval for the cost-utility ratio will be calculated and an acceptability curve will be presentedFor the economic evaluation a societal perspective is employed. The relevant costs are divided into direct medical costs and productivity costs.The costs of health care utilization during the twelve months follow-up consist of visits to a general practitioner, medical specialist, physiotherapist, manual therapist, prescribed and over the counter (OTC) medicines, alternative practitioners and hospitalization and appliances. In the patient questionnaire we ask for the health care consumption in the past six weeks. The costs for the period between two measurements (mostly 3 months) are established through linear interpolation. The medical consumption is valued based on resource costs and guideline costs The productivity costs are defined as the costs of absence from work due to PFPS, including the impact of compensation mechanisms  the costThe patellar pain may affect Health Related Quality of Life. This is measured with a generic instrument, the EuroQol instrument EQ-5D ,21 The EThe PEX-study has been designed after reviewing the literature on exercise therapy for patellofemoral pain syndrome . It was Based on available literature our research group expects to discover  changes from exercise therapy in perceived recovery, pain severity and functional disability in the PEX study.The PEX study is a randomized clinical trial where exercise therapy is compared to usual care. The trial started in April 2005 and is expected to finish in June 2007. The first results will be available around December 2007.The author(s) declare that they have no competing interests.SMABZ, BWK and EMH conceived of the study, developed the design of this trial and contributed to the content of the article. MAK, JANV and MYB participated in the design of the study. RL participated in the design and coordination of the study and wrote the article. MM coordinates the trial and is responsible for data acquisition.All authors read and approved the final article.The pre-publication history for this paper can be accessed here:


To discuss the role of depression in chronic lower back pain and comment on appropriate methods of screening and co-management.The current scientific literature was investigated using the online web databases CINAHL, Medline/PUBMED, Proquest, Meditext and from manual library searches.Databases were searched from 1980 to the present (2005). Articles were searched with the key words "depression" and "low back pain". Over three hundred articles were sourced and articles were then selected on their relevance to the chronic spinal pain states that present to manual therapy practitioners.Pain is a subjective awareness of peripheral nociceptive stimulation, projected from the thalamus to the cerebral cortex with each individual's pain experience being mediated by his or her psychological state. Thus a psychological component will often be associated with any painful experience. A number of studies suggest (among other things) that the incidence of depression predicts chronicity in lower back pain syndromes but that chronic lower back pain does not have the reciprocal action to predict depression.The aetiology of chronic pain is multifactorial. There is sufficient evidence in the literature to demonstrate a requirement to draw treatment options from many sources in order to achieve a favourable pain relief outcome. The treatment should be multimodal, including mental and emotional support, counseling and herbal advice. While a strong correlation between depression and chronic low back pain can be demonstrated, an apparent paucity of literature that specifically addresses the patient response to chiropractic treatment and concurrent psychotherapy identifies the need for prospective studies of this nature to be undertaken. It is likely that multimodal/multidisciplinary treatment approaches should be encouraged to deal with these chronic lower back pain syndromes. Specific causes for acute back pain, such as infections, tumours, osteoporosis, spondyloarthropathies, and trauma actually represent a minority of pain syndromes requiring specific therapeutic approaches . ChronicIt is also important to recognise that chronic pain can occur in the absence of any pathological process . The IASLow back pain is defined as pain and discomfort localised below the costal margin to the inferior gluteals folds with or without leg pain as viewed from the rear . Low bac"Yellow flag" factors are those psychosocial conditions that are associated with an increased risk of developing or perpetuating chronic pain and long-term disability . Yellow The term acute (includes sub-acute) low back pain is defined as pain that has duration of less than three months . ChronicThere often exists a strong functional overlay of psychosocial factors or yellow flags that influence this change . It is rEvidence suggesting either a positive or negative pain outcome when psychosocial aspects of a patient's clinical presentation are addressed appears varied. This review discusses the role of depression in chronic lower back pain and comments on appropriate methods of screening and co-management.The current scientific literature was investigated using online search engines to examine the web based databases CINAHL, Medline/ PUBMED, Proquest and Meditext and from manual library searches.The current scientific literature was investigated from 1980 to the present (2005).Articles were searched with the key words "depression" and "low back pain". Over three hundred articles were sourced and articles were then selected on their relevance to the chronic spinal pain states that present to manual therapy practitioners. Approximately 60 references were selected for this review.A majority of studies suggest (among other things) that the incidence of depression predicts chronicity in pain syndromes but that chronic pain does not have the reciprocal action to predict depression.Pain is a subjective awareness of peripheral nociceptive stimulation, projected from the thalamus to the cerebral cortex with each individual's pain experience being mediated by his or her psychological state. Thus a psychological component will often be associated with any painful experience. But, is depression predictive of chronic low back pain? It has been suggested that the presence of depressive symptoms predicts future musculoskeletal disorders, but not vice versa . AnotherThe results of chiropractic treatment of 526 patients with chronic low back pain with radiation below the knees were recorded in a prospective, longitudinal observational study . The stuOther literature however is equivocal on this point with some authors suggesting that addressing the issue of depression with cognitive behavioural therapy aimed at increasing patient coping strategies gives a poor prognosis towards regaining normal functional capacity -31.They propose that a causal relationship exists whereby disability caused by chronic pain affecting activities of daily living leads to depressive illness. It is implied that a successful therapeutic intervention that targets low back pain could have beneficial effects on depression , howeverDespite this apparent disparity, it is worthy of note that chiropractors, as primary contact health care practitioners, should look for signs of the psychosocial aspects of chronic pain. Practitioners need to be mindful of the possibility of further exacerbating the pattern of pain by only addressing the musculoskeletal aspects of the problem . MultimoSomatisation is a disorder that takes the form of an expression of distress characterised by clinically significant physical symptoms that cannot be explained fully by a physical disorder. It is stated that somatisation is one of the most common of the psychiatric phenomena seen in general medical practice  and as sPatients with this somatoform disorder and a habit of 'doctor shopping' have been shown to be at a higher risk of a poor outcome after treatment for pain. This is particularly seen with quality of life issues ,39.BenDebba and coworkers  have exaIdentification of the underlying or contributing issue of depression is one that requires appropriate screening tools. Signs that may lead a practitioner to suspect that a patient requires further specific screening for an underlying psychological problem are self reported symptoms that reproduce a pain pattern inconsistent with known anatomical structures and neurology. Variable test results may similarly alert the practitioner and lead to the same conclusion.Depression associated with low back pain and other pain populations is often different to the classical signs and symptoms of "clinical depression" . Much ofPincus & Williams suggest that, instead of searching for a direct causal path (depression as vulnerability from developing chronic pain or chronic pain leading to development of depression) we accept that this solution does not describe the experience of most of our patients . They suBanks and Kerns concluded in their review that "there is growing empirical evidence to suggest that depression is most commonly secondary to chronic pain" . HoweverCommonly used indices and questionnaires such as the Revised Owestry Low Back Pain Disability Questionnaire (ODI) and the When investigating correlation of pain intensity measured by a Visual Analog Score, the social and anxiety/depression dimensions of the ODI do not appear to be responsive .As such, the ODI should be used as a whole instrument rather than attempt to use subscale components. While the ODI has a demonstrated sensitivity and ability to measure changes in low back pain disability for the purpose of evaluating clinical progress, the lack of sensitivity to identification of possible underlying depressive states demonstrate a need to use a more appropriate instrument.Screening with a depression specific tool such as the Beck Depression Inventory (BDI)  may, in The BDI is a 21 item, self-report inventory, with each item consisting of 4 statements rank-ordered in terms of increasing severity for a particular depressive symptom. In use, subjects identify the degree to which each item statement describes the way they have been feeling over the past week. Higher scores indicate greater depressive symptomatology. The BDI has been demonstrated as a sensitive measure of depression in chronic pain patients ,53.The fear avoidance beliefs questionnaire (FABQ) was developed to determine if patients' beliefs in physical activity and work affected their low back pain. Research suggests that specific fear-avoidance beliefs about work are strongly related to work loss due to low back pain. These findings are incorporated into a biopsychosocial model of the cognitive, affective and behavioural influences in low back pain and disability. Researchers have recommended that fear-avoidance beliefs should be considered in the management of low back pain and disability .The Distress and Risk Assessment Method (DRAM) questionnaire was developed in an attempt to integrate the physical and psychological assessment of the patient. It is derived from a simple set of scales that were developed for use with low back pain patients. It can distinguish between patients with no psychological distress; those at risk of developing major psychological overlay and those that are distressed . Other mThe prevalence of major depression in patients with chronic low back pain is approximately three to four times greater than that reported in the general population . Within It is argued that, in patients with clinical levels of depression, treatment modalities, including cognitive behavioural therapy and administration of anti-depressant medication, specifically targeting depressive symptomatology deserve serious consideration as an integral component of pain management programs .In a multimodal treatment program of 90 patients with chronic low back pain admitted to an 8-week program of functional restoration and behavioural support the combined functional and psychological treatment resulted in significant improvements among patients by the end of the program . The proA chiropractor needs to consider applying a management program with components that address the psychological aspects of the perception of chronic low back pain. All appropriate patients need to be reassured and given information that explains why they need to become active participants in their treatment. Literature designed to provide this content has been shown to assist positive outcomes in chronic lower back pain patients . CollectSimple stress management advice such as yoga, relaxation techniques, an exercise regime and herbal remedies such as skullcap and valerian  may be aWhile some techniques remain unproven psychological cognitive behavioural therapeutic (CBT) options have been demonstrated to have clearly advantageous outcomes with regard to decreasing the pain and distress of chronic pain syndromes ,66.Thus, it is likely that multiprofessional rehabilitation will evolve to provide the component parts of the management programs required to maximise outcomes in patients with chronic low back pain -36.A randomised controlled trial to examine the treatment outcomes of patients presenting for chiropractic treatment with a history of chronic back pain requires the participation of a clinical psychologist/psychiatrist employing psychometric testing. This testing would determine the presence of underlying depression and the need to administer specific treatment modalities. Groups could be broken down into control, manual therapy, manual and cognitive therapy and cognitive therapy to determine which form of therapy demonstrated the best outcomes.Recent studies have attempted to investigate psychological outcomes in manual therapy based trials. These studies are relatively recent and provide a clear path for future research in the field ,67,68.The aetiology of chronic pain is multifactorial. There is sufficient evidence in the literature to demonstrate a requirement to draw treatment options from many sources in order to achieve a favourable pain relief outcome. A requirement for chiropractors to adopt a broader scope of both practice and case management is suggested. Treatments administered should be multimodal with a need to include mental and emotional support, counseling and natural remedy advice .While a strong correlation between depression and chronic low back pain can be demonstrated, an apparent paucity of literature that specifically addresses the patient response to chiropractic treatment and concurrent psychotherapy identifies the need for prospective studies of this nature to be undertaken. It is likely that different modes of therapy  will have different outcomes. Future studies should focus on effectiveness and the dose response characteristics of these interventions in isolation and in combination.


An enzyme-linked immunosorbent assay (ELISA) has been developed for measuring the in vivo binding of a hexafluorinated 2-nitroimidazole (CCI-103F) in tumour tissue biopsies. The binding of CCI-103F is believed to reflect the presence of hypoxia in tumours. The ELISA provides a sensitive and convenient method of measuring CCI-103F binding which does not require the injection of radioactive reagents. The ELISA is based on reagents prepared from synthetic antigens formed by the reductive activation and binding of CCI-103F to proteins in novel test tube experiments. Calibration of the ELISA involved comparing the ELISA with the radioactivity contained either in protein-CCI-103F adducts formed in vitro with tritiated CCI-103F or in tissues isolated from a tumour-bearing dog which had been injected with tritium-labelled CCI-103F. The two approaches to calibration are compared. The scope and limitation of the ELISA for measuring the binding of CCI-103F is discussed and an example of the application of the ELISA to measuring changes in tumour hypoxia in canine patients undergoing fractionated radiation therapy is presented.


Recent research suggests that agreement between patients' and health professionals' perceptions may influence the outcome of various painful conditions. This issue has received little attention in the context of low back pain and physiotherapy interventions. The current study aimed at exploring the relationship between patient-physiotherapist agreement on baseline low back pain intensity and related functional limitations, and changes in patient outcomes four weeks later.Seventy-eight patient-physiotherapist dyads were included in the study. At baseline, patients and physiotherapists completed a Numerical Rating Scale and the Roland-Morris Disability Questionnaire. Patients' perceptions were reassessed over the phone at follow-up.Using multiple regression, baseline level of patient-physiotherapist agreement on pain intensity was associated with both outcome measures at follow-up. Agreement on functional limitations had no impact on outcomes.The results of this study indicate that patient-physiotherapist agreement has some impacts on the short-term outcomes of low back pain. Further research is needed to confirm these findings. It is well known that low back pain has important negative consequences on the individual and the society. In the last decades, an important body of research has attempted to identify factors associated with the outcome of low back pain. Psychosocial factors have been found to have a predominant influence on the quality of recuperation of individuals with low back pain ,2. Past decoded by an observer, such as a healthcare professional, who then reacts to the person's pain [According to Prkachin and Craig's Sociocommunications Model of Pain Experience ,5, a perPast studies revealed important discrepancies between the perceptions of patients and healthcare providers on the patient's pain experience -9. LevelAlthough most of the evidence tends to indicate that low patient-professional agreement has a negative impact on patient outcomes, only a small number of studies have addressed this issue, and many of these present important methodological limits . Furthermore, a recent study revealed contrasting results. Indeed, Cremeans-Smith et al.  found thLiterature pertaining to patient-healthcare professional agreement is scarce in the area of low back pain. In one of the few published studies, Cedraschi et al.  observedTo our knowledge, no studies have specifically examined the influence of agreement between patients' and professionals' perceptions of the patient's condition on low back pain outcome, in the context of physiotherapy interventions. Therefore, the objective of this study was to prospectively explore the existence of a relationship between patient-physiotherapist agreement on baseline 1) pain intensity and 2) functional limitations, and changes in patient-reported low back pain intensity and related functional limitations, measured four weeks after baseline. Based on the results of previous research, it was anticipated that higher agreement between patients' and physiotherapists' perceptions would be associated with better improvements in patients' pain intensity and functional limitations.A prospective longitudinal observational design was used. Measurements were made after the initial physiotherapy consultation (baseline), during which the first assessment was carried out by the physiotherapist, and four weeks later by telephone.Individuals with back pain and their respective physiotherapist were recruited in two private practice physiotherapy clinics of the Quebec City area , between June and October 2003. The Quebec City area is a mainly French-speaking agglomeration of over a million inhabitants that includes more than 70 private physiotherapy clinics.th rib and the gluteal fold, or cruralgia or sciatica, with or without low back pain [Red Flags [Eligible patients had to: a) be aged 18–75 years, inclusively, b) present non-specific low back pain , definedack pain , c) haveack pain  since itack pain . The exced Flags , which aEligible physiotherapists had a Bachelor's degree in physiotherapy, were members of the Board of Physiotherapy of the Province of Quebec and practiced in one of the participating clinics. Physiotherapists who had acquired clinical training in addition to physiotherapy, such as osteopathy or acupuncture, were excluded.r  [r ≥ 0.35, if this was in fact the real correlation coefficient.The target sample size for patients was 75, considering an alpha level of 0.05 and a desired statistical power of 0.80, and allowing for an anticipated loss of 20 % of subjects at follow-up and for missing values . This saothesis) . The finIndividuals were recruited by convenience sampling. The research coordinator (KP) carried out this procedure instead of the participating physiotherapists, in order to limit response contamination. For feasibility reasons, the physiotherapists' sample size was limited to the number of eligible and consenting physiotherapists. Written consent was a requirement for patient and physiotherapist participation.Patient-physiotherapist agreement constituted the baseline measurements and main independent variables. Agreement was measured for two variables: perceptions of patients' pain intensity and functional limitations. Agreement was operationally defined based on the absolute and signed differences between patients' and physiotherapists' ratings (patient's rating minus physiotherapist's) . ChangesPain intensity was measured using an 11-point Numerical Rating Scale (NRS) ranging from 0, «no pain», to 10, «worst pain imaginable» . The scaPerceptions of functional limitations were measured using the Roland-Morris Disability Questionnaire (RMDQ), a self-administered back-specific questionnaire derived from the Sickness Impact Profile (SIP) . It contImmediately after initial consultation, the patients completed: a) a general information questionnaire, b) a questionnaire on pain perceptions, including the NRS, c) the RMDQ, and d) the 14-item Psychological Distress Index (PDI-14) ,41, a quAfter the assessment, the physiotherapists completed the NRS, the RMDQ and responded to questions concerning the consultation. For feasibility reasons, it was tolerated that the physiotherapists completed the questionnaires on the same day of the consultation (rather than immediately after). The physiotherapists were instructed to give their own perceptions of the patients' conditions, rather than what they thought their patients' perceptions were, or what the patients stated during the assessment . The phyPatients and physiotherapists completed the questionnaires in separate rooms. They were asked not to discuss study participation. The coordinator was present with the patients for the initial data collection, to answer their questions and to verify integrity of the data. The physiotherapists were told to proceed with their usual assessment and treatments. Three physiotherapists and two individuals with back pain who were not involved in the study pre-tested the questionnaires.Descriptive statistics were computed to summarize the participants' characteristics and clinical ratings. Results of cross-sectional analyses have been published elsewhere . AbsolutBased on the literature, the following potentially confounding variables were considered in the analyses: 1) patient's and physiotherapist's gender and age, as well as patient's level of education, occupation , psychological distress, financial compensation, history of low back pain, pain duration and site of pain. In addition, the patient's baseline rating of pain intensity was considered as a possible confounder of the relation between agreement on functional limitations and changes in this variable at follow-up. Patient's baseline rating of functional limitations was also tested for confounding in the relation between agreement on pain intensity and change in pain at follow-up. Confounding was judged at a 20 % threshold of change in the standardised regression coefficient of the independent variable (measure of agreement). Patients' age and gender were forced in the models. In order to verify the stability of the results, a second set of regression analyses was conducted using rank-transformed dependent variables. According to Conover and Iman , this prThe possibility that patients assessed by the same physiotherapist would be in better agreement and/or more homogeneous at follow-up (cluster effect) was considered. However, calculations of intra-physiotherapist (intra-class) correlation coefficients using multilevel modeling with the GENMOD procedure in SAS indicated that the cluster effect was negligible (data not shown). The number of clusters (physiotherapists) was also considered too small for appropriate application of multilevel analysis . TherefoAll the statistical tests were bilateral. Statistical significance was set at α = 0.05. Data were analysed using SPSS version 11.0.Seventy-eight patients and their respective physiotherapist (n = 9) participated in this study, resulting in 78 patient-physiotherapist dyads. The secretaries of the clinics introduced the project to 139 patients. Of the 116 individuals who accepted to be contacted by the research coordinator, 81 were found eligible (69.6 %), but 3 did not participate. It was estimated that 16 patients would have been eligible among the individuals who did not accept to be contacted (n = 23), based on the proportion of patients who were found eligible to participate among the patients who accepted to be contacted by the coordinator (81 eligible/116 accepted to be contacted). Therefore, the overall estimated participation rate for the patients was 61.4 % (number of participating patients/estimated number of eligible patients). Comparative statistics of available data demonstrated that patients excluded and included did not differ in terms of gender and age (data not shown). All physiotherapists were eligible for study participation and none of them refused entry. There were no losses of participants to follow-up (100 % retention rate), which was carried out a mean of 27.8 ± 1.8 days after baseline (range 25.0 – 35.0).Selected characteristics of participating patients and physiotherapists are presented in Table The physiotherapists were full-time workers and their highest level of education was a Bachelor's degree. Continuing education in which they had participated in the past included McKenzie Technique, Manual Therapy and Sports Physiotherapy. The physiotherapists' general treatment modalities included education, manual therapy, various exercises, mechanical traction, electrotherapy and thermal modalities.Mean ratings and absolute differences between patients' and physiotherapists' ratings are provided in Table p > 0.05) (data not shown to prevent from unduly prolonging this article). Data from all dyads are presented since exclusion of the two most extreme cases did not affect the results.Tables Dyadic agreement on pain intensity, but not functional limitations, was found to be associated with changes in pain intensity after four weeks. Patients who rated pain intensity more than 3 units higher than their physiotherapist on the NRS reported reduced pain at follow-up compared to baseline. This was the case in four dyads. Patients in these four dyads had pain duration at baseline between 2 and 10 days and were not receiving compensation. They completed follow-up questionnaires 27 or 28 days after baseline. They had not changed their medication since baseline, had not consulted another professional (except a referring doctor in one case), and only one of them was still undergoing treatment.Agreement on pain intensity also had an impact on 4-week changes in functional limitations. Patients who rated pain intensity more than 3 units lower than their physiotherapists on the NRS presented reduced functional limitations at follow-up compared to baseline. This was the case for only two dyads, in which patients had had pain for 1 and 7 days, were not receiving financial compensation, had not consulted another professional and were no longer receiving treatments at follow-up (carried out 27 and 33 days after baseline). Both patients reported no pain and functional limitations four weeks after baseline. There was no significant association between level of agreement on functional limitations and patients' changes for this variable at follow-up.The aim of this study was to explore the existence of a relationship between patient-physiotherapist agreement and short-term patient outcomes that are most relevant in low back pain. Dyadic agreement on perceptions of pain intensity was associated with changes in patient outcomes, in the short term. Lower patient-physiotherapist agreement on pain intensity was associated with positive changes in pain intensity and functional limitations at follow-up compared to baseline. Agreement on perceptions of functional limitations had no impact on pain intensity and functional limitations after four weeks.The finding that higher disagreement on pain intensity was favourable to pain outcome was surprising. Indeed, most other studies demonstrated that higher discrepancies between patient and professional are detrimental to patient care and outcome ,18-20,47It was furthermore surprising to find that physiotherapist's overestimation of pain was associated with lower functional limitations at follow-up. No reports of the specific effect of a professional's overestimation of pain have been presented in the literature to our knowledge. One may suppose that the physiotherapist's overestimation of pain intensity may have led him or her to pay more attention to the patient's pain. This may be perceived positively by the patients and therefore may favour the quality of the patient-physiotherapist relationship and consequently improve outcome. Still, positive clinical impact of physiotherapist overestimation of pain is hard to explain at this point. It is possible that this finding reflects a statistical effect, such as regression to the mean. In addition, since this result was obtained using the rank-transformed dependent variable, it is not possible to interpret the size of the effect, which may not represent a clinically important change.R2 (Tables Our findings suggest that high patient-physiotherapist discrepancies (more than a 3-unit difference in ratings on the NRS) are needed to have a clinical impact in the short term. Observations of the regression coefficients in the relationships between agreement on pain intensity and changes in both outcome measures suggest that high differences between patients' and physiotherapists' ratings may be associated with reduced pain and functional limitations at follow-up compared to baseline, although only two associations were found to be statistically significant. These results should be considered with extreme caution. Indeed, very few dyads were involved in these statistically significant associations. All the patients in these dyads were in the acute phase of pain and had an excellent outcome of their back pain problem after four weeks. Furthermore, the size of the effect was generally small in most models, as indicated by the values of the regression coefficients and adjusted 2 Tables , which sThis study has several limitations. The sample size was relatively small. This may have yielded higher variability in the agreement measures (high difference scores were recorded scarcely) and therefore masked real effects of agreement. Because of the non-random sampling method of recruitment and the particular socio-demographic characteristics of the participating patients , the results of this study may only be generalisable to clinical encounters between patients and physiotherapists with characteristics similar to the study participants'. Measures of agreement may have been influenced by the fact that patients and physiotherapists were informed of the aims of the study before entry. Knowledge of this information may have affected the way both parties answered the questionnaires . FurtherUp to now, few studies have evaluated the impact of patient-provider agreement on patient outcomes, especially in a prospective manner. Studying the impact of patient-physiotherapist agreement on the outcome of low back pain represents an innovative and relevant project as highlighted by the findings of recent research on low back pain. Still, the results of the current study do not allow us to formulate any definite conclusions about the influence of patient-physiotherapist agreement on changes in patient outcomes. Replication of our results is necessary before any recommendations can be made to physiotherapists. Further research is also warranted to verify the impact of patient-physiotherapist agreement on other outcome variables, in the longer term, and in different populations.The author(s) declare that they have no competing interests.KP contributed to the conception and design of the research, acquired the data and participated in analysing and interpreting the data, as well as in writing and reviewing the article.CED contributed to the conception and design of the research and participated in analysing and interpreting the data, as well as in writing and reviewing the articleBoth authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here: