Shoulder pain is common with rotator cuff disease as the most frequently used clinical diagnosis. There is a wide range of treatment options for this condition, but limited evidence to guide patients and clinicians in the choice of treatment strategy. The purpose of this study was to investigate possible prognostic factors of short-term outcome after corticosteroid injection for rotator cuff disease.We performed analyses of data from 104 patients who had participated in a randomized controlled study. Socio-demographic, clinical and radiographic baseline factors were assessed for association with outcome at six-weeks follow-up evaluated by Shoulder Pain and Disability Index (SPADI) and patient perceived outcome. Factors with significant univariate association were entered into multivariate linear and logistic regression analyses.In the multivariate analyses; a high SPADI score indicating pain and disability at follow-up was associated with decreasing age, male gender, high baseline pain and disability, being on sick-leave, and using regular pain medication. A successful patient perceived outcome was associated with not being on sick-leave, high active abduction, local corticosteroid injection and previous cortisone injections. Structural findings of rotator cuff tendon pathology on MRI and bursal exudation or thickening on ultrasonography did not contribute to the predictive model.Baseline characteristics were associated with outcome after corticosteroid injection in rotator cuff disease. Sick-leave was the best predictor of poor short-term outcome. Trial registration: Clinical trials NCT00640575 Shoulder pain is common with a one-year prevalence reported up to 47% in a general population ,2. A larSubacromial impingement syndrome or rotator cuff disease is the most frequently used clinical shoulder diagnosis ,8. PatieThe purpose of the present study was to assess to what extent socio-demographic factors, occupational factors and clinical and radiological findings predicted outcome in patients with rotator cuff disease receiving corticosteroid injection treatment. We hypothesized that baseline socio-demographic factors and patient reported pain and disability were moderately associated with outcome at six weeks, and that structural findings identified by routine MRI and ultrasonography would contribute to the prognostic model.We performed an analysis of data from a randomized controlled trial comparing local and systemic corticosteroid injection in rotator cuff disease .One hundred and six patients with a clinical diagnosis of rotator cuff disease had been randomized six weeks previously to systemic or ultrasonographically guided corticosteroid injection. Two patients were not available for follow-up at six weeks and were excluded from analyses in the present study. We reported previously that no difference was found between systemic and local corticosteroid injection at six-weeks follow-up. A detailed description of patients, treatments and concomitant treatment is reported in that paper . The comPrimary outcome was the Shoulder Pain and Disability Index (SPADI)  measuredAll patients filled in a standardized questionnaire including the potential prognostic factors and outcome measures and underwent a clinical examination. The same physician examined all patients at baseline and follow-up. Patients were asked to rate their pain in activity from 0 (no pain) to 9 (severe pain), the highest level of professional education (primary school/secondary school/university), work status (not working/working or partly working), sick-leave (no/yes or part time), pain medication (daily or weekly/less often than weekly/seldom/never), duration of shoulder complaint  concomitant neck pain (yes/no), previous episodes of shoulder pain (yes/no), dominant arm affected (yes/no), bilateral shoulder pain (yes/no), beliefs of precipitating cause of shoulder pain (minor trauma/overuse/stress/unknown), previous treatment (physiotherapy/corticosteroid injections). Emotional distress was measured using the 25-item Hopkins symptom check list (HSCL-25) . PatientWe interviewed employed patients about work tasks . Patients evaluated statements about the amount of time they were lifting heavy objects (10 kg), working with hands above shoulder level, or conducting repetitive tasks on six-point ordinal scales ranging from "all the time" to "never". Patients reported perceived physical work load, occupational stress, job satisfaction, and comfort with co-workers and supervisors at work on six-point ordinal scales ranging from "extreme" to "not at all".Descriptions from routine MRI were recorded for evaluating the influence of MRI verified rotator cuff ruptures and presence of calcifications in the rotator cuff on outcome. MRIs taken before referral to the outpatient clinic were accepted if images were obtained within the last three months. Data were extracted from the radiologist's evaluation. Rotator cuff tendons were categorized as normal, with tendinopathy, partial-thickness and full-thickness ruptures. Calcifications were registered as present or non-present. Eight patients were unwilling to be examined by MRI and had diagnostic ultrasound examination. The presence of bursal exudates and thickening of the bursal walls were recorded by diagnostic ultrasound in all patients before injection treatment by visual estimation (present/not present) by the consultant physician providing the injections.Active ranges of abduction and flexion were measured with a handheld digital inclinometer according to a standardized protocol . The effWe did a secondary analysis of a randomized clinical trial; hence no formal sample size calculation was performed before starting the study. There is no straightforward method of estimating sample size in multivariable prognostic research. We required at least 10 outcomes for each predictor studied .Univariate and multivariate linear and logistic regression analyses were used to investigate the associations between potential prognostic variables and short-term outcome after injection treatment. Factors showing a univariate association with the outcome at issue (p < 0.2) were extracted as candidate variables to be used in the multivariate analysis.In the multivariate linear model, all potential predictors were entered into the multivariate model. Adjustments were made for gender and treatment group. Variables not statistically associated with the dependent variable on p < 0.05-level were eliminated using a manual backward stepwise technique except for gender and treatment group that were kept regardless of significance level. We used an additional sequential block model to investigate the predictive power of structural pathology measured by routine MRI and ultrasonography on outcome of shoulder pain and disability.We used a stepwise forward technique in the multivariate logistic regression model because not more than one variable per 10 patients in each group were allowed simultaneously in the model.Predictors that are highly correlated contribute little independent information. We included the clinically most important predictor if r > 0.7 between two predictors. Continuous variables were checked for linearity using curve estimation plots. Models were checked for normality, homoscedasticity and colinearity by inspecting residuals and calculating variance inflation factor (VIF) . We usedTable 2 change = 0.03, p = 0.68). Factors with a univariate association with the patient perceived shoulder condition at six-weeks follow-up are reported in table At baseline, mean SPADI score was 52 points, 51 points in the systemic group and 53 points in the local group. At six-weeks follow-up this was reduced to 31 points, 32 points in the systemic group and 29 points in the local group. There were no gender differences in SPADI score at baseline, but at six-weeks follow-up there was a lower SPADI score in females (28 points) than males (35 points). The overall improvement observed at follow-up in both groups, exceeds the minimal clinical important change in SPADI . IndepenAmong employed patients (n = 86), significantly more men had manual labour . There was no association between gender and the other occupational variables included. Patients on sick-leave experienced their work as more physically demanding , reported more frequently working above shoulder level  and lifting heavy objects . Frequent work with arms above shoulder level was associated with a poor or moderate outcome . Other measured occupational factors were not significantly associated with outcome. Level of education did not influence outcome, but was associated with sick-leave  and overhead work .The present study confirmed that socio-demographic factors and patient reported pain and disability are strong predictors of outcome. Structural findings in rotator cuff and subacromial bursa did not contribute to predict outcome. There might be several reasons for these findings.Sick-leave and low active abduction were identified as negative predictors by evaluating outcome both by SPADI and the patient perceived global assessment, and may be regarded as the most robust findings in the present study. The difference in construct measured by the two outcome measures and the statistic model applied are likely to influence the results. In addition to sick-leave; regular pain medication; previous episodes of shoulder pain and gender were the strongest predictors for perceived pain and disability six weeks after treatment. The sick-listing process is complex; both work related  and individual factors like comorbidities and coping ability are associated with sick-leave and health care use . A longiThe observed association between SPADI and gender in the present study was unexpected. There is a higher prevalence of musculoskeletal disorders among women based on self-reports ,31 and wIn the present study, structural changes in rotator cuff and subacromial bursa on routine radiological examination did not predict short-term outcome after corticosteroid injection therapy. There is an ongoing debate regarding aetiology and pain mechanisms in rotator cuff disease. Both extrinsic subacromial impingement and intrinsic tendon degeneration from age, genetic disposition and tensile overload within the rotator cuff tendons are regarded as mechanisms resulting in rotator cuff disease. The subacromial bursa has been identified as a key structure mediating pain -38, thouThere are several limitations of the present study. First, the sample size is small which tend to over fit the predictive model to the data and spuriously overestimate associations between factors and outcome . SecondlBaseline characteristics are predictors of outcome after corticosteroid injection treatment in rotator cuff disease. Sick-leave was the best predictor of poor short-term prognosis. Findings from routine radiological examination did not predict outcome.The authors declare that they have no competing interests.OME, KE and JIB designed the study. OME recruited the patients in contributions with NGJ, SK and EBH. OME, KE and JIB performed the statistical analysis. OME drafted the manuscript together with KE, JIB, SK, NGJ and EBH. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/11/239/prepub


This study evaluated the benefits and safety of a multimodal pain control protocol, which included a periarticular injection of local anesthetics, in patients undergoing total hip arthroplasty.Between March 2006 and March 2007, 60 patients undergoing unilateral total hip arthroplasty were randomized to undergo either a multimodal pain control protocol or a conventional pain control protocol. The following parameters were compared: the preoperative and postoperative visual analogue scales (VAS), hospital stay, operative time, postoperative rehabilitation, additional painkiller consumption, and complication rates.There was no difference between the groups in terms of diagnosis, age, gender, and BMI. Although both groups had similar VAS scores in the preoperative period and on the fifth postoperative day, there was a significant difference between the groups over the four-day period after surgery. There were no differences in the hospital stay, operative time, additional painkiller consumption, or complication rate between the groups. The average time for comfortable crutch ambulation was 2.8 days in the multimodal pain control protocol group and 5.3 days in the control group.The multimodal pain control protocol can significantly reduce the level of postoperative pain and improve patients' satisfaction, with no apparent risks, after total hip arthroplasty. Total hip arthroplasty (THA) is performed for pain relief, normal joint motion, and a deformity correction of the hip. However, its efficacy is often limited by perioperative pain management.Of the patients who underwent primary THA performed in our hospital between March 2006 and March 2007, 60 patients were enrolled in this study. The exclusion criteria included those with severe psychiatric disorders, a history of drug addiction, allergy to any study medication, cerebral infarction or a severe neurological lesion, and severe heart or renal disease. The study population was divided randomly into 2 groups: Group I (n=30) received our multimodal pain management including periarticular injections of multimodal drugs; and group II received only standard pain management. The results of the two protocols were compared prospectively in terms of the level of pain measured before and until 5 days after surgery, hospital stay, operative time, postoperative rehabilitation, postoperative consumption of parenteral pain medication, and complications of pain medications, such as nausea .The mean age of the patients was 53.1 years . There were 36 males and 24 females. The presumed cause was osteonecrosis of the femoral head in 43 cases, acetabular dysplasia with advanced osteoarthritis in 8 cases, sequelae of Legg-Calvé-Perthes' disease in 5 cases, and sequelae of pyogenic arthritis in 4 cases. There were no differences in gender, age, presumed cause, height, weight, and BMI between the two groups .Preemptive analgesia was performed for central sensitization 2 hours before surgery in group I while it was not applied in group II. In all cases, surgery was performed under general anesthesia. In group I, epidural anesthesia and a periarticular injection of multimodal drugs were also performed intraoperatively. In group II, intravenous patient-controlled analgesia was used postoperatively. Isoflurane was used for inhalational anesthesia. For intravenous patient-controlled analgesia, different doses of morphine were administered depending on the patient's age, height, and weight. All procedures were carried out by the same surgeon using a minimally invasive anterolateral approach according to a standard protocol. The periarticular injection (90 ml) contained 5 mg of morphine HCl, 40 mg of methylprednisolone, and 6.8 mg of ropivacaine dissolved in 70 ml of 0.9% normal saline. One-third (30 ml) of the mixture was injected before inserting the prosthesis, another third (30 ml) was administered immediately before reducing the prosthesis into the synovial sheath, joint capsule, deep fascia, and damaged muscle layer, and the remainder (30 ml) was infused into the subcutaneous tissues and adipose layer . For posp < 0.05.The pain was assessed by the patients using a 100 mm visual analogue scale . They were asked to make measurements at a specific time before surgery, immediately after sur gery, and from the 1st to the 5th postoperative day. Depending on the level of pain, the patients were assigned to different postoperative rehabilitation programs ranging from quadriceps strengthening to straight leg raising. The days on which comfortable ambulation was achieved with the aid of crutches were also recorded. The doses of additional parenteral analgesics prescribed on an asneeded basis were assessed until the 5th postoperative day. The occurrence of complications such as nausea, vomiting, and surgical site infection was also investigated. Statistical analysis was performed suing a Student's t-test and Chi-square test. Statistical significance was defined as p = 0.263). The mean VAS scores measured every day at a specific time from immediately after surgery until the 4th postoperative day were respectively, 3.0, 2.0, 2.1, 2.7, and 2.4 in group I and 7.6, 4.9, 3.6, 3.6, and 3.3 in group II. Significant pain relief was noted in group I (p < 0.05). The mean VAS score obtained on the 5th postoperative day was slightly lower in group I than in group II , but there was no significant difference between the two groups (p = 0.275)  .p = 0.190). The mean operative time from the skin incision to closure was 114.5 minutes  in group I with periarticular injections and 110.1 minutes  in group II. This shows that the periarticular injections extended the surgery time slightly but the difference is not statistically significant (p = 0.442).The mean hospital stay was 18.8 ± 6.0 days in group I using our multimodal pain control protocol and 20.6 ± 6.3 days in group II. There was no significant difference between the two groups (p = 0.000).The average time required for the patients to be able to perform straight leg raising excercises without pain and comfortable ambulation with the aid of crutches was 2.8 days and 5.3 days in groups I and II, respectively. This indicates that, group I with our multimodal pain control protocol showed more rapid recovery than group II (p = 0.236). There were 9 and 12 medication-related complications, such as nausea and vomiting, in groups I and II, respectively, showing no significant difference (p = 0.725). There were no cases of wound infection or a delay in wound healing due to the extended period of drainage.The two groups consumed a similar level of additional analgesics as a supplement to the regular intake of NSAIDs prescribed until the 5th postoperative day, 2.5 and 3.1 times in group I and II, respectively; Pain is a sensation perceived through several steps after tissue trauma: transduction, transmission, modulation in the spinal cord, and perception in the cerebral cortex. Multimodal pain control protocols using a combination of analgesic regimens with different mechanisms of action have been designed to promote effective pain control and reduce medication-related side effects.Our multimodal pain control protocol can be characterized by the use of preemptive analgesia, epidural anesthesia and a periarticular injection during surgery, and various medications after surgery. Reports have shown that preemptive analgesia prevents central sensitization and reduces the level of postoperative pain.However, the use of epidural anesthesia, which is an invasive procedure, and the dditional expenses should be taken into consideration when applying a multimodal pain control protocol. In addition, although there were no complications associated with periarticular injections in this study, Vendittoli et al.According to Burns et al.,In conclusion, multimodal pain control protocols using a mixture of more than two drugs with different mechanisms of actions effectively improve the patients' satisfaction by providing early postoperative pain relief without increasing the risk of complications and prolonging the surgery time in patients undergoing THA.


Patients with chronic low back pain (cLBP) have high rates of comorbid psychiatric disorders, mainly depression. Recent evidence suggests that depressive symptoms and pain, as interacting factors, have an effect on the circulating levels of inflammatory markers relevant to coronary artery disease. Our previous work showed a higher serum level of an inflammatory marker tumour necrosis factor-alpha (TNFα) in patients with cLBP, which did not correlate with intensity of low back pain alone. In the present study we investigated the cross-sectional associations of depressive symptoms, low back pain and their interaction with circulating levels of TNFα.Each group of 29 patients with cLBP alone or with both cLBP and depression was age-matched and sex-matched with 29 healthy controls. All subjects underwent a blood draw for the assessment of serum TNFα and completed a standardised questionnaire regarding medication, depression scores according to the German version of Centre for Epidemiological Studies Depression Scale (CES-D), pain intensity from a visual analogue scale, and back function using the Roland and Morris questionnaire. The correlations between TNFα level and these clinical parameters were analysed.P = 0.002) and without  depression showed significantly higher TNFα serum levels than healthy controls (median = 0 pg/ml). The pain intensity reported by both patient groups was similar, while the patients with depression had higher CES-D scores (P < 0.001) and worse back function (P < 0.001). The variance analysis showed that the interaction between TNFα level and pain intensity, CES-D scores, sex, body mass index and medication was statistically significant.There were no differences in TNFα level between cLBP patients with and without depression. Both cLBP patients with (median = 2.51 pg/ml, Depression as a comorbidity to cLBP did not influence the serum TNFα level. It seems that TNFα somehow acts as a mediator in both cLBP and depression, involving similar mechanisms that will be interesting to follow in further studies. The most common of these disorders is depression. Equally, depression is frequently associated with pain. Some 30 to 60% of cases of depression are accompanied by pain, and ce versa . Pain isce versa . The cosce versa . The accce versa -8.To date, however, pain and depression have been considered as separate entities and therefore treated in isolation; the pathophysiology of both pain and depression are not yet wholly clarified. Patients with pain or depression have often been observed to present common clinical features such as lethargy, anorexia , sleepinOver the past decade, numerous studies have demonstrated that cytokines seem to play an important role in both pain and depression, respectively -19. CytoOur previous work revealed elevated TNFα serum level in patients with cLBP, and that confounding parameters such as age, sex, body mass index, alcohol, cigarettes, pain rating and back function did not influence the TNFα serum level . This obTo date, no studies have investigated the TNFα profile in coexisting pain and depression. In the prospective cross-sectional clinical study described here, we set out to determine whether comorbid depression might affect the TNFα serum level in patients with low back pain, or whether TNFα might regulate both pain and depression together. Our hypothesis was that patients with both cLBP and depression display higher TNFα serum levels than patients with cLBP alone and there are cross-sectional associations of pain, depressive symptoms and their interaction with TNFα in cLBP.All participants gave informed consent, and the study was approved by the local ethics committee of the University of Heidelberg, Germany. Participants were consecutively recruited from the Department of Orthopaedic Surgery of the University of Heidelberg. Each group of 29 patients with cLBP alone or with cLBP together with depression (cLBP + DE) were matched with 29 healthy controls by age and sex.The inclusion criterion for pain was cLBP as the main symptom, defined as disabling pain of at least 6 months' duration that led to the patient being on sick leave for at least 6 weeks. Patients with other pain locations as their main symptom and patients with multiple major pain locations were excluded from this study.The inclusion criteria for the diagnosis of depression were: an International Statistical Classification of Diseases and Related Health Problems (10th revision) diagnosis of a current and at least moderate depressive episode; and a minimum German version of Centre for Epidemiological Studies Depression Scale (CES-D) score of 25.Exclusion criteria in patients and controls were: tumour disease (diagnosis from history and by radiographic examination/magnetic resonance imaging (MRI)); trauma/fracture (history and radiographic examination); inflammatory systemic disease or infection - for example, spondylodiscitis ; nucleus pulposus prolapse with corresponding radicular pain ; structural pathology of the lumbar spine - for example, spinal stenosis or spondylolisthesis ; rheumatological disease; serious cardiopulmonary, vascular or other internal medical conditions; any sensorimotor and/or neurological deficits in the lower extremity ; spinal surgery in the year before admission to multidisciplinary therapy; radiographically apparent degenerative changes in the lumbar spine (grade II or above according to the Kellgren and Lawrence classification ); or medAt study entry, the initial evaluation included clinical and radiographic examination and also MRI of the lumbar spine in all patients of the entire study, and blood count in all patients and controls. Patients were evaluated by standardised questionnaires and physical examinations, including analysis of blood samples.The average pain intensity of all patients was determined from a visual analogue scale recording from 0 (no pain) to 10 (severe pain) during the past 24 hours and the past week. Measures of pain-related disability was assessed using the Roland and Morris questionnaire , which ir = 0.49) and increases with recovery from depression (r = 0.86) [The CES-D is a well-established self-reporting instrument to assess the level of depression, with 20 items and a potential overall score of 0 to 60. It has high specificity (94%) for the identification of acute depression if a score of at least 23 points is reached and the correlation coefficient to other instruments for measuring depression, such as the Hamilton Depression Scale, is acceptable ( = 0.86) . To idenAt the given time points, venous blood was taken from the cubital vein between 8:00 and 9:00 am. Blood samples were centrifuged at 2,000 rpm at 4°C within 30 minutes of withdrawal, and serum was stored at -80°C. TNFα serum levels were analysed in duplicate using a Bio-Plex cytokine assay  according to the manufacturer's instructions. The median fluorescence intensity of standards and patient samples were determined. Using the Bio-Plex Manager software, serum levels of TNFα were deduced from the standard curve. The intra-assay coefficient of variation was 5 to 10%.P < 0.05 was considered statistically significant; P < 0.01 was highly significant. The data were analysed using SPSS 15.0 software .The nonparametric Mann-Whitney test was used to compare groups and was adjusted with Bonferroni correction. Correlations between the individual groups and cytokines were investigated using Pearson correlation analysis. Variance analysis was used to evaluate the interaction between TNFα level, pain intensity and depression scores. Drug intake was analysed as captured/noncaptured without considering the dose. P = 0.002 for cLBP + DE, P = 0.004 for cLBP). No differences in TNFα levels between the cLBP + DE group and the cLBP group were seen in this study.The circulating TNFα serum levels of patients with and without depressive symptoms were 2.51 pg/ml and 2.58 pg/ml (median), respectively . Even the pain intensity of both patient groups did not differ from each other (P > 0.05). Patients with both cLBP and depressive symptoms, however, had significantly higher CES-D scores (P < 0.001)  than patients with cLBP alone. The medication (inclusive antidepressants) intake between the two groups was contrastable, except that patients in the cLBP + DE group were taking significantly more nonsteroidal anti-inflammatory drugs (M01A) than patients with cLBP alone at T0 (P = 0.037).Table  P < 0.00 , however, this single correlation disappeared after assessment of all variables .In an unadjusted analysis, no correlation was found between TNFα serum level and age, sex, body mass index, pain intensity, CES-D score or back function. The single correlation was found between the TNFα serum level and intake of analgesics in the cLBP + DE group (P = 1.000) and CES-D scores (P = 1.000).In the variance analysis, using TNFα as a conditioned variable presented no significant interactions between TNFα, pain intensity in the past 24 hours  axis that exists in patients with cLBP and in those with depression. In animals, stress can activate proinflammatory pathways in the brain by activation of microglial cells ,67. In hIn individuals with depression there is evidence for malfunction of cortisol receptors leading to cytokine-induced cortisol resistance, impaired feedback inhibition of the HPA axis and sustained activation of immune cells ,73. DeprHistorically, pain and depression have been conceptualised and treated as discrete phenomena, although they are highly comorbid disorders. Our findings illustrate the importance of shared common neurochemicals (TNFα) in the development of both disorders, and may provide a suggestion for the physicians - who should carefully evaluate patients presenting with either cLBP or depressive symptoms and tailor their treatment accordingly.Potential confounding factors for the TNFα serum level were analysed in the present study. Age, sex, body mass index, pain intensity, CES-D score and back function did not correlate with the TNFα serum level individually.The present study clearly shows that depression as a comorbidity did not influence the TNFα level in cLBP patients. In other words, a high TNFα level in patients with cLBP was not induced by accompanying depression. Our hypothesis was therefore not supported. Our previous work and the present study, taken together, confirm that there is no causal relationship between the TNFα serum level and cLBP, just as there is no causal relationship between cytokine alterations in the blood and depressive disorders. Rather, it seems that TNFα somehow acts as a mediator in both cLBP and depression, by similar mechanisms. In the further study, we followed the development both of pain intensity and depression scores parallel to the TNFα level in a longitudinal design of 6 months, and tried to determine the potential interaction between TNFα, pain and depression.CES-D: German version of Centre for Epidemiological Studies Depression Scale; cLBP: chronic low back pain; HPA: hypothalamic-pituitary-adrenal; IL: interleukin; MRI: magnetic resonance imaging; TNF: tumour necrosis factor.The authors declare that they have no competing interests.HW conceived the hypothesis for the manuscript, participated in data collection, wrote the first draft of the manuscript and had primary responsibility for the manuscript process. CA participated in data collection and performed the initial statistical analyses. SG interpreted the results of statistical analysis. WR participated in the interpretation of data, and contributed to and approved the final manuscript. MS conceived the study and participated in its design and helped to draft the manuscript. WR conceived the study and supervise its design. All authors read and approved the final manuscript.


P = 0.001) reduced within the experimental group with the application of cryotherapy. This study highlights the need for adopting alternative therapies such as cryotherapy for effective pain management in hospital settings.Pain during areteriovenous fistula (AVF) cannulation remains a common problem in hemodialysis (HD) patients. This study was undertaken to assess the effect of cryotherapy on pain due to arteriovenous fistula puncture in hemodialysis patients. A convenience sample of 60 patients  who were undergoing hemodialysis by using AVF, was assessed in a randomized control trial. Hemodialysis patients who met the inclusion criteria, were randomly assigned to experimental and control groups using a randomization table. Objective and subjective pain scoring was done on two consecutive days of HD treatment . The tools used were a questionnaire examining demographic and clinical characteristics, an observation checklist for assessing objective pain behavior, and a numerical rating scale for subjective pain assessment. Descriptive statistics were used as deemed appropriate. Chi square, two-sample and paired t-tests, the Mann Whitney test, Wilcoxon's signed rank test, the Kruskal Wallis test, and Spearman's and Pearson's correlations were used for inferential statistics. We found that the objective and subjective pain scores were found to be significantly ( Chronic renal failure is a devastating medical, social, and economic problem for both patients and their families in India. Most CKD patients reporting to tertiary care centers in India are in the final stage where renal replacement therapy (RRT) is the only option at that stage.2Pain inflicted by the insertion of large cannulae into the AVF is a significant cause of concern for both children and adults on regular HD. Although AVF puncturing causes pain,Research evidence shows that cutaneous stimulation6Patients undergoing hemodialysis via an AV fistula in the Dialysis unit of a tertiary care hospital, and who were older than 16 years of age, capable of giving adequate response to pain, and not having any other problem resulting in pain were enrolled for this randomized control trial. Patients having radiation injuries, peripheral vascular diseases, Raynauld's syndrome, connective tissue disorders, diabetic neuropathy, unconsciousness or disorientation, and requiring more than one attempt for fistula puncturing were excluded from this study. All the patients having an AVF in our unit and who fulfilled the inclusion criteria during the study period were approached. Sixty-eight patients were screened, of whom two refused consent, hence, 66 were randomly assigned to the experimental and control groups using a randomization table. Thus, 60 patients completed the study, of whom six were drop-outs (they had undergone multiple punctures or developed aneurysm). Thus, 30 patients each in the experimental and control groups completed the study.The tools used for data collection were a questionnaire for collecting demographic and clinical data, an observation checklist for assessing objective pain behaviors, and a numerical rating scale for subjective pain assessment. Experts had established the content validity of the tools. The observation checklist was a five-point scale that rated objective pain behaviorsHemodialysis patients who met the inclusion criteria were enrolled in the study and consent forms were signed before their participation in the study. Demographic data were collected by interviews using the questionnaire. Random assignment to the experimental and control groups was done based on a randomization table. Objective and subjective pain scoring was done on two consecutive days of hemodialysis treatment, without intervention in the control group and with cryotherapy on the second visit in the experimental group. The same group of staff members performed the punctures for both experimental and control group patients as per the unit schedule. Thus, the practical experience of staff members performing the punctures was comparable within the two groups.Cold application was done with ice cubes wrapped in gloves on the web between the thumb and index finger of the hand not having the AV fistula . The procedure was started ten minutes before venipuncture and continued throughout the puncturing procedure (approximately two minutes). The researcher herself performed the ice massage, while another staff member did the AVF cannulation (SPB).Data analysis was done using STATA; both descriptive and inferential statistics were used. Descriptive statistics used in the study were frequencies, percentage, mean, median, range, and standard deviation. Chi square, two-sample and paired t-tests, the Mann Whitney test, Wilcoxon's signed rank test, the Kruskal Wallis test, Spearman's and Pearsons correlations were used for inferential statistics as deemed appropriate.P = 0.87), the duration of HD (P = 0.15), the duration of AV fistula use (P = 0.06), sex (P = 1.00), educational qualification (P = 0.13), and occupation (P = 0.73) of the subjects [vs 20%, P = 0.05).The experimental and control groups were comparable with respect to demographic and treatment-related variables such as age  and subjective  pain scores as compared to the male subjects.There was no association between the baseline (day 1 of HD) pain scores (objective and subjective) and the selected variables such as the duration of AV fistula use, educational qualification, and the age of the subjects. Females however, had significantly higher objective (4.5 ± 0.65 P = 0.001) from an average of 3.8 on day 1 of HD (when the patient received routine care) to 0.7 on day 2 of HD (when cryotherapy was given). There was a significant reduction (P = 0.001) in the subjective AV fistula puncture pain scores (1−2.5) on day 2 of HD as compared to the scores (2−7) on day 1 of HD.The objective AV fistula puncture pain scores on days 1 and 2 of HD within the experimental group were found to be significantly reduced (P = 0.23) on two consecutive days of HD (when patient received only routine care). There also was no significant difference (P = 0.89) in subjective AV fistula puncture pain scores on day 2 of HD as compared to the scores on day 1 of HD [AV fistula puncture pain scores on days 1 and 2 of HD within the control group were found to be similar ( 1 of HD .P = 0.001) reduced within the experimental group with the application of cryotherapy. Thus, cryotherapy was found to be an effective pain management technique in these patients. Studies using cutaneous stimulation to decrease acute pain have shown the benefit of these procedures. In 1980, Melzack et al.et al.et al.Hemodialysis patients3The mechanisms involved in the reduction of pain by using cryotherapy can be best explained by the gate control study proposed by Melzac.15P = 0.23) or subjective (P = 0.89) scores. This proves that there is no significant variation in the pain scores of these two different AV fistula-puncturing procedures in the same individual. It also strengthens the conclusion that the reduction in pain scores within the experimental group was because of the cryotherapy applied during puncturing. It was also found that there was no significant correlation between the AV fistula puncture pain scores and variables such as the duration of AV fistula use and the age of the subjects. We also noted that females reported higher pain scores when compared to males. Jackson et al.In our study, we found that a comparison of day 1 and day 2 pain scores within the control group revealed no significant difference in the objective  it is a small sample-sized study and the results need to be confirmed by larger multicentric studies. ii) Also, although patients with diabetic neuropathy were excluded from the study, subjects having diabetes mellitus as a co-morbidity were not uniformly divided between the two randomized groups.We therefore conclude that cryotherapy is effective in reducing AV fistula puncture pain of hemodialysis patients. AV fistula puncture-related pain intensity was associated with the female sex while no correlation existed with the duration of fistula use (number of punctures undergone), the educational qualification, or the age of the subjects.


Population mean changes from clinical trials are difficult to apply to individuals in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration.The numbers of patients with pain relief over baseline  at 2, 4, 8 and 12 weeks of treatment were obtained using the WOMAC 100 mm visual analogue pain subscale score for each treatment group in seven randomised placebo-controlled trials of etoricoxib in osteoarthritis lasting ⩾6 weeks. Dropouts were assigned 0% improvement from baseline from then on. The numbers needed to treat (NNTs) were calculated at each level of response and time point.3554 patients were treated with placebo, etoricoxib 30 mg and 60 mg, celecoxib 200 mg, naproxen 1000 mg or ibuprofen 2400 mg daily. Response rates fell with increasing pain relief: 60–80% experienced minimally important pain relief (⩾15%), 50–60% moderate pain relief (⩾30%), 40–50% substantial pain relief (⩾50%) and 20–30% extensive pain relief (⩾70%). NNTs for etoricoxib, celecoxib and naproxen were stable over 2–12 weeks. Ibuprofen showed lessening of effectiveness with time.Responder rates and NNTs are reproducible for different levels of response over 12 weeks and have relevance for clinical practice at the individual patient level. An average 10 mm improvement in pain equates to almost one in two patients having substantial benefit. Clinical trials are performed usually for regulatory purposes, with outcomes typically reported as statistical comparisons between treatment group population means. The results of clinical trials can be difficult to translate into clinical practice. A report that an intervention shows an average 10 mm reduction more than placebo on a 100 mm visual analogue scale has little immediate impact.Moreover, few of us are average. Most drugs provide a good response in half or fewer of the patients treated,9Genetic influences help determine the clinical response to analgesic drugs for non-specific anti-inflammatory drugs (NSAIDs),16Average data from skewed distributions can produce misleading results.20An added factor contributing to differences in treatment response observed in clinical practice compared with a clinical trial is the handling of dropouts. Commonly, a “last observation carried forward” technique is used in clinical trials, where data from patients with good pain control but intolerable adverse events will still be included in efficacy calculations using the population mean. In clinical practice, this same patient would be considered a treatment failure.We used individual patient data from seven randomised placebo-controlled trials in osteoarthritis to investigate the effects of different levels of pain relief assessed at various time points on estimates of efficacy.Merck Research Laboratories provided pain response data from seven randomised placebo-controlled trials of etoricoxib in osteoarthritis lasting ⩾6 weeks .We calculated the number of patients in each treatment group in each trial achieving various Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) thresholds of pain relief over baseline of ⩾15% , ⩾30% (moderate), ⩾50% In each study patients were asked, “During the last 48 hours, how much pain do you have (1) walking on a flat surface; (2) going up or down stairs; (3) at night while in bed; (4) sitting or lying; (5) standing upright?”. On a 100 mm visual analogue scale, patients placed an “x” ranging from 0 (“no pain”) to 100 (“extreme pain”). The Western Ontario and McMasters Universities (WOMAC) 100 mm visual analogue pain subscale score was calculated as the average of the responses to the five questions.Criteria used in defining responders included:For patients who did not drop out, only actual measured values were used for calculations. Last observation carried forward was not used.For patients who withdrew for any reason, measurements made within 7 days of the last dose were used to calculate the response.Thereafter, patients were assigned 0% improvement.We calculated the number and percentage of responders for each level of response for each drug and time point and the number needed to treat (NNT) compared with placebo (with 95% CI).Clinical trial reports were used to obtain, for each active treatment, the difference between active treatment and placebo for the WOMAC pain subscale score. This was defined in the company clinical trial reports as the mean time-weighted average change from baseline (flare/randomisation visit) over the 6- or 12-week treatment period ((WOMAC baseline − WOMAC treatment average) − (WOMAC baseline − WOMAC placebo average)). Average results for each treatment arm were pooled using RevMan 5.0.Information was available on 3554 patients (two-thirds women) with an average age of 62 years (see online supplement). Six trials involved patients with osteoarthritis of the knee or hip and one of the knee only. Osteoarthritis was established clinically and radiographically. Initial pain had to be a minimum of 40/100 mm at inclusion, plus ⩾15 mm increase and worsening in investigator global assessment since baseline. The actual numbers of responders for each level of response for each drug in each trial and at each time point are shown in the online supplement.The percentage of patients achieving levels of pain relief with placebo at each threshold rose between weeks 2 and 12 . At the NNTs calculated for ⩾15%, ⩾30% and ⩾50% pain relief were very similar with etoricoxib 60 mg and 30 mg, celecoxib 200 mg and naproxen 1000 mg , fig 2. There were three direct comparisons, each in two trials, of daily doses of etoricoxib 60 mg and naproxen 1000 mg, etoricoxib 30 mg and celecoxib 200 mg, and etoricoxib 30 mg and ibuprofen 2400 mg. No statistically significant differences were found between them at any level of response or any duration of treatment.The additional reduction in the WOMAC pain subscale score for each active treatment over placebo between the flare/randomisation visit and end of treatment is shown in Population mean changes have no easy resonance outside a clinical trial. An average of 10 mm out of 100 mm  NNTs for ⩾70% for both doses of etoricoxib, celecoxib and naproxen. For these three drugs, NNTs were reasonably stable over 2–12 weeks. Ibuprofen 2400 mg daily was different, with NNT values generally increasing (worsening) with longer duration. The longitudinal responder analysis provides more insight than population average differences . This apA range of ±0.5 NNT was proposed to determine whether an NNT has “clinical relevance”—whether the NNT is within acceptable bounds of clinical “accuracy”.The results of the responder analysis achieve the same global conclusions as the original trials—namely, that etoricoxib and its comparators have useful analgesic properties in osteoarthritis. Arguably the most important outcome from these analyses is that, for osteoarthritis, patients and professionals can be provided with trial data that translate into clinical practice by using realistic estimates of the chance of achieving a particular level of benefit. For pain, a mean difference of 10 mm over placebo translates into about 40% having substantial benefit and 30% not having even minimal benefit. Most people with osteoarthritis treated with an NSAID at an appropriate dose can expect to get at least a minimal benefit (though 1 in 5 will not), almost 1 in 2 can expect a substantial benefit and about 1 in 5 an extensive benefit. The prospect of a 1 in 2 chance of substantial benefit has considerably more impact than an average 10% improvement in pain. Moreover, the information is conveyed in terms of both the likelihood of benefit (1 in 2) and the extent of the benefit .Patients and professionals are interested in the known associated risks of both common and rare harm. These, too, can be conveyed in terms of likelihood of harm and its consequences.Responders are defined not just by the level of response but by the outcome used to define response. We chose the WOMAC pain subscale, combining pain associated with walking, climbing stairs, sitting, lying down and at night while in bed. Whether pain is the most appropriate outcome for responder analysis or whether function, sleep, quality of life or compound outcomes like the OMERACT-OARSI set of responder criteriaResponder analysis looks promising and much more helpful than an average change of a few millimetres based on populations of responders combined with non-responders.Population mean change in pain intensity reported in clinical trials may be difficult to translate into clinical decision-making and patient expectations of benefit. Responder analyses and NNTs calculated from them are reproducible for different levels of response and over at least 12 weeks of treatment with effective drugs. This offers the possibility of providing patients and professionals with information on the chance of achieving particular degrees of pain relief, improving clinical decision-making and patient communication.


It is widely believed that non-specific low back pain (LBP) consists of a number of subgroups which should be identified in order to improve treatment effects. In order to identify subgroups, patient characteristics that relate to different outcomes are searched for. However, LBP is often fluctuating or recurring rather than clearly limited in time. Therefore it would be relevant to consider outcome after completed treatment from a longitudinal perspective (describing "course patterns") instead of defining it from an arbitrarily selected end-point.The objectives of this pilot study were to investigate the interobserver reliability of a diagnostic classification system and to evaluate whether diagnostic classes or other baseline characteristics are associated with the LBP course pattern over a period of 18 weeks.Patients visiting one of 7 chiropractors because of LBP were classified according to a diagnostic classification system, which includes end-range loading, SI-joint pain provocation tests, neurological examination and tests for muscle tenderness and abnormal nerve tension. In addition, age, gender, duration of pain and presence of leg pain were registered in the patient's file. By weekly SMS-messages on their mobile phones, patients were asked how many days they had LBP the preceding week, and these answers were transformed into pain course patterns and the total number of LBP days.A total of 110 patients were included and 76 (69%) completed follow-up. Thirty-five patients were examined by two chiropractors. The agreement regarding diagnostic classes was 83% (95% CI: 70 - 96). The diagnostic classes were associated with the pain course patterns and number of LBP days. Patients with disc pain had the highest number of LBP days and patients with muscular pain reported the fewest . Men had better outcome than women  and patients without leg pain tended to have fewer LBP days than those with leg pain . Duration of LBP at the first visit was not associated with outcome.The study indicated that there is a clinically meaningful relationship between diagnostic classes and the course of LBP. This should be evaluated in more depth. Much has been written on non-specific low back pain (LBP) in the scientific literature. Presently, however, there are no easy answers to the clinicians' questions on how best to treat this condition; it seems that a number of different treatments have an effect, but only to a very limited degree -3. In anDifferent approaches exist to identify specific profiles of patients within the amorphous definition of non-specific LBP. Clinicians typically attempt to detect the pain generating structure and classify their patients accordingly into diagnostic subgroups. This information is then used both to determine the most relevant type of treatment and to predict outcome of treatment (prognosis). Such a pathoanatomical classification has also been suggested by some researchers  whereas In randomized trials, the outcome is typically calculated as the difference between the patients' status before and the status after treatment. However, LBP is a fluctuating or episodic condition for many -20. ThesPresently, very little is known of what happens between the time, when a patient seeks care, and when the final outcome is measured. However, with the advent of a new method to collect data using mobile phones, study subjects can be surveyed at frequent and regular intervals with the help of automatically generated text messages. This makes it possible to identify course patterns rather than end-point outcome thus approaching this problem from a different angle. Both diagnostic subgroups and other clinical characteristics could be held up against the clinical course, in order to see if they represent clinically relevant subgroups. After all, what matters for the patient is probably rather the every-day events than the arbitrarily selected point of outcome 3, 6 or 12 months after treatment took place.For these reasons, a practice-based pilot study was performed, in which clinical data were collected at base-line and over a period of 18 weeks as continuous follow-ups by means of weekly text-messages. The rationale for the study was that clinical observations at the first consultation for an event of LBP would predict the ensuing course pattern. We have previously reported that improvement occurred early in the course  and thatThe method of the study has been described elsewhere . In brieSeven chiropractors were invited to participate in the study on the condition that they followed an instruction program and agreed to use a specific clinical procedure. The inclusion criteria for the patients were that they had LBP with or without sciatica as the main complaint, were 18 - 65 years old and that they had a mobile phone. Patients were not included if one of the following non-inclusion criteria was present: Previous back surgery, pregnancy, other significant musculoskeletal problems in addition to the LBP, or inability to read or speak Danish. Prior to inclusion patients received written and verbal information about the study. Chiropractors were free to choose the kind and duration of treatment they found appropriate in each case.Prior to data collection, the participating chiropractors had been informed of the purpose of the study and the rationale for the diagnostic classification system by the first author. At a one-day workshop they had been instructed on the performance of the clinical tests and their interpretation, and this was practised. The first author then visited the participating clinics once to supervise their clinical procedures when they examined LBP patients and to discuss which diagnostic class each patient belonged to. Questions were then answered and any mistakes rectified. After a period during wgich the group had had the possibility to practice the classification system in their own clinic, an evening meeting was undertaken to discuss any remaining problems and uncertainties before starting the collection of data.As part of the patient history age, gender, and duration of present complaint were noted down in the patient file, and in addition the chiropractors interviewed the patient at their own initiative. After this, the patient had a physical examination following a standardised protocol to classify the case according to a slightly modified version of the classification system previously described by Petersen et al. .This classification system outlines an algorithm involving mechanical loading strategies as described by McKenzie , five paThe single elements were performed as described in the original classification system, but in contrast to the original description, the chiropractors were allowed to use more than one of the classes if a patient fulfilled the criteria for more than one. Moreover, we excluded the diagnostic classes "adherent nerve root syndrome" and "nerve root entrapment syndrome" since these classes did not seem clinically meaningful, and it had not been possible to evaluate their reliability due to few cases in the only pre-existing reliability study .The chiropractors could use the result of the classification in this information to the patient, or inform about their findings as they used to, patients were hence not blinded from their diagnosis, as in the normal clinical situation.Reliability was tested with pairs of two observers, either two chiropractors from the same clinic or one of the participating chiropractors and the first author. Both clinicians were present during both the history and the physical examination. The examination was performed by one chiropractor (examiner A) while the other was allowed only to observe (examiner B). Both filled in an examination sheet without discussing the case. The chiropractors took turns with the roles of examiner A and B at a sequence not described in advance.Participants were sent weekly text messages, beginning on the Sunday following the first consultation. If by the ensuing Thursday there had been no response, a reminder was sent to them. Information used in the present report relates to the following questions sent by SMS:Question 1. Using a number from 0 to 7, please answer how many days you have been bothered by your lower back this week.Question 2. Using a number from 0 to 7, please answer how many days you have been off work because of your lower back this week. (Answer with X if you are not working)The answers were automatically entered into a data file that was later used for the analysis.The independent variables were: diagnostic class (10 categories), leg pain (yes/no), age (continuous variable), gender, and duration of LBP at the time of base-line .The outcome variables were generated from data collected weekly by means of SMS during 18 weeks. Based on question 1, "LBP days", patients were divided into 13 course patterns describing their individual course during 18 weeks  and in relation to all chosen classes (level 2). The more manifest diagnoses  were given higher priority in relation to defining the main class in level 1 than the other classes. Dysfunction, postural syndrome and SI-joint pain ranked higher than facet-joint pain, abnormal nerve tension, muscle pain, and abnormal pain syndrome. Agreement was only calculated as percentages since there were too few observations to calculate meaningful kappa-values. In case of disagreement between examiners, we used examiner A's classification for the analyses of the main study.th week with no more than two weeks' pause in a row. Missing values during weeks 1 - 12 were replaced by the mean of the adjacent values from the week before and after the one missing. Due to the relatively small number of patients included in the pilot study, the three disc classes described in the classification system were collapsed into one as were pain course patterns consisting of less than six persons.The study population consisted of patients who participated at least until the 12The analyses were done in two stages. First, each of the independent variables was tested against each of the outcome variables by Fisher's exact test or regression analysis with one explanatory variable. Thereafter, the variables that were associated with one of the outcome variables were considered for a multivariable analysis, providing that these associations had a p-value of less than 0.1. The multivariable analyses were performed by means of regression with robust variance estimations with LBP days as dependent variable. Results were considered statistically significant if p-values were below 0.05. The statistical package STATA 10.1  was used for the analyses.Seven chiropractors  from five chiropractic clinics in Denmark included participants for the study. Six of these chiropractors had graduated from the University of Southern Denmark and one from Palmer College, California, USA.A total of 139 patients  underwent a physical examination in the project. The data from the examination was missing in two cases, 108 patients participated in the longitudinal study, and 29 were included only for the reliability study . The conclusions of each examiner appear in Additional file Nine different course patterns were identified Table  20]. Th. Th20]. The majority of the study population (53%) did not report any days with sick-leave. The median number of days with sick-leave in the 34 patients with any sick-leave was 4 days (interquartile range 2 - 8). Due to small numbers this variable was not used in the analyses of prognostic factors.The median age within the five pain course patterns varied from 36 to 49 years with patients in the' improved-recovered' and 'improved-stayed so' groups being the youngest (p = 0.01)  had a pain course pattern with unchanged pain in the first weeks as compared to males (15%) , and patients with leg pain tended to report more LBP days, but differences were not significant (Tables % vs. 24%The diagnostic classes were associated with both the pain course patterns and the total number of LBP days Tables  and 4. TThe number of LBP days was tested in a model including diagnostic class and gender. Both gender and the diagnostic class were significantly associated to the total number of LBP days Table . The assThis appears to be the first study to compare baseline characteristics of LBP patients to pain patterns generated by very frequent follow-ups over a period of time. Moreover, it was the first attempt to study whether the prognosis of primary care patients with LBP is related to diagnostic classes as defined by the classification system described by Petersen . AlthougFirst, it appears that at least some of the diagnostic classes relate to the prognosis. Patients classified as having disc-related pain reported more pain days and were less likely to experience the pain course 'mainly recovered' than others. Patients with disc pain had on average between 13 and 19 more days with pain than patients with muscle pain, mechanical dysfunctions, or SI-joint pain. It would be relevant to investigate such differences in more depth including whether diagnostic classes differ not only regarding pain, but also in relation to activity of daily living or disability. If similar associations between diagnosis and prognosis are confirmed by other studies, the differences are large enough to be important to patients and indicate that this classification system makes a distinction between relevant subgroups of patients.In accordance with previous studies  men had Because of the small numbers within each diagnostic class, statistical testing in relation to agreement was unworkable and the agreement was therefore only evaluated in percentages that do not take into account agreement by chance. The agreement concerning the diagnostic classes was high when based on the most manifest class, and markedly lower if absolute agreement was demanded. However, we consider the obtained agreement sufficient for the classification to be meaningful. The reliability of the classification system was tested in a set up with two chiropractors being present at the same consultation. This could have introduced bias toward higher agreement, but was chosen to avoid an altered symptom response at the second examination. The same decision was made in earlier studies ,27. The The main limitation of this pilot study was the relatively large drop out from follow-up. As discussed in previous papers ,21 this As a consequence of the quite small cohort we chose to pool the three disc classes from the original classification system into one. This may limit the prognostic value of the classification since we did not distinguish between mechanically reducible and irreducible discs, i.e. pain that can be centralized and pain that cannot, which is known to be of predictive value -32.In conclusion, our results suggest that different diagnostic classes have different pain courses and indicate that patients with different low back conditions can be identified through the physical examination. The next step will be to perform a large-scale practice based study with a sufficient number of patients to make it possible to include more of the diagnostic classes and evaluate prognosis within each of these.The authors declare that they have no competing interests.Both authors participated in the design of the study and drafting of the manuscript. AK instructed the chiropractors who included patients, collected the data and did the data analyses.Diagnostic Classes. The table lists the classes of the original classification system and the classes used in this study.Click here for fileAgreement between observers. Two chiropractors' conclusion and their agreement regarding diagnostic class examining 35 LBP patients.Click here for file


Nearly one million cancer patients in India need oral morphine for pain relief. Despite doctors prescribing oral morphine in our center, many cancer patients with severe pain found to be not facilitated with adequate pain relief.This audit was conducted to look at the “oral morphine prescribing practices for severe cancer pain” at a tertiary care hospital.Twenty case files of patients, who were admitted with severe cancer pain, and receiving oral morphine were analyzed in pre- and posteducational session. Local standards were set to assess the adequacy of pain relief. Deficiency in achieving analgesia was found in preinterventional audit. A clinical audit was conducted before and after the educational session on oral morphine prescribing. The education for doctors and nurses focused on starting patients on morphine, titration, and administering rescue dose. Then local guidelines on oral morphine prescribing were circulated. And analysis of following factors were done following pre- and posteducational session: Pain intensity at the beginning of treatment, starting dose of morphine, increments in morphine dose, number of rescue doses given, and fall in pain intensity at the end of 1 week. The outcomes were compared with the standards.Preintervention audit showed that only 50% of patients achieved adequate pain relief. Rescue dose was administered in only 20% of patients. While reaudit following the educational session showed that 80% of patients achieved adequate pain relief and 100% received rescue doses.Educational sessions have significant impact on improving oral morphine prescribing practice among doctors and nurses. It was found failing to administer regular as well as rescue doses resulted in inadequate pain relief in patients receiving oral morphine. Studies found that one million people suffer from cancer pain in India, but only 0.4% of them are able to access oral morphine.Despite the WHO and other local palliative care services publishing guidelines for cancer pain management, 50% of patients with cancer pain experience inadequate analgesia.3Limited availability of strong opioids especially morphine, strict narcotic act,3 lack of13Few strong opioids available in our country are morphine, buprenorphine pethidine, and fentanyl. They are available as oral, sublingual, and injectables, respectively. Suppositories of strong opioids are not available in India; syringe drivers and fentanyl patches are not affordable by everyone in our clinical setting.Morphine as oral and parenteral preparation is the only option left to treat severe cancer pain in most palliative centers in India. As per WHO recommendation, oral rouOral morphine is cost-effective, available as small tablets and liquids so that patients with some dysphagia can swallow it and can be self-administered at home. When com1More than 90% of our patients in our palliative care center at St. John's Hospital with severe cancer pain receive oral morphine following WHO principles of cancer pain management.7Despite doctors prescribing oral morphine in our center, many cancer patients with severe cancer pain do not achieve adequate pain relief. Hence an audit was planned to look at the current standards of practice in oral morphine prescribing patterns at St. John's medical college Hospital, Bangalore. This audit aimed to assess “oral morphine prescribing practices for severe cancer pain.”A clinical audit was conducted with the sample size of 20 in each phase in patients receiving oral morphine for severe cancer pain. Only in-patients were included for the ease of assessing pain relief at a set interval of 1 week from the start of morphine. Numerical scale of 0-10 points had been used to measure pain relief.A discussion was held with our palliative care team and the following local standards had been set to assess pain relief, which would be appropriate for our clinical setting.Standard I. Eighty percent of patients should achieve adequate pain control at the end of 1 week. Drop of “6” and/or above in 0-10 point numerical scale was determined as adequate pain relief.Standard II. All 100% of patients who has breakthrough pain should receive “breakthrough dose” in addition to regular dose of morphine according to local guidelines [idelines .Standard III. In all 100% of patients, the regular increments (titration) of morphine dose should be in line with local guidelines.After setting the guidelines, analysis of 20 case sheets  of patients with severe cancer pain who were on oral morphine was done by using the data collection sheet . The folAn educational session on oral morphine prescribing for severe cancer pain was conducted for the doctors and nurses at St. John's hospital and local guidelines were circulated. Only the specialties which treat cancer patients were targeted for educational sessions; they were the department of Medicine, Surgery, Obstetrics and Gynecology, and Orthopedics.The educational session was one-and-half-hour lecture covering pain assessment, WHO ladder, oral morphine administration, and side-effects of morphine. A brief case presentation of patient who had been receiving oral morphine was made to help the audience to understand the morphine prescription pattern.Assessing pain with 11-point numerical scale, starting dose of morphine, correct frequency of administration, administering BT doses, titrating morphine according to local guidelines, and common side-effects that can occur had been stressed during the educational session.There was an additional lecture conducted in those wards within the next 2 weeks following the common lecture with the aim to cover the staffs who could not attend the common lecture.The local guidelines on oral morphine prescribing was designed, which was adapted from WHO7 and EurA period of 2 months was given for adapting the changes in practice. Then reaudit of 20 charts was done and the following were assessed again: Pain intensity at the beginning of treatment, starting dose of morphine, increments in morphine dose, number of BT doses given, and fall in pain intensity at the end of 1 week.Twenty charts of patients were analyzed before and after the educational intervention. Male patients (16) were higher compare to female patients (4), and this proportion almost remained the same in reaudit .The age distribution ranged from 26 to 72 years; majority of them were in advanced stage of cancer (18). Six of them were on palliative chemotherapy and four patients were receiving palliative radiotherapy.Assessment of pain at the end of 1 week of treatment had shown that 50% of patients did not achieve adequate pain relief. Adequate pain relief was set as achieving a score of 6 and above in the 0-10 point numerical scale .It was observed that morphine was not given at fourth hourly interval. Often it was given as required, three times a day or four times a day. Only 10% received fourth hourly dose . This miBT dose was not routinely administered. Only 20% had received the BT dose, which is the same as fourth hourly dose of morphine. Of the remaining patients, 20% received injection pethidine 25 mg IV and 10% received injection morphine 2 mg IV as BT dose, which was not compliant with guidelines. And the rest did not receive any BT medicine at all .According to guidelines, increments should be made by adding the number of BT dose to the total dose of morphine and adjust the dose as fourth hourly. But it was found in 20% of patients that increments in morphine dose were not according to the guidelines. These preinterventional results revealed that all three set standards had not been met .After the educational session, reaudit was done on 20 case files at the end of 2 months. The fall in pain intensity at the end of 1 week has improved from 50% to 80% following the educational session .BT dose was given to all patients, which complied with the guidelines. In all patients, the BT dose was the same as the fourth hourly dose of morphine. The number of BT dose ranged from two to four times a day.In all patients, the increments of morphine dose were in line with local guidelines. The morphine dose was reviewed daily and adjusted according to the number of BT doses given in a day. The audit carried out after the educational session had revealed that all three of the set standards were met Graphs –3.It was also interesting to find that inappropriate starting dose could have contributed for inadequate pain relief. In 55% cases, the starting dose of morphine was 2.5 mg, which was not recommended by the guidelines.This audit showed that 80% were able to achieve adequate analgesia; BT doses were administered in 100% patients; and titration of morphine dose was according to local guidelines in 100% patients following educational session.Inability to achieve adequate pain relief in patients who are taking oral morphine with severe cancer pain is a global problem faced in the world of palliative care. This exi2et al. reported that educational deficit of healthcare professionals and improper allocation of money toward developing knowledge of healthcare professionals are the main barriers of achieving adequate pain relief in cancer.[Zenz n cancer.A similar audit conducted in a hospice at Singapore had revealed that lack of BT doses (two-third) resulted in inadequate pain relief. This hadet al.[Troller et al. who condAnother audit done in New England and South Wales showed tThere are no relevant audits conducted in India that is available to compare morphine prescribing practices in India.The reasons for not administering BT doses were explored during the educational session as that had significant impact on pain relief. These were as follows: Nurses have been too busy and unable to take frequent drug rounds; nurses have thought that they are giving “too much morphine” that could cause serious side-effects like respiratory depression; doctors are hesitant to give BT dose because they thought it can harm kidneys and can cause addiction and respiratory depression.Few patients had expressed (to nurses) concern that they might develop a “habit” of popping a pill for all their aches and pains. This threw light on an important point that patient education is an essential part for morphine prescription. This may require a separate audit to explore this aspect.There were a few limitations in conducting this audit. It was difficult to cover all doctors and nurses through educational session for the following reasons: Staffs on long leave, change of duties, and huge staff turnover in our hospital. Ongoing education is necessary to improve the quality of oral morphine prescribing in our hospital. And preinterventional audit had difficulty in retrieving data on pain because of lack of regular pain documentation.This audit showed that educating healthcare professionals on oral morphine prescribing helped in better prescribing practice, which resulted in achieving adequate analgesia. This audit found that failure to administer morphine at fourth hourly interval and inadequate administration of BT dose in patients receiving oral morphine for cancer pain were the main reasons for inadequate pain relief.


Between 1992 and 2001 the UK general practice incidence of post-herpetic neuralgia and trigeminal neuralgia declined, whilst the incidence of painful diabetic neuropathy increased. The most common first line treatments were compound analgesics. As therapeutic options have subsequently changed, this study presents updated data on incidence and prescribing patterns in neuropathic pain.A descriptive analysis of the epidemiology and prescription treatment at diagnosis of incident post-herpetic neuralgia ; trigeminal neuralgia ; phantom limb pain (57) and painful diabetic neuropathy  using computerised UK general practice records (THIN): May 2002 to July 2005.Primary care incidences per 100,000 person years observation of 28  27–30) for post-herpetic neuralgia, 27 (95%CI 26–29) for trigeminal neuralgia, 0.8 (95%CI 0.6–1.1) for phantom limb pain and 21 (95%CI 20–22) for painful diabetic neuropathy are reported. The most common initial treatments were tricyclic antidepressants  or antiepileptics  and opioid analgesics (phantom limb pain). The mean number of changes before a stable drug regimen was 1.2 to 1.5 for trigeminal neuralgia, painful diabetic neuropathy and post-herpetic neuralgia, and 2.4 for phantom limb pain.The incidence of phantom limb pain and post-herpetic neuralgia are decreasing whilst painful diabetic neuropathy plateaued and trigeminal neuralgia remained constant. Despite more frequent use of antidepressants and antiepileptics for first line treatment, as opposed to conventional non-opioid analgesics, changes to therapy are common before a stable regimen is reached. A fifth of adults in Europe have moderate or severe chronic pain but, although only 2% are managed by a specialist , most puIt was anticipated that prescribing patterns for the neuropathic pain conditions would have changed recently with negative publicity concerning co-proxamol , increasThe study was an observational, descriptive study of patients with an incident diagnosis of one of four neuropathic pain syndromes. All data were obtained from the Health Information Network database (THIN), which is an observational database containing primary care records from throughout the UK. Details of demographics, primary care diagnoses and prescription treatment are routinely recorded against date in individual patient records. Information on referrals, secondary care diagnoses and deaths are also captured because of the structure of the UK National Health Service (NHS). Within the NHS, the general population are registered with one General Practitioner (GP) and remain on that GP's list whilst being treated by hospital specialists or hospitalized. Major events from before computerization are added retrospectively. Medical events are recorded using the Read Coding system .The study population comprised all patients who were permanently registered at one of the practices contributing to THIN at any time in the study period, May 2002 to July 2005; that is over 2.9 million patients from 295 practices, 51% female and 20% over 60 years of age. The files of all patients in the study population were searched for a record of any of the four forms of neuropathic pain studied [see Additional file The person years observation and incidence per person years observation were estimated for each form of neuropathic pain. Those with a first record of their neuropathic pain dated during their period of observation counted as incident cases and formed the neuropathic pain cohorts. A period of observation was assigned for each patient. The start of observation was the later of May 2002, or one year after the date that either the practice started using the Vision Computer System or the patient registered at that practice. The year was added to allow time for the recording of prevalent events. The end of observation was the earliest of the following: death, transfer-out of the practice, the final data collection or the end of July 2005. Incidence rates were age adjusted by direct standardisation to the UK figures for 2005 .The computerised treatment records of each patient in the incident neuropathic pain cohorts were searched for an initial treatment, defined as any treatment for neuropathic pain started within 28 days of the first record of the diagnosis. If more than one therapy was prescribed in this period then that nearest to the first record was the initial treatment. When more than one item was prescribed on the same day, the initial treatment was considered to be the combination of these therapies. For the four study conditions, the number of patients with each initial drug regimen (drug and daily dose), therapeutic class, and number of therapies per patient were counted. Therapeutic class was based on the British National Formulary . Daily dTo understand changes in treatment a sub-group of patients who received an initial treatment and who could be followed for at least one further year were identified. Prescription records during the year were searched for any changes in neuropathic pain treatment. Changes to therapy included each switch, new treatment, discontinuation or addition of a concomitant drug. A switch was defined as prescriptions for more than one drug, where the prescription for the first drug was dated before that of the second, with less than 56 days between these prescriptions, and no subsequent treatment for the first drug in the 56 days after the prescription for the second drug. A new treatment was defined as prescriptions for more than one drug, where one prescription was dated after the other, with between 56 days and 6 months between the prescriptions and no subsequent treatment for the first drug in the 56 days after the second prescription. Concomitant therapy was defined as prescriptions for more than one treatment where the date of the second prescription was on or after the starting treatment date but on or before the date of the last prescription in a treatment episode (one or more prescriptions separated by less than 56 days). A discontinuation was defined as no further prescriptions for that drug. Stable therapy was defined as more than two prescriptions for the same drug or drugs (ignoring daily dose) with less than 56 days between them, and without a break of more than 6 months with no neuropathic pain treatment. The number of patients who reached a stable therapy regimen within the year was counted.Ethics approval was given by London MREC, reference number 05/MRE02/77.Incident cases of one or more of the four neuropathic pain conditions were identified for 5,445 patients during the period of observation. There were 1,923 incident cases of post-herpetic neuralgia, incidence 28.2 per 100,000 person years  and 1,862 cases of trigeminal neuralgia, incidence 27.3 (95% CI 26.1–28.6) and 57 of phantom limb pain, incidence 0.8 (95% CI 0.6–1.1). The incidence of painful diabetic neuropathy was 27.2 (95% CI 26.0–28.4), n = 1,867, and 26.1 per 100,000 person years when the stricter definition was used excluding those whose pain treatment did not start at the time of the first diagnosis record. The age standardised incidence rates (to UK 2005) were 27.3 per 100,000 person years for post herpetic neuralgia, 26.7 for trigeminal neuralgia, 0.8 for phantom limb pain and 26.7 for painful diabetic neuropathy.A treatment for neuropathic pain was initiated at the time of the first diagnosis record for between 49.4% and 73.5% of patients with a neuropathic pain condition Table . The meaWithin those patients in the phantom limb pain cohort, and followed for at least one year, no initial treatment (drug and daily dose combination) had been prescribed to ten or more patients. For post-herpetic neuralgia and painful diabetic neuropathy the most common drug and dose combinations were amitriptyline 10 or 25 milligrams per day and 10 milligrams 'dose not specified'. Carbamazepine 200 milligrams per day was the most common treatment for trigeminal neuralgia, followed by amitriptyline 10 milligrams per day and 10 milligrams 'dose not specified'.This large study aimed to provide updated incidence rates and prescribing practices for four neuropathic pain conditions as seen by UK general practitioners rather than in secondary care clinics. The population was similar to that of the UK in terms of age and sex, 51% were female as in the UK 2001 census data, while there were slightly fewer elderly patients, 20% over 60 years of age compared to 21% .The incidence rate of 28.2 per 100,000 patient years for post-herpetic neuralgia is in-line with other published findings ,16 whichOur finding of an incidence of trigeminal neuralgia of 27 per 100,000 person years is consistent with the previous database study, however these rates are considerably higher than those previously published . ThiIncidence rates for painful diabetic neuropathy, from both this and the previous UK general practice study are considered to be maximum incidences. The data source did not allow separation of patients with non-painful diabetic neuropathy who had a treatment for depression or other pain initiated at the same time as the neuropathy was first recorded from those treated for painful diabetic neuropathy. Although the crude incidence of painful diabetic neuropathy increased, age-adjusted rates (taking into account the new dataset) were the same for the 1998–2001 and 2002–2005 data.A treatment was initiated at the time of diagnosis for between 40% and 74% of patients in the neuropathic cohorts. Other patients may have been established on a treatment before a firm diagnosis was made, particularly as definitions for both phantom limb pain and post-herpetic neuralgia include a delay between the precipitating event and diagnosis. The prescribing of antidepressants and antiepileptics is in-line with UK guidelines for neuropathic pain treatment ,24, althWhen compared to prescribing in the previous, similar UK primary care study  the 2002The study used the most up to date records available. This allowed us to provide current incidence figures, but meant that we had one year of follow-up on 56% to 66% of the cohorts. The remainder will either have left the practice before the end of the year or have been diagnosed within a year of either the last data collection or the end of the study period. Fewer patients with post-herpetic neuralgia and trigeminal neuralgia were followed to stable regimen than those with phantom limb pain and painful diabetic neuropathy. This difference may be partly the result of our definition rather than an indication that patients with post-herpetic neuralgia and trigeminal neuralgia have more difficulty achieving effective pain relief. Stable therapy was defined as more than two prescriptions for the same treatment. As post-herpetic neuralgia may wane while trigeminal neuralgia can be intermittent these patients may not require a third consecutive prescription.Results of the January 1992 to April 2002 analysis suggested that, for the most commonly prescribed treatments, changes to a treatment regimen appeared to be less frequent when initial therapy was with frequently used antidepressants or antiepileptics rather than compound analgesics. Our ability to explore this further in more recent cohorts is limited given that conventional analgesics were prescribed less frequently and severity of pain or underlying disease cannot be accounted for in the dataset. However, the mean change in therapy within cohorts was slightly greater in this study (2–3 changes compared to 1–2 changes) despite a larger proportion receiving antiepileptics and antidepressants. Conversely, the mean duration of the initial treatment increased, 50 to 90 days compared to 47 to 76 days previously, as did the number of initial prescriptions with more than one item (28% to 43% compared to 7% to 19% previously) [Incidence rates of phantom limb pain and post-herpetic neuralgia as seen in UK general practice continue to change, although the reasons for this are not clear. Treatment patterns at the time of the first diagnosis have also changed as the use of antidepressant and antiepileptics has increased and is common across all conditions studied with most patients prescribed one item. Although this is in line with directives, frequent changes to therapy before a stable regimen is reached suggest that pain relief with tolerability are difficult to achieve.THIN: The Health Information Network database; NHS: National Health Service; GP: General Practitioner; UK: United Kingdom.Gillian Hall has received funding for research and payment for consultancy from a number of pharmaceutical companies and charities and has no direct stock holding in any pharmaceutical company. Dawn Carroll was an employee of Pfizer Inc. Henry McQuay has received research support, consultancy and lecture fees from pharmaceutical companies, charities and government sources, and has no direct stock holding in any pharmaceutical company.All authors formulated the research questions. GH participated in the design of the study and was responsible for the analysis and interpretation of the patient database and drafting and finalising the paper. DC and HMcQ participated in the design of the study and commented on the paper. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:Read codes with terms used for identification of four neuropathic pain cohorts.Click here for file


According to the International Association for the Study of Pain criteria of 1994, pain is a diagnostic requirement for Complex Regional Pain Syndrome type I. However, other authors have suggested that patients can rarely present with the sensory and vascular symptoms of Complex Regional Pain Syndrome without pain. This entity has not been reported following hip surgery in the English medical literature.We present two cases of Complex Regional Pain Syndrome-like symptoms following hip surgery and with the total absence of pain. The first case was a 29-year-old Caucasian woman who had a reattachment of the greater trochanter following non-union of an intertrochanteric osteotomy of the hip. Five weeks later, the patient presented with features of Complex Regional Pain Syndrome but with the absence of pain. The second patient was a 20-year-old Caucasian woman who had undergone an open debridement and repair of a torn acetabular labrum. Ten days later, the patient presented with features suggestive of Complex Regional Pain Syndrome which was again painless. Both patients were non-weight bearing at presentation and the symptoms resolved following recommencement of weight bearing.The authors believe these symptoms are manifestations of vascular changes to the lower limb as a result of non-weight bearing status. Painless Complex Regional Pain Syndrome-like symptoms may occur in patients who are kept non-weight bearing following hip surgery. However, vascular insufficiency and deep venous thrombosis must be excluded before this diagnosis is made. If the clinical situation permits, early weight bearing may relieve symptoms. Orthopaedic and vascular surgeons should be aware of this entity when a postoperative patient presents to them with the above clinical picture. This is also relevant to general practitioners who are likely to see the patients in the postoperative period. Pain out of proportion to the injury is an essential criterion for the diagnosis of Complex Regional Pain Syndrome (CRPS) type I -3]. We . We 3]. A 29-year-old Caucasian woman had a varus intertrochanteric osteotomy with trochanteric advancement for an old malunited femoral neck fracture. The femoral neck fracture was sustained in a childhood injury and was treated conservatively. The patient underwent reattachment of the greater trochanter for a failed trochanteric fixation approximately 4 weeks after her initial operation. She was discharged 2 days after the second procedure. Approximately 5 weeks later, the general practitioner referred her to the vascular surgeons with painless discolouration of the right leg. Clinical examination revealed a discoloured right foot associated with mild swelling and several small blisters on her toes. The most prominent feature was that the right foot exhibited bluish discolouration which evidently subsided to near-normal colour on elevation Figure . The femHandheld Doppler examination demonstrated a relative decrease in the audible quality of the biphasic pulse when compared to the normal side. Duplex scan of the right lower limb excluded the possibility of any superficial or deep venous thrombosis. The patient was commenced on 50% weight bearing status and was discharged home. A recent follow-up demonstrated significant improvement in symptoms since commencement of weight bearing status.A 20-year-old Caucasian woman who presented with symptoms of right hip impingement underwent open debridement and repair of a torn acetabular labrum. The patient was discharged on the 5th postoperative day following an uneventful recovery period. She was to remain non-weight bearing for 6 weeks. Ten days following discharge, she presented to the clinic complaining of her right foot going blue and cold and with the complete absence of pain. The discolouration occurred when the limb was in a dependent position. Clinically, all peripheral pulses were present and normal. The patient was reviewed by a vascular surgeon who excluded the possibility of arterial insufficiency and deep venous thrombosis.The patient was discharged with the advice to commence on weight bearing of the operated hip. In the follow-up clinic 5 months later, she was found to have complete resolution of her vascular symptoms.According to the International Association for the Study of Pain (IASP) criteria of 1994, pain, evidence of change in blood flow or abnormal sudomotor activity and the absence of conditions that would otherwise account for symptoms are essential diagnostic entities of Complex Regional Pain Syndrome type I. Eisenberg and Melamed [et al. reported a series of 829 patients with reflex sympathetic dystrophy (RSD) and among them, 7% of the patients did not have pain as a symptom [Veldman  symptom . AlthougThe authors of this article postulate that in the hip, CRPS-like symptoms develop following a period of non-weight bearing. In both of our patients, the symptoms occurred during non-weight bearing and subsided after weight bearing was commenced. Unilateral lower limb suspension experiments in normal patients have shown an increase in flow mediated dilatation of arteries of the lower limb along with a decrease in venous capacitance . This mePainless Complex Regional Pain Syndrome-like symptoms may occur in patients who are kept non-weight bearing following hip surgery. However, vascular insufficiency and deep venous thrombosis must be excluded before this diagnosis is made. If the clinical situation permits, early weight bearing may relieve symptoms.Written informed consent was obtained from the patients for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.JGA postulated the concept and designed the study, interpreted the data and revised the final manuscript. AJSK identified and re-examined the cases, acquired the data and analysed it, reviewed the literature and wrote the article. SKSW also re-examined the cases for the study, assisted in data acquisition, analysed the data and assisted in writing up the article.