Chronic problems from whiplash trauma generally include headache, pain and neck stiffness that may prove refractory to conservative treatment modalities. As has previously been reported, such afflicted patients may experience significant temporary relief with injections of local anesthetic to painful trigger points in muscles of the shoulder and neck, or lasting symptomatic improvement through surgical excision of myofascial trigger points. In a subset of patients who present with chronic whiplash syndrome, the clinical findings suggest an affliction of the spinal accessory nerve  by entrapment under the fascia of the trapezius muscle. The present study was undertaken to assess the effectiveness of SAN neurolysis in chronic whiplash syndrome.A standardized questionnaire and a linear visual-analogue scale graded 0-10 was used to assess disability related to five symptoms  before, and one year after surgery in a series of thirty consecutive patients.The preoperative duration of symptoms ranged from seven months to 13 years. The following changes in disability scores were documented one year after surgery: Overall pain decreased from 9.5 +/- 0.9 to 3.2 +/- 2.6 (p < 0.001); headaches from 8.2 +/- 2.9 to 2.3 +/- 2.8 (p < 0.001); insomnia from 7.5 +/- 2.4 to 3.8 +/- 2.8 (p < 0.001); weakness from 7.6 +/- 2.6 to 3.6 +/- 2.8 (p < 0.001); and stiffness from 7.0 +/- 3.2 to 2.6 +/- 2.7 (p < 0.001).Entrapment of the spinal accessory nerve and/or chronic compartment syndrome of the trapezius muscle may cause chronic debilitating pain after whiplash trauma, without radiological or electrodiagnostic evidence of injury. In such cases, surgical treatment may provide lasting relief. Among patients who develop permanent debilitating symptoms after whiplash trauma (referred to as chronic whiplash syndrome henceforth), headaches and/or pain and stiffness in the neck and shoulder are the most frequent complaints and reasons for disability -3. In adChronic symptoms from whiplash trauma have commonly been linked to pathology of the spine and its supporting tissues, i.e. facet joints , spinal Based upon these observations, a therapeutic approach to chronic whiplash has been developed in which offending tender points that have been identified by a positive response to infiltration with anesthetic are surgically exposed and then excised . TypicalIn a similar vein, Hagert et al. have reported that they treated chronic compartment syndrome of the trapezius and entrapment of the spinal accessory nerve (SAN) in patients with a history of overuse syndrome  and a clThe study group consisted of 30 consecutive patients treated by one surgeon (NAN). The indication for surgery was established based upon the following:• unremitting posttraumatic neck pain with a steady state for no less than six months, most typically as a result of a motor vehicle crash-related injury;inter alia;• lack of lasting response to conservative or minimally-invasive therapeutic procedures, including physical therapy, chiropractic treatment, zygapophyseal blocks, • lack of a clearly delineated pain generator pertaining to the spine, such as a disk herniation, fracture, or foraminal or central spinal stenosis;• prompt response to anesthetic infiltration of key tender points in the region of the upper trapezius muscle (at least 50% reduction of the most intrusive symptoms).During its extracranial course, the SAN forms a plexus with fibers from spinal nerves C3 and C4  before t® 0.5%) and short-acting IV sedation (Propofol®), the posterior aspect of the trapezius muscle is exposed through a sagittally oriented skin incision across the shoulder. While the patient is still anesthetized generally thickened fascia, including septae between bundles of the muscle, are excised from the painful area of the muscle according to preoperative skin markings corresponding to the previously identified key tender points. The dissection is continued anteriorly along the leading edge of the trapezius until the SAN was identified. In most of the cases adhesions were identified between the nerve and the underlying fascia.Patients are placed in a lateral or beach-chair position on the operating table. Under local anesthesia  pain and differentiate it from "new"  pain.Patients generally signaled incremental improvement during resection of fascia and/or interfascicular septae within the trapezius. Although the SAN neurolysis in some cases was observed to have a direct effect on the patient's headache complaints, the fasciectomy tended to have a greater immediate effect on mobility.A linear visual analogue scale graded from 0 (not disabling) to 10 (completely disabling) was used to define a 'disability score' for each of five different indices: pain, headache, insomnia, muscle weakness, and neck/shoulder stiffness. Assessments were made for the week preceding surgery, and at follow-up 12-18 months post op.Hospital charts were reviewed for information pertaining to surgical technique and findings. Outcome data was compiled from questionnaires completed by the patients 12-18 months after the operation.t-test for paired samples was used for the analysis of outcome data. Statistical significance was defined as p ≤ 0.05.Student's The study group consisted of 6 males and 24 females presenting to UNMC for treatment for chronic symptoms after whiplash. The average age at the time of surgery was 43 years (range 27-66). The mean and median time from the onset of symptoms until surgery was 41 months (range 7-156) and 24 months, respectively. All of the patients stated that their condition had reached a steady state at the time of the operation.Fourteen patients reported that their condition had been precipitated by a classic rear-impact motor vehicle crash. The remaining 16 patients reported various other mechanisms of trauma, including falls and sports injuries.Only "pain" was identified by all 30 patients as an independent preoperative reason for disability. Each of the remaining four variables  was a reason for disability in 26 or more patients prior to surgery Table .Four clinical signs were documented in all cases prior to surgery: (1) asymmetric posture, typically with the shoulder elevated on the side of greatest pain; (2) decreased and painful range of motion in neck and shoulder(s); (3) tenderness to palpation along the horizontal portion of the upper trapezius muscle; and (4) greater than 50% of reduction of pain and increased mobility following infiltration of 2-3 cc of local anesthetic into 1-3 key areas of focal tenderness in the upper trapezius.Neck/shoulder stiffness, which was observed but not objectively measured in most patients before surgery  reported improvement in all 5 of the assessed indices  and an additional 10 patients (33%) reported improvement in at least one parameter, for a total of 93% of patients reporting a lasting positive outcome one year or more following the surgery. One patient did not report any benefit from the operation, noting that her condition was unchanged. Another patient reported increased stiffness after the operation, but at the same time noted that three other symptom areas had improved Table .Mean VAS-scores were significantly lower than before surgery for all five variables Table . SpecifiPrior to the operation, 27 patients complained of head pain/headache. After surgery 22 patients stated that their head pain had been reduced by at least 50%, and 10 of these patients stated their headaches had been completely eliminated Figure . Of the Fourteen patients of 29 stated that the severity of their sleep deprivation (insomnia) had decreased by 50% or more as a result of the operation. The average number of hours of sleep per night increased from 4 ± 1 to 6 ± 2 for the entire cohort. Similarly, postoperative perception of disability decreased by at least 50% in 15 of the 26 patients reporting weakness, and in 20 of the 28 patients reporting stiffness, in comparison with pre-operative perceptions.We describe the long-term outcome after surgical fasciectomy and SAN neurolysis for symptoms associated with chronic whiplash pain. In this series of 30 patients, 29 described a lasting overall improvement that they attributed to the treatment, although in one case with satisfactory pain reduction, the procedure resulted in increased neck stiffness. One patient who did not benefit from the surgery reported no degradation or other worsening of symptoms or disability during the year following the operation.Our results suggest that some of the most common symptoms found in chronic whiplash  may be secondary to either primary injury in, or secondary dysfunction of the spinal accessory nerve and/or the trapezius muscle. We conclude, with caution, that the condition represents an indication for surgical treatment in selected cases where more conservative measures have proven ineffectual.per se, as a reason for some preoperative symptoms [What is less clear is how or why the trapezius muscle and SAN are involved in perpetuating the chronic whiplash syndrome. The traditional portrayal of SAN as one of pure motor function has been challenged by anatomical studies ,21, and symptoms ,25.Based upon the present data we cannot discern to what extent preoperative symptoms were expressions of dysfunction in the SAN versus the trapezius muscle and/or fascia. It has been reported, however, that patients with chronic whiplash syndrome exhibit higher EMG activity in the upper trapezius muscles than healthy control subjects, as well as a reduced ability to relax the muscle to baseline levels after a dynamic task . LarssonThe conclusions that can be drawn from this investigation are limited by the size of the study group, the retrospective, non-randomized study design, and the subjective assessment instrument. It is not possible to draw a firm conclusion as to the relative importance of fasciectomy versus neurolysis, since dissection of the SAN was necessary in all patients to protect the nerve during resection of fascia from the ventral aspect of the trapezius.The results described herein offer a potentially new direction in evaluation and surgical treatment of chronic whiplash syndrome. Entrapment of the spinal accessory nerve and/or chronic compartment syndrome of the trapezius muscle may cause chronic debilitating pain after whiplash trauma, without radiological or electrodiagnostic evidence of injury. In such cases, surgical treatment may provide lasting relief. Continued research using randomized and controlled study designs will further advance the understanding and extrapolability of the present findings.SAN: Spinal accessory nerveThe authors declare no competing interests. No external funding was received for this research.All coauthors participated in two or more key elements  of this investigation, and read/approved the final manuscript.Pre-operative shoulder function. Video documentation of shoulder range of motion before surgery. Limited range of motion in right shoulder prior to surgery, in a patient with 10-year history of chronic whiplash from a motor vehicle crash.Click here for filePatient feed-back during surgery. Video documentation of surgical procedure. Functional progress during neurolysis of spinal accessory nerve and trapezius fasciectomy. The unanesthetized patient cooperates actively and provides guidance to the surgical team.Click here for filePost-operative shoulder function. Post-operative status. Video documentation of range of motion in right shoulder one day after trapezius fasciectomy and neurolysis of spinal accessory nerve.Click here for file


Herpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors.Patients diagnosed with HZ were consecutively enrolled by a network of Italian General Practitioners and Hospital Units in the health district of Pescara, Italy, over two years. Uncertain cases were referred for microbiological investigation. Data were collected through electronic case report form (e-CRFs) at enrolment and at 1, 3, 6 and 12 months after enrolment. Pain intensity was coded on a five-degree semi-quantitative scale at each time point. PHN was defined as pain of any intensity during follow-up and quantified using an area-under-the-curve (AUC) method.Four hundred and forty-one patients composed the final sample. Mean age was 58.1 years (SD = 20.4 years); 43.5% of patients were males; 7.9% did not receive prescription of antivirals. Intense/very intense pain at presentation was reported by 25.2% of patients and was significantly associated with female gender, older age, cigarette smoking, trauma and/or surgery at HZ site (logistic regression). PHN was diagnosed in 51.2% of patients at one month and in 30.0% of patients at three months. PHN was significantly associated with pain intensity at presentation, age, smoking, trauma and missed antiviral prescription . The same factors were also independent predictors of the overall pain burden as described by the AUC method (linear regression).Smoking, traumas and surgery at the HZ site emerged as new predictors of both HZ-related pain intensity and persistence, opening new perspectives in the prevention of HZ-related pain. An independent line of evidence was provided for the efficacy of antiviral therapy in preventing PHN and reducing total pain burden. Herpes zoster (HZ) is a common disease, characterized by localized, monolateral pain and vesicular rash, due to the reactivation of latent varicella-zoster virus (VZV), with an incidence of 2.2 to 5.2 cases/1,000 patient-years . AlthougWe carried out a prospective, monocentric cohort study, enrolling a large sample of consecutive unselected patients with HZ, in order to evaluate intensity of pain at presentation, pain persistence during follow-up and the overall pain burden, as well as several potential correlates of pain intensity at presentation and predictors of PHN.A network was established among 41 general practitioners (GPs) in the district of Pescara, Italy. Between 1 May 2006, and 30 April 2008, GPs enrolled all incident cases of HZ observed. In addition to GPs, the Infectious Diseases (ID) Unit, the Dermatology Unit, and the Department of Pain Medicine and Palliative Care, shortly Pain Management Clinic (PMC) of the Pescara General Hospital, Pescara, Italy, reported consecutive data on HZ patients observed. Enrolling physicians were connected through a dedicated software, avoiding repeated enrolments. The study was approved by the local Ethics Committee. Enrolling physicians were requested to report prescribed antivirals and untreated cases; they were suggested to prescribe antivirals whenever active lesions were present, in accordance with current local trends in prescription. An informed consent was signed by patients at enrolment, and an e-CRF was filled in with demographic and clinical information. One or more pictures of lesions were also included for patients consenting to be pictured, to allow expert review. A one-year follow-up was planned for enrolled cases.©, Italy) [Diagnosis of HZ was clinical whenever enrolling physicians felt it appropriate, with no additional evidence needed. Patients were enrolled whatever the stage of the rash and the time interval from the rash onset. The extent of the rash was codified as mild-moderate or severe according to the number of lesions , defined as papules, vesicles or crusted vesicles . When GP, Italy) ,31.HZ patients were asked about pain severity at presentation, as well as at every further visit or phone call. Follow up visits or phone calls were performed at 1, 3, 6 and 12 months after enrolment. Pain intensity was coded on a five-degree semi-quantitative scale . All patients reporting intense or very intense pain were granted immediate access to PMC. Use of analgesics  at enrolment was reported. Adverse events other than pain were classified according to the Common Terminology Criteria for Adverse Events, Version 3.0, USA .et al. [PHN was defined as the presence of pain of any intensity at follow-up visits, measured with the above described scale. At each follow-up visit or phone call patients were asked to report on the worst pain intensity experienced since their last visit or phone call, possibly specifying the time of occurrence within the interval. To take into account the total burden of pain in the individual patient, pain during follow-up was quantified using an area-under-the-curve (AUC) method, similar to that proposed by Coplan et al. . BrieflyA number of potential correlates of pain intensity at presentation and predictors of PHN were evaluated: age; gender; familial status ; educational level ; hypertension; diabetes mellitus; HCV and/or HIV infection; alcohol abuse (binge drinking or ≥ 80 grams daily); current or former cigarette smoking ; familial history of major cardiovascular events (occurred in first degree relatives aged ≤ 60 years); malignancies, neurological diseases, major depression or psychiatric illnesses, allergy . Clinical history was considered positive for trauma when patients recalled any type of trauma at the site of lesions  up to six months ahead of enrolment. Surgical interventions at the site of lesions were considered whenever performed. Other potential predictors were: site of lesions, pain intensity at presentation, rash severity and prescribed NSAIDs. Finally, patients prescribed antivirals were compared to those not prescribed antiviral therapy for any reason.P < 0.15 at univariate analysis; change in significant odds ratios (OR) > 20%; age and gender forced to entry. Standard post-estimation tests were used to assess final model validity , as well as to investigate potential predictors of PHN at one or three months (two separate models). In all models, covariates were included in a stepwise forward process with the following inclusion criteria: ve power ), perforve power ), and teve power . The modve power . Time waP-value < 0.05 for all analyses, which were carried out using Stata version 10.1 .To evaluate independent associations between pain burden and other variables under investigation, a linear regression analysis was used. The dependent variable of the model was AUC, which was transformed into its square root because of its skewed distribution (Shapiro-Wilk test). Because of the incomplete follow-up for some participants, the total follow-up duration was included as a covariate into the final model, whose validity was assessed as follows: the assumption of constant error variance was checked graphically, plotting Pearson residuals vs fitted values, and formally, using Cook and Weisberg's test for heteroskedasticity. High leverage observations were identified using Pearson, standardized and studentized residuals, Cook's D influence, Welsch distance and hat diagonal matrix . High leOverall, 519 patients were enrolled, 68.0% by the GPs and 32.0% by the Hospital Units. Microbiological investigation was requested for 63 subjects (12.1%), and HZ was diagnosed in 28 of them. HZ was not confirmed for the remaining 35 patients, who were excluded. Forty-three subjects were also excluded because of diagnosis of other dermatological diseases by expert review of clinical and pictorial data (n = 6), insufficient data provided at the first visit (n = 9), consent withdrawal during follow-up (n = 28). As a consequence, 441 patients were followed for a mean of 335 days (SD = 82 days). Twenty-four (5.4%) patients were hospitalized for a mean of 9.3 (3.2) days; no patient died during follow-up. The baseline characteristics of the sample are summarized in Table P < 0.05, Table Intense or very intense pain at presentation was reported by 25.2% of the patients ; by 30.0% (n = 130) during the time interval one to three months; by 9.8% (n = 43) during the time interval three to six months; by 7.5% (n = 33) during the time interval 6 to 12 months. The frequency of PHN was clearly and tightly related to the semi-quantitative grading of pain at presentation at the one- and one- to three-month time points .The results of the repeated measures analysis (GEE) investigating potential independent predictors of PHN during the follow-up are shown in Table We also reported the results of separate logistic regression models investigating potential independent predictors of PHN at one month and three months Table . The resP < 0.05, Table An AUC was obtained for each patient. Age, pain intensity at presentation, smoking, missed antiviral prescription and trauma were significantly and independently associated with total pain burden as measured by the AUC in the final linear regression model (all Our prospective observational cohort study was aimed at investigating pain intensity at the onset of HZ and its correlates, as well as predictors of PHN and overall pain burden in real-life clinical settings. Our study was designed and executed independently of any restraint or support by pharmaceutical companies.et al. in their prospective cohort [A quarter of the enrolled sample presented with intense or very intense pain, according to the adopted semi-quantitative five-degree scale. This percentage was lower than the 41% rate of patients with severe or very severe pain observed by Chidiac e cohort . Other re cohort ,17,18,20et al., 2001, indicating that older age and rash severity were associated with more severe acute pain assessed within 72 h of rash onset [Some data suggest that the perception of pain from myocardial ischemia is significantly less severe and delayed in the elderly compared to younger patients . Furthersh onset . Trauma sh onset -26. Our sh onset -26. Our sh onset . The stash onset . Furthersh onset ,43. Thessh onset . Moreovesh onset . In our sh onset ,44,45.et al. defined PHN as ZAP rated as ≥ 3 on a 0-to-10 VAS scale and persisting or appearing > 90 days after the rash onset [The other major aim of our study was to consider and quantify pain persisting any longer than rash healing, looking for predictors of such persistence. Remarkable differences exist as to the time interval considered for the diagnosis of PHN -16,46. Msh onset ,14,47. Ish onset ,46. We dsh onset ,49. Painsh onset . This mash onset . On the in vitro studies, will be necessary to demonstrate a causal linkage. Our survey included a very limited number of patients with comorbilities, which are known to increase the risk of HZ. Such few cases did not allow us to stratify our analyses for comorbid patients. However, our sample allows us to confirm previous data, suggesting that most of incident cases of HZ occur in otherwise healthy and relatively young adults [A number of parameters have been proposed as predictors of PHN, pain intensity and age at presentation being the only ones consistently emerging in most of previous investigations ,9,17-21.g adults ,7.Our study provides new insights into the knowledge of pain intensity at presentation and pain persistence due to HZ in a large, monocentric, prospective cohort of unselected Caucasian patients. Cigarette smoking, traumas and surgery at the site of the HZ emerged as new predictors of both intensity and persistence of pain, all of which may well deserve further investigation. A new, independent line of evidence is provided as to the efficacy of antiviral therapy in reducing the incidence of PHN and the total burden of pain caused by HZ.AUC: area-under-the-curve; CNS: central nervous system; e-CRF: electronic case report form; GEE: generalized estimating equations; GP: general practioners; HZ: herpes zoster; ID: infectious diseases; IQR: interquartile range; NSAIDs: non-steroidal anti-inflammatory drugs; OR: odds ratio; PCR: polymerase chain reaction; PHN: post-herpetic neuralgia; PMC: pain management clinic; PNS: peripheral nervous system; SD: standard deviation; VZV: varicella-zoster virus; ZAP: zoster-associated pain.The authors declare that they have no competing interests.GP, CC, CG, CDA and LP conceived and designed the study. GP, MT EP and LM performed most of the analyses on collected data, suggested and elaborated most of data interpretation criteria, and drafted the manuscript. CR, FS, AC, AA, FDM, GC and LP contributed to the study design, contributed substantially to the acquisition of data and to medical care of the enrolled patients. EP, LC, LC and DDA carried out most of laboratory assays. LM and GP performed most of the final statistical analyses; GP, LM and EP relevantly contributed in manuscript revision. AV was involved in critical evaluation, interpretation and discussion of data, as well as in critical revision of the final manuscript and its revision. The VZV Pain Study Group made substantial contributions in designing the study, enrolling patients, collecting data, and carrying out the educational phase of the protocol. All authors read and approved the final version of the present manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/8/58/prepub


Pain measurement in nonverbal older adults is best based on behavioural observation, e.g. using an observational measurement tool such as Doloplus-2. The purposes of this study were to examine the use of Doloplus-2 in a nonverbal nursing home population, and to evaluate its reliability and validity by comparing registered nurses' estimation of pain with Doloplus-2 scores.In this cross-sectional study, Doloplus-2 was used to observe the pain behaviour of patients aged above 65 years who were unable to self-report their pain. Nurses also recorded their perceptions of patient pain  before they used Doloplus-2. Data on demographics, medical diagnoses, and prescribed pain treatment were collected from patient records. Daily life functioning was measured and participants were screened using the Mini Mental State Examination.In total, 77 nursing home patients were included, 75% were women and the mean age was 86 years . Over 50% were dependent on nursing care to a high or a medium degree, and all were severely cognitively impaired. The percentage of zero scores on Doloplus-2 ranged from 17% (somatic reactions) to 40% . Cronbach's alpha was 0.71 for the total scale. In total, 52% of the patients were judged by nurses to be experiencing pain, compared with 68% when using Doloplus-2 (p = 0.01). For 29% of the sample, nurses were unable to report if the patients were in pain.In the present study, more patients were categorized as having pain while using Doloplus-2 compared with nurses' estimation of pain without using any tools. The fact that nurses could not report if the patients were in pain in one third of the patients supports the claim that Doloplus-2 is a useful supplement for estimating pain in this population. However, nurses must use their clinical experience in addition to the use of Doloplus-2, as behaviour can have different meaning for different patients. Further research is still needed about the use of Doloplus-2 in patients not able to self-report their pain. Pain is a major problem in the nursing home population -5. PreviPain is a subjective and persistent phenomenon and the gold standard in pain assessment is to use scales based on the patient's self-report . A cliniPain assessment tools based on behavioural observation methods include observation of changes in behaviour and functioning involving, for instance, sleep, appetite, physical activity, mobility and facial/body language ,16. FaciA number of studies have focused on the development and validation of tools measuring pain in nonverbal older adults, based on behavioural observation methods. Husebø et al.  developeThe Doloplus-2 has been translated into Norwegian and tested in Norwegian nursing home populations ,26. The Therefore, the objectives of the present study were to evaluate Doloplus-2 in a nonverbal nursing home population by:• examining the use of Doloplus-2 and unscored items, minimum and maximum scores for the tool and subscales;• evaluating the reliability  of Doloplus-2; and• comparing registered nurses' estimations of the pain using the Doloplus-2 tool.The data for this study were obtained from a cross-sectional survey designed to explore pain and quality of life in patients in nursing homes in central Norway. The data were collected from September 2005 to May 2006.In-patients aged 65 years and over from seven Norwegian nursing homes were included in the study. Central Norway consists of three counties . Nursing homes are owned by municipalities and their funding depends on the ranking of priorities in municipal budgets. This can lead to different levels of qualified staff among nursing homes and variations in care, pain assessment and pain management. There are also policy differences among municipalities governing which patients receive nursing-home care rather than community care. To achieve a representative sample, nursing homes were stratified into six strata, by urban and rural status, in each of the three counties in Central Norway. One nursing home was drawn from each stratum. In Møre and Romsdal, two nursing homes were included from rural areas because of low patient numbers in these nursing homes.Patients were excluded if they had been in the nursing home for less than one week, had a short life expectancy (estimated by the nursing staff) or were younger than 65 years. All eligible patients were scored on Mini Mental State Examination (MMSE) by the investigator (KT), and the patients were categorized as nonverbal if they scored zero on this test.Demographic data , medical diagnoses (including pain-related diagnosis and dementia), and prescribed treatment were collected for all patients from their medical or nursing records by the investigator (KT).Prescribed medications were classified according to the Anatomical Therapeutic Chemical (ATC) System  and werePain-related diagnoses were based on previous research and consisted of fractures, knee and hip prostheses, osteoporosis, stroke, cancer, migraine and headache, myalgia, arthritis, amputation, angina pectoris, herpes zoster, low-back pain, duodenal ulcers, ventricular ulcers and gastritis ,2,28.Barthel's Activities of Daily Living Index (ADL) was used as a screening instrument for patients' daily life functioning. This 10-point scale measures patients' degree of self-reliance, with a total score ranging from zero to 20. Lower scores indicate greater dependence on nursing care . ADL scoThe Doloplus-2 consists of a list of 10 items divided into three subgroups: five somatic items , two psychomotor items  and three psychosocial items  . Each itThe Doloplus-2 was administered by the primary nurse (the registered nurse with the best knowledge of the patient's behaviour) ,22,26. TImmediately before applying the Doloplus-2, the primary nurse answered a single question: 'Do you believe that this patient is experiencing pain?' Response options were 'no', 'yes' or 'don't know'. This measurement was done to compare the results with the Doloplus-2 scoring done by the same nurse.As patients in this study were cognitively impaired, guidelines from the Ministry of Health and Care Service in Norway were followed when recruiting . RelativThe Regional Committees for Medical Research in Ethics, Southeast Norway, the Norwegian Social Science Data Services and the Ministry of Health and Care Service approved the study.Descriptive statistics were used to present demographic and clinical characteristics of the sample and gain an overview of not scored items on Doloplus-2. The percentages of minimum and maximum scores were calculated by assessing the percentages of lowest (0) and highest possible scores on the subscales  and for the total questionnaire . Mean scCronbach's alpha coefficients were calculated to assess the internal consistency reliability of Doloplus-2. The alpha coefficient was calculated for the total questionnaire and for subscales. Alpha was also used to explore whether scales could be shortened by the deletion of single items. If Cronbach's alpha changes little when an item is deleted, then the item is a candidate for being removed from the scale . In accoThe criterion validity was calculated by comparing registered nurses' subjective and Doloplus-2 pain assessments for each patient by Fisher's exact test. Comparison of the groups in respect of pain-related diagnoses and pain management was also calculated by Fisher's exact test.The statistical software SPSS for Windows v.16.0 was used for analyses. A two-tailed P value below 0.05 was considered statistically significant.In total, 307 patients were registered in the seven nursing homes. Of these, 41 refused to participate, one patient had been admitted for less than one week, and one was excluded because of short life expectancy. Based on MMSE, 136 nonverbal patients were registered. Of these, 50 did not participate because their relatives/legal guardians refused on their behalf. As Doloplus-2 forms were incomplete for nine patients, 77 patients were included in the present study.The mean age of the sample was 86 years (SD ± 6.6), with a range from 68 to 100 years. The majority of patients were female (75%), 61% were widows or widowers and 20% were married  to eight on the somatic reactions subscale  of patients were judged by registered nurses to be experiencing pain, and 19.5% (n = 15) as not having pain Table . HoweverWhen pain was proxy rated, 36 of 40 (90%) patients in the 'pain' group scored ≥ 5 on Doloplus-2 (indicating pain) and 11 of 15 (73.3%) in the 'no pain' group scored < 5 on Doloplus-2 (indicating no pain). However, more than 50% in the 'don't know' group scored ≥ 5 on Doloplus-2 (indicating pain) , but significantly more of the 'no pain' group received no prescribed pain medication compared with the 'pain' group  in the proxy-rated pain group.This is one of the first studies evaluating behaviour-based pain tools in a complete nonverbal patient group. The present study included 77 nonverbal nursing home patients, with a mean age of 86 years. The majority of the patients had medium or high level of dependence on nursing care.Earlier research using Doloplus-2 in cognitive impaired patients concludes that using the scale demands specific administration skills . In the According to the guidelines for Doloplus-2, nursing staff should not score patients on pain if the items are inappropriate or if it is suspected that the patient's change in behaviour is probably not a result of pain, but caused by depression, dependence, or cognitive functioning . We founWe observed the highest percentage of minimum scores on the psychosocial reaction scale (31 out of 71) and the maximum score was on the psychomotor reactions scale Table . Hølen eWhen estimating internal consistency reliability of the Doloplus-2 in the present study, Cronbach's alpha coefficients were between 0.47 and 0.72, the lowest being for the somatic reactions subscale. These values are all below the alpha scores recommended by Fayers and Machin  for indiThe items in Doloplus-2 are clearly heterogeneous, reflecting a variety of important issues or dimensions. It could therefore be problematic to achieve a high Cronbach's alpha coefficient in a nonverbal population. In the present study, the alpha scores obtained after deleting an item were comparable with the overall alpha coefficient for the scales, except for somatic complaints . In addition, 56% had high or medium dependence on nursing care. All these factors can influence patients' behaviour and thus impact on the observations made of them. Only a minority of the patients had a dementia diagnosis in their records, but all were subjectively judged as 'patients with dementia' by the nursing staff. This is in concordance with the study of Selbæk et al.  that shoIn our study, neither proxy rating nor Doloplus-2 were affected by pain-related diagnosis, but significantly more of the 'no pain' group received no pain medication compared with 'pain' group in the proxy rated. Previous studies have demonstrated that proxy-rating assessment can be affected by knowledge of whether patients were receiving prescribed pain medication  concludeOne limitation in this study was the relatively small sample size. With a larger sample, the threshold level of five could also have been evaluated. There are no published studies evaluating the Doloplus-2 using a cut-off point of five for separating patients with or without pain. However, pain cannot be ruled out if a patient is a few points below the cut-off point scores, because patients may have different 'pain signatures' . It is aOne may question the use of nonverbal patients for evaluating Doloplus-2 in the present study. Previous studies have included both communicative and nonverbal patients provided they had reduced communicative function ,26. DoloConcordance (90%) was found between proxy rating and Doloplus-2 scores with respect to estimating 'pain' with the two different assessment methods, suggesting that the two measures are addressing the same pain construct. About half of the patients for whom nurses rated their pain prevalence as 'don't know' when using proxy rating were scored ≥ 5 (indicating pain), and less than half scored < 5 (indicating no pain) with Doloplus-2. The influence of prescribed pain medication was reduced when staff used Doloplus-2 instead of proxy rating. Previous research has demonstrated that the prevalence of identified pain decreases with increasing cognitive function, despite similar prevalence of pain-related diagnosis ,8. The dIn the present study, more patients were categorized as having pain using Doloplus-2 compared with nurses' estimation of pain without any tool. Previous studies have demonstrated that proxy rating of pain without using an assessment scale leads to underestimating of patients' pain ,2. The fBased on the results from this and previous Norwegian studies, we recommend the use of Doloplus-2 in addition to proxy rating when assessing pain in patients without the ability to self-report. There may be a risk of overestimating patients' pain with Doloplus-2 and a risk of underestimating pain when using only proxy assessment. However, it is better to overestimate rather than underestimate pain and when in doubt, behaviour changes following analgesic administration may resolve the question of whether pain is indeed present. It appeared that nursing staff's pain estimation was influenced by their knowledge of prescribed pain medication, and there was a risk of under-reporting pain when using the proxy assessment on patients not currently receiving pain medication. Therefore, behavioural observation methods should be used as only one strategy to help inform nurses about pain in older nonverbal persons. Overall, further research is needed on pain in the elderly, and especially in nonverbal patients, to further improving their pain management.The authors declare that they have no competing interests.KT, SK, ØK and TR contributed to the design of this study. KT and TR organized and performed the data collection. KT, PF and TR performed the statistical analysis. All authors participated in interpretation of the data, drafting the manuscript and all read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2318/10/9/prepub


Protoporphyria (PP) resulting from two rare, inherited diseases of heme biosynthesis leads to dermal phototoxicity by accumulation of the heme precursor protoporphyrin IX. No standardized tools to quantify the degree of PP-related phototoxicity and its change by medical intervention have been published.Results from a questionnaire completed by 17 affected individuals were used to determine the relative importance of two main components of PP-related phototoxicity, skin pain and sunlight exposure time, with respect to the effectiveness of any particular medical treatment.Inter-rater reliability was 0.71 (n = 490), repeated estimates by four identical individuals showed high reproducibility .Exposure times [multiplied by] Freedom from Pain" (ETFP). The minimal clinically important difference (MID) was 15 (10.2-20.4) ETFP scores, representing 28% of the standard deviation of the clinical trial data and 2.9% of its total range.Six different models were developed, three of them showed good correlation with effectiveness estimates. Data from an unpublished trial indicated that the model with highest potential of responsiveness was the so called "Among the six models proposed to assess the effectiveness of therapeutic interventions in PP the ETFP model demonstrates the highest sensitivity using the existing data from a clinical trial of afamelanotide in PP. The results of this study have provided sufficient validation of the ETFP model that is likely to prove useful in future clinical trials. Erythropoietic protoporphyria , a rare inherited disease of heme biosynthesis, is due to mutations of the enzyme ferrochelatase that catalyzes the ultimate step in heme biosynthesis, the insertion of iron into protoporphyrin IX to form heme . RecentlLight-induced phototoxic reactions in PP are of variable severity: Immediately or within a few minutes of sunlight-exposure, PP-patients feel stinging pain in sun-exposed skin that disappears upon termination of light-exposure. On prolonged exposure, erythema, edema and skin lesions may develop and an incapacitating pain may occur. The pain cannot be alleviated by pain killers such as acetaminophen or salicylic acid derivatives. Even non-steroidal-anti-rheumatics are ineffective. The severity of phenotype is related to erythrocytic or plasma protoporphyrin levels .Our recent systematic literature review on treatment options of dermal phototoxicity in protoporphyria (PP) showed that available publications are of insufficient quality to prove efficacy of any treatments that have been proposed to date . A majorDermal phototoxicity in PP is largely a subjective perception because initial symptoms are rarely accompanied by physical signs. An optimal measure of subjective symptoms is the recording of patients' experience -11. ToolThe scientific value of a disease-specific PRO is dependent on the following criteria: Rationale for choosing selected endpoints, documentation of psychometric characteristics  and interpretation guidelines including minimal important difference . EvaluatThree different information sources for development and verification of various models were used: (1) a systematic review on treatment options of dermal phototoxicity in erythropoietic protoporphyria rendered information on possible items reflecting the severity of phototoxicity (2) a questionnaire described below for the construction of an optimized model (3) unpublished data from a trial of afamelanotide in PP  for checking additional aspects of the model. This work was conducted according to the Declaration of Helsinki and has been approved by the institutional and cantonal ethics review board .As stated in the Introduction, skin pain of variable intensity is the main symptom of PP-related phototoxicity. Conditioned by their immediate pain reaction upon sunlight-exposure and by their life-long experience of the incapacitating pain from severe phototoxic reactions, adult PP-patients are often able to anticipate the impending risk of phototoxicity depending on the actual weather. In case of presumed high risk of phototoxicity, patients tend to avoid sunlight exposure as much as possible. If sunlight-avoidance is strictly followed, patients no longer suffer from phototoxicity, but the disease markedly limits outdoor-activities and activities in rooms lit by direct sunlight and thus, it affects social and working capabilities of the patients.A PRO to determine PP-related phototoxicity contains therefore two components: pain and sunlight exposure. A daily recording of both pain intensity and sunlight exposure time reflects the actual functioning of the patient. The two components, pain and sunlight exposure interact with each other, as patients suffering from pain will decrease their sunlight exposure and patients who extend their sunlight exposure will increase their risk of pain. A tool was therefore developed to include both components and was tested for its ability in documenting the effect of a medical treatment on acute disease activity in PP.For content validity, patients and clinicians should be involved in identifying and confirming the content of measure. Here, we relied on the information obtained from a systematic review on therapeutic studies in PP and the tools used in these studies to assess effectiveness : Both paConstruct validity refers to the degree to which the measure reflects what it is supposed to measure rather than something else. In the case of PP, the goal was to construct a model that enables a reliable quantitative measure of the construct 'PP-related dermal phototoxicity' for the purpose of determination of the effectiveness of medical interventions.The model required the establishment of a relationship between the effectiveness of a particular medical intervention and the phototoxicity score. As outlined above, time of sunlight tolerance and pain intensity are the two main and interdependent factors in PP-related phototoxicity. Due to the subjective nature of phototoxicity, only PP-affected persons can define the relative importance of these two factors for their well-being. To quantify the relative weight of both factors, a questionnaire was developed and sent to 27 affected persons. An estimate of effectiveness of any particular medical treatment was requested if, after variable sunlight exposure, a specified pain intensity resulted. The proposed sunlight exposures were 15 min, 30 min, 1 hour, 3 hours, 6 hours, 10 hours and 12 hours. Under each of these exposure times, pain intensities of none, mild, moderate, severe and intolerable were separately listed  during a regular a medical visit. Care was taken not to influence the estimates by highlighting the intended context only. Ultimately, 17 PP-patients felt sufficiently at their ease to answer each of the 35 lines in the questionnaire, resulting in a total of 490 estimates.http://www.med-ed-online.org/rating/reliability.html, accessed 3rd Aug. 2009).Using an 11-point Lickert scale as a reference, pain intensities were converted into pain scores so that no pain equaled to 0, mild to 2, moderate to 5, severe to 8 and intolerable to 10 scores, respectively. Sunlight exposure times were converted in 15-minute blocks. Inter-rater reliability was assayed by the method of Ebel Reliability refers to the consistency with which an instrument measures a given construct  and deteRepeatability requires testing and retesting of stable patients. PP-related phototoxicity occurs in separate attacks; therefore patients do not exhibit stable symptoms. Hence repeatability assessment was replaced by analyzing the reproducibility of effectiveness estimates from the same individuals 4 months after the initial inquiry. The questions were rephrased with "pain intensities" as the main attribute  or by inter-rater calculator according to Ebel RL [http://www.med-ed-online.org/rating/reliability.html accessed Aug 2009). Stata version 10 was used.Statistical tests were performed by Analyse- it- for- excel, version 2.11, by Vassar Stats  Ebel RL http://wwInter-rater reliability was calculated among 17 individuals who filled out the 35-line questionnaire. The reliability for a score was 0.71 based on one rater. Both, pain and exposure time independently influenced the effectiveness estimates  and the Passing-Bablok test showed a high degree of reproducibility . The variable pain intensity measured on a Lickert type scale was called either "pain" or "pain score". Sunlight exposure time was named either "exposure time" or "exposure". The effectiveness estimate was used as the independent variable with pain intensity or sunlight exposure time as the dependent variables. As expected, pain correlated inversely and sunlight exposure time correlated directly with effectiveness (data not shown). The different directions of correlation required to first invert the direction of one of the two components so that both components were in the same direction, and then to combine the two components into a single score i.e. either sum or product. The following conversions were performed: 'freedom from pain' was defined as 10 minus pain score, 'sun avoidance' was defined as 13 hours minus sun exposure time in 15-min blocks. The scale of 'freedom from pain' ranged from minimum 0 to maximum 10 scores, where zero meant intolerable pain and 10 means no pain; that of 'sunlight avoidance' ranged maximum 52 to minimum 0, where 52 meant no sunlight exposure and 0 means 13 hours of sunlight exposure within a day.Five different models each comprised of two components, pain intensity and sunlight exposure, were tested for correlation with estimated efficacy by both linear regression analysis and the Spearman's correlation table . In the Model 1: P/E = Pain intensity Divided by sun Exposure time (PDE).• Model 2: E*(10 - P) = Exposure time times Freedom from Pain  = Pain times Sun Avoidance (PTSA).• Model 4: E+ (10 - P) = Sum of Exposure time plus Freedom of Pain (SE&FP).• Model 5: (52-E) + P = Sum of Sun Avoidance plus Pain (SA&P).• All five models were significantly correlated with estimated efficacy, p < 0.0001. PDE, SE&FP and SA&P showed less correlation with effectiveness estimates than PTSA and ETFP table . Whereas2 = 0.648. This resulted inModels 2 to 5 can be expressed by the same formula M = a +b*sunlight exposure + c*pain score +d*sunlight exposition * pain score. For example, model 2 (ETFP) is represented by factors a = 0, b = 10, c = 0 and d = -1. Based on the questionnaire data, the values of a, b, c and d and their standard errors were estimated by linear regression as follows: a = 69.5 SE 2.6, b = 0.854 SE 0.103, c = -7.55 SE 0.43, d = -0.0244 SE 0.0165; rModel 6: E&P&EP = 69.5 + 0.854 *Exposure -7.55*Pain score -0.0244 *Exposure * Pain score . These data are therefore not informative with respect to drug efficacy in the clinical trial. Informative data are those that feature either long exposure and low pain levels or high pain intensities after moderate to long exposures. As ETFP is highly discriminatory for both areas, ETFP could have some advantage compared to E&P&EP. However, only the data that are obtained from clinical trials on effective substances will enable the responsiveness between the two models to be compared.2 = 0.28). A MID of 15.0 ETFP-scores resulted. The second anchor derived from the frequency distribution of the effectiveness estimates of the patients. The patients chose between 0 and 100% on a 101-scale. However, they preferred certain values, as illustrated by a histogram of the frequency of levels chosen  Whereas most PRO's are related to stable disease situations, PP is characterized by attacks; (2) PRO's are validated by comparison to another quantitative standardized measure, which has not been published for PP; (3) The responsiveness of PRO is validated by an effective treatment, which is also not available in PP.To overcome such limitations, we started from PP-patients' expectation of the effectiveness of any medical treatment, and calculated quantitative correlation factors of the different models with the patients' expectations. The three models 'E&P&EP', 'PTSA' and 'ETFP' were found to best represent these expectations. Distribution of iso-score lines made plausible that ETFP may show highest responsiveness.Internal consistency, one component of model reliability, tests for correlations among different items that constitute a PRO. Cronbach's alpha, the measure of internal consistency, should be above 0.7 to support acceptable reliability . CronbacThe proposed model showed a good inter-rater reliability of 0.71, well above the acceptance level of 0.6, indicating that the patients have very comparable expectations towards effectiveness of a medical treatment. This finding was surprising, because the disease severity as measured by the DLQI varied considerably among PP-patients [ETFP equals 28% of the standard deviation of the trial data, and 2.9% of the total range. The MIDE&P&EP was equal to 96% of the standard deviation and to 5.6% of total range. These values imply that the sensitivity for assessment of changes in dermal phototoxicity is higher for the ETFP model than for the E&P&EP model. The ETFP model may therefore serve in the future as a tool to evaluate efficacy of therapeutic interventions in PP, such as treatment by narrow band UV[The distribution of iso-score lines suggested a higher responsiveness for the 'ETFP' than for the E&P&EP model. MID estimated by two different anchors were 15 (10-20) ETFP scores and 6.4 (7.7-15.4) E&P&EP scores. A comparison of these values to the afamelanotide trial data will illustrate the potential responsiveness in a clinical trial. As ETFP-scores exhibited a standard deviation of 53 and a range from 0 to 520 in the afamelanotide trial, the MIDw band UV,31, applw band UV,33 or onAmong the six models proposed to assess the effectiveness of therapeutic interventions in PP the ETFP model demonstrates the highest sensitivity using the existing data from a clinical trial of afamelanotide in PP. The results of this study have provided sufficient validation of the ETFP model that is likely to prove useful in future clinical trials.Pain intensity Divided by sun Exposure time (PDE), Model 1; E*(10 - P): Exposure time times Freedom from Pain (ETFP), Model 2; P*(52 - E): Pain times Sun Avoidance (PTSA), Model 3; E+ (10 - P): Sum of Exposure time plus Freedom of Pain (SE&FP), Model 4; (52-E) + P: Sum of Sun Avoidance plus Pain (SA&P), Model 5; E&P&EP: 69.5 + 0.854 *Exposure -7.55*Pain score -0.0244 *Exposure * Pain score, Model 6.EPP: erythropoietic protoporphyria; XLDPT: X-linked dominant protoporphyria; PP: Protoporphyria; PRO: Patient-reported outcome; DLQI: dermatological life quality index; MID: minimal important difference; P/E: The authors declare that they have no competing interests.EIM developed the study design, contributed to the acquisition of data, their analysis and interpretation and wrote the manuscript, CEM was involved in the study design, XSY and CEM assisted in the analysis and interpretation of data and critically reviewed and revised the manuscript. All authors have read and approved the final manuscript.


To compare the effectiveness of a custom-made leather wrist splint (LS) with a commercially available fabric splint (FS) in adults with chronic wrist pain.Participants  were randomly assigned to treatment order in a 2-phase crossover trial. Splints were worn for 2 weeks, separated by a one-week washout period. Outcomes were assessed at baseline and after each splint phase using the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Canadian Occupational Performance Measure (COPM) and Jamar dynamometer by an observer blinded to treatment allocation.Both styles of wrist splint significantly reduced pain , improved hand function and increased grip strength compared to baseline  with no increase in wrist stiffness. There was a consistent trend for the LS to be superior to the FS but this was statistically significant only for patient perceived occupational performance (p = 0.008) and satisfaction (p = 0.015). Lastly, 72% of patients preferred the custom-made leather splint compared to the commercially available splint.Leather wrist splints were superior to a commercially available fabric splint for the short-term relief of pain and dysfunction. Chronic wrist pain is a common clinical presentation, usually as a result of osteoarthritis (OA) or the inflammatory process of rheumatoid arthritis (RA). Patients with chronic wrist pain benefit from a multi-disciplinary approach incorporating pharmacotherapy and surgical opinion along with conservative Physical and Occupational therapies. Occupational therapists provide patient education regarding joint protection techniques, provide assistive devices and hand splints with the goal of preserving and optimizing hand function .Traditionally wrist splints have been prescribed on the presumption that stabilizing the wrist joint allows inflamed joints to rest, reduces swelling, alleviates pain and improves hand function . The effResearch on the effects of wrist splinting remains inconclusive with regards to the benefits and potential adverse effects of splinting. A Cochrane review examining Occupational therapy in management of RA, reported that limited evidence exists for the use of wrist splints to reduce pain in patients with RA. This reThe recent Cochrane review demonstrated a trend to increases in grip strength when patients with RA are splinted . Pinch aResearch has not conclusively demonstrated a functional benefit of wrist splinting in OA or RA. Data regarding the impact of splint wearing on hand dexterity is inconclusive with two review articles reporting trends that dexterity is compromised ,3, whilsIn our location we observed a clinical benefit of custom-made leather wrist splints for patients with chronic wrist pain, with many patients anecdotally reporting an increase in hand function and decrease in pain. Absence of the palmar metal insert and the "skin like" movement of the leather splint were postulated to allow limited wrist movement in combination with mechanical stability thus permitting improved functional performance. The objective of this study, therefore, was to compare the effectiveness of a custom-made leather wrist splint with a commercially available fabric splint on pain and hand function in adults with chronic wrist pain.st carpometocarpal joint pain), were seeking compensation, were unable to identify functional restrictions or were likely to require a change in pharmacological management during the trial. Diagrammatic representation of patient enrollment and follow-up is presented in Figure The setting was a tertiary referral public hospital clinic in Southern Tasmania, Australia. Patients were referred to the outpatient occupational therapy department, by rheumatologists. The inclusion criterion was a diagnosis of chronic wrist pain impairing functional activity. Potential participants were excluded if they were under 18 years of age, had significant co-morbidities  by the one occupational therapist. Patients who could not achieve this wrist position due to pain were cast in less than 15 degrees wrist extension. Where both wrists were affected the one with the greatest pain was splinted. Two different splint designs were used in this study. All splints were fitted by one occupational therapist. The Futuroy Figure . No metaBaseline evaluation included the collection of demographic data  summarized in Table Power grip strength (kg of force) was measured using a calibrated Jamar dynamometer. Grip strength was assessed using standardized technique and instruction, using the second grip position . All measurements were taken without splints applied. The Jamar dynamometer is considered to be a reliable and valid instrument for measuring handgrip strength when calibrated and using standard positioning and instructions .General hand function, stiffness and pain were measured using the Australian/Canadian Osteoarthritis Hand Index VA 3.0 (AUSCAN). This tool uses a 10 cm visual analogue scale (VAS) scale where patients report on pain, stiffness and functional difficulty in set activities during the previous 48 hours. The VAS is anchored with 1 = no pain and 10 = extreme pain. The AUSCAN is reliable and valid for use in clinic patients with OA, and has also been demonstrated to have similar levels of reliability and validity when used in a community dwelling population of adults with hand problems .The Canadian Occupational Performance Measure (COPM) provides a measure of patient self-perceived occupational performance in activities of daily living (ADL) . It is aPrior to the assessment of outcome measures, patients were asked if they had undergone any changes to their pharmacotherapy regimen, to identify potential exclusions. At the conclusion of the trial patients were asked by an independent assessor to identify their preference for the leather splint, fabric splint or neither splint.t-tests for follow-up baseline comparisons and unpaired t-tests for treatment comparison, with statistical significance set at p = 0.05 (two tailed). All analyses were performed on SPSS version 16 (Chicago Illinois).Differences in the effect of the LS and FS were compared to baseline and also between the two splint styles on all outcome measures. These were calculated using paired Of the 38 patients identified, 4 were deemed ineligible and 4 declined to participate. 5 patients were withdrawn from the study following the first phase due to inability to attend or change in medication regimen. The characteristics of the sample N = 25) are shown in Table 5 are shoBoth splints achieved a statistically significant decrease in pain with a trend to superiority for the LS. Again, both splints achieved a statistically significant improvement in function (AUSCAN), however there was no significant difference between the splints on this measure. The baseline score for stiffness was a mean 4.6 cm on VAS. There was a significant reduction in stiffness with the LS, but not with the FS. There was no significant difference in effect between the leather and fabric splints with regards to stiffness. The baseline measurement for grip strength was a mean of 17.1 kg. Both splints achieved a statistically significant increase in grip strength, with no significant difference between the splints.COPM results were reported as mean scores due to a lack of precision when individual scores were used . BaselinMagnitude of effect was calculated for pain scores. The standardized mean difference for pain with the FS was 0.43, and 0.79 with the LS. With regards to splint preference the LS was ranked as most preferred by 72% of patients. Of the remaining patients, 16% preferred the FS and 12% indicated no preference for either splint.The objective for this trial was to determine whether splints relieve pain, and increase perceived function in patients with chronic wrist pain. Of particular interest was the hypothesis that the LS would be more effective than the FS, as noted anecdotally in clinical practice. Findings suggest that both the LS and FS can safely be used in the conservative management of chronic wrist pain in OA and RA, due to lack of adverse effects on stiffness and grip strength, and improvement in patient perceived function. Furthermore, it conclusively demonstrates a significant improvement in patient perceived performance and satisfaction whilst using a splint.Both splints reduced pain, increased grip strength adding supportive evidence to Haskett's study  and the The results demonstrate a trend for the LS to be more effective than the FS in all AUSCAN measures  and in grip strength testing. The LS demonstrated the greatest benefit at increasing patient perceived functional performance and satisfaction, measured by the COPM. This functional change was not demonstrated by Haskett . MajoritThe inclusion of a joint stiffness measure allowed for the assessment of a potential adverse effect of splinting. Neither splint increased joint stiffness indicating that use of a wrist splint during patient chosen functional activity does not exacerbate joint stiffness in patients with wrist pain. This may have been due to the fact that there was no minimum wear-time specified, so patients were able to remove the splint and exercise their joints as they saw fit to prevent stiffness.The calculation of magnitude of effect enables comparison with the benefit of other treatment modalities. Both splint styles produced positive effect sizes on pain. The LS effect size indicates a large clinically significant treatment benefit (0.79), the FS effect size is small to moderate (0.43) . These eThe study is limited in its ability to assess for a carry-over effect due to the lack of assessment of outcomes following the washout period. In addition, there is no supporting literature that provides the optimal length of a wash out period. There is also the potential for a honeymoon effect influencing the patient's subjective responses to the first splint phase. The blinding of the outcome assessor is a notable strength of the study design. The sample size was sufficient for comparisons to baseline but not consistently for comparisons of the LS and FS and subgroup analyses but it is reasonable to conclude that the results can be generalized to a population of adults with chronic wrist pain.Therapists must carefully consider the type of splint prescribed, and achieving optimal splint fit and comfort has been shown to be important in achieving pain reduction and functional improvement. This trial supports Haskett's  finding The authors declare that they have no competing interests.RN, JT and GJ drafted the manuscript. JR and WR conceived of the study, participated in its' design and coordination. WR was a blinded assessor. GJ and SQ performed the statistical analysis. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Population mean changes are difficult to use in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. A consensus group has defined what constitutes minimal, moderate, and substantial benefit based on pain intensity and Patient Global Impression of Change scores.We obtained individual patient data from four randomised double blind trials of pregabalin in fibromyalgia lasting eight to 14 weeks. We calculated response for all efficacy outcomes using any improvement (≥ 0%), minimal improvement (≥ 15%), moderate improvement (≥ 30%), substantial improvement (≥ 50%), and extensive improvement (≥ 70%), with numbers needed to treat (NNT) for pregabalin 300 mg, 450 mg, and 600 mg daily compared with placebo.Information from 2,757 patients was available. Pain intensity and sleep interference showed reductions with increasing level of response, a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses. Maximum response rates occurred at 4-6 weeks for higher levels of response, and were constant thereafter. NNTs  for ≥ 50% improvement in pain intensity compared with placebo after 12 weeks were 22 (11 to 870) for pregabalin 300 mg, 16 (9.3 to 59) for pregabalin 450 mg, and 13 (8.1 to 31) for pregabalin 600 mg daily. NNTs for ≥ 50% improvement in sleep interference compared with placebo after 12 weeks were 13 (8.2 to 30) for pregabalin 300 mg, 8.4 (6.0 to 14) for pregabalin 450 mg, and 8.4 (6.1 to 14) for pregabalin 600 mg. Other outcomes had fewer respondents at higher response levels, but generally did not discriminate between pregabalin and placebo, or show any dose response. Shorter duration and use of 'any improvement' over-estimated treatment effect compared with longer duration and higher levels of response.Responder analysis is useful in fibromyalgia, particularly for pain and sleep outcomes. Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time. Short trials using 'any improvement' as an outcome overestimate treatment effects. Fibromyalgia is surrounded by controversy regarding its aetiology and its status as a valid disease entity. Genetic and neurobiological evidence now exists to support differences between fibromyalgia patients and controls . CandidaFibromyalgia is characterised by widespread pain for longer than three months with pain on palpation at 11 or more of 18 specified tender points . Sleep dIt is increasingly recognised that medicines typically provide a good response in half or fewer of patients treated ,12. ThisHere we present an analysis of the efficacy of pregabalin in fibromyalgia using individual patient data from four randomised, double blind, placebo controlled trials (RCTs). With this analysis we aimed to identify which outcomes were appropriate for a responder analysis based on the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement on interpreting changes in chronic pain clinical trial outcomes . This suIMMPACT defined response in dimensions other than pain, including physical and emotional functioning, as well as global rating of improvements. In theory, any measurement on any scale could be used for a responder analysis, with a wide range of possibilities of what constitutes a responder. The use of change from baseline, with several different levels of response, should allow an assessment of the utility of both the scale, and the level of response. Utility can be assessed by the occurrence of statistically or clinically significant differences between active therapy and placebo for a particular scale, especially if there appears to be a dose response. The absence of a significant difference between an effective therapy and placebo at all levels of response would be an indication that that particular scale lacks utility for measuring response in a particular circumstance.The particular circumstance of fibromyalgia is interesting because many different measurements are made using different scales, allowing different scales and levels of response to be examined.Pfizer Inc provided Excel files containing individual patient data from four multi-centre clinical phase 2/3 or phase 3 RCTs of pregabalin (Lyrica) in the treatment of fibromyalgia that were conducted in the USA and other countries and were completed by July 2008 . PfizTrial patients were at least 18 years old. Women were not pregnant or lactating, and either postmenopausal, surgically sterilised, or using contraception. Important exclusion criteria were: severe pain due to other conditions, rheumatic diseases other than fibromyalgia, active infections, untreated endocrine disorders, severe depression, active malignancy, being immunocompromised, other severe acute or chronic medical or psychiatric conditions, or laboratory abnormalities. Trial patients had to fulfil ACR criteria for fibromyalgia and have pain scores of ≥ 40 mm on the 100 mm visual analogue scale (VAS) after stopping any relevant pain or sleep medication. Patients were randomised to receive pregabalin , or placebo, predominantly with a 2-week dose escalation phase followed by fixed dosing for up to 14 weeks of total trial duration.We calculated the proportion of patients achieving reductions in pain scores of any improvement (≥ 0%), ≥ 15%, ≥ 30%, ≥ 50%, and ≥ 70% compared to baseline pain scores between weeks 1-12. Sleep improvement was calculated in an analogous manner from weekly averages of sleep quality scores. Improvements in end of trial outcomes , were calculated by comparing data at the trial endpoints with baseline data and calculating the percentage improvement with the individual baseline score set as 100%. We chose levels of improvement for non-pain outcomes also at the above-mentioned cut-points in order to allow ready comparison with pain as an outcome, although it has to be kept in mind that those cut-points do not necessarily have the same clinical relevance for non-pain outcomes as they do for pain .The following two rules were applied to the data set to handle missing data.• For patients who did not drop out, only actual measured values were used for calculations. Last observation carried forward was not used except where no other data were available .• From discontinuation day forward patients were assigned 0% improvement.A responder is then defined as any patient who achieves at least the predefined level of change specified or greater. For example, a patient with exactly 50% pain relief and a patient with 57% pain relief would both be counted as responders at the 50% level.Trial quality was assessed using the Oxford Quality Scale . Validithttp://www.spreadsheet-factory.com) run by one of the authors (Jocelyn Paine). Response data were pooled and used in an intention-to-treat analysis including all randomised patients who received at least one dose of trial drug. We calculated the number and percentage of responders for each level of response , pregabalin dose , and time point . NNTs were calculated with 95% confidence intervals by the method of Cook and Sackett, [Calculations of responder rates and numbers needed to treat (NNT) were performed independently of Pfizer using a spreadsheet consultancy  NNTs at higher doses of pregabalin, given that pregabalin has been shown in randomised trials and meta-analysis to be effective in fibromyalgia, with higher doses being more effective and with more adverse events . Any scaIn the four trials 2757 patients aged between 18 and 82 years were treated with pregabalin or placebo. More than 90% were women. One trial lasted 8 weeks ; the others lasted 13 or 14 weeks. All trials were of high quality and validity, scoring 5/5 on the Oxford Quality Scale and 16/16 on the Oxford Pain Validity Scale. Pregabalin doses of 300 mg (685 patients) and 450 mg (687 patients) were used in all four trials, 600 mg (564 patients) was used in three, and 150 mg (132 patients) in one; placebo was given to 689 patients. We used doses of 300 mg, 450 mg, and 600 mg in our pooled analysis.Data for weekly pain response with pregabalin 450 mg daily are shown in Figure The corresponding NNTs Table  generallFigure The corresponding NNTs Table  generallFigure Additional file Most of these demonstrated sensitivity, in that the proportion of responders fell with increasing levels of response, though this was less marked with some of the individual domains of SF-36, particularly physical and emotional role limitations, social functioning, bodily pain, and vitality. For these the differential between lowest and highest levels of response was not large. Sensitivity to detect an effect of pregabalin treatment defined by statistical significance over placebo to enable NNT to be calculated was apparent for MOS Sleep Disturbance, MOS Sleep Problems Index, and SF-36 general health perception, bodily pain, and vitality.Analyses presented here involved 2,757 patients with ACR-defined fibromyalgia investigated in high quality randomised double blind trials for eight to 14 weeks. This represents the largest body of evidence available in fibromyalgia, more than double the number of patients investigated in three trials of duloxetine,  and fourThe principal findings were that simple outcomes like pain, sleep, and PGIC were amenable to responder analysis. They demonstrated stepped reductions in value with increasing level of response, showed a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses of pregabalin. With our approach  this was not generally the case with less simple outcomes, including fatigue, Fibromyalgia Impact Questionnaire scores, anxiety, depression, and most domains of SF-36, apart perhaps vitality. Therefore, responder analysis as performed here is probably not suitable for most of the outcome measures identified in fibromyalgia clinical trials [A minority of patients experience substantial or moderate benefit, though always significantly more than with placebo, whichever IMMPACT definition of benefit is used. Similar levels of response have been seen for duloxetine, amitriptyline, and tramadol/paracetamol in fibromyalgia, ,32,33 anWeekly analyses for changes in pain intensity and sleep interference demonstrated that maximum benefits for moderate (≥ 30%), substantial (≥ 50%), or extensive (≥ 70%) response occurred at four to six weeks, and thereafter remained reasonably constant. By contrast, response rates for any benefit (≥ 0%) and minimal benefit (≥ 15%) dropped over 12 weeks. Those with a useful response for pain and sleep tend to continue with the treatment; those not achieving moderate or substantial improvement after 4-6 weeks are unlikely to do so later and may be better served by alternative therapies. Pregabalin seemed equally effective at treating pain and sleep disturbance in fibromyalgia, though it is not clear if these improvements occurred in the same patients.NNTs for reduction in pain intensity and sleep interference calculated at different levels of response at weekly intervals increased with time for all three doses of pregabalin. An increase in NNTs over time has been seen before in arthritis . It may Changing NNTs over time are an important finding with implications for efficacy comparisons between drugs. Drugs tested in shorter duration trials (six weeks or less) are likely to appear more effective than the same drug in longer duration trials (eight weeks or more). Four of 10 randomised trials of amitriptyline in fibromyalgia were of six weeks or less,  though tFor the PGIC rating at the end of the trial, higher levels of improvement showed pregabalin to be progressively less effective, at least when NNTs were considered. This illustrates the problem with using 'any improvement' as an outcome, as has been the case in many neuropathic pain studies in the past. Use of 'any improvement' as an outcome overestimated efficacy compared with more substantial levels of improvement.Table The strengths of our analysis are that we analysed a large number of individual patient data in a clinically important chronic pain condition, using validated instruments for measuring clinically important trial outcomes, based on large, modern, rigorous, and methodologically sound trials. Our approach is limited in that we have analysed individual patient data for the drug treatment of fibromyalgia for only one agent . More individual patient analyses with other treatments for fibromyalgia are needed to confirm that our findings are generalisable. Finally, any work on fibromyalgia as it is presently defined is limited because 'fibromyalgia' is probably a heterogeneous group of clinical entities with multifaceted patterns of pain, driven by complex pathways of neural mechanisms in which different pathways and mechanisms are not clearly correlated with different pain patterns, likely to be different between individuals, and further complicated by co-morbid conditions and increased age. Chronic pain is associated with functional, structural, and chemical changes in the brain, including loss of gray matter . IndividQuite large differences in response levels between individuals with fibromyalgia are to be expected, and were found in this analysis, where responder rates with pregabalin were higher than with placebo. Responder analysis in fibromyalgia looks promising. However, responder analysis in the form that we have undertaken in this paper (using percentage change from baseline) is appropriate only for certain outcomes (such as pain and sleep) and not for others; it is informative where it works but not universally applicable. The full potential and limitations of responder analysis will be realised only when more data can be analysed and compared.ACR: American College of Rheumatology; CI: confidence interval; NNT: number needed to treat; NSAID: non-steroidal anti-inflammatory drug; RCT: randomised controlled trial; VAS: visual analogue scale; HADS: Hospital Anxiety and Depression Scale; FIQ: Fibromyalgia Impact Questionnaire; SF-36: Short Form 36; MAF: Multidimensional Assessment of Fatigue; PGIC: Patient Global Impression of Change; MOS: Medical Outcomes StudySS has received research support and grants from Bandolier, Reckitt Benckiser, and Georg-August-University Göttingen. RAM and HJM have received research grants, consulting, or lecture fees from pharmaceutical companies, including Pfizer, MSD, GSK, AstraZeneca, Grünenthal, Menarini, Futura, and others. RAM and SD have also received research support from charities and government sources at various times. RAM is the guarantor. No author has any direct stock holding in any pharmaceutical company.RAM and SS were involved with the original concept, planning the study, writing it, analysis, and preparing a manuscript; JP performed the calculation; SD and HJM were involved with planning, and writing. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/11/150/prepubWeekly pain response levels compared to baseline. This PDF file illustrates pain relief in patients treated with pregabalin at doses of 300-600 mg or placebo.Click here for fileNNTs for weekly pain response levels. This Excel file compares pregabalin at doses of 300-600 mg to placebo.Click here for fileWeekly sleep response levels compared to baseline. This PDF file illustrates sleep response in patients treated with pregabalin at doses of 300-600 mg or placebo.Click here for fileNNTs for weekly sleep response levels. This Excel file compares pregabalin at doses of 300-600 mg to placebo.Click here for fileEnd of trial responder analyses for other measures. This Excel file details the effects of using different levels of response on a variety of outcomes, including fatigue, sleep, depression, anxiety, and the various domains of SF-36.Click here for file


Primary - To measure the prevalence of pain in HIV/AIDS with patients.Secondary - To assess the type, site, severity, management of pain and impact of pain on quality of life in these patients.Multicentre cross-sectional survey (This paper is a pilot study).ART centre at St. John's Medical College Hospital, Bangalore and Snehadan, A supportive and care centre for HIV/ AIDS patients at Bangalore.Data sheet, Brief pain inventory and Short – Form McGill pain questionnaire.This is an ongoing study and the pilot study includes 140 HIV/AIDS patients in different stages of the disease.About 66.7% (28/42) in-patients and 24.5% (24/98) out-patients complained of pain. Of the 52 patients who reported pain, 32% (14/52) reported neuropathic pain and 68% (38/52) reported noci-ceptive pain. Headache was most common followed by pain in the soles of feet and low back. Only 26.9% (17/52) received any form of analgesic. Pain severity significantly affects the quality of life.Pain is a common and debilitating symptom of HIV/AIDS. It is however, under-estimated and under treated. Pain is often called the fifth vital sign and can reveal a lot about the health status of a person. Pain also affects the quality of life through its effect on such things as mood, activity, appetite, sleep, hygiene and the ability to focus and concentrate. Pain is almost always under-estimated as it is subjective. One patient's severe pain would be moderate pain for another patient. Assessment of pain in a patient is very important.et al.,[et al.,[et al.,[It is more than a decade since pain has been acknowledged and studied in HIV/AIDS patients in different parts of the world. India has the second highest population of HIV/AIDS patients in the world, however, prevalence of pain in these patients has never been acknowledged. In HIV patients, pain is often underestimated, as the focus is on the disease itself. Á multi-centre study on under-estimation and under treatment of pain in HIV disease published in the BMJ in 1997[et al., in their,[et al., in their,[et al., observed,[et al., said thePain experienced by HIV patients can be due to multiple sources: firstly, the HIV infection itself or its consequences ; secondly, treatments for AIDS; or, thirdly, it can be unrelated to the disease and its treatment. HIV relaThis study has been designed as a cross-sectional survey. As this is a pilot study, data from two centres is being presented here. HIV/ AIDS patients from ART centre at St. John's Medical college hospital and support and care centre ‘Snehadan,’ were recruited. The ART centre is an outpatient facility, whereas ‘Snehadan’ is for in-patients. All HIV positive patients, irrespective of their staging, have been included in this study. Patients who were already diagnosed with diabetic neuropathy, arthritis, gout, sciatica and trauma induced pain were, however, excluded.A data sheet, brief pain Inventory and short–form McGill pain questionnaire on type of pain by Ronald Melzack was used in this study. The data sheet included patient demographics, WHO staging of the disease, CD4 count, ART or not, presence of pain, substance abuse, since diagnosis and the performance status of the patients. The Brief pain Inventory (BPI) has been used previously to measure pain in HIV/AIDS patients. The BPI A total of 42 in-patients and 98 out-patients participated. Patients’ ages ranged from 18-68 yrs with a maximum number of patients in the 31-40 years age group (56). The sample consisted of 59% males and 41% females. Of the 140 patients, 87% were literate and 71% were employed. The number of patients in the first and second stages of the disease was equal to the number of patients in the third and fourth stages. Ninety percent of the patients were able to walk .Pain was significantly more common for in-patients (66.7%) than for out-patients (24.5%). Almost 79% of patients who complained of pain were in stages III and IV of the disease, whereas 19.2% of stage I complained of pain. When we looked at the number of patients in these two stages of the disease amongst the in-patients and the out patients, 90% of the in-patients and 40% of the out-patients were in the third and fourth stages of the disease. Amongst patients who complained of pain, 60% were on ART. The site of the pain in these patients varied. The three major causes (sites) of pain were headache (28.75%), soles/leg pain (25%) and backache (19.23%) .Least pain was reported by 73.08% of the patients as 0-3, by 23.08% as 4-6 and by 3.84% as 7-10 on the numerical scale. Average pain was reported by 50% of the patients as 1-3, by 48.07% as 4-6 and 1.92% as 7-10; where as worst pain was reported by 13.47% as 1-3, 42.30% as 4-6 and 44.23% as 7-10 on the numerical scale. When we looked at the type of pain almost 68% had noci-ceptive pain and 32% had neuropathic pain. People who described their pain as aching, cramping, splitting, tender or heavy, according to the McGill Short –Form Pain Questionnaire were categorized as having noci-ceptive pain and those who described their pain as shooting, stabbing, sharp or burning were categorized as having neuropathic pain. Headache can be grouped under noci-ceptive pain. Of the 28.75% of the patients who reported headaches, 25% were on ART. About 23.75% of the patients described pain in two sites and 11. 85% described pain in three sites.Only 26.92% of patients received any analgesics . None of the patients received any form of opioids. Amongst the patients who received analgesics only 21.1% had 70% and more of pain relief. The rest of the patients did not have adequate pain relief.The brief pain inventory also looked at the quality of life of these patients. There was significant impairment in their quality of life. Around 73% of patients reported that the pain affected their general activity. Sixty seven percent reported that it affected their mood, while 63% reported that it affected their sleep. As high as 73% reported that the pain affected their working ability thereby reducing productivity.This survey is the first of its kind in India. Prevalence of pain is high in HIV patients. There is inadequate assessment of pain, inadequate management and inadequate pain relief for HIV/ AIDS patients with pain. The added effect of this is impaired quality of life and reduced productivity. As shown in other studies, in this study also there is higher prevalence of pain amongst the in-patients. This suggests that pain increases as the disease progresses.Inadequate assessment of chronic pain leads to inadequate management and relief of pain. For example, if a patient reports pain, the doctors should be able to assess it's duration and frequency, what is causing the pain, what is the severity and what is the type of pain. Health care professionals should be able to differentiate between different types of pain so that optimum treatment can be given. We have not got out of our habits of prescribing analgesics on a PRN or SOS basis. For chronic pain analgesics should be prescribed round the clock and as long as it is required. Pain in HIV can be due to different opportunistic infections that these patients can have. Along with analgesics, we should never forget to look at the root cause of the pain and treat it accordingly.None of the patients in our study received any form of opioids. This might not hold true if it is a multi-centric study with a big sample size. Most of the doctors, in the field of HIV/AIDS care, are not familiar with pain management. This is where Palliative care training can make a big difference to the quality of life of these patients.One limitation noticed in the pilot study was that we had only looked at whether the patients were on ART or not. The actual drug that the patient was on was not looked at. Therefore the study could not co–relate headaches with zidovudine or peripheral neuropathy with stavudine. This needs to be rectified in the main study being planned at 40 different centers in Karnataka.