In patients who experience unilateral chronic pain, abnormal sensory perception at the non-painful side has been reported. Contralateral sensory changes in these patients have been given little attention, possibly because they are regarded as clinically irrelevant. Still, bilateral sensory changes in these patients could become clinically relevant if they challenge the correct identification of their sensory dysfunction in terms of hyperalgesia and allodynia. Therefore, we have used the standardized quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain (DFNS) to investigate somatosensory function at the painful side and the corresponding non-painful side in unilateral neuropathic pain patients using gender- and age-matched healthy volunteers as a reference cohort. Sensory abnormalities were observed across all QST parameters at the painful side, but also, to a lesser extent, at the contralateral, non-painful side. Similar relative distributions regarding sensory loss/gain for non-nociceptive and nociceptive stimuli were found for both sides. Once a sensory abnormality for a QST parameter at the affected side was observed, the prevalence of an abnormality for the same parameter at the non-affected side was as high as 57% (for Pressure Pain Threshold). Our results show that bilateral sensory dysfunction in patients with unilateral neuropathic pain is more rule than exception. Therefore, this phenomenon should be taken into account for appropriate diagnostic evaluation in clinical practice. This is particularly true for mechanical stimuli where the 95% Confidence Interval for the prevalence of sensory abnormalities at the non-painful side ranges between 33% and 50%. In clinical practice, the assessment of chronic pain includes documentation of pain location, intensity, quality and onset/duration aimed to elucidate the underlying pathophysiological mechanism. Sensory testing is an important part of this assessment which is aimed at identifying phenomena such as hyperalgesia (increased response to painful stimuli) and allodynia  for thermal and mechanical stimuli There are only a few studies reporting bilateral sensory abnormalities in chronic pain conditions. Huge and co-workers, 2008 investigated thermal sensory function at the affected and non-affected side of acute and chronic complex regional pain syndrome (CRPS) patients and found bilateral sensory changes for both patient groups In spite of the studies referred to above, the occurrence of contralateral sensory changes in situations where the pain is experienced only unilaterally is still not generally acknowledged. Possibly this is because it is regarded clinically irrelevant. However, bilateral sensory changes could become clinically relevant in patients with unilateral pain if they challenge the correct qualification of sensory dysfunction. For example, if a mechanical stimulus which is known to be slightly painful presented at the non-affected and affected side is rated by the patient as equally painful at both sides, one could conclude normal sensory functioning. However, if both the non-affected and affected side of this patient are hyperalgesic for this particular stimulus, the conclusion of a mechanical hyperalgesia could be overseen.As the neuropathic pain is characterized by both, positive and negative sensory phenomena, it is critical for those phenomena to be captured and, for their optimal utility, to be measured quantitatively. The German Research Network on Neuropathic Pain (DNFS) established a standardized Quantitative Sensory Testing (QST) protocol which allows a comprehensive somatosensory characterisation of chronic neuropathic pain patients, using reference values from healthy volunteers There is a long tradition of quantitative measurement of somatic sensory function, well documented in a number of publications By using reference values from healthy volunteers, QST does not rely on reference values obtained from the patient’s own contralateral side. Thus, it offers a unique opportunity to study bilateral somatosensory function in patients with chronic unilateral pain in a detailed, standardized manner.Based on previous reports we hypothesize that bilateral somatosensory abnormalities are frequently present in unilateral chronic pain patients and that bilateral sensory changes may exist for the same QST parameter. To test this we selected a large cohort of patients with unilateral neuropathic pain. We examined the painful side and its corresponding contralateral area using the standardized DNFS QST protocol comparing values with those obtained from age- and gender-matched healthy volunteers.The study adhered to the declaration of Helsinki and was approved by the independent, medical ethical committee “Stichting Beoordeling Ethiek Bio-Medisch Onderzoek”, P.O. Box 1004, 9400 BA Assen, The Netherlands. This committee is acknowledged by the Central Committee on Research Involving Human Subjects . Patients and healthy controls were recruited from the local region. All participants signed an informed consent form.In total, 209 age- and gender-matched healthy volunteers (age range 20–73 years), 138 females (age 45.3±13.4 years) and 71 males (age 48.7±14.0 years) underwent the QST assessments on their dorsal hand and foot. These body locations have been indicated by Rolke et al., 2006 as reference sites for QST Patients were recruited from the outpatient Department of the Pain Management Unit of the University Medical Center Groningen, The Netherlands. All patients were diagnosed as suffering from neuropathic pain by the physicians of the pain management unit. Neuropathic pain diagnosis was made on grounds of coherent patient history, medical history, physical examination, including neurologic function tests such as EMG. Each clinical diagnosis was additionally confirmed by an experienced pain specialist of the Pain Management Unit based on patient’s files. In total, 81 neuropathic pain patients  underwent the QST assessment, each at the area where the most profound pain was experienced and at their contralateral counterpart .Prior to undergoing the QST assessments, patients were asked to rate their ongoing pain level using a Numerical Rating Scale (NRS) of ‘0’ indicating ‘‘no pain’’, and ‘100’ indicating ‘‘most intense pain imaginable’’. Patients did not discontinue their regular pain treatment if applicable.The QST battery consisted of seven tests, measuring thirteen parameters and was applied according to the standardized protocol of Rolke et al., 2006 Thermal QST tests were performed using the Medoc Pathway System  and consisted of six parameters: threshold assessments for warm and cold detection  and heat pain and cold pain . In addition, paradoxical heat sensations (PHS) during the thermal sensory limen (TSL) procedure of alternating warm and cold stimuli were identified.Mechanical QST tests consisted of seven different parameters. The mechanical detection threshold (MDT) was determined with a standardized set of modified von Frey filaments . The mechanical pain threshold (MPT) was measured using a set of seven pinprick devices (flat contact area of 0.2 mm in diameter) with fixed stimulus intensities that exerted forces of 8, 16, 32, 64, 128, 256, and 512 mN. Mechanical pain sensitivity (MPS) was assessed using the same set of seven weighted pinprick stimuli to obtain a stimulus–response function for pinprick-evoked pain. Dynamic mechanical allodynia (DMA) was assessed as part of the test above, using a set of three light tactile stimulators as dynamic innocuous stimuli: cotton wisp, cotton wool tip fixed to an elastic strip and a standardized brush .Vibration detection threshold (VDT) was performed with a Rydel–Seiffer graded tuning fork  that was placed over a bony prominence. The wind up ratio (WUR) test was assessed with a pinprick intensity of 256 mN. The pressure pain threshold (PPT) was determined over muscle with a pressure gauge device .The Medoc Pathway System was maintained and calibrated according to the manufactures guideline . All mechanical devices were inspected regarding their function prior to each testing. The standardized von Frey filaments (Marstock) were replaced once a filament of concern was bent. Each pinprick device underwent a functionality test and inspection of the contact tip. The tip was replaced once bent including a calibration of the device. Two of the three light tactile stimulators i.e. cotton wisp and cotton wool tip fixed to an elastic strip were replaced after each testing. The standardized brush was replaced once the brush hairs were not conforming to the usual shape . The pressure gauge device and tuning fork were not replaced during the assessment period.QST data of patients with neuropathic pain were compared with reference data from gender and age matched healthy volunteers. Both, patients and healthy subjects were divided into three age groups each . QST values of chronic pain locations and their mirror image area at the upper extremities were compared to QST reference values obtained from the dorsal hand of healthy controls , whereas values from chronic pain locations at lower extremities and their mirror image area were compared to reference values obtained from the dorsal foot of healthy controls . QST values from each patient were transformed to z-scores as described by Rolke et al., 2006 Because “dynamic mechanical allodynia” (DMA) never occurs in healthy volunteers, the QST parameter could not be used for z-score analysis. Alternatively, patients ratings greater than NRS 10  were regarded as clinically relevant and were identified as abnormal.For the QST parameter “wind up ratio” (WUR), twenty-three patients  rated the single pinprick stimulus as “0” making ratio calculations (painfulness of one pinprick stimulation vs. painfulness of a train of ten pinprick stimulations) for Wind-up impossible. For these patients WUR was not used for subsequent analyses.For each QST parameter, the proportion of patients with sensory abnormalities at the painful, affected side was calculated. To estimate the prevalence of sensory abnormalities in the general patient population we calculated the 95% confidence intervals of the calculated proportions using the ‘Wilson Estimate’ of proportion For each QST parameter, the proportion of patients with sensory abnormalities at the non-painful, contralateral side was calculated applying the same procedure (see 2.4.2.).For each patient, the presence or absence of a sensory abnormality at the contralateral side for a particular QST parameter was determined when the patient had already shown a sensory abnormality for this QST parameter at the affected side. This allowed the direct identification of a relationship between bilateral sensory abnormalities for the same QST parameter. To increase statistical power we recalculated the above proportions but now pooled the thermal QST parameters  into one overall thermal QST domain and pooled the mechanical QST parameters  into one overall mechanical domain.Again we estimated the prevalence of sensory abnormalities in the general patient population with the ‘Wilson Estimate’. All proportions are reported as percentages.To identify correlations between ongoing background pain and values for each QST parameter Pearson correlations were calculated.The overall numbers of sensory abnormalities for the affected and contralateral side across the thirteen QST parameters were compared to identify possible relationships using Pearson correlations.From the healthy volunteer cohort (n = 209) investigated in this study, a total of 418 locations were assessed and 5434 measurements were analysed by means of z-score profiling.Although the majority of the QST results obtained in healthy volunteers confirmed normal sensory function for this cohort, incidental sensory abnormalities (4.3%) were observed for all QST parameters with the exception of DMA. Age, -gender, -and location matched normative QST data are presented in Out of the total of 418 different body areas that were tested across all healthy controls 64.0% (258 locations) showed normal sensory function and 36.0% (160 locations) showed a sensory abnormality for at least one QST parameter. Sensory abnormalities were regarded as sensory gain in 20.3%, sensory loss in 12.0% and a mixture of sensory gain and sensory loss in 3.6% of the cases .Demographic data of the patients are shown in For the 81 patients investigated in this study, 2106 QST data measurements were obtained from both the affected and contralateral side. The total of 2083 measurements were analysed by means of z-score profiling.In patients with neuropathic pain, sensory abnormalities were observed in all QST parameters at both affected and contralateral side . In our At the contralateral side, 74% of the patients had at least one QST abnormality. In 24% of the patients a mixture of sensory gain and loss was present. Almost 35% of the patients showed only sensory gain and 16% had only sensory loss at the contralateral side .95% Confidence Intervals confirmed that the prevalence of normal sensory function differs significantly between healthy controls and patients at the painful and non-painful side . A significant difference was also present between the painful side and non-painful side of the patients (p<0.05).Sensory abnormalities at the affected side ranged from 8.6% (n = 7) for CPT to 49.4% (n = 40) for PPT. 95% Confidence Intervals confirmed that the prevalence differed significantly from zero (p<0.05) for all QST parameters with highest incidence for MPT (95CI: 27%-48%) and PPT (95CI: 39%-60%) .For the nociceptive parameters  there were predominantly changes reflecting hyperalgesia, whereas for the non-nociceptive ones  they reflected hypoesthesia .For the nociceptive parameters CPT and HPT, thermal pain threshold were decreased indicating a thermal hyperalgesia. An increased pain due to blunt pressure (PPT) and an increased sensitivity to mechanical pain (MPS) were observed indicating only hyperalgesia for these parameters. For MPT a greater incidence for mechanical hypo- than hypersensitivity was detected. WUR was more frequently increased than decreased indicating a greater incidence for hyper- than hyposensitivity.Thermal hypoesthesias were observed also in most of the patients for CDT, WDT and TSL. For MDT there was predominantly a sensory loss observed indicating a mechanical hypoesthesia. It was possible to detect hyperesthesia for VDT for one patient, but for the large majority VDT responses indicated hypoesthesia.In 27% (n = 22) of the patients a sensory gain for PHS was detected at the affected side. DMA was present in 26% of the patients, in 6% of very mild intensity, however, 20% of patients showed a clinically relevant increased response for DMA indicating a dynamic allodynia.Sensory abnormalities at the contralateral side ranged from no abnormalities for CPT to 30.9% (n = 25) for PPT. With the exception of CPT, 95% Confidence Intervals confirmed that the prevalence differed significantly from zero (p<0.05) for all QST parameters with highest incidence for MPT (95CI: 11%-27%) and PPT (95CI: 22%-42%) .Overall there were less sensory abnormalities at the contralateral side than at the affected side.For nociceptive parameters there was predominantly sensory gain observed, suggesting the presence of hyperalgesia, whereas for non-nociceptive parameters predominantly a sensory loss was identified suggesting hypoesthesia .Only sensory gain for HPT, PPT and WUR were observed suggesting hyperalgesia. For MPT sensory loss was more frequently observed than sensory gain indicating a greater incidence for mechanical hyposensitivity than hypersensitivity. In contrast, for MPS was sensory gain was more frequently observed than sensory loss indicating a greater incidence for mechanical hypersensitivity than hyposensitivity.Thermal hypoesthesias were observed for most of the cases for CDT and for TSL, only 7.4% of patients showed hyperesthesia for TSL and 1.2% for CDT. WDT abnormalities were observed in 14.8% of the cases and this was due to both sensory loss and gain. For MDT at the contralateral side sensory loss was observed three times as often as sensory gain, indicating a greater incidence for mechanical hypoesthesia. There was only hypoesthesia for VDT at the contralateral side.In 9.8% of the patients a sensory gain for PHS at the contralateral side was detected. DMA was present in 19.8% of patients, but mostly of very mild intensity. However, 3.7% of patients showed a clinically relevant sensory gain for DMA indicating a dynamic allodynia.Here we describe one patient in greater detail for better understanding of the magnitude of somatosensory abnormalities based on raw values of the QST battery.A 25 year old woman (ID1) suffered from a cut injury at her left hand with a lesion of the digitalis nerve. Subsequently, she developed severe pain at left palm including digits IV and V. Bedside tests using von Frey filaments and a brush confirmed impaired sensibility including allodynia of left hand. These sensory signs were within neuroanatomical plausible distribution of the digitalis nerve. The clinical diagnosis “peripheral nerve injury” was made. The QST assessment took place in the area of greatest pain complaints and on the same contralateral site. Normative data obtained from dorsal hand were from 63 age- and gender matched volunteer’s ± SD indicated in brackets. For the affected side the patient rated the different pinprick forces with a NRS score of 53.1 indicating an increased sensitivity for mechanical pain (MPS) (0.62±1.00). The NRS ratio for Wind up (WUR) test was increased to 6.5 suggesting central sensitisation (NRS 2.53±2.33). Her ratings for DMA pain of NRS 54.7 indicated allodynia. Clinically, this QST profile indicates a predominant gain of sensory function due to small and large fibre sensitisation. At the contralateral side the patient displayed a decreased threshold for MDT of 0.5 mN (2.22±2.27 mN) and a decreased threshold for CDT of 24.9°C (30.7±0.77°C). DMA pain of NRS 3.5 indicates minor allodynia. Clinically, for the contralateral side a predominant gain of sensory function was found indicating small and large fibre sensitisation.To further investigate the extent of contralateral abnormalities we determined the presence or absence of abnormalities in each of the QST parameters at the contralateral side given that an abnormality for the same parameter was present at the affected side . This ocTo increase statistical power with the purpose to allow a more accurate estimation of the prevalence of sensory abnormalities in the general chronic pain patient population, thermal and mechanical QST parameters were combined into one thermal and one mechanical domain. For the affected side this grouping resulted in 21.4% (95CI: 18%–25%) thermal abnormalities and 29.0% (95CI: 25%–33%) mechanical abnormalities. For the contralateral side 11.6% (95CI: 9%–14%) thermal abnormalities and 13.7% (95CI: 11%–17%) mechanical abnormalities were found. To investigate the occurrence of bilateral manifestations of sensory abnormalities we calculated the prevalence of thermal and mechanical abnormalities at the contralateral side given that there was an abnormality at the affected side for the same QST domain in the same patient. This resulted in 95% CI’s for bilateral abnormality ranging from 12%–25% and 33%–50% for thermal and mechanical QST domains, respectively.All patients reported ongoing spontaneous pain  at their affected side before the QST assessment took place see . There wThe number of sensory abnormalities for patients varied between 0 and 8 for the affected and 0 and 6 for the contralateral side for the thirteen QST parameters assessed see . The oveThis QST study shows that patients with unilateral neuropathic pain have a diversity of sensory abnormalities at the painful side, and to a lesser extent, at the contralateral non-painful side. Using the standardized QST protocol with 13 different parameters to obtain a complete sensory profile, it was demonstrated that bilateral sensory abnormalities are apparent in a considerable number of the patients that experience chronic unilateral pain.There was a significant correlation between the number of abnormalities at the painful side and the contralateral side. Even more so, if a particular abnormality was detected at the painful side, this abnormality was then the most likely abnormality to occur contralaterally. This was particularly striking for the mechanical stimuli group where the estimated prevalence of sensory abnormalities at the non-painful side was 33%–50% (95% CI) once a mechanical abnormality was detected at the painful side. These results have implications for the evaluation of patients in clinical practice, since often the non-affected side is used as the reference side. Our results show that using the contralateral side as the reference to identify sensory abnormalities at the affected side might lead to misinterpretation of the clinical manifestation.Z-score transformation of QST data revealed one or more somatosensory abnormalities in 36% of all members of the healthy control group. This number is in line with previous findings reporting 41% abnormalities using the QST protocol In our healthy volunteers, abnormalities were observed across all QST parameters with the exception of DMA. The detected sensory abnormalities reflected gain of function for the most part, some loss of function and in a minority fraction both gain and loss of function .Although previously reported otherwise As expected, the large majority (91%) of neuropathic pain patients showed sensory abnormalities at their affected side. Maier and colleagues (2010) In accordance with previous studies, sensory loss was predominantly found in non-nociceptive parameters Maier and co-workers (2010) reported abnormal QST values for the affected side across the different clinical neuropathic pain entities ranging between 8%–36% (compared to 7%–48% in this study) Contralateral sensory changes in patients with chronic pain have been acknowledged in a number of clinical studies Comparing the overall sensory findings from the contralateral side with those obtained from the healthy controls, a significant difference was shown indicating abnormal sensory function at the contralateral side in patients with unilateral neuropathic pain. In addition, a significant correlation was found for abnormal sensory function at the contralateral sides compared to the affected side. The pattern of sensory abnormalities for nociceptive and non-nociceptive parameters at the contralateral side was in line with that at the affected side but less severe. All patients had unilateral pain causing events and most showed bilateral sensory abnormalities. This finding points to a central component in processing the pain and controlling sensory function bilaterally.Preclinical studies have also found evidence for bilateral sensory changes upon unilateral induction of pain and these studies correlated the severity of pain with occurrence of bilateral changes. Hubbard and colleagues (2008) demonstrated in a rat model using painful cervical nerve root compression that the occurrence of contralateral allodynia depended on the load of compression In healthy volunteers and patients with rheumatoid arthritis, an intradermal administration of capsaicin induced mechanical hyperalgesia and allodynia at the side contralateral to the injection area In line with these findings, in the present study we have also found a significant correlation between background pain and QST abnormalities at the contralateral side in patients who experienced a unilateral pain-causing event. This supports previous suggestions that high pain intensities can induce sensory abnormalities at the contralateral side in patients with unilateral pain. Additional studies are needed to evaluate, for instance, if the severity of pain determines the onset of contralateral changes and if ongoing pain is the driving force for the maintenance of contralateral abnormalities in chronic pain patients.An interesting finding is that the presence of sensory gain or loss at the affected side was related to sensory gain or loss for the same QST parameter at the contralateral side, ranging from 20% to 57% dependent on the QST parameter. In particular for the group of mechanical stimuli, the estimated presence of sensory abnormalities at the non-affected side was substantial (ranging from 33%–50%). Although sensory abnormalities at the contralateral side were less pronounced compared to those at the affected side, there was a significant correlation between the numbers of sensory abnormalities at both sides in patients.Contrary to recommendations to use the contralateral side as a reference to identify sensory abnormalities in patients Since most (n = 77) patients in the present study continued their pain medication it cannot be excluded that the medication itself might have influenced the onset or maintenance of somatosensory changes seen bilaterally.These results firmly establish evidence for a cautious use of the contralateral side as a reference site in clinical practice. A way to overcome this problem is the use of reference values for either normative response or for pathological response to QST parameters to allow a precise identification of sensory abnormalities in patients.per se. This has implications for appropriate diagnostic evaluation in clinical practice.In conclusion, our data provide detailed evidence for bilateral sensory abnormalities in unilateral neuropathic pain patients using a standardized, elaborate QST protocol. Our results show that in these patients, the contralateral side should not be regarded as normal or healthy Table S1Quantitative Sensory Testing normative data of healthy volunteers. Quantitative Sensory Testing (QST) normative values assessed on dorsal hand (A) and dorsal foot (L) for female (F) and male (M) according to three age groups (18–45 years (y), 46–60 years and 61–75 years of age) in healthy volunteers. QST parameters: Cold Pain Threshold (CPT), Heat Pain Threshold (HPT), Warm Detection Threshold (WDT), Wind Up Ratio (WUR) (intensity of perception of single vs. series of 1 Hz stimuli as NRS), Cold Detection Threshold (CDT), Thermal Sensory Limen (TSL), Paradoxical Heat Sensation (PHS), Mechanical Pain Threshold (MPT), Mechanical Pain Sensitivity (MPS), Mechanical Detection Threshold (MDT), Vibration Disappearance Threshold (VDT), Pressure Pain Threshold (PPT). The absence of DMA is normal and therefore described. Numeric Rating scale (NRS) indicate “0” as “no pain” and “100” as the ‘‘most intense pain imaginable’’. Unit of each QST parameter is indicated. Values indicate mean ± SD for each QST parameter.(TIF)Click here for additional data file.


This study was conducted to assess whether patient-reported outcomes (PROs) differ by the underlying diagnosis (rheumatoid arthritis (RA)/inflammatory arthritis, osteoarthritis (OA), avascular necrosis of bone (AVN), other) in patients undergoing primary total hip arthroplasty (THA).We used prospectively collected data to assess the association of diagnosis with index hip function and pain. Moderate-severe activity limitation and moderate-severe pain were assessed at two- and five-year follow-up after primary THA using multivariable-adjusted logistic regression analyses. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.P = 0.01) and 0.4 (0.2 to 0.8) (P = 0.01), respectively, at two-years, but not at five-years, 0.7 (0.4 to 1.4) (P = 0.36) and 0.9 (0.4 to 1.8) (P = 0.78), respectively. At two-years, neither OA nor AVN were significantly associated with higher odds of moderate-severe pain (1.6 (0.6 to 4.5) (P = 0.40) and 2.8 (0.9 to 8.5) (P =0 0.06)), respectively. At five-years, AVN was associated with higher odds of moderate-severe pain with OR 4.1 (1.2 to 14.1) (P = 0.02), but not OA, 2.1 (0.7 to 6.5) (P = 0.22).There were 5,707 primary THAs at two-years and 3,289 at five-years, 51% were women and the mean age was 65 years. The underlying diagnosis was RA in 3%, OA in 87%, AVN in 7% and other in 3%. In multivariable-adjusted analyses, compared to RA, diagnoses of OA and AVN were significantly associated with lower odds of moderate-severe activities of daily living limitations with an OR (95% CI) of 0.5 (0.3 to 0.8) (We found that patients with OA and AVN had better functional outcomes and those with AVN worse pain outcomes after primary THA, compared to patients with RA/inflammatory arthritis. Insights into mediators of these relationships are needed to better understand these associations. Total hip arthroplasty (THA) has been termed the operation of the century . In patiDo patients with OA have better PROs after primary THA compared to RA? The published literature is sparse and the answer unclear. In the largest of published studies, 381 patients were studied with two-year follow-up in 331 and five-year follow-up in 89 patients, pain and function  at two years post-THA did not differ by the underlying diagnosis  and worsThe methods and results are described as recommended in the Strengthening of Reporting in Observational studies in Epidemiology (STROBE) statement .For this study, we used the Mayo Total Joint Registry that prospectively collects data on all joint replacements performed at the Mayo Clinic, Rochester, MN, USA. Data in the registry include patient demographics, operative diagnosis, surgery and implant details, dates of evaluation, reoperations and complications, current radiographs and pain and functional assessments ,14. All The operative diagnosis was the main variable of interest, categorized as osteoarthritis (OA), rheumatoid or inflammatory arthritis (RA), avascular necrosis of bone (AVN) and other. This was based on preoperative diagnosis  as well as operative findings. We adjusted for covariates that included known and suspected correlates of pain and function after THA. Covariates were demographics , body mass index (BMI), American Society of Anesthesiologist (ASA) class, distance from the medical center and implant fixation  obtained from the Total Joint Registry and linked databases. Anxiety, depression and medical comorbidity using the validated Deyo-Charlson index  were basa priori as undesirable outcomes of THA as in previous studies [Study outcomes were PROs of moderate-severe ADL limitation and moderate-severe pain obtained from self-reported validated Mayo hip questionnaires at two years or five years  after THA. We defined these composite outcomes  studies ,24, sincPatients self reported limitations in seven key ADLs that specifically assessed index hip function, including walking, climbing stairs, putting on shoes/socks, picking up objects from the floor, sitting in a chair, getting in/out of the car and rising from a chair to a standing position. For four ADLs , limitations were categorized into ‘no’, ‘mild’, ‘moderate’ or ‘severe’ limitation. The remaining three ADLs , that did not have a response corresponding to the ‘mild’ category, were categorized into ‘no’, ‘moderate’ or ‘severe’ limitation, as previously . The prePostoperative index hip pain was assessed with a single question on the hip questionnaire, namely ‘Do you have pain in the hip in which the joint was replaced? no pain, slight, moderate, severe.’ This validated question -17 is siWe tried to minimize confounding bias by including several covariates previously known or suspected to be associated with pain and ADL limitation after THA including the preoperative status, but recognize that residual confounding is a limitation of cohort study design. We accounted for correlation of observations  using appropriate statistical methods. We anticipated non-response to be higher at five than at two years, and acknowledge this as a study limitation limiting the generalizability of results. We included a large enough sample to study pain and ADL limitation without having too long of a study period (to avoid significant secular trends in implants and procedure) and, therefore, chose all eligible patients from 1993 to 2005. No formal sample size calculations were done.P-values are reported. Subgroup analyses were done for patients younger and older than 65 years to assess the association of diagnosis with pain and ADL outcomes, since patients with AVN or RA are expected to be younger than those with OA. We performed sensitivity analyses by restricting the study sample to surgery from 1998 to 2005, to examine whether change in RA management in the recent years impacted the noted associations in the main analyses.We used univariate and multivariable-adjusted logistic regression models to assess the association between the operative diagnosis and moderate-severe ADL limitation and moderate-severe pain two and five years after primary THA. The multivariable models included age, gender, BMI, ASA class, distance from the medical center, implant fixation, Deyo-Charlson index, anxiety and depression as well as respective preoperative variable/s – preoperative pain for pain outcome and preoperative limitation in seven ADLs for ADL limitation outcome. Individual ADL limitations were only examined as exploratory analyses, to avoid multiple comparisons and results are presented in Additional file a priori not to impute any missing data and to treat them as missing. A P-value <0.05 was considered significant. Analyses were done using SPSS, version 21 .All regression analyses used a generalized estimating equations (GEE) approach to adjust the standard errors for the correlation between observations on the same subject due to both hips having been replaced. Responder and non-responder characteristics were compared using logistic regression analyses, which were pre-specified to include demographics, comorbidity, implant-related factors and underlying diagnosis. We decided The Mayo Clinic Institutional Review Board approved this study and all investigations were conducted in conformity with ethical principles of research.2 in 76% of patients, and ASA score was class III/IV in 38%. The underlying diagnosis was OA in 87%, RA or inflammatory arthritis in 3% and AVN in 7% . Mean Deyo-Charlson score was 1 and depression and anxiety were present in 7% and 5%, respectively. Characteristics were similar in the five-year cohort and also similar to patients who responded to the preoperative questionnaire [see Additional file Clinical and demographic characteristics are shown in Additional file Responders to the two-year post-primary THA survey were more likely to be older  and less likely to have BMI ≥40 , ASA class III-IV  or live further from the medical center  Table . At fiveP = 0.07).In unadjusted analyses, we noted that compared to RA/inflammatory arthritis, the odds of overall moderate-severe ADL limitation at two years were significantly lower in OA and AVN patients Table . On the In adjusted analyses, compared to patients with RA/inflammatory arthritis, those with OA and AVN had significantly lower odds of overall moderate-severe ADL limitation at two years Table . No diffSensitivity analyses performed by restricting the analyses to the time period of surgery to 1998 to 2005 revealed minimal change in ORs and no change in significance for association of OA or AVN with moderate-severe activity limitations at two years, with ORs of 0.4  and 0.4 , respectively. The OR of association of diagnosis with moderate-severe pain at five years and the level of significance showed minimal change.P = 0.03), and 0.5 (0.2 to 1.0), P = 0.06) just as those 65 years and older did (0.4 (95% CI 0.2 to 0.9), P = 0.03 and 0.4 (0.2 to 0.8), P = 0.008).Subgroup analyses for patients <65 and those 65 years and older showed that ORs noted in the main analyses changed little: OA and AVN patients younger than 65 years had lower odds of moderate-severe ADL limitation at two years (0.4 (95% CI 0.2 to 0.9), In univariate analyses, we found that compared to those with RA/inflammatory arthritis, patients with OA had significantly lower odds of moderate-severe limitations in walking, climbing stairs, putting on socks/shoes, picking up objects and rising from a chair at two years post-primary THA Table . At fiveIn multivariable-adjusted analyses, patients with OA had significantly lower odds of limitation in rising from a chair at two years Table . PatientIn this prospective study of a large cohort of patients with primary THA, we found that after adjusting for important predictors, patients with OA had significantly better functional outcomes compared to those with RA/inflammatory arthritis at two-year follow-up. Results were notable for overall ADL limitation and key ADLs. Pain outcomes were not significantly different for OA versus RA. We also found that patients with AVN experienced better ADL outcome at two years compared to RA patients. In contrast, patients with AVN reported worse pain outcomes at five years compared to those with RA. Several findings in our study are of interest and merit further discussion.One of the main findings of our study was that patients with OA had significantly better functional outcomes compared to those with RA at the two-year follow-up, as indicated by lower odds of overall moderate-severe ADL limitation. These findings were confirmed for patients younger and older than 65 years. To our knowledge, this is the first study to have analyzed the association of diagnosis with functional outcomes adjusted for known correlates of outcome in a large sample of patients at both the two- and five-year follow-up after primary THA. On the other hand, we found no significant differences in risk of moderate-severe pain between OA and RA in multivariable-adjusted models. The greater ADL limitation noted in RA patients compared to OA patients may be due to the systemic inflammatory processes in RA versus OA , a higheet al. reported that patients with OA experienced better functional outcomes one year after THA compared to those with RA [et al. suggested that RA was associated with less optimal functional improvement at 10 years as compared to other diagnoses  in their other studies [et al. studied 293 patients who underwent total hip or total knee replacement at 2.5 years and found greater improvements in pain and function in OA compared to RA [et al. examined the predictors of successful joint arthroplasty outcome in a cohort of 233 patients with either hip or knee joint replacement and found that RA was associated with 0.33 odds of good outcome compared to OA, based on WOMAC total score improvements, a pain and function composite [Previous studies that have examined functional outcomes in THA patients have reported contradictory findings. In a study of 381 patients, pain and function  at two years post-THA did not differ by the underlying diagnosis [ with RA . A study studies . Kirwan omposite . Two of omposite , as do tomposite ,33, whicAnother important study finding was the lack of difference in pain outcomes in RA versus OA patients after THA. This is reassuring given that the most common symptom leading to THA is severe, refractory hip joint pain. This implies that patients with RA can be reassured that their pain outcomes will be similar to the majority of patients with OA undergoing THA.Another interesting finding from our study is that patients with AVN were less likely to have moderate-severe ADL limitations and more likely to report moderate-severe pain compared to patients with RA. To our knowledge, this is a new finding and adds to the literature. A recent systematic review of outcomes of THA in patients with AVN found that most studies had a low evidence level of III and IV and provided data only related to revision rates , indicatThe practical implications of our study are several-fold. First our study highlights the importance of studying both pain and functional outcomes in arthroplasty patients, as discussed previously . AlthougOur study has several limitations and strengths. Survey non-response may have introduced some bias, and the direction of this bias is unclear. Our response rates are similar to the average 60% response rate reported for large surveys of this size ; howeverOur study is among the first well-powered studies adjusted for important covariates and confounders that showed that the underlying diagnosis for primary THA is a significant predictor of functional outcomes and pain up to five years post-THA. We found that compared to RA, OA was associated with better overall functional outcome after primary THA. Compared to RA, AVN was associated with better overall functional and worse pain outcomes after primary THA. Future studies need to investigate the underlying pathophysiology and reasons for these significant findings, which can help us understand better the true mechanism of pain and functional outcomes after primary THA.ADL: Activities of daily living; ASA: American Society of Anesthesiologists; AVN: Avascular necrosis of bone; BMI: Body mass index; CI: Confidence interval; OA: Osteoarthritis; RA: Rheumatoid arthritis; OR: Odds ratio; PROs: Patient-reported outcomes; RA: Rheumatoid arthritis; THA: Total hip arthroplasty.There are no financial conflicts related directly to this study. JAS has received research grants from Takeda and Savient; and consultant fees from Savient, Takeda, Allergan and Regeneron. DGL has received royalties/speaker fees from Zimmer, has been a paid consultant to Zimmer and has received institutional research funds from DePuy, Stryker and Zimmer. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.Study design and protocol: JAS. Revision of study protocol: JAS, and DGL. Data analyses: JAS. Review of analyses and results: JAS, and DGL. Manuscript draft: JAS. Manuscript revision: JAS and DGL. Submission: JAS. Both authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/210/prepubTable S2. Demographic and clinical characteristics of Primary THA cohort. Table S3. Moderate severe functional limitation by diagnosis at three time-points.Study outcomes definition. Click here for file


The fusion of the pelvic joints in patients with severe pelvic girdle pain (PGP) is a controversial and insufficiently studied procedure. The aims of this study were to evaluate physical function and pain after sacroiliac joint (SIJ) fusion.A single-subject research design study with repeated measurements was conducted; pre-operatively and at 3, 6 and 12 months post-operatively. The outcome measures considered were the Oswestry disability index (ODI), visual analogue scale (VAS), and SF-36. Eight patients with severe PGP received open-accessed unilateral anterior SIJ fusion and fusion of the pubic symphysis.Seven patients reported positive results from the surgery. At 1 year post-operation, significant (p < 0.001) reductions in ODI (54 to 37) and VAS (82 to 57) were reported. The physical functioning, bodily pain, and social functioning scores in the SF-36 were also improved.Positive and significant changes in disability and pain at 1 year after SIJ fusion were observed. Despite these positive results, open accessed anterior fusion of the SIJ was associated with adverse events and complications such as infection and nerve damage. The sacroiliac joint (SIJ) may be the source of pain for 13-30% of patients with low back pain ,3. This SIJ fusion was first described by Smith-Petersen in 1921 . Pelvic A randomized controlled trial is the gold standard to examine the effect of an intervention. As SIJ fusion is performed on few patients, a single-center randomized controlled design is difficult to establish due to the low number of participants. However single subject research design (SSRD) have been recommended as a useful method to examine clinical accountability . If propThe primary aim of this prospective study was to examine changes in pain and physical function at 3, 6, and 12 months after SIJ fusion. The secondary aims were to evaluate post-operative health-related quality of life and patient satisfaction with treatment.During the study period, from 2007 and 2010, a total of 20 patients with PGP were referred to our pelvic centre, but only 9 patients met the study’s inclusion criteria  and registered in the Clinical Trials Database (reference number: NCT00900601).Function was measured according to the Oswestry disability index (ODI) , each paThe patients received unilateral SIJ fusion, of the most painful SIJ, and symphysiodesis. An anterior approach with a skin incision over the iliac crest was used to reach the SIJ. The joint was partially resected, and grafted with cancellous bone from the ipsilateral iliac crest. Two AO reconstruction plates or AO-DC plates  were used Figure  to achieThe graphed data were analysed according to the guidelines for SSRD . The levNine consecutive patients received unilateral anterior SIJ fusion and fusion of the pubic symphysis. One patient developed chronic fatigue syndrome during the follow-up and dropped out of the study after 6 months. The remaining eight patients followed the study protocol; the baseline characteristics of these patients are presented in Table The ODI scores of each patient are presented in Figure The VAS scores of each patient are presented in Figure At baseline, seven out of eight patients had bilateral SIJ symptoms. At the 1-year follow-up, only two patients experienced pain in the fused joint; however, six of the seven patients reported discomfort in the contralateral side. Seven patients had pain in the pubic symphysis before surgery, and five still had pain in this area at the 1-year follow-up Figure .The patients showed low health-related quality of life scores at baseline as compared to the general Norwegian population . These pAll patients reported that surgery had a positive effect; one patient reported a minor effect, two reported some effect, and five reported a good effect from the surgery. None of the patients reported an excellent result. Concerning tolerance of physical activity, seven patients reported some improvement, and one patient reported major improvement.The fusion was evaluated with CT at the 1-year follow-up, and all patients had either solid fusion or significant bone bridging in the SIJ. However it was difficult to evaluate the fusion in the pubic symphysis because of the plate artefacts, but no patient had plate or screw loosening or other signs of non-union.There were 3 major complications: one infection, one complex regional pain syndrome with drop-foot and one loss of bladder sensation. In addition there were 3 patients with transient sensitivity loss to the lateral femoral cutaneous nerve, a possible complication of bone harvesting from the iliac crest. All patients reported high post-operative pain and required epidural treatment for 5–7 days. They were hospitalised for 7–10 days and were discharged with opioids.The primary aims of this study were to evaluate changes in disability and pain intensity after SIJ fusion in patients with severe PGP. Pre-operatively, these patients showed severe disability and high pain levels. One-year post-operatively, clinically significant reductions in both disability and pain were observed. The SF-36 scores for physical function, bodily pain and social functioning also improved significantly. Seven out of eight patients reported a positive effect from the procedure.Pelvic fusion in PGP is a rare procedure and is only performed in severe cases where conservative treatment modalities have been unsuccessful. A randomized controlled trial of this procedure is not possible, as the alternative treatment modality (conservative treatment) has already been tried. For this reason, an alternative study design was sought. The SSRD with multiple measurements is designed to study small samples of patients. A sample size of three patients is considered sufficient for external validity ,16 and aOutcomes for SIJ fusion have been reported in several case series -14. A poSurgery is generally associated with a risk of complications. Because of the location of the SIJ an open approach to this structure is quite an aggressive surgical procedure. One of our patients developed a complex regional pain syndrome despite displays of normal neurological function in the first two post-operative days. This phenomenon has been found to occur after anterior SIJ fusion and is most likely due to nerve root compression . When peWe fused the pubic symphysis for every patient based on experience that this procedure increases pelvic ring stability in patients operated for unstable pelvic ring fractures . After 1Non-specific PGP is thought to be a multi-factorial disorder with genetic, social, psychological, neuro-physiological and patho-anatomical factors involved in the pain syndrome . SIJ fusBecause conservative treatment has proven effective for patients with PGP , this shOne year after open unilateral anterior SIJ fusion combined with symphysis pubis fusion, positive and significant changes in both physical function and pain were observed. Despite these positive results, this procedure was associated with adverse events and complications.SIJ: Sacroiliac joint; PGP: Pelvic girdle pain; ODI: Oswestry disability index; VAS: Visual analogue scale; SSRD: Single subject research design.This study was supported by grants from the Norwegian Foundation for Health and Rehabilitation and Sophies Minde Ortopedi AS. The authors declare that they have no competing interest.All authors have been involved in the planning of the study, data collection, data analysis and the writing. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/15/85/prepub


Purpose. To retrospectively evaluate the clinical significance of radiotherapy for oligometastases of bone in prostate cancer (PCa). Methods and Materials. Between 2003 and 2008, 35 PCa patients with oligometastases of bone were treated with radiotherapy. Results. The median radiotherapy dose was 40 Gy. The 3-year overall survival rates for all patients, for patients that received a radiotherapy dose of ≥40 Gy (n = 21) and for those that received <40 Gy (n = 14), were 77.2%, 90.5%, and 50.0%, respectively. Fourteen out of 16 patients (87.5%) who had pain were improved 1 month after radiotherapy. The median duration of pain relief was 12 months. Pathological fracture and spinal cord compression (SCC) were not seen at the treated sites but developed at nonirradiated sites in three patients (8.6%) and in one patient (2.8%), respectively. Although the high-dose group (≥40 Gy) achieved better survival than the low-dose group (<40 Gy), it was not independent prognostic factor in multivariable analysis. Conclusions. Radiotherapy of bone oligometastases in PCa was effective for long-term pain relief. Pathological fracture and SCC were not seen at the treated sites. A larger clinical trial is warranted to study the actual benefit following radiotherapy for oligometastases of bone in PCa. Patients with bone metastases from prostate cancer frequently experience skeletal morbidities as a result of their disease. Skeletal-related events (SREs), such as pathological fractures and spinal cord compression, are major causes of morbidity in patients with prostate cancer and may lead to other comorbidities including pain , 2. Soloway et al.  reported The aim of radiotherapy for metastatic bone disease is not only relief of bone pain but also healing and prevention of pathological fractures, with anticipated effects including improved mobility, function, and quality of life , 5. In a The objective of this retrospective study was to evaluate the effect of radiotherapy on bone oligometastases and oligo-recurrence in patients with prostate cancer. We were also interested in the disease behavior in patients with bone oligometastases and oligo-recurrence. Between January 2003 and December 2008, 136 Japanese men diagnosed with prostate cancer with bone metastases received radiotherapy directed at the metastatic bone lesions at Kitasato University Hospital, Japan. Their medical records were evaluated retrospectively. Thirty-five of the patients had bone metastases of EOD I, referred to as oligometastases or oligo-recurrence of bone in this study. EOD I has been defined by Soloway et al. [ We analyzed the overall survival and the effect of radiotherapy on pain relief and the incidence of SREs, including pathological fracture and spinal cord compression. Short-term pain relief was determined by comparing symptoms prior to radiotherapy to that 1 month after its completion. Pain relief response was classified as follows by taking the best point from the start of treatment: “response,” when pain decreased or the daily dosage of the analgesic was decreased; “no change,” when pain was unchanged and the dosage of the analgesic did not change; and “progressive disease,” when pain increased or the dosage of the analgesic was increased.  For long-term pain relief, the time to progression was defined as the interval between the initial date of radiotherapy and the date when increased pain or increased dosage of the analgesic was first documented after the best pain relief response at treated sites.  Local treatment for prostate cancer might affect overall survival we divide patients into oligo-recurrence group which has treated enough locally such as prostatectomy and oligometastases group which has not been treated with local therapy for the prostate. Overall survival was calculated as the time interval from the last day of radiotherapy for bone metastases to the time of death. Progression-free survival for bone pain was defined as the proportion of patients surviving with decreased pain from the onset of pain relief to pain relapse at a treated site. Patients were followed for a median of 36 months  after radiotherapy.  Radiotherapy was performed using one port postero-anterior field for the middle thoracic spine/upper lumbar spine and two ports anteroposterior parallel opposed fields for the other spine, legs, and pelvic bone. The energy of radiotherapy was 6 or 10 MV X-rays.P  value < 0.05 was used to determine the level of statistical significance. Analyses were performed with Stata version 11 for Windows . The survival rate was calculated using the Kaplan-Meier method. Differences in patient characteristics between the two groups were compared by chi-square test or Fisher exact test, as appropriate. Multivariable analysis was performed by employing the Cox proportional hazards regression model to examine the interaction between total radiotherapy dose (≥40 Gy versus <40 Gy) and other clinical variables and to estimate the independent prognostic effect of radiotherapy on survival by adjusting for confounding factors. Within the present study population, there were 11 deaths, which allow a maximum of two variables to be included in a multivariable regression model. Therefore all potential confounding factors of radiotherapy dose were reduced to one single composite characteristic by applying a propensity score . The con3  if α/β of 3 was applied. The reasons for radiotherapy were pain relief in 16 patients (45.7%), prevention of SREs in 17 patients (48.6%), and spinal cord compression in 2 patients (5.7%). Treatment characteristics are given in P = 0.0116). There is no significant difference between Oligo-recurrence group and Oligometastases group (P = 0.021), which indicated that high-dose group decreased the hazard of death by four times that of low-dose group (P = 0.637), which suggests that high-dose radiotherapy was not an independent risk factor for overall survival  has previously studied various treatment fraction regimens for palliation of bone metastases. The RTOG 9714 study, a recent phase III trial centered on prostate cancer and breast cancer with osseous metastases, revealed 8 Gy per single fraction was equal to 30 Gy in 10 fractions for the pain relief of osseous metastases at 3 months after irradiation . HoweverIn Japan, longer courses of radiotherapy with higher total doses of radiation remain the most commonly used, typically with a regimen of 30–40 Gy given in 10–20 treatment sessions. While conventional radiotherapy was used in this study, the results reveal a median duration of pain relief of 12 months, with approximately half of the patients experiencing relapsed bone pain. The bone pain trial which include 34% of prostate cancer patients in patient population showed 40% of pain relapse at 12 months . Althoug For patients without bone pain in this study, the main purpose of radiotherapy was prevention of SREs, including pathological fracture and spinal cord compression. The current study demonstrated that the complications were not seen in treated sites; however, three patients experienced pathological fracture and one patient had spinal cord compression in a nontreated site after radiotherapy. These results indicate that radiotherapy for metastatic bone disease may potentially decrease the incidence of SREs in treated sites. Both pathological fractures and spinal cord compression with neurologic deficit negatively affect quality of life . Moreove Our study has several limitations. Because it is retrospective, patient populations differ between total radiation dose received (≥40 Gy and <40 Gy). There was also no control group, that is, one that did not receive radiotherapy. Therefore, in the future, a large prospective study is required to investigate the actual benefits, including overall survival associated with radiotherapy for oligometastases and oligo-recurrence of bone in prostate cancer.


Tonsillectomy is one of the most common surgical operations and has such complications as pain, hemorrhage and laryngospasm. Pain management is of vital importance in order to reduce the suffering and restlessness in children having undergone tonsillectomy. Different studies differ in their findings as to the use of ketamine for postoperative analgesia. The aim of this study was to investigate the effect of peritonsillar injection of ketamine preoperatively on postoperative pain relief.This was a randomized controlled trial (RCT) on sixty 3-12-year-old children. Children were randomly assigned to the intervention and control groups. Peritonsillar injection consisted of 1 mg/kg ketamine in the intervention group and of normal saline in the control group. An injection of 1 cc was administered on each side five minutes prior to tonsillectomy. Pain assessment was performed using the self-report Oucher Scale and CHEOPS  and sedative state assessment was performed using the Wilson Sedation Scale. Pain, medication and complications were studied for 24 hours. Data analysis was performed using chi-squared test and t-test.The ketamine group had a lower pain score compared with the control group (1.40±1.003 compared with 1.53±1.074). The average pain was less in the control group two hours after the surgery. The difference was statistically significant. There was no difference between the two groups in terms of nausea and vomiting incidence.The peritonsillar injection of ketamine five minutes prior to the surgery reduces the post-tonsillectomy pain without causing any complications. Inflammatory and infectious diseases of the throat, tonsils and adenoids account for a large portion of children’s diseases and healthcare costs. In most cases, these diseases lead to either tonsillectomy or adenectomy, both common child surgeries . TonsillSeveral analgesics are used for post-tonsillectomy pain relief, such as narcotics, NSAIDs and local anesthetics. Nonetheless, narcotics can reduce the muscular tone of the upper airway, weaken the cough reflex, and cause respiratory depression, nausea and vomiting after the surgery. The positive effects of preoperative analgesia in the treatment of postoperative pain have been shown in several studies , 4. WithIn several studies, normal saline was used preoperatively in the placebo group to investigate the postoperative effects of the analgesia of other drugs in children undergoing tonsillectomy. Mollier et al showed that postoperative pain in the preoperative peritonsillar injection with bupivacaine was less compared with the control (placebo) group injected with normal saline .In their study, Dal et al  not onlyThis is a triple-blind RCT study; the patients, the ENT specialist performing the surgery, the anesthesiologist administering the anesthetic and the anesthesiology assistant (MSc) recording the pain and restlessness levels and the postoperative results did not know the patients’ assignment to the two groups or the medication used. The data analyst did not know which patient had received ketamine and which normal saline, either. The statistical population of the sample was the 3-12-year-old tonsillectomy candidates at the Imam Khomeini Hospital, Ardabil, Iran. The sample size with 80% power of study and considering 20% flaw was calculated to be 30. Patients’ assignment to normal saline or ketamine groups was random.After acquiring permission from the Ethics Committee of the university and registering in the Clinical Trials System of the Ministry of Health and Medical Education, and acquiring the written consent of patients’ parents, 60 patients in classes I and II in the ASA Physical Status Classification System, ranging between 3 and 12 years in age, who were tonsillectomy candidates were studied.Exclusion criteria included metabolic and endocrine diseases, coagulation disorders, mental challenge, developmental disorders, any drug allergy history, peritonsillar abscesses, hypertension, psychotic disorders, chronic pain, and receiving analgesics.Having ensured that the patients were NPO prior to the surgery, we gave all patients pre-anesthetic five minutes before administering the anesthetic. Anesthesia was performed identically in all patients . Prior to anesthesia, duringthe operation and in the recovery room, the peripheral arterial blood pressure, the PR and SpO2 were recorded. An anesthesiology assistant (BSc) prepared the 2 ml normal saline and ketamine syringes with special coding.After tracheal intubation and administering anesthesia prior to surgical incision, the peritonsillar injection of 2 ml of normal saline and ketamine, in the control and intervention groups respectively, was performed fan-wise in the tonsillar bed and around it, from the upper and lower poles of the tonsils, by a surgeon, and the operation started five minutes later. Hemostasis was performed with sutures in both groups. The blood pressure, the heartbeat, the heart rate, and SpO2 were recorded every ten minutes throughout the surgery. The durations of the anesthesia and the operation were recorded by an anesthesiology assistant.The data was collected using a 3-part questionnaire. The first was for the personal and social information of the patients, the second was for the CHEOPS (pain assessment) and the self-report Oucher Scale, and the third was for the Wilson Sedation Scale, the scientific validity and consistency of which have been shown in several studies  and 4.The Oucher Scale is a self-report tool to measure pain in children aged 3-12 years old. The scale, which is used by all children’s healthcare personnel across the globe and can be accessed at oucher.org. Moreover, the content and structural consistencies of this scale have been documented using statistical tests. This scale is one of the most valid, oldest and most commonly used self-report pain scales in children, which was devised by Beyer. The scale consists of 6 child portraits showing different levels of pain, arranged vertically, from the lowest level at the bottom to the highest at the top, numbered 1 to 6 . Pain assessment was performed by an anesthesiology assistant after the patient left the recovery room, assisted by the patient’s company.The first part of the questionnaire was completed upon the patient’s entry to the OR, after extubation and the patient’s transfer to the recovery, and pain assessment using the CHEOPS and the Oucher Scale, sedation assessment using the Wilson Sedation Scale, and the assessment of complications were performed by an anesthesiology technician (MSc). Postoperative pain level assessments, the Wilson Sedation Scale and complications assessment were performed 5', 15', 30', 1 hour, 2 hours and 4 hours after the surgery, and the scores and the average score were recorded.If the CHEOPS showed a pain score of 5+, acetaminophen was administered for pain relief. If other complications were present, proper treatments were performed.All the questionnaire data were coded and recorded into SPSS. Then, the average Oucher Scale, CHEOPS and Wilson Sedation Scale scores were calculated. To compare the difference between the pain levels in the two groups, the t-test and the chi squared test were used, and to compare the sedation state, the Fischer’s exact test was used.P>0.05)  .There was no significant difference in sleep patterns between the two groups on the first night after the surgery. Also, no complications, such as apnea and laryngospasm, were seen during the surgery or after the extubation in either group. P>0.05). There was also no significant difference in the time of discharge from the recovery room or the bed between the two groups. Respiration and hemodynamic patterns were identical in both groups. There was no significant difference in pain levels between males and females . The pain level on the CHEOPS in the ketamine group was also lower than that of the control group, which was a significant Difference (1.33±0.844 compared with 1.53±1.358) (The ketamine group had a lower pain score compared with the control group (1.40±1.003 compared with 1.53±1.074). The average pain level on the Oucher Scale 2 hours after tonsillectomy was 1.22±0.828 in the ketamine group and 1.29±0.610 in the control group, which was a significant difference (3±1.358) .P<0.374). Only in 1.33% of the ketamine group was delirium seen in the recovery room. In neither group did patients need readmission after discharge.16 point 67 percent of the ketamine group and 23.33% of the control group needed analgesic in the recovery room, but the difference was not significant (The results of this study showed that pain levels experienced a falling trend on both the Oucher Scale and CHEOPS after the operation. On the CHEOPS, the average pain level 120 minutes after the surgery was lower in the intervention group than in the placebo group. On the Oucher Scale, the average pain level 120 minutes after the surgery was also lower in the ketamine group than in the control group.Safavi et al also showed in their study that low-dose single peritonsillar injection of ketamine postponed the need for painkillers postoperatively and caused significant pain relief effects on the first day after the surgery . Dal et Certain studies have shown that the positive effects of ketamine have persisted a few days after the surgery. Persistent effects of ketamine are caused by its effect on reducing secondary hyperalgesia and/or on preventing the spread of central sensitivity to peripheral pain .There were no postoperative cases of apnea or laryngospasm in the ketamine group. Ketamine does not restrain the swallowing or pharyngeal reflexes, and stimulates the respiratory system by increasing the respiratory volume and rate of respiration .Studies have shown that the preoperative administration of an NMDA receptor antagonist reduces the swallowing pain in adults after tonsillectomy .In a large scale study on 1026 patients, pain levels in the ketamine group were shown to be lower than in the control group and patient satisfaction to be more . In someAcute administration of narcotics may lead to delayed hyperalgesia which in turn results in the hyperactivity of NMDA receptors, activated by the narcotic stimulation, which may cause severe, acute pain. By blocking NMDA receptors, ketamine restrains this hyperalgesia and increases the duration and intensity of the pain relief induced by the narcotic .Low doses of ketamine do not delay regaining consciousness; therefore, low-dose IV administration of ketamine in children undergoing tonsillectomy under general anesthesia reduces the postoperative pain .The control group experienced more vomiting in the recovery room, but the difference was not significant. Nausea and vomiting were not major problems in the intervention and control groups, either , while PThe need for analgesics was lower in the ketamine group than in the control group, but the difference was not significant. In the study by Marzban et al, the time of the first administration of the analgesic was longer in the ketamine group than in the control group, and the control group needed more peptide analgesics .The limitations of this study were pain assessment in children and that the follow-up period spanned only the first 24 hours. In this study, the quantity and the dose of the ketamine injected in the tonsils were lower and slower than those injected IV. Therefore, it did not have sedative effects and the nausea and vomiting were less. We could not measure and study the serum levels of ketamine and norketamine after the peritonsillar injection; thus, we cannot say with certainty that the analgesic effects of this drug two hours later were due to its systemic absorption. The cultural differences among the patients may have also influenced the results of the study.Low-dose peritonsillar injection of ketamine before tonsillectomy reduces the swallowing pain and postoperative pain in children. The most likely explanation for the pain relief following the peritonsillar injection of ketamine is desensitization of the central nervous system to pain impulses. It is suggested that the onset and quality of oral feeding be investigated in future studies.


Chronic pain is one of the most common health complaints in industrial nations. For example, chronic low back pain (cLBP) disables millions of people across the world and generates a tremendous economic burden. While previous studies provided evidence of widespread functional as well as structural brain alterations in chronic pain, little is known about cortical changes in patients suffering from lumbar disc herniation. We investigated morphometric alterations of the gray and white matter of the brain in patients suffering from LDH. The volumes of the gray and white matter of 12 LDH patients were determined in a prospective study and compared to the volumes of healthy controls to distinguish local differences. High-resolution MRI brain images of all participants were performed using a 3 Tesla MRI scanner. Voxel-based morphometry was used to investigate local differences in gray and white matter volume between patients suffering from LDH and healthy controls. LDH patients showed significantly reduced gray matter volume in the right anterolateral prefrontal cortex, the right temporal lobe, the left premotor cortex, the right caudate nucleus, and the right cerebellum as compared to healthy controls. Increased gray matter volume, however, was found in the right dorsal anterior cingulate cortex, the left precuneal cortex, the left fusiform gyrus, and the right brainstem. Additionally, small subcortical decreases of the white matter were found adjacent to the left prefrontal cortex, the right premotor cortex and in the anterior limb of the left internal capsule. We conclude that the lumbar disk herniation can lead to specific local alterations of the gray and white matter in the human brain. The investigation of LDH-induced brain alterations could provide further insight into the underlying nature of the chronification processes and could possibly identify prognostic factors that may improve the conservative as well as the operative treatment of the LDH. Chronic low back pain (cLBP) disables millions of people across the world and generates a tremendous economic burden. Recent studies estimated the direct and indirect costs of back pain up to $624.8 billion The adult brain has a remarkable capacity for morphological alterations following learning and adaption processes to a changed environment The study was approved by the Local Ethics Committee of the Medical Faculty of the University of Magdeburg in compliance with national legislation and the Code of Ethical Principles for Medical Research Involving Human Subjects of the World Medical Association (Declaration of Helsinki).The study comprised two groups: 12 patients (mean age 43.9±12.9 years) with chronic low back pain were enrolled in the study. The individual duration of the back pain exceeded at least 3 month. All patients were diagnosed with isolated lumbar disc herniation either at the level L4–5 or L5-S1 using spinal MRI. The second group consisted of 12 age- and gender-matched subjects and served as control group. No member of the control group had suffered from any back pain or neurological disorder. All participants gave their informed written consent. All subjects were neurologically examined prior to the MR imaging. The current mean level of back pain was quantified with the visual analogue scale (VAS).3.MR imaging was performed on a 3 Tesla Siemens Magnetom Trio scanner  using an 8-channel phased array head coil. A high-resolution anatomical dataset of the entire brain was acquired using a T1-weighted magnetization prepared rapid gradient echo (MPRAGE) sequence  resulting in an isotropic resolution of 1 mmMRI data was analyzed using the voxel-based morphometry toolbox VBM8  implemenDifferences of the GM and WM between both groups were estimated using a univariate voxel-based two-sample-t-test. The GM and WM volumes were compared as absolute units. In order to allocate the cytoarchitectonic reference the anatomical SPM toolbox by Eickhoff et al. The control group reported a mean pain intensity of 0 and the neurological examination revealed no neurological deficits. LDH patients reported a mean pain intensity level of 7.2±0.9 ranging between 6 and 8. All patients suffered from low back pain and sciatica that radiated at least into one leg in a classic dermatomal distribution. In all patients, the pain was accompanied by numbness and tingling for at least 3 month. However, the clinical examination revealed no muscle weaknesses in any of the patients. The MRI examination of the spine discovered lumbar disc herniation at the level L4–5 in 5 patients and at the level L5-S1 in 7 patients.The examination of the T1-weighted MRI data of all subjects revealed no pathological brain alterations. Using voxel-based morphometry The present findings are consistent with most morphometric studies investigating structural brain plasticity in patients suffering from chronic pain Interestingly, no GM and WM changes were found in the primary somatosensory cortex. While short lasting pain leads to substantial increase of the gray matter in the somatosensory cortex The current study has some limitations that need to be addressed. The nature of cross-sectional studies allows only limited conclusions on the dynamic pattern of the observed cerebral changes. Despite the significant structural differences between the LDH patients and the healthy control group the VBM analysis cannot account for the underlying cytoarchitectonic reasons. Thus, a variable size of cells, increased or decreased synaptogenesis or an altered number of astro- and microglia might account for the GM and WM changes found


Musculoskeletal pain is a common symptom in childhood and in a few cases is the initial sign of a severe disease such a chronic inflammatory disease or a malignancy.To identify the predictive factors for malignancies in children presenting with musculoskeletal pain, and ultimately diagnosed to have JRA or malignancy.Patients and methods: it is a retrospective case-control chart review study examining data from the initial visit of all the patients referred to our Department for musculoskeletal pain during the period January 2001–December 2010 and then diagnosed with a tumour or with JRA. The value of given diagnostic test as a predictive factor for neoplasia in comparison to JRA, were assessed by calculating its sensitivity, specificity, positive predictive value, negative predictive value.No significant difference was found for sex, age and pattern of pain. Fever and lymphadenopathy were more frequent in children with neoplasia. Elevation of CRP and of ESR and an abnormal platelet count were not relevant parameters. Anaemia and an abnormal neutrophil count were most frequent among patients with tumours.High LDH level presents with a higher frequency and a statistically significant difference (sensitivity 88% and specificity 32.6%) among the tumours group and resulted a useful predictive factor for tumours, with high sensitivity.Our results suggest to take into great account even “soft” changes in the neutrophil count particularly if it is associated to a low Hb level, and to evaluate LDH that, if associated to other abnormal laboratory data should require to go thoroughly into the analysis to always exclude a malignancy.


Brief cessation advice delivered to smokers during routine primary care consultations increases smoking cessation rates. However, in previous studies investigating recall of smoking cessation advice, smokers have reported more advice being received than is actually documented in their medical records. Recording of smoking cessation advice in UK primary care medical records has increased since the introduction of the Quality and Outcomes Framework (QOF) in 2004, and so we compare recall and recording of cessation advice since this time to assess whether or not agreement between these two data sources has improved.For each year from 2000 to 2009, the proportion of patients in The Health Improvement Network Database (THIN) with a recording of cessation advice in their notes in the last 12 months was calculated. In 2004, 2005 and 2008, these figures were compared to rates of patients recalling having received cessation advice in the last 12 months in the Primary Care Trust (PCT) Patient Surveys, with adjustment for age, sex and regional differences between the populations.In 2004 there was good agreement between the proportion of THIN patients who had cessation advice recorded in their medical records and the proportion recalling advice in the Patient Survey. However, in both 2005 and 2008, more patients had cessation advice recorded in their medical records than recalled receiving advice.Since the introduction of the QOF, the rate of recording of cessation advice in primary care medical records has exceeded that of patient recall. Whilst both data sources have limitations, our study suggests that, in recent years, the proportion of smokers being advised to quit by primary care health professionals may not have improved as much as the improved recording rates imply. The delivery of brief smoking cessation advice during routine general practice consultations, a simple intervention usually lasting no more than one or two minutes, has been shown to be effective in increasing cessation rates, and is The introduction of the Quality and Outcomes Framework (QOF) in April 2004 provided, for the first time, a financial incentive for GPs to document in smokers' medical records that they have been offered cessation advice, worth approximately £4,500 to each general practice per year[The Health Improvement Network (THIN) is a database containing the electronic primary care medical records of almost seven million patients from 446 general practices throughout the UK, and is broadly representative of the UK population in terms of patient demographic characteristics documentThe Primary Care Trust (PCT) Patient Surveys monitor patients' experiences of NHS services. In 2004Previous work using the Patient Survey has shown that the provision of smoking cessation advice by primary health care professionals varies with patient sex and age. ConsequThis study was approved by the Leicestershire and Rutland Research Ethics Committee.All analyses were completed using STATA version 11.0 .The number of patients aged 16+ registered with a THIN practice in England increased from 1.8 million in July 2000 to 2.0 million in July 2009. At each index date, 49% of patients were male, with a mean age of 47 years (interquartile range 32-61). Figure The proportion of THIN patients with cessation advice documented in their medical records increased considerably over the study period, from 1.2% of patients in 2000 to 10.9% in 2009, with the majority of this increase occurring between 2003 and 2005. However, although similar in 2004, the predicted recall rate was subsequently lower and increased less over the survey period . In 2004 there was good agreement between recording of cessation advice in THIN and predicted recall rates, but in both 2005 and 2008 agreement between recorded and predicted recall of cessation advice was much less strong with recall rates being much lower.This study is, to our knowledge, the first to compare, at a population-level, smoking cessation advice recorded in medical records with patients' recall of such advice as reported in large surveys; in 2004 there was close agreement between both data sources but this decreased substantially in 2005 and 2008.Some of the longitudinal changes in the proportions of patients recalling cessation advice, or having this documented in their medical records, may be due to changes in population smoking prevalence. Ideally, this study would have assessed recorded and recalled advice within smokers only, but the ability to confidently identify smokers in THIN was poor in the early years of this analysis and it wtried to get help to quit smoking from local health care services rather than whether they had received cessation support at their GP surgery). One explanation for the findings reported here is that patients' propensity to recall advice may have changed over time - in the latter years of this study patients may simply have found cessation advice from health care professionals less memorable. However, for diminished recollections of advice to explain findings, patient recall would have to have diminished quite substantially in a very short period, so it seems likely that other reasons account for the difference.This study is limited by a lack of data on patients' recall of smoking cessation advice prior to 2004 . However, this manuscript has not been discussed with any third parties.LS conceived the study, performed the statistical analyses and wrote the first draft of the manuscript. All authors contributed to its critical revision and approved the final version.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/291/prepub