Multidimensional scores did not consistently match the QST parameters in patients with a lumbar disc herniation. Commonly used clinical scores in spine research show low or no correlation with QST. Nevertheless, mechanical thresholds seem to play an important role to detect and follow up a sensory deficit investigated by QST.The improvement of pain and functionality is the major goal of a surgical intervention. Thus, the purpose of the present prospective study was to evaluate whether subjective sensory deficits in patients with lumbar radiculopathy caused by a lumbar disc herniation are related to clinical status, using several outcome scores and the quantitative sensory testing (QST) pre- and 12 months postoperatively. We applied the QST in 52 patients with a single lumbar disc herniation treated by lumbar sequestrectomy pre- and 12 months postoperatively. Further evaluation included numeric rating scale (NRS) for leg, EuroQoL-5D (EQ-5D), Core Outcome Measure Index (COMI), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI) and PaindDetect questionnaire (PD-Q). Patients were then categorized into two groups based on their subjective recovery of sensory function. The patients’ self-assessment and QST were correlated with each other for the pre- and postoperative visit after 12 months. The two groups showed postoperative differences in mechanical and vibration detection threshold as well as in the postoperative PD-Q ( Due to the high prevalence of spinal degenerative diseases, the frequency of surgical interventions for degenerative spine pathologies rose dramatically within the last decade , 13. TheIn the past decades, quantitative sensory testing (QST) gained popularity as a diagnostic tool to quantify pain and assess sensory function, especially to document a treatment’s effectiveness , 19–21. The improvement of pain and functionality is the major goal of a surgical intervention. Moreover, it is important to assess the patient’s postoperative improvement accurately, so that new diagnostic and therapeutic interventions can be applied when needed. Thus, the purpose of this prospective study was to evaluate whether quantitative pain sensation in patients with lumbar radicular pain caused by a lumbar disc herniation is related to clinical status and various outcome scores as well as QST pre- and 12 months postoperatively.The study was purely observational, and there were no recommendations for additional diagnostic measures or interventions. Pain management was not delayed or altered by participation in this study. All subjects signed the informed consent form. The study was approved by the Local Ethics Committee in accordance with the ethical principles originating from the Declaration of Helsinki and in compliance with Good Clinical Practice. Patients were considered for inclusion if they had a single-level disc herniation confirmed on MRI, pain and a sensory deficit described as numbness in the corresponding nerve root distribution area of L3 to S1. All patients had an indication for sequestrectomy according to the guidelines of DGNC and DGOOC. No previous back surgery has been performed in any of the patients. None of the included patients presented a history of peripheral nervous system disorders. Neither metabolic nor toxic damage to the peripheral nerves was revealed. All data were recorded the day before surgery and 12 months postoperatively.The QST was performed pre- and postoperatively by a single investigator. Patients were not distracted during the testing and were given clear and identical instructions. The thermal tests were performed using a Sensory Analyzer TSA-II . Cold and warm detection thresholds were measured first  then cold pain and heat pain thresholds . The mechanical detection threshold (MDT) was measured with a standardized set of modified von Frey hairs  that exert forces upon bending between 0.25 and 512 mN. The vibration detection threshold (VDT) was performed with a Rydel-Seifer tuning fork . The mechanical pain threshold (MPT) was measured by a custom made pinprick set with forces from 8 to 512 mN. Mechanical pain sensitivity (MPS) was assessed using the same pinprick stimuli to obtain a stimulus response function for pinprick evoked pain. A pressure gauge device  was used to measure the pressure pain threshold (PPT) , 15.Standardized spine outcome measures were prospectively evaluated in this study: 1) the numeric rating scale (NRS) for leg pain on a 0–10 rating scale, with higher scores indicating worse pain . (2) The the numet test, Mann-Whitney U test and Fisher’s exact test were used to analyse differences in clinical and demographic characteristics and in clinical outcome variables. Spearman’s rho correlation was performed to assess the relation of patients’self-assessment on pain and QST variables. A p value <0.05 was considered statistically significant. All statistical computations were performed with SPSS version 21.0 . Figures were designed using GraphPad Prism .All patients with a complete preliminary examination were considered for inclusion into the cohort. All values were expressed as mean ± SD. The Kolmogorov-Smirnov test was used for testing normal distribution. The unpaired Student’s The preoperative assessment was compared with the postoperative visit after 12 months.The patients were categorized into two groups based on their subjective recovery of sensory function (incomplete (persisting hypaesthesia) vs. complete restoration of sensation). Pre- and postoperative assessment was compared as well as any improvement or deterioration during the postoperative course of 12 months.The patients’self-assessment and QST parameters were correlated with each other for the pre- and postoperative visit after 12 months.Statistical evaluations were carried out for the following conditions:Fifty-two patients, 31 men and 21 women, with a single lumbar disc herniation causing lumbar radiculopathy and a sensory deficit, were prospectively included in the trial. The loss to postoperative 6 months follow-up was 1.9 % and to 12 months follow-up was 3.8 %. A recurrent disc herniation occurred in nine (17.3 %) patients, while an accidental durotomy occurred in one patient. These patients were excluded from further statistical analysis as these factors could have influenced the outcome data. Therefore, 38 patients were thus analysed after 12 months follow-up.The patients’ postoperative course after treatment with lumbar sequestrectomy was assessed using both patients’ self-assessment by different scales and scores and QST parameters. Three stages were observed:p = 0.000). CDT (24.4 °C (±5) vs. 27.8 °C (±2)), MDT (16.5 mN (±18) vs. 9.2 mN (±22)), MPS (1.5 (±2) vs. 2.4 (±2)), VDT (5.5 Hz (±2) vs. 6.6 Hz (±1)) and PPT (6.7 kg (±2) vs. 8.1 kg (±2)) improved from baseline to 12 months follow-up (p < 0.005).Firstly, patients’ self-assessment and QST parameters demonstrated changes in the patients’ condition during the postoperative follow-up period of 12 months. Lumbar sequestrectomy resulted in a dramatic reduction of leg pain at rest (NRS 6.0 ± 2 vs. 0.8 ± 2) postoperatively (p > 0.05). Twelve months postoperatively, the patients were categorized into two groups based on their subjective sensory rating , but there were no differences in preoperative QST values between groups A and B (p > 0.05). Postoperatively, CDT, MDT, MPS, VDT and PPT improved significantly after surgery in group B, but in group A, an improvement was only measured in CDT, MDT and MPS, respectively (p < 0.05) . Differences between group A and B were assessed in the PD-Q 12 months postoperatively (group A: 7.8 (±5) vs. group B: 4.0 (±4); p < 0.005).Secondly, the patients were asked for the subjective sensory improvement 1 week, 6 and 12 months postoperatively. There have been no differences between patients with and without subjective sensory deficits after 1 week and 6 months postoperative (5) Figs. . The patp < 0.05). NRS for leg correlated significantly with ODI, EQ-5D and COMI preoperatively (p < 0.05). Postoperatively, EQ-5D, EQ-5D VAS, COMI, PD-Q and ODI showed a significant correlation with NRS for leg (p < 0.05).In the third stage, the pre- and postoperative examinations were then correlated with each other Tables  and 3. AWe investigated whether common multidimensional scales and self-reported sensory deficits described as numbness in patients with lumbar radiculopathy are associated with the corresponding QST parameters. Patients demonstrated a postoperative difference in the mechanical perception thresholds according to their postoperative sensory rating. Additionally, postoperative PD-Q showed a significant difference between patients whose sensory deficits recovered and those deficits remained. In contrast, multidimensional scores did not consistently match the QST parameters in patients with a lumbar disc herniation.It continues to be challenging to assess the patients’ subjective pain and sensation and the extent of pain and of a sensory deficit in an objective and quantitative fashion. Multidimensional scales and scores are used to convey the subjectiveness of pain and sensation into objective quantities in order to measure the success of a surgical intervention or any deterioration after surgery . TherebyIt is conceivable that numerous factors like pain-related psychological variables account for the variability in pain intensity or disability. Especially depression is an important factor which influences pain and function after surgery . TherefoThe PD-Q was originally developed and validated as a screening tool to identify patients with neuropathic pain. QST is a valuable tool to obtain reliable quantitative measures of the presence of positive sensory signs such as allodynia and mechanical or thermal hyperalgesia, as well as negative signs like numbness . ParticiAlthough there was no correlation between QST values and the PD-Q, it seems that QST values are reflected by responses to verbal descriptors from the PD-Q.According to the postoperative sensory rating, patients could be categorized in two groups. Upon investigation, there was an improvement in both groups, but still, there was a significant difference in VDT and MDT postoperatively. Thus, our results clearly indicate that mechanical perception thresholds are sensitive and clinically useful parameters, which give quantitative data that may be used in the follow-up of recovery of a sensory deficit .Strengths of our study include the use of the validated, standardized comprehensive DFNS QST protocol, which enables identification of a sensory abnormality within individuals. Furthermore, we are able to present a homogenous study population, while we excluded individuals with major depression or chronic pain/neurological disorders. However, the high loss of follow-up, the small patient cohort and missing control group are the limitations of our study. The fact that there was no correlation between the varying outcome parameters and QST may be especially attributed to the low patient number.QST is a structured psychophysical test machinery that is a useful method to differentiate altered sensory and increased pain in patients with lumbar radiculopathy caused by a lumbar disc herniation. Commonly used clinical scores in spine research show low or no correlation with QST parameters. NRS, ODI and EQ-5D are measurements that emerged over the years to assess outcomes because they best reflect the interests of physicians and patients as it concerns current functional status and outcome. Nevertheless, mechanical thresholds like MDT and VDT seem to play an important role to detect and follow a sensory deficit.


Recent studies have confirmed the existence of neuropathic pain (NeP) components in patients with musculoskeletal disorders. However, the presence of NeP in patients with rotator cuff tears has not been investigated thus far. Therefore, we studied the prevalence of NeP and the prognostic factors for NeP in patients with rotator cuff tears.U test. For multivariate analysis, forward stepwise regression was performed using factors that demonstrated statistical significance in the univariate analysis.Data were collected from 110 patients with rotator cuff tears, diagnosed by physical examination and magnetic resonance imaging, who attended an outpatient clinic between August 2013 and August 2014. The measured parameters included visual analog scale (VAS) pain scores, painDETECT questionnaire (PDQ) responses, a physical examination, and magnetic resonance imaging. To evaluate the factors associated with NeP, we performed a two-stage analysis. For univariate analysis, we used the Mann-Whitney n = 12; 10.9 %), possible NeP group , and a nociceptive pain (NoP) group . In the univariate analysis between the NeP group and NoP group, NeP was affected by sex (p = 0.034), VAS score , and positive Neer and Hawkins impingement signs (p = 0.039). In the multivariate analysis, VAS score (p = 0.031) was an independent prognostic factor for NeP.Patients were classified into three groups according to their PDQ score: an NeP group  was a prognostic factor for NeP. Clinicians should remain vigilant for heterogeneous etiologies of pain in patients with rotator cuff tears. Rotator cuff tear is one of the major causes of pain and dysfunction of the shoulder in the middle-aged population. According to a recent epidemiological study, the prevalence of rotator cuff tears was found to be 20.7 % in the general population, with a mean age of 58 years , and increased with age . RotatorThe primary etiology of pain in musculoskeletal disorders is mechanical stimulation and inflammation . HoweverThis study was conducted in accordance with applicable laws and regulations, including the guidelines of the Declaration of Helsinki for human experimentation. All patients provided written informed consent and the protocol and informed consent forms were approved by the local institutional review board . Two hospitals  participated in this study and used the same protocol.The inclusion criteria were as follows: patients with (1) shoulder pain, and (2) rotator cuff tear on magnetic resonance imaging (MRI) scan. The exclusion criteria were as follows: (1) moderate or severe joint degeneration according to the radiographic classification established by Samilson and Prieto  and muscPatients who enrolled in this study were selected from a source population of outpatients who attended one of the two participating hospitals for the treatment of shoulder pain between August 2013 and August 2014. Clinical assessment consisted of a structured interview, completion of the PDQ, a visual analog scale (VAS) for pain, a detailed physical examination, plain radiographs, and MRI scans. Among the 133 patients who met the inclusion criteria, 23 patients were excluded, leaving 110 patients enrolled in the study , was used to evaluate the current pain experienced at the initial visit, the most severe pain experienced during the past 4 weeks, and the average pain experienced during the past 4 weeks.Range-of-motion assessment included the measurement of forward elevation, lateral/scapular elevation, external rotation with the arm at the patient’s side, and internal rotation behind the back, which was recorded as the highest vertebral spinous process attained. Manual muscle tests for strength and Neer and Hawkins impingement tests were performed, as well as supraspinatus , infraspAnteroposterior and axillary (West Point) radiographs and MRI scans were obtained for all symptomatic shoulders.The size of the rotator cuff tear was established based on the extent of the tear in the anteroposterior direction as measured in a sagittal oblique plane on T2-weighted MRI. Tears were then classified into 5 grades: partial , small (<1 cm), medium (≥ 1 cm and < 3 cm), large (≥ 3 cm and < 5 cm), and massive (≥ 5 cm). When a fluid-equivalent signal was visible or when the tendon could not be visualized in at least one section of a fluid-sensitive sequence, a full-thickness rotator cuff tear was diagnosed. MRI studies were also evaluated to assess the specific location of the rotator cuff tear. The presence of fluid in the glenohumeral joint and subacromial space was also evaluated in the coronal oblique plane on T2-weighted MRI to detect hydrarthrosis.U test for univariate analysis. For multivariate analysis, logistic regression with a forward stepwise technique was performed using factors that demonstrated statistical significance in the univariate analysis. A P value of < 0.05 was considered statistically significant. Power analyses were performed with EZR  [To assess the association between pairs of qualitative variables, we used the Mann-Whitney , Japan) , which iTwelve patients (10.9 %) were classified into the NeP group (score ≥ 19), 33 patients (30.0 %) into the possible NeP group (score 13 to 18), and 65 patients (59.1 %) into the NoP group (score ≤ 12) (Table p = 0.034), and the mean VAS score (average pain during the past 4 weeks) was significantly higher in the NeP group than in the NoP group (p = 0.013). Other demographic data, including age, history of trauma, and duration of symptoms, did not differ significantly between the groups . Other physical examination results, including the supraspinatus, infraspinatus, lift-off, and belly press tests, did not differ significantly between the groups  than in the NoP group  whereas NeP was not affected by sex or the results of the Neer and Hawkins impingement tests , sex, and the results of the Neer and Hawkins impingement tests. The VAS score (average pain during the past 4 weeks) was found to be an independent prognostic factor for NeP  . Inflammn = 411) of patients with chronic pain who were recruited from 10 specialized pain centers [This study has several limitations. First, the reliability of the PDQ for identifying NeP in patients with rotator cuff tears has not been assessed thus far. However, the original validation study included a large sample  was a prognostic factor for NeP in these patients. This is a novel approach to an important subject and will hopefully encourage future research on the topic of neuropathic shoulder pain in patients with rotator cuff tears, as there is currently a paucity of information. We believe that the creation of an animal model with NeP and rotator cuff tears is needed to clarify the etiology of NeP in patients with rotator cuff tears. Our results indicate that clinicians should remain vigilant for heterogeneous etiologies of pain in patients with rotator cuff tears.


Background: Minimally invasive cosmetic procedures are the most commonly performed aesthetic techniques by plastic surgeons. Patients are interested in a pain-free experience. Surgeons desire patient satisfaction and time-efficient utilization of office staff and resources. Clinical evidence exists for use of vapocoolant technology to reduce pain associated with intravenous cannulation in the pediatric population and in hemodialysis patients. Applying vapocoolant technology to facial rejuvenation is a novel approach to decrease pain associated with neurotoxin or filler injection. Methods: A randomized, prospective study was conducted, testing 15 subjects receiving filler injections and another 15 patients receiving neurotoxin injections using a split-face model. The vapocoolant spray used was composed of a 95:5 ratio of 1,1,1,3,3-pentafluoropropane and 1,1,1,2-tetrafluoroethane. Within each group, individual patients randomly received injection (filler or neurotoxin) alone versus injection (filler or neurotoxin) plus vapocoolant on an equivalent half of his or her face. An independent examiner recorded from each patient on a scale of 1 to 10 perceived pain for injection alone versus injection plus vapocoolant spray. Results were calculated as a percentage change of pain scores experienced after injection for each person between the control (nonvapocoolant) and treatment (vapocoolant) sides of the face. Results: Vapocoolant spray at the time of cosmetic facial injections leads to a 59% decrease in perceived pain score with neurotoxin injections  and 64% decrease in perceived pain score with filler injections . These results were statistically significant with P < .05. Conclusion: Vapocoolant spray reduces pain associated with facial rejuvenation procedures. Minimally invasive cosmetic procedures are the most commonly performed aesthetic techniques by plastic surgeons and continue to increase in popularity. In 2016, 4.6 million botulinum toxin type A neurotoxin  and 2.5 million soft-tissue dermal filler  injection procedures were performed.1,3-7-Patients desire a pain-free experience. The anticipated and procedural pain of injection of neurotoxin and dermal fillers is of concern and anxiety to patients.2Few studies have explored the potential of vapocoolant spray for facial neurotoxin and filler injection analgesia. To date, 2 split-face control studies have been published analyzing the effectiveness of vapocoolant spray for botulinum toxin type A injections. A 2009 nonblinded study of 52 patients by Weiss and LavinWe present the first randomized, prospective, split-face model study to analyze the efficacy of vapocoolant spray for decreasing the pain of both neurotoxin and dermal filler facial injections.Institutional review board approval was obtained from the University of Louisville School of Medicine. Male and female English-speaking literate volunteers aged 22 to 66 years who were either naive to or had prior exposure to neurotoxin or filler injections were studied. Subjects enrolled in other clinical studies or having consumed any narcotic medications within 48 hours of participation were excluded. The data collection sheet is demonstrated in t test.A randomized, prospective study was conducted testing 30 total people, with 15 patients receiving filler injections and another 15 patients receiving neurotoxin injections using a split-face model. The vapocoolant spray used was composed of a 95:5 ratio of 1,1,1,3,3-pentafluoropropane and 1,1,1,2-tetrafluoroethane. Within each group, subjects received in random order either the injectable corresponding to their group alone as a control or the injectable used in conjunction with the vapocoolant spray. Therefore, each patient randomly received injection (filler or neurotoxin) alone versus injection (filler or neurotoxin) plus vapocoolant on an equivalent half of his or her face. An independent examiner recorded from each patient on a pain scale of 1 to 10  for injection alone versus injection plus vapocoolant spray. The results were then calculated as a percentage change of pain scores experienced after injection for each person between the control (nonvapocoolant) and vapocoolant sides of the face. Statistical significance was calculated using the paired 2-tailed Average patient age for filler was 50.33 years  and for neurotoxin was 39.53 years . Six of 15 patients receiving fillers were filler naive. Seven of 15 receiving neurotoxin were neurotoxin naive.P = .0002). The average pain score for filler injection decreased from 4.3 without spray to 1.57 with spray (P = .00006). Nine of 15 patients receiving neurotoxin treatment reported pain scores of 0 to 1 with vapocoolant spray. Eight of 15 patients receiving dermal filler reported pain scores of 0 to 1 with vapocoolant spray  and 64% decrease in perceived pain score with filler injections . These results were statistically significant at P < .05 .Maximizing patient comfort is important to patient satisfaction with all procedures. This is particularly true with elective cosmetic procedures. To provide patient satisfaction with cosmetic injections, several patient values must be considered: the ability to fit treatments into a busy schedule; instant pain relief; and reduced anxiety over injections. The use of an efficacious, cost-effective, fast-acting analgesic technique is thus essential to deliver pain-free facial rejuvenation. Vapocoolant spray is ideal because it is quick and cost-effective, provides adequate pain relief, and yields patient satisfaction. This allows surgeons the efficiency and capacity to treat more patients, utilize cutting-edge technology to benefit patient care, reallocate clinical staff for other priorities, and spend more time on more profitable clinical procedures.,15,Each form of local anesthesia has inherent benefits and disadvantages. Vapocoolant is a compressed liquid form of halogenated alkanes that upon decompression and exposure to the warm skin environment changes to vapor. Upon skin contact, the phase change from liquid to vapor causes an endothermic reaction that cools the skin. The drop in temperature decreases the conduction velocity of A-δ and C nerve fibers and dampens pain signals.8-Ice is cheap, readily available, and easy to use. Its analgesic and vasoconstrictive properties have been known for centuries, and multiple studies have analyzed its effectiveness for neurotoxin injection analgesia.18,20,9,23,EMLA, or eutectic mixture of local anesthetics, is a topical anesthetic cream composed of 2.5% lidocaine and 2.5% prilocaine that is demonstrated to be an effective analgesic for neurotoxin injections.18,Vibration therapy has been shown to reduce pain for cosmetic facial dermal filler and neurotoxin injections.4,3,Other forms of anesthesia commonly used for dermal fillers includes spot contact cooling systems, local anesthetic, and the combination of anesthetic with filler.3The application of vapocoolant spray is safe and local and provides instant relief from anxiety and pain of injection. Our study is the first to look at vapocoolant spray for pain control for both neurotoxin and dermal filler cosmetic injections. Using a split-face model, each patient randomly received injection (filler or neurotoxin) alone versus injection (filler or neurotoxin) plus vapocoolant on an equivalent half of his or her face and a blinded investigator collected the data of the patient's perceived pain score.Pain is a subjective experience. Consequently, truly objective data cannot be obtained for perceived pain scores. It is not possible to control for how anticipated pain and anxiety may affect reported pain scores. Individuals may over- or underestimate their perceived pain. Although the patient feels which side receives vapocoolant spray, a placebo-like effect may influence the results. However, the tendency for individuals to over- or underestimate pain is likely balanced out in the aggregate analysis. Because it is difficult to standardize perceived pain between individuals, the individual pain scores were converted to the percentage change of perceived pain for each individual to further balance out the variability among subjects. Our aggregate analysis showed statistically significant decreases in pain of 59% and 64% for neurotoxin and dermal filler injections, respectively, when patients were treated with vapocoolant spray. There was no statistical difference in pain scores between patients who were naive to facial injection procedures and those who had prior experience(s). Our results demonstrate the vapocoolant anesthesia spray to provide statistically significant improvements in pain control during neurotoxin and dermal filler cosmetic injections.We present the first randomized, prospective, split-face study to analyze vapocoolant spray for pain control for both neurotoxin and dermal filler cosmetic injections. Our results demonstrate vapocoolant spray to provide statistically significant pain reduction for facial rejuvenation injections. Vapocoolant spray overcomes the shortcoming of other local anesthetic methods, as it is easy to use, acts instantly, does not distort the injection site, and is cost-effective. The use of an efficacious, cost-effective, fast-acting analgesic technique is essential to deliver pain-free facial rejuvenation. Our study demonstrates vapocoolant spray to meet these criteria to provide optimal pain relief and patient satisfaction for neurotoxin and dermal filler facial rejuvenation injections.


One of the most important reasons for postoperative pain is the extrusion of debris from the apical foramen during preparation and shaping of root canals. The aim of this clinical trial was to evaluate the severity of postoperative pain with the use of two different engine-driven NiTi systems. n=45), and root canal cleaning and shaping was done using either RaCe or Reciproc instruments. The severity of postoperative pain was determined with visual analogue scale (VAS) at 4-, 12-, 24-, 48- and 72 h and 1-week intervals and postoperative pain was compared between the two groups. The chi-squared test and repeated-measures analysis were used to compare the data between the two groups. Ninety mandibular molars were randomly divided into two groups (P<0.001). Based on the results of the statistical analyses, the two groups were matched regarding the age and gender, with no significant differences. In addition, except for 4- and 24-h and 1-week intervals, postoperative pain was significantly less in the RaCe group compared to the Reciproc group (Based on the results of the present study, use of RaCe files for cleaning and shaping of root canals in necrotic mandibular molars resulted in less severe postoperative pain compared to Reciproc files. The incive pain . Despite the limitation of root canal treatment procedures to the apical end of the root canal, the extrusion of some root canal debris into the periapical area, do occur . In spit° is completed in several reciprocating movements. The reciprocating movement relieves stress on the instrument and, therefore, reduces the risk of cyclic fatigue. At the same time, reciprocation ensures that the instrument stays centered in the canal [In order to facilitate the root canal therapy procedure and decrease the chair time, some engine-driven single-instrument NiTi systems with the use of a new NiTi alloy, referred to as M-wire, are introduced that prepare the root canal system with a reciprocal back-and-forward motion with a speed of 300 rpm (150 degrees counterclockwise and then 30 degrees clockwise). The Reciproc instruments  available at three different sizes and tapers; R25 (25/0.08), R40 (40/0.06) and R50 (50/0.05) -9. In rehe canal .The advantage of reciprocating movements over rotary movements is that there are lower risks of file fracture due to the continuous rotation at canal curvature areas; however, these movements have some disadvantages such as limited cutting efficacy, the need for the application of more force toward the root apex and lower ability to remove debris from the root canal . In rootα=0.05, study power of 80% and an acceptable level of difference in pain severity, the final sample size was estimated to be 90 samples (n=45). The study was carried out on patients referring to the Department of Endodontics, Tabriz Faculty of Dentistry during one year (from November 2013 to November 2015). All the patients who were eligible to be included in the study signed an informed consent form. In this double-blind clinical trial, the frequency and severity of postoperative endodontic pain were evaluated and compared between two groups of subjects who underwent root canal treatment with RaCe  and Reciproc  systems. The protocol of the study was approved by the Ethics Committee of Tabriz University of Medical Sciences (Grant No.: TBZMED.REC.1394.659). A pilot study was carried out with 5 samples to determine the samples size because no similar study was available when the research plan was proposed. Considering The inclusion criteria consisted of age over 18 years, systemic health, presence of mandibular molars with necrotic pulp, absence of pain before treatment, normal periapical status or radiographic lesions under 2 mm in size, tooth sensitivity to percussion, the capacity of tooth restorability, absence of a sinus tract and absence of periapical abscess or facial cellulitis. The exclusion criteria consisted of systemic diseases, breastfeeding, pregnancy, allergy to lidocaine, healthy pulp, reversible pulpitis, irreversible pulpitis, periapical lesion measuring over 2 mm, absence of lip anesthesia after administration of local anesthesia, pulpal bleeding after pulp exposure, use of analgesics 48-72 h before initiation of treatment, use of corticosteroids one week before treatment, sensitivity to palpation and age under 18 years. Clinical diagnosis of necrotic pulp was established by the absence of response to thermal and electric tests. The pulpal status of each tooth was evaluated with thermal tests consisting of cold test with Green Endo Ice  and heat test with hot gutta-percha and electric pulp tester ; the periradicular status was evaluated with percussion, palpation and preoperative radiographies. Local anesthesia was achieved with inferior alveolar nerve block injection of 2% lidocaine containing 1:80000 epinephrine . After 15 min, the subjects were questioned about the presence of lip numbness. In some cases supplementary injections were used; followed by isolation of teeth with a rubber dam and endodontic access cavity preparation. Then the canal orifices were located and a rubber dam was used for isolation. The root canal path and length were determined with a #15 K-file  and the working length was determined using an apex locator . Then the WL was confirmed with digital radiography using Kodak RVG.The subjects were randomly divided into two groups; in group A, RaCe rotary files  and in group B Reciproc files  were used. RaCe instruments were used in crown-down technique according to the manufacturer’s instructions; with the following sequence: 40/0.10 and 35/0.08 for the preparation of the coronal third of each root canal followed by 30/0.06 in the middle third, 25/0.04 in the apical third and 30/0.04 up to the working length. The final apical size was achieved with 30/0.04 or 35/0.04 file. Reciproc instruments were also used according to the manufacturer’s instructions; R25 (25/0.08) was used for narrow canals and R40 (40/0.06) was used for wide canals.Concomitant with the use of files for cleaning and shaping of the root canals, 17% ethylenediaminetetraacetic acid (EDTA)  in gel-form was used as a lubricant. During all the preparation procedures with both systems, the root canals were irrigated with 30 mL of normal saline using a syringe connected to a 25-guage needle after each file. The needle was inserted into each root canal as far as possible, without binding. Finally the pulp chamber and the root canals were irrigated with 5 mL of 2.5% sodium hypochlorite solution. After the final rinse with normal saline solution, the root canals were dried with paper points and the standard ISO-sized matching master cones were fitted and checked with radiography. Then the root canals were obturated with gutta-percha  and AH-26 sealer , using the lateral compaction technique. A temporary filling material  was placed and the occlusion was checked. Then the patient was referred to the restorative department for the final restoration.Visual analogue scale (VAS) was explained to all the patients orally and in written form so that the patients would be able to mark their pain severity at 4-, 12-, 24-, 48- and 72-h and 1-week postoperative intervals. The following VAS classification was used : 0; no pIt should be pointed out that the patients were not aware of the technique used and the forms were finally analyzed by a blinded clinician. The Statistical Package for Social Science software  was used for statistical analysis of data. The T-test was used to compare quantitative data between the two groups; the chi-squared test was used to compare qualitative data between the two groups. Repeated-measures analysis was used to compare pain severities at different time intervals within each group and between the two groups. Statistical significance was set at 0.05.P<0.001). Based on the results of the same test and also P<0.001). Base on repeated-measures analysis, in both groups the severity of pain decreased significantly from 4 h postoperative interval to 1 week except for the 24-h interval (It is important to prevent pain and inflammation after endodontic treatment. Although very severe post endodontic pain is uncommon, still a notable number of patients complain of mild, moderate and severe pain after endodontic procedures. Although a number of factors, including irreversible pulpitis, preoperative pain and teeth with large periapical lesions, have been reported as predictors of postoperative endodontic pain, it is still possible to avoid it by modifying the root canal therapy technique or at least decrease its severity. One of the most effective techniques to prevent such pain is providing an effective treatment by creating properly cleaned and shaped root canals so that the odds of apical extrusion of root canal contents is minimized. NiTi rotary instruments have become very popular in recent years because they facilitate root canal shaping and decrease iatrogenic errors at the same time; in addition, they are more flexible than manual stainless steel instruments -17.Furthermore, the crown-down preparation technique is a very useful due to decreasing stresses on the rotating instruments and since coronal widening of the root canal facilitates the penetration of the disinfecting solutions into the apical third of the canal,this technique improves root canal debridement , 19. DurIn the present study, single-file reciprocating preparation technique with the Reciproc system resulted in more severe postoperative pain compared to the RaCe system with the crown-down technique and full rotational movement. However, the differences between 4-h and 1-week postoperative intervals were not significant statistically. Since the possible confounding factors such as patients’ age and gender, the tooth type, the type of the background pathologic conditions, the type of the irrigation solution used and the dentist rendering treatment, were similar in both groups, the difference in the severity of postoperative pain can be attributed to the technique/system used for root canal preparation . et al. [To date, few studies have been carried out on this subject. Gambarini et al.  comparedet al. [In a recent study by Pasquilini et al. , the patet al. [According to Gambarini et al. , two poset al. . This reOn the other hand, the Reciproc technique uses a single file with an increased taper, which is directly inserted towards the apex. In the majority of cases, the reciprocating file should be moved to the apex with force in order to reach the working length, which increases the odds of root canal debris being pushed toward the apical foramen. In addition, reciprocating files have lower cutting efficacy compared to rotary files, which increases the frictional force and the need for rotation due to the entanglement of the residual debris within dentin . In addition to the tendency to push the intracanal debris beyond the apex, other factors too, might be involved in increasing pain severity in such patients, including the effect of preoperative pain and the pulpal pathology . For exaIn addition, attention should be paid to differences in classification of pain severity and also differences in evaluated patients -31. For Another important consideration in the present study was the absence of significant differences between the two groups at 4-h and 1-week postoperative intervals. The absence of differences between the two groups shortly after the treatment procedure might be attributed to the effect of local anesthetic agents. On the other hand, as mentioned previously, the principal mechanism of pain in these patients is the extrusion of root canal debris into the surrounding tissues and induction of inflammation and infection, and it appears that 4 h does not provide the adequate opportunity for the appearance of such pain was reported in all the patients in both groups that might confirm the possible mechanisms discussed previously . Consistet al. [This issue draws more attention to the fact that some studies have reported similar success rates for the rotary and reciprocating techniques in eliminating infection. For example, in two studies by Martinho et al. , 37, theBased on the results of the present study; preparing and shaping the root canals in the necrotic mandibular molars with RaCe Rotary systems, resulted in less severe postoperative pain compared to the Reciproc files.


The experience of pain in disorders of consciousness is still debated. Neuroimaging studies, using functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET), multichannel electroencephalography (EEG) and laser-evoked potentials, suggest that the perception of pain increases with the level of consciousness. Brain activation in response to noxious stimuli has been observed in patients with unresponsive wakefulness syndrome (UWS), which is also referred to as a vegetative state (VS), as well as those in a minimally conscious state (MCS). However, all of these techniques suggest that pain-related brain activation patterns of patients in MCS more closely resemble those of healthy subjects. This is further supported by fMRI findings showing a much greater functional connectivity within the structures of the so-called pain matrix in MCS as compared to UWS/VS patients. Nonetheless, when interpreting the results, a distinction is necessary between autonomic responses to potentially harmful stimuli and conscious experience of the unpleasantness of pain. Even more so if we consider that the degree of residual functioning and cortical connectivity necessary for the somatosensory, affective and cognitive-evaluative components of pain processing are not yet clear. Although procedurally challenging, the particular value of the aforementioned techniques in the assessment of pain in disorders of consciousness has been clearly demonstrated. The study of pain-related brain activation and functioning can contribute to a better understanding of the networks underlying pain perception while addressing clinical and ethical questions concerning patient care. Further development of technology and methods should aim to increase the availability of neuroimaging, objective assessment of functional connectivity and analysis at the level of individual cases as well as group comparisons. This will enable neuroimaging to truly become a clinical tool to reliably investigate pain in severely brain-injured patients as well as an asset for research. In the haviours . The terigations . This coigations ,8,9. Sper cortex . This stpathways . By defipathways . Howeverural LIS ,14,15,16Although consciousness is at the centre of human experience and enables our interaction with the world, it largely remains a mystery. The study of consciousness requires a recognition of its multi-level nature. The height of human consciousness involves an awareness of past, present and future, of abstract concepts and of matters which go well beyond the individual in the here and now. This level of functioning also involves processes such as reasoning, memory and language. On the other hand, the most basic level of consciousness, that which Damasio calls “core consciousness”, can be presumed to be a biologically simpler phenomenon, which is a prerequisite of higher levels of consciousness . WhetherIn fact, the hardest problem we have to face when investigating consciousness and its disorders lies with our poor knowledge about its neural correlates. Over the past century, observations of patients with focal brain lesions allowed us to infer the anatomical organisation of the human brain and to identify the distinctive neural substrates of the main human abilities such as motor function, language, emotion, decision-making and attention. However, consciousness seems to escape this model as there is a great variability of brain lesions, which are associated with consciousness impairment and no linear relationship between the extent and localisation of brain damage and the ensuing disorder of consciousness. Consciousness can be regarded as an emergent phenomenon that is not the product of a single cortical area but the result of large-scale dynamics within widespread neural networks. Recent neuroimaging evidence has suggested that UWS/VS should in fact be considered a global disconnection syndrome in which higher order association cortices are functionally disconnected from primary cortical areas ,25. ThisAll of these elements suggest that, although far from localising consciousness in the human brain, evidence from functional neuroimaging studies is certainly helping to disentangle the neural substrates of consciousness and to improve our ability to distinguish UWS/VS, MCS and functional locked-in state. Studies looking at responses to noxious stimuli are also playing an important role in this research as the degree of cortical engagement during noxious stimulation differs among patients with increasing levels of consciousness .Patients with UWS/VS or in an MCS have, by definition, suffered severe brain damage leading to a loss of consciousness and to concomitant neurological impairments. This means that each patient’s neurological picture tends to be complex and highly individual. Along with compromised consciousness, concomitant impairments may prevent patients from revealing their true level of consciousness or communicating pain. These include aphasia, low or fluctuating levels of arousal, severe spasticity or rigidity and a combination of other motor and cognitive symptoms as a result of multiple focal lesions or diffuse brain damage. We recently suggested that in some cases the behavioural unresponsiveness of patients is the consequence of the variable combination of sub-syndromes involving the pyramidal and extrapyramidal tracts, brainstem pathways and cortical areas . AccuratCentral to the issue of pain in DOCs is the important distinction between nociception and pain. Nociception is a physiological term describing the neural mechanisms of encoding and processing an actually or potentially tissue-damaging event . Pain, oResponses to noxious somatosensory stimuli in individuals with DOCs are of clinical, scientific, therapeutic and ethical importance, first and foremost in guiding appropriate pain management and optimizing physical comfort . ConscioRecently, a European survey investigated beliefs concerning the experience of pain in patients with DOCs and found that 96% of the medical doctors and 97% of the paramedical professionals thought that patients in an MCS can feel pain . When asThe central nociceptive system in healthy subjects, known as the pain matrix, includes the primary (S1) and secondary (S2) somatosensory cortices, the lateral thalamus, the insular cortex, the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex (DLPFC), and the parietal cortex. Specifically, S2 and S2 cortices, the lateral thalamus, and the posterior insula belong to the lateral neuronal network that encodes sensory-discriminative information while the anterior insula, the ACC, and the prefrontal cortex belong to a medial network that encodes affective-cognitive information . SeveralA later case series focused on the potential prognostic value of somatosensory evoked potentials (SEPs) and functional magnetic resonance imaging (fMRI) during noxious stimulation . The resFurther studies have investigated the neural correlates of empathic responses in patients with DOCs. In healthy individuals, listening to pain cries has been reported to elicit functional activation within the pain matrix of the brain, so several studies have used this task to assess affective consciousness in behaviourally unresponsive patients. In a recent study, brain haemodynamic responses to pain cries, compared with neutral human vocalisations, were investigated through fMRI in a large sample of patients with UWS/VS . The finA similar experimental paradigm was used by a further study to improve accuracy in differentiating patients in UWS/VS and MCS . On expoUltimately, a more comprehensive knowledge about brain functioning can help to personalise rehabilitation by recognising the patient’s strengths and limitations. This may include identifying possibilities for therapies using neuromodulation, with neuroimaging being used also in the monitoring of changes in time within the same patient and evaluating the effectiveness of treatment strategies ,66,67. SA degree of caution is, of course, required in the interpretation of neuroimaging findings . Both paWhen interpreting findings about the degree of both consciousness and pain perception in behaviourally unresponsive patients, it should be taken into account that diagnostic processes may vary between centres, and it is important that clinical descriptions and diagnostic criteria used are reported . ResearcNeuroimaging is contributing to our understanding of the substrates of consciousness and pain perception in patients with DOCs. Findings suggesting partial brain activation within the pain matrix even in patients with persistent UWS/VS caution against facile assumptions about the nonsentient state of behaviourally unresponsive patients. On the other hand, such evidence does not allow us to conclude that the perception of pain in these patients resembles the constellation of pain experiences of healthy subjects. Moreover, it cannot be excluded that pathological and chronic pain mechanisms may develop along the prolonged clinical course of the disease due to the engagement of pathological neuroimmune pathways . In MCS What cannot be concluded from the evidence is that any individual patient with a DOC does not have any sentient experience of pain. Given the remaining uncertainty about this issue, a “just in case” approach to analgesics is advocated on ethical grounds , with me


Transforaminal epidural injections with steroids (TESI) are used increasingly for patients with sciatica. However there is much debate about their safety and effectiveness. It is important to identify patients that benefit most from TESI and only few trials have yet evaluated the effects in patients with acute sciatica.We describe a prospective, randomized controlled trial (RCT), with the aim to evaluate the hypothesis that TESI plus Levobupivacaine (TESI-plus) added to oral pain medication is more effective compared to pain medication alone or compared to transforaminal injection with a local anesthetic of short duration among patients with acute sciatica. We will recruit a total of 264 patients with sciatica (<8 weeks) caused by a herniated disc, from two clinical sites. Participants are randomly assigned one of three study groups: 1) oral pain medication (control group), 2) oral pain medication and TESI-plus (intervention group one), 3) oral pain medication and transforaminal epidural injection (TEI) with Levobupivaine and saline solution (intervention group two). Primary outcomes are functional status (Roland-Morris Disability Questionnaire), pain intensity for both leg and back, ), and global perceived recovery . The secondary outcomes are health-related quality of life (EQ5D-5 L) and patient satisfaction . We will also collect information on healthcare utilization and costs, to perform an economic evaluation. All outcomes are measured at three and six weeks, three and six months after randomization. We defined a minimal clinically relevant difference between groups as a difference between both intervention groups and the control group of 20 points for pain (100-point VAS), four points for functional status (24-point RDQ) and a 20% difference on dichotomized GPR (recovered versus not recovered).A clinically relevant outcome in favor of TESI-plus implies that future patients with acute sciatica should be recommended TESI-plus within the first few weeks rather than being treated with pain medication alone in order to relieve pain and improve their functioning. In case of a negative result (no relevant differences in outcome between the three study arms), pain medication will remain the mainstay of treatment in the acute stages of sciatica.NTR4457 Dutch National trial register:  Sciatica is characterized by neuropathic pain radiating from the lower back into the leg along following the sciatic nerve . The priDuring the first few weeks of symptoms treatment is focused on pain control by means of medication and mobilization by physical therapy. Disc surgery should only be proposed if symptoms persist after conservative treatment. There is no agreement on how much time (in terms of weeks) conservative therapy should be followed before surgery is advisable .Epidural steroid injections are used increasingly as an alternative to pain medication in patients with sciatica, especially in acute patients with severe pain. In the United Kingdom, the number of epidural injections increased from 47 803 in 2000 to 70 967 in 2010 (increase of 49%) ) and disability  Rolland Morris Disability scale ) . The pooIn 2014, the American Food and Drug Administration (FDA) gave out a safety warning after several neurologic events had been reported in patients undergoing epidural corticosteroids, including some fatal events of spinal cord infarction and stroke , 17. HowIt is important to select patients that benefit most from epidural corticosteroids while closely monitoring their safety , 23. GivThe goal of study is to evaluate the effectiveness of TESI-plus and oral pain medication versus oral pain medication alone in improving pain, physical functioning and recovery among patients with sciatica within eight weeks after onset in outpatient clinics. Our hypothesis is that patients who are randomized to receive TESI-plus (intervention group one), will experience less pain and better functional status compared to patients randomized to receive pain medication alone (control group). A second hypothesis is that TESI-plus is more effective than transforaminal injection with Levobupivacaine and saline solution (intervention group two). Levobupivacaine is a local anesthetic with a short-lasting effect and is usually injected in a small volume. Its supposed effectiveness is minor. We are interested to see if the type of transforaminal epidural injection matters .We followed the CONSORT statement when designing and reporting this study, a checklist invented to improve the quality of reports of RCTs .(Control) oral medication only;(Intervention group one) oral medication and TESI-plus;(Intervention group two): oral medication and TEI with Levobupivacaine and saline solution.A multicenter, randomized controlled, prospective, single-blind trial will be performed, along with a full economic evaluation from a societal perspective. The subjects will be enrolled at two Dutch hospitals, the Zaans Medisch Centrum, Zaandam and Onze Lieve Vrouwe Gasthuis, Amsterdam. The two hospitals are located in a populated area of The Netherlands. The subjects will be allocated to one of three groups:Follow-up will be six months. Figure This trial will be carried out in accordance with the Declaration of Helsinki. The Boards of Directors of the two hospitals approved the execution of the study in their centers.On August 20th 2015, the RCT was evaluated positively by the Medical research Ethics Committees United, Nieuwegein, The Netherlands (registration number NL 45805.100.15) and the protocol was registered at the Dutch Trial Register (number NTR 4457). All patients will give their (written) informed consent before participation in the trial.Patients eligible for this study have to have < 8 weeks of sciatic symptoms and will be seen by a neurologist of one of the two study centers upon referral by their general practitioners (GP). Additional inclusion criteria are: a) age between 18 and 75 years; b) a magnetic resonance imaging (MRI) confirmed disc herniation with nerve root impingement causing clinical symptoms; c) pain experienced on average over the last week rated on a numerical rating scale (NRS) (>4/10); d) good understanding of Dutch language; e) internet access in order to complete online questionnaires.Exclusion criteria are: a) severe weakness of the legs  score <3); b) spinal surgery < 1 year at the symptomatic lumbar level; c) lumbar spinal stenosis or spondylolisthesis as the cause of radicular pain diagnosed by MRI; d) pregnancy; e) severe comorbidity (e.g. cancer).Neurologists at the participating clinics will perform a complete physical and neurological examination. For specific description see ‘baseline measurement’. In case of a clinical suspicion of a herniated disc, MRI of the lumbar spine will be performed. If patients meet the eligibility criteria, they will get oral and written information about the trial. After being informed the patients will be asked to participate. Upon agreement, the informed consent form will be signed and patients will be randomized by one of the trial nurses. At the start baseline data will be registered. Transforaminal injections will be performed by an experienced anesthesiologist within two working days after randomization. After randomization the clinical and research settings will be separated: all patients will be followed by their own neurologist in the outpatient department and by the research nurse who is responsible for the (web based) questionnaires.Images will be made by a 1.5 T MRI scan, gradient strength 33 mT/m, slew rate 125 T/m/s  with a dedicated receive-only spine coil. All participants will be imaged with the same protocol. MR studies will start with a coronal plan scan , followed by a sagittal T1-images , a sagittal T2-images  and a transverse T2-images . The lumbar spine (T12-S1) will be studied on sagittal images, including imaging of the neural foraminae. Transverse images will be obtained from L3 to S2, with slices angulated parallel to the disci.Patients in the control and intervention groups use painkillers both over the counter and by prescription. Usually the GPs choose Paracetamol with or without non-steroidal anti-inflammatory drugs (NSAIDs) and, if necessary, opioids following the WHO-pain ladder . In addiThe procedure is similar for both intervention groups. The study participant is brought to a fluoroscopy room and placed in a prone position on the procedure table. Fluoroscopy is used for localization of MRI confirmed disc herniation. Target identification and needle entry into the targeted space is done following internationally accepted procedures . The skiThe study participants of intervention group one receive 1 ml of 5% Levobupivacaine followed by 1 ml of 40 mg/ml Methylprednisolone in an opaque syringe. The study participants of intervention group 2 receive 1 ml 5% Levobupivacaine followed by 1 ml NaCl 0.9%. The total volume of the two injections is the same (2 ml).After the epidural injection the washout of the contrast fluid is demonstrated on an X-ray image. The image will be saved. Finally the needle is removed and the patient is brought to the recovery area.We use the core outcome set for clinical trials in low back pain . The queThe following potential prognostic factors for recovery at 6 months will be assessed at baseline: age, gender, education, profession, work and marital status, co-existing joint problems, presence of vascular risk factors  and all primary and secondary outcomes.) .Neurological examination, performed by six different neurologists working in the outpatient departments of the participating hospitals, is standardized for all participants. Tests include physical examination of the leg muscles using the Medical Research Council (MRC) scale for muscle strength; sensory examination: tests for perception of light touch, pin prick, and vibration sense of the lower extremities; reflex examination: tests for reflexes in the patellar (L4) and ankle (S1); straight leg raising (or Lasègue’s sign): with the patient laying on the back, one leg is lifted upwards by flexing the hip while the knee remains extended. The test is positive if the patient experiences radicular pain when the leg is at an angle between 30 and 70°. A finger-floor distance of more than 25 cm, absence of knee or ankle tendon reflex, leg paresis and a positive straight leg raise test are an indication for a herniated disk with nerve compression on MRI . The addThe three primary outcomes are pain, physical functioning and global perceived recovery.Pain intensity (average previous week) of both back and leg will be rated using a 100 mm VAS: 0 = no pain to 100 = worst imaginable pain . The VASGPR will be rated on a 7-point Likert scale that ranges from ‘completely recovered’ (-3) to ‘worse than ever’ (+3). The GPR will be dichotomized into success (categories ‘completely’ and ‘much recovered’) and non-success . The GPR is a commonly questionnaire in back pain research .Functional status will be rated using the Dutch version of the Roland-Morris Disability Questionnaire (RDQ) . The RDQA minimal clinically important difference is defined as an improvement of 20 points for pain (both leg and back) (100 point VAS), 4 points for functioning (24 point RDQ), and a 20% difference between groups for recovery (recovery vs. non recovery).The Euroqol-5 dimensions- 5 levels (EQ-5D-5 L) will be used to determine quality of life . The EQ-Patient satisfaction will be assessed using a written 7-point NRS ranging from ‘not satisfied at all’ to ‘completely satisfied’. No gold standard is available for the measurement of patient satisfaction, but in spinal disorders a seven-point global question is recommended .All measurements were registered using web-based questionnaire, which will be sent at baseline, and at three and six weeks, three and six months follow-up.The economic evaluation will focus on the comparison of intervention group 1 and the control group.Intervention costs will be estimated using hospital accounting records. Health care utilization costs , informal care and unpaid productivity will be collected using self-completed cost questionnaires at three weeks, six weeks, three and six months . Work abTable All adverse events (AEs) during the study will be recorded on the case record form (CRF), whether or not caused by the study procedure. Registration includes: the event, onset and end date, severity, relation to the study and action taken. AEs considered related to the study will be judged by a medically qualified investigator and followed until resolution (or if the event is regarded stable). All AEs that result in withdrawal from the trial will be followed until there is satisfactory recovery. The investigator will judge whether an AE is severe enough to require the study participant’s removal. A study participant may withdraw from the trial if he or she experiences as an intolerable AE. If either side effect will happen, the study participant will get appropriate medical care until symptoms resolve or become stable. There will be an end of study assessment.n = 88 per arm) anticipating a 10% loss to follow up.Sample sizes were calculated for the three primary outcomes pain, functional status and global perceived effect . A number of 48 patients is needed in each arm to detect a difference of 20 points (VAS for both leg and back pain) between intervention group one and the control group between the intervention group one and two (SD 30). A 20 points difference is considered clinically relevant. A number of 22 patients in each arm is needed to detect a difference of 4 points on the RDQ (SD 4). A number of 79 patients in each arm is needed to detect a difference on the dichotomised GPE of 20%. We aim to include a total of 264 patients . Alea® will generate a random schedule of blocks with maximum size of 6. A unique randomization number will be generated for each participant. An independent research nurse will allocate the participants to their group. Patients that belong to one of the intervention groups do not know the type of injection. Coding will not be broken during the trial.This pragmatic trial is partially blinded. The patients do not know the type of injection received, but the anesthesiologist knows the different injection fluids. The neurologists that do the clinical follow-up of the study participants are blinded for the type of injection. The same applies to research nurses and the statistician. All patients will be assigned a unique number to ensure anonymity.Baseline characteristics will be compared of the main outcome measures, potential confounders  and prognostic factors.P < 0.05.The analysis will be performed according to the intention-to-treat method for all three comparisons . All continuous variables will be analyzed using a maximum likelihood estimation for linear mixed models under ‘missing at random’ assumptions. In these analyses we will take into account the levels of patient, time of measurement and hospital, if necessary based on the likelihood ratio test. Regression coefficients and odds ratios with 95% confidence intervals (CI) for all follow up data, adjusted for baseline characteristics will be calculated, with a level of significance of All patients will be analyzed, regardless of the treatment received and violations from the study protocol. Secondly, the per-protocol analysis includes participants with all primary endpoint data available, and for who there haven been no major protocol violations. Protocol violations will be reviewed by the research team, blinded to allocation, and before locking the trial database. Data will be compared between complete and incomplete records to identify possible selective drop-out in the case of missing data.The economic evaluation will be done following an intention-to-treat approach and from a societal perspective.A multivariate imputation (by chained equations) will be used to impute missing costs and effect data. Bootstrapping with 5000 replications will be used to estimate a 95% CI for differences in total costs between treatment groups.Cost-effectiveness ratios will be calculated by dividing the difference in mean costs by the mean effect in pain intensity of the two treatment groups. Cost-utility will be expressed in costs per quality adjusted life year (QALY) and based on the EQ5D-5 L. Uncertainties with regard to cost-effectiveness and cost-utility ratios will be estimated using bootstrapping techniques and graphically shown in cost-effectiveness and utility planes. Acceptability curves for cost-effectiveness will also be made. Sensitivity analyses will be carried out for the most important cost drivers in order to assess the robustness.Sciatica is considered to have three pathogenic components: a mechanic component that consists of impingement of the nerve root due to disc herniation; an inflammatory component that can be shown by elevated cytokines in serum and biopsies , 27; a nWe hypothesize that inflammation is predominant during the acute phase of sciatica and wanes after several months in correlation with clinical improvement in most patients. From this idea epidural corticosteroids that are administered locally at the site of the lesion are likely to be effective during the first weeks of an episode of sciatica. We could only find three previous RCTs that have addressed acute treatment of sciatica with epidural corticosteroids before –49. PoolA clinically relevant outcome in favor of TESI-plus implies that TESI-plus should be recommended for patients with acute sciatica within the first few weeks rather than being treated conservatively with pain medication alone in order to relieve pain and improve their functioning. In case of a negative result  pain medication remains the mainstay of treatment in the acute stages of sciatica.Regardless of the outcome of our study surgery within the first 2–3 months is reserved for patients with severe pain irresponsive to medication or TESI and patients with neurological deficits (cauda syndrome or weakness).Recently the safety of TESI has been debated in the literature –22. ThouThe trial started in February 2016. The results will be available at the end of 2017.


The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group (P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups (P < 0.05) also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications.Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group ( Lumbar intervertebral disc herniation, also known as rupture of fibrous annulus of lumbar spine, refers to a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion , 2. The Acupuncture, one of the nonsurgical treatments, is a commonly used method to treat lumbar intervertebral disc herniation . The acuIn our department, the patients with lumbar intervertebral disc herniation received the combined therapies of Taiyi miraculous moxa roll and cupping therapy to adjust the dredging sweat pore and remove obstruction. The curative effect observation and comparative analysis were also performed in the patients who received acupuncture therapy alone. Hence, the results are described as follows.n = 35) and control group (n = 35). The treatment group received Taiyi miraculous moxa roll combined with cupping therapy, while control group received acupuncture therapy alone. The difference between the two groups in gender, age, disease course, and index score of pretreatment was not significant (P > 0.05), but was comparable  [Patients with qi stagnation and blood stasis syndrome were selected according toedicine) . The patThe inclusion criteria were as follows: (1) meeting the diagnostic criteria of lumbar intervertebral disc herniation; (2) meeting qi stagnation and blood stasis syndrome; (3) range of ages being 20–70; (4) participating voluntarily in the clinical trial.The exclusion criteria were as follows: (1) patients without the above diagnostic criteria; (2) patients suffering from other diseases with low back pain; (3) patients suffering from other severe primary diseases, neurosis, or psychosis; (4) patients with surgical indication; (5) pregnant or nursing women; (6) patients receiving other clinical trial.Patients of treatment group received Taiyi miraculous moxa roll combined with cupping therapy that was given once every three days, a course of ten days. Patients of control group received acupuncture therapy alone which was given once every other day, a course of ten days. After two courses of treatments at the same time, the therapeutic effect, symptoms, and signs were observed and analyzed. the treatment of diseases with acupuncture [Jiaji acupoint is located in Jiajixue on both sides of intervertebral disc disorder according to the site of lumbar intervertebral disc herniation which was detected by CT or MRI. Other acupoints were selected according topuncture , includiThe prescription is composed of moxa (100 g), sulfur (6 g), frankincense (3 g), myrrh (3 g), Radix Aconiti (3 g), Radix Aconiti Kusnezoffii (3 g), pangolin (3 g), musk (3 g), realgar (3 g), asarum (3 g), cinnamon (3 g), clove (3 g), xinyi (3 g), and angelica (3 g), which were ground into powder, mixed together, and stored in a dry airtight container.First of all, spread out a piece of mulberry squared-paper (40 cm wide). Then, spread moxa (25 g) evenly on the paper mixed with powder (6 g) and roll it tightly. Next, apply egg white on the surface and paste a piece of mulberry paper again, rolling it tightly into a moxa stick. And then, cut the moxa stick into a centimeter length of moxa rolls. At last, sprinkle a little borneol on each moxa roll.Firstly, patients lie in side or prone position with full exposure of the acupoints and pay attention to keeping warm. Secondly, location in a distance of 2.5 cm from Jiajixue on both sides of intervertebral disc disorder is the puncture point, piercing from 10 degrees outward. When there is an obvious sense of loss, stop inserting the needle. Meanwhile, when the patients could feel a radioactive tingling or an electric shock, the needle should be stopped with respect to lifting, thrusting, and rotating. Place a special hard paper on the needle handle close to the skin, insert a moxa roll into the needle handle, and light it up. In accordance with the above steps, the moxa roll is placed over the selected points, ignited, and allowed to remain onto the acupoint until it burns out completely or the patient feels a burning pain. Nip the remaining moxa roll away and replace new one to continue the therapy. Each acupoint needs burning three moxa rolls. Do the moxibustion until the skin turns red without blistering for the degree. Finally, during the moxibustion, prevent the moxa ashes from burning skin or clothes.Use flash-fire cupping at the selected acupoints. The cup retaining time at each acupoint is within 10 minutes. Use sterilized cotton to clean up the wound after removing the cup. Remind the patients to keep the wound clean to prevent infection and also to keep warm and avoid the cold .∗ 40 mm) to insert Geyu , Shenyu , Dachangshu , Yaoyan , Huantiao (pain side), Yanglingquan (pain side), Weizhong (pain side), and Kunlun (pain side). The acupuncture needles were inserted swiftly and vertically into the acupoints. Adjust the depth of needle insertion according to patients' specific situation, referring to the process of the patient produces acupuncture acid, hemp, or bilge sensation. After the arrival of qi, uniform reinforcing-reducing method was performed, with retaining needle for 30 minutes, and with intermission thrice at interval.Acupoint selection conducted in the acupuncture alone therapy was described as follows. After sterilizing the skin at the acupoints, use acupuncture needles , pain affect (A), and visual analogue scale (VAS) . In detaStandards for Diagnosis and Curative Effect of Chinese Medical Symptom were adopted to evaluate the efficacy with cure, improvement, and invalidity .X ± SD). The effective rate was analyzed with Pearson's chi-squared test (χ2), and P < 0.05 was considered as statistically significant. The Minimum Standards of Reporting Checklist contains details of the experimental design, statistics, and resources used in this study.All the data was analyzed by software SPSS 18.0. The measurement data was analyzed by mean ± standard deviation (P < 0.05), indicating that the combined therapies of modified Taiyi miraculous moxa roll and cupping were superior to acupuncture therapy alone referring to the total effective rates. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture.Total effective rates after alone and combined therapies are shown in P < 0.05), indicating that both of alone and combined therapies can alleviate the clinical symptoms and signs, but the combined therapies were superior to the alone therapy. Moreover, the scores of McGill in both groups before and after therapies were statistically significant (P < 0.05), indicating that both of alone and combined therapies can relieve pain. There was no significant difference in the scores of pain sense (S) and pain effect (A) between the two groups after therapies (P > 0.05). However, there was obvious difference in visual analogue scale (VAS) and in the McGill scores between the two groups after therapies (P < 0.05). Therefore, the combined therapies of modified Taiyi miraculous moxa roll and cupping were still better than acupuncture therapy.With alone and combined therapies, JOA and McGill scores are shown in Lumbar intervertebral disc herniation belongs to the category of low back pain, back and leg pain, and arthralgia in TCM . TCM belMany patients with lumbar intervertebral disc herniation try to seek the TCM therapy because they did not want to receive trauma therapy. Therefore, it is hard to get the anatomical data in TCM therapy research. In our study, modified Taiyi miraculous moxa roll was applied to the patients in the treatment group. To avoid the influence of self-limitation or fluctuated symptoms in the patients with long-term low back pain, the period of treatments was designed to be short term, 10 days, in the clinical trial. The special ingredients of Chinese herbs in the moxa roll can induce lasting and moderate effects on the acupuncture points by warm acupuncture. Otherwise, the bioactive ingredients can be absorbed by the acupuncture points resulting in a therapeutic effect. The modified Taiyi miraculous moxa roll combined with cupping therapy is based on the theory of flow blood blocking meridians and promoting without pain, which is a treatment that addresses both symptoms and root causes. The combined therapies could improve the symptoms and prevent the recurrence through promoting and activating meridians, restoring the normal function of the lumbar nerve.In conclusion, combined effects of modified Taiyi miraculous moxa roll and cupping therapy on lumbar disc herniation are much more effective than that of acupuncture alone therapy in the study. Furthermore, combined therapies of modified Taiyi miraculous moxa roll and cupping are potentially safe and cost-effective. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications.


Referred craniofacial pain of cardiac origin might be the only symptom of ischemic heart accidents. This study aimed to determine the frequency of craniofacial pain in patients with ischemic heart disease.P<0.05 was considered significant.This cross-sectional study was accomplished on 296 patients who met the criteria of having ischemic heart disease. Data regarding demographics, medical history and referred craniofacial pain were recorded in data forms. In addition, patients underwent oral examination to preclude any source of dental origin. Chi-square test, Student’s t-test and backward regression model were used to analyze the data by means of SPSS software version 21. A total of 296 patients were studied comprising of 211 men (71%) and 85 women (29%) with the mean age of 55.8. Craniofacial pain was experienced by 53 patients out of 296, 35 (66%) of whom were male and 18 (34%) were female. None of the patients experienced craniofacial pain solely. The most common sites of craniofacial pain were occipital and posterior neck (52.8%), head (43.3%), throat and anterior neck (41.5%) respectively. We found no relationship between craniofacial pain of cardiac origin with age, diabetes, hypertension, and family history. On the other hand, there was a significant relationship between hyperlipidemia and smoking with craniofacial pain of cardiac origin.Radiating pain to face and head can be expected quite commonly during a cardiac ischemic event. Dental practitioners should be thoroughly aware of this symptomatology to prevent misdirected dental treatment and delay of medical care. Key words:Craniofacial pain, ischemic heart disease, myocardial infarction, angina pectoris, referred pain. History of previous cardiovascular disease such as hospitalization in coronary care unit (CCU), consumption of cardiovascular medications, history of severe chest pain as well as risk factors of coronary heart disease like diabetes mellitus, hypertension, smoking, hyperlipidemia, and family history of heart disease were all recorded in data forms. Patients with history of chronic headache, earache, severe psychiatric disorders, pain in the tempororomandibular joint (TMJ) region, surgery or presence of a diagnosed mass in the jaws, and recent odontogenic pain were excluded from the study. Meanwhile, all eligible patients underwent oral examination by means of dental mirror and flashlight while lying on their beds, and those who found to have dental problems  were banned from entering the study.On the day after angiography, patients were fully informed about details of the study, and then requested to fill out the data forms, which was sub divided into two part, providing demographics and pain characteristics . Thereafter patients were shown anatomic illustrations representing chest, abdomen, back, shoulders, arms, face, neck, and mouth, and asked to mark site of their pain on the picture  Fig. 1)1). To enThe study protocol was approved by oral medicine department of Shahid Beheshti University of Medical Sciences and Shahid Rajaie Cardiovascular, Medical & Research Center. All patients were obtained informed consent to participate in the study.-Data analysis:P<0.05 was considered significant.To analyze the data, SPSS software version 21 was used. Descriptive statistics was used to report the results. Moreover, Chi-square test was used to examine differences between two genders in terms of symptoms, and Student’s t-test to assess the distribution of age between two groups (with pain and without pain). In order to analyze the effect of gender, age, type of cardiac disease, and coronary risk factors on chance of having craniofacial pain, backward regression model was utilized. The present study was aimed to determine the frequency of craniofacial pain of cardiac origin in patients with ischemic heart disease hospitalized in Shahid Rajaie Cardiovascular, Medical & Research Center in the year 2014-2015. A Total of 296 patients entered the study comprising of 211 men (71%) and 85 women (29%) age ranging 29 to 85 years with the mean age of 55.8. Of the total sample, 133 patients were hospitalized for MI, 71 for unstable angina, and 92 for stable angina. In regard to medical records, 166 patients had history of hospitalization in CCU, 209 were taking cardiovascular medications, and 150 experienced severe chest pain. Meanwhile, medical history taking revealed diabetes in 95 patients, hypertension in 134, smoking in 106, and hyperlipidemia in 148 and presence of ischemic heart disease in first-degree relatives in 149.Craniofacial pain was experienced by 53 patients out of 296, 35 (66%) of whom were male and 18 (34%) were female. The age range of men was 57.9 and that of women was 62.8. Thirty six patients (66%) were hospitalized because of MI, and 17(34%) for unstable angina.None of the patients experienced craniofacial pain solely, but all had concomitant pain in mid-chest or left chest. In case of craniofacial pain, the most common sites of pain were occipital and posterior neck 52.8%), head (43.3%), throat and anterior neck (41.5%) respectively. Pain in the left mandible was recorded in 28.3% of patients. The right neck was the least frequently site of referred craniofacial pain (3. 7%) .We found no relationship between age and craniofacial pain of cardiac origin. However, there was a statistically significant difference between men and women with craniofacial pain in terms of sex (p=.001) and smoking (p=.003) with craniofacial pain of cardiac origin . We found a significant difference between men and women with craniofacial pain with respect to age in a way that mean age of women was significantly more than of men (p=0.025).In accordance to our results, there was no association between age and craniofacial pain in similar studies .Previous studies have demonstrated significant differences between men and women in terms of referred pain to craniofacial region. Kreiner et al.  and Dane .Kreiner et al.  noticed   and smoking (p=0.03).It is noteworthy that the previous studies neither addressed craniofacial pain after angiography, nor considered coronary risk factors such as diabetes, hypertension, hyperlipidemia, smoking, and family history. Our study found no relationships between craniofacial pain of cardiac origin with diabetes, hypertension, and family history. However, there was a significant relationship between craniofacial pain with hyperlipidemia (et al. (In Kreiner et al.  study, tRegarding the crucial risk of ischemic heart disease and possibility of pain referral solely to the craniofacial area, it is recommended that further studies be conducted with larger sample size, more elaborate oral examination including radiographic imaging as well as detailed inspection of facial, muscular, and temporomandibular structures, and recording pattern of pain.Radiating pain to face and head areas can be expected quite commonly during a cardiac ischemic event. Since dental practitioners may play an important role to detect such atypical symptoms of cardiac origin; they should be thoroughly aware of this symptomatology in order to prevent misdirected dental treatment and delay of medical care.


Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis.Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only.Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group.Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option. The number of patients affected is on the rise and by 2020 this figure would have probably multiplied2. In Malaysia, 9.3% of adult Malaysians have knee pain and more than half of them have clinical evidence of OA. The prevalence ranges from 1.1% to 5.6% in the various ethnic groups in Malaysia3.Studies have shown that 15% of the world population suffers from osteoarthritis which includes 39 million people in the European countries and more than 20 million of Americans5. The underlying causes of OA are multifactorial with several predisposing factors such as mechanical trauma, obesity, genetic factors, inflammatory joint disease, previous joint infection, advancing age, metabolic factors, osteoporosis, and ligamentous laxity6. Diagnosis of OA is made with clinical assessment and radiological investigation as an adjunct8. Less than 50% of patients with radiological changes of osteoarthritis are symptomatic; therefore, treatment is based on symptoms rather than radiological changes9.Knee OA is characterized by degeneration of the articular cartilage which will eventually lead to the joint destruction10. Currently, there are numerous ongoing efforts to develop new tissue engineering- based strategies for treatment of OA11. Recent studies show that drugs such as glucosamine, chondroitin sulphate and intra-articular injections of hyaluronic acid not only favor pain relief, but also prevent the progression of the disease13.The mainstay of treatments for early stage of knee osteoarthritis are analgesics, activity modification and physiotherapy. Over time, patients usually become refractory to the initial treatment regime, hence reconstructive surgery becomes the subsequent treatment modality. Analgesics widely used in knee OA patients only help in reducing inflammation and pain but they are ineffective in delaying disease progression13. It is a large glycosaminoglycan which is composed of long repeating disaccharides of glucuronic acid and N-acetylglucosamine15. Viscosupplemention with intraarticular HA in knee osteoarthritis is widely regarded as an effective treatment in improving pain and function due to its protective effect on articular cartilage, acting as lubricant and shock absorbent17.Hyaluronic acid (HA) is a naturally occurring polysaccharide in the synovial fluid and is responsible for the elastoviscocity of synovial fluid18. Platelets store more than 1500 active proteins in α and dense granules20. α granules contain numerous growth factors (GF) like platelet derived GF(PGDF), transforming GF(TGF-β), platelet-derived epidermal GF, vascular endothelial GF, insulin like GF-1, fibroblastic GF and epidermal GF which promotes healing potential in degenerating articular cartilage22. Meanwhile, the dense granules contain adenosine diphosphate, adenosine triphosphate, calcium, histamine, serotonin, and dopamine which aids in regeneration of the degenerated tissues20. Studies have suggested that the combination of HA and plasma rich with growth factors enhance the regeneration of articular cartilage23.Contemporary studies in the developed countries have demonstrated the additional use of platelet rich plasma (PRP) in treatment of knee osteoarthritis. PRP is platelet concentrate (2-10 times of baseline concentration) that is obtained from patient’s autologous blood sample by centrifugationThe objective of this study is to analyse the efficacy of intraarticular injection of HA and PRP versus HA injection alone in patients with grade III and IV knee osteoarthritis patients. It is envisaged that this study will make a significant contribution in improving the quality of life in patients suffering from severe knee osteoarthritis who are not fit for operation, not keen for surgical intervention or financially restricted.This is a cross-sectional study with retrospective review of medical records which was conducted from October 2013 to April 2014 at Malacca General Hospital and has been approved by the hospital and National Clinical Research Centre (CRC) Ethics Committee. Data was collected and reviewed from intra-articular knee injections registry. A total of 254 patients had received intra-articular knee injection from October 2013 to March 2014. Of the 254 patients, 70 had grade III or grade IV knee osteoarthritis.Our inclusion criteria was patients with Grade III and IV primary knee OA based on Kellgren Lawrence classification, who received 4 ml High Molecular Weight Hyaluronic Acid (HMWHA) with concentration of 22mg/ml alone or with combination of PRP. This is due to the availability of multiple concentrations of hyaluronic acid in practice which may cause inconsistency of the final results.Patients with grade I and II knee osteoarthritis, secondary knee osteoarthritis, patients who received HA injection with concentration and molecular weight other than mentioned in inclusion criteria, patients with osteoarthritis of other joints, those with other inflammatory and non-inflammatory joint disease, coagulopathies and with local or systemic infections were excluded from this study.Sixty-four patients (101 knees) who fulfilled the criteria were selected and the six patients were excluded based on the exclusion criteria. The study group comprised 24 men and 40 women, with an average age of 66 (range 50 - 87) years. One hundred and one knees had received intraarticular injection; 37 patients with bilateral knee injections (74 knees) and 27 patients with unilateral knee injection. Of these, 56 knees had received HA and autologous PRP combination intra-articular injections, whereas 45 knees had received only HA injections.et al have concluded that it is the ideal measurement tool to assess functional outcome as it showed the best performance on all measurement properties24.Knee assessment and pain score were routinely recorded and documented in our centre with International Knee Documentation Committee (IKDC) questionnaires and Visual Analogue Scale (VAS) prior to their injections, and after two months and six months following injection. IKDC was chosen over other measurement tools like Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) due to its high reliability and validity. Higgins The data were collected and reviewed from the medical records of the selected patients. The retrospectively collected data were then analysed using SPSS version 18 with paired t-test. The statistical analysis was conducted with 95 percent confidence interval and a p-value of <0.05 as threshold of statistical significance.6 average Daltons) hyaluronic acid with concentration of 22mg/ml. HMW HA was specifically selected because many earlier studies showed greater and longer efficacy in reducing pain and other symptoms and recovering articular function as compared to LMW HA26.We have standardized patient selection by only including patients who had received specific HA and PRP concentration or preparation method. All patients included in the study had received 4 ml high molecular weight . Three separate layers are produced at the end of the centrifugation: plasma, buffy coat (platelet) and RBCs. Ninety-five percent of the plasma layer is discarded, the remaining layers are mixed, by which process about 2.5 - 3 ml of PRP is produced at the end with platelet concentration of 1.4 - 1.6 million/µl on average.Sixty-four patients were selected for the study based on our inclusion criteria as mentioned above. Among these, 101 knees were given intra-articular injection . Forty-seven knees were injected with only HA and 56 knees were injected with HA plus PRP.As illustrated in In addition, progress was also evident via VAS scale in terms of decrement in the severity of pain in both the groups. It showed statistically significant – improved outcome in the long run as better pain control was achieved during the six months evaluation compared to two months evaluation in both groups. During the six months evaluation, the HA group demonstrated improvement with a mean score of 0.8. On the other hand, HA+PRP group showed better improvement in pain score with a mean score of 1.9 as demonstrated in Further analysis which was done on variables such as gender, age and ethnicity was not statistically significant in terms of outcome.3. This study is mainly targeted to group of patients with grade III and IV knee OA in our centre who refused surgical intervention or were not fit for operation because of their underlying medical comorbidities. Hence, they resorted to analgesics as a temporary measure for pain relief and tend to be dependent on them in order to continue with their normal activities of daily living (ADL)2. Long term complications of dependency on analgesics are detrimental to one’s health2. It is envisaged that this study will make a significant contribution in improving the quality of life and pain control in these patients by providing HA or HA plus PRP as an optional treatment modality in these group of patients.The growing incidence of knee OA worldwide places an enormous economic burden with direct and indirect cost including medical management, rehabilitation, arthroplasty and loss of occupational productivity as a result of functional disability6 Daltons) closely resembles the molecular weight of endogenous HA  in the extracellular matrix30. Studies have demonstrated that HMW HA down regulates the gene expression of osteoarthritis associated cytokines and enzymes in fibroblast like synoviocytes (FLS)29. In addition, HMW HA has anti-inflammatory property and regulates the suppressor T-cells for cell proliferation30. Supporting evidence also shows that the HMW HA typically resides longer in the synovial joint as compared to LMW HA30. This property improves the efficacy of HMW HA in inhibiting glycosaminoglycan release from the articular cartilage and results in better outcome in the long run30. This was evident in our study as more significant improvement was noted during six months evaluation compared to two months post-injection in both groups of patients as reflected in the IKDC and VAS scores.In our study, high molecular weight (HMW) HA was chosen instead of low molecular weight (LMW) HA mainly because the HMW HA 23. The enhancement of the migratory ability leads to better regenerating capability and slows down the natural progression of the disease23. Combination of HA and plasma rich in growth factors also halts the degeneration process and this positive biological interaction improves the efficacy of this intra-articular treatment, making it superior to analgesics alone which only provide temporary relief and do not treat the underlying pathology23.A combination of HA and PRP was used in this study as newer experimental studies focus on promoting cartilage repair, whereby sheer attention has been directed toward autologous PRPOur study shows that combination of HA and PRP results in significant improvement in IKDC and VAS scores compared to HA injection alone. This implies that the addition of PRP with HA improves functional outcome and pain control for up to six months of duration. However, we could not comment further on synergism between the two compounds as we did not include a control group of patients who received PRP injections only.Majority of patients in our study group were not active and were less mobile compared to the general population. The highest level of activities in 80% of our study population based on IKDC score were light activities such as walking, housework or yard work. Future studies would be on patients who were more active with greater demands being placed on their knees to determine whether the significant improvement in IKDC score can also be observed in such group of patients.Being a retrospective study, our research have certain limitations such as inability to measure certain statistical values. Besides that, the short duration of the present study is one of the limitations. A longer duration follow up would provide more information on the long term functional outcome. Although the inclusion criteria for this study was in our consideration quite comprehensive, and there is still a possibility of selection bias since the study was based on treatment in a single institution.Our study is strongly suggestive that combination of HA and PRP to be more effective compared to HA alone. Hence, we suggest combination of intra-articular HA and PRP injection as an optional treatment modality in the treatment of grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to 6 months of duration when surgical treatment is not an option.