The use of opioid analgesics to control pain after median sternotomy in cardiac surgical patients is worldwide accepted and established. However, opioids have a wide range of possible side effects, concerning prolonged extubation time, gastrointestinal tract dyskinesia and urinary tract disorders mostly retention. All these may lead to a prolonged ICU stay or overall hospitalization time increase.To determine whether a continuous subcutaneous regional anesthetic infusion delivered directly to the sternotomy site would result in decreased levels of postoperative pain and opioid requirements in cardiac surgical patients undergoing median sternotomy.The continuous subcutaneous infusion (OnQ Painbuster system) was applied in 37 patients. 3 patients were exempted due to prolonged ICU stay. 29 patients underwent CABG, 5 had AVR, 1 MVR and modified Maze, 1 patient had a 3-valve repair due to endocarditis and another one had reconstruction of the left ventricle. Requirements of opioid analgesics were recorded for 96 hours after operation. Pain was assessed using the visual analog scale and the total postoperative hospital length of stay was also measured.The postoperative pain was significantly diminished (0 – 3 at VAS). The mean postoperative length of stay was 5,8 days, rather improved compared to the average stay of 6,7 days.Continuous subcutaneous infusion of ropivacaine directly at the median sternotomy significantly diminishes postoperative pain and the need for opioid analgesic use. Moreover, it seems to reduce overall postoperative length of stay for all cardiac surgical patients. One of the majors concerns of any surgical patient entering an ICU is pain. In cardiac surgical patients, pain is mostly due to median sternotomy (or sometimes thoracotomy) and it seems to be higher on the first two days which is the usual length of stay at the cardiac ICU . TraditiThere are several methods to deliver opioid analgesia, mostly patient controlled or nurse controlled. None of them seem to be free of opioid adverse effects, though. This is especially true in cardiac surgical patients after median sternotomy. These patients need to remain calm and relaxed. Most important, they should be able to take easy, deep breaths to avoid atelectasis and get out of bed as soon as possible. All these cannot happen when they are in pain .Multimodal analgesia, combining the use of nerve blockade followed by intravenous analgesia in the usual manner has been tried but failed to show any particular benefit in clinical trials ,4,6. TheThe study population included 76 adult patients. They all underwent median sternotomy. The various cardiac operations included CABG (43 patients), AVR (17 patients), MVR (9 patients), MVR and ablation for atrial fibrillation (AF) (5 patients), triple valve operation for endocarditis (1 patient) and reconstruction of an aneurysm of the left ventricle – Dor operation (1 patient). The exclusion criteria were prolonged ICU stay more than three days, failure of the patients to comprehend and cooperate with the visual analog pain scale (VAS) preoperatively and failure to understand and sign the appropriate informed consent. The demographic characteristics of the patients and operative management are summarized on table Each of the patients was given a thorough explanation of the study by one of the surgeons in our department. Then, the patient was introduced to the VAS. This was our choice to try to calculate and rate the pain derived from the median sternotomy. Patients were taught to use the colors on the scale and match them with the severity of pain. The scale ranged from 0 (no pain) to 10 (maximum pain imaginable). Study participants were informed that they could use intravenous drugs to alleviate severe postoperative pain but they should do so only when the pain was really disturbing and severe. This study did not incur any additional cost to the patient. The cost of the cardiac operation was fully covered by the patients' insurance organizations, as usual.Cardiac operations were performed in the usual manner and at the end of the operation the sternum was reapproximated with heavy wire. Exactly above the sternum and before closing the subcutaneous fascia, two especially designed catheters were placed on the sternum, through the skin using matching introduction hollow needles and sheaths. These slim catheters were equipped with multiple small side openings towards their end. The drastic length of each catheter, the part with the holes was 12,5 cm . They were placed right above the wired sternum and stabilized by sticking the tip of the catheter under the first wire. This method of stabilization was developed by our group with intend to avoid placing extra absorbable sutures to stabilize the catheters. It also helped in removal of them. We did not experience any catheter breaks on removal, as noted by other groups [The choice of the proper anesthetic to use was between two long acting local anesthetic agents, namely ropivacaine and bupivacaine. Literature suggests though that ropivacaine sustains significantly less cardiotoxicity than bupivacaine ,3. For tThe catheters were removed after four days. Nurses at the ICU and the ward were supplied with a form for each patient. In that form they filled the number of times they used intravenous opioids to comfort the patients during the first four postoperative days and the dosage given. They also marked the time passed to extubation, the time until the first bowel movement and the time needed for the patient to sit on a char and to ambulate. After patients' extubation and until day four, a surgeon of our department asked them twice daily to mark on the VAS the severity of the sternotomy pain. Patients also were asked of the occurrence of pruritus, nausea and vomiting by the same surgeon and all answers were noted. The time intervals from arriving at the ICU to discharge from ICU and discharge from the hospital were assessed as usual according to the department's standardized protocol for all patients undergoing cardiac surgery.A total of 79 adult patients were enrolled in this study. However, three patients were excluded because they required prolonged intubation, more than two days. The postoperative course was uncomplicated for the rest 76 patients. During the first four postoperative days, the patients who received continuous subcutaneous anesthetic infusion experienced far less sternotomy pain than the rest of the departments' patients who were treated with opioid infusions in the usual way. Of the 76 patients, 57 did not need any supplemental opioid iv infusions and the rest needed only small infrequent doses, compared with the rest of the patients. All cases of significant pain complaints were checked with continuous ECG monitoring and troponine tests to rule out ischemic causes.All 76 patients cooperated very well with the VAS and the results were excellent. The VAS rates were between 0 and 3 with a mean overall VAS score of 1,4. Moreover, the subjective pain estimation on behalf of the patients was equally good. table  None of There was no drug toxicity identified in any of the 76 patients neither were any concerns about it during the overall postoperative course. There were no wound infections or wound healing complications in any of the patients in the study. Also, there were no complications related to placement or removal of the catheters. None of the patients experienced any discomfort at all related to the catheters or the catheter removal.The postoperative length of hospital stay for the patients received catheter delivered analgesia was reduced. There was a difference in extubation time between the ropivacaine group and patients treated for pain with opioids (control group). A difference was also noted in the time needed for the first bowel movement. It was also obvious that patients enrolled in this study spent less time in the ICU, were able to get sit on the chair and get out of the bed sooner than the control group. table . The meaThe difference in the mean LOS is statically significant and expresses the quicker discharge from the ICU and the hospital for the patients who received continuous subcutaneous catheter derived analgesia for their median sternotomy incisions.Of note, none of the 76 patients had any pulmonary complications.The effective management of pain is of paramount importance to both patients and doctors. This is particularly true to surgical patients. The most important source of postoperative pain is the surgical incision. There is increasing evidence that improved postoperative pain management, especially after major operations, has significant physiologic benefits. Surgical patients who can breathe easily and mobilize shortly after the operation enjoy much lesser respiratory complications, namely atelectasis and infections. On the other hand, mortality and morbidity after major operations are related at least partly to the pathophysiologic response to the major injury sustained by the surgical incision and to postoperative complications related to pain. Postoperative pain and the subsequent use of opioid analgesics to alleviate it is a major drawback to the uncomplicated postoperative recovery.Postoperative pain after major procedures is mostly dealt with by ICU personnel and alleviated with use of opioid analgesics. This is mostly true for thoracic and abdominal operations during which huge muscle masses are incised or split apart . HoweverIn cardiac surgery, most operations are performed through a median sternotomy. The current trend in postoperative management of cardiac patients is directed to early extubation and to fast-tracking of patients out of the ICU and subsequently the hospital. However, there have been no advances in methods to improve the control of pain after median sternotomy. Pain in cardiac ICUs is still treated with iv opioid analgesics. These agents are usually sufficient enough to relieve patients from postoperative pain and dismobility. However, opioids do have well known and above mentioned adverse effects. This can be a major setback to the well renounced fast-tracking postoperative cardiac surgical protocol. Cardiac surgical patients need to remain calm, breath with ease and get out of bed as soon as possible. The cardiac ICU personnel are fully aware of that and use opioid analgesics in a free manner to promote it. However, their side effects can undermine this fast-tracking protocol and prolong ICU stay of cardiac surgical patients.Several alternative methods have been proposed instead of the traditional opioid use. NSAIDS were implied alone or combined with opioid administration but failed to show any particular benefit over opioids alone . The so Considering all the above facts we decided to proceed to a clinical trial implying direct and continuous infusion of a long acting topical anaesthetic agent directly on the sternotomy wound after cardiac operations. The nature of different cardiac procedures was not of importance because the postoperative pain is currently indifferently treated with opioids and the method of continuous anaesthetic infusion was examined to be efficient in every cardiac procedure. The severity of the operation and the preoperative condition of the patients were not considered drawbacks because this method has been already thoroughly tested in other surgical specialties as mentioned and proved generally safe.The results were complimentary of the method of continuous infusion of local anaesthetics. This study clearly demonstrates that the use of ropivacaine as a long acting local anaesthetic delivered directly in the subcutaneous tissue of the median sternotomy incision can reduce or even negate the use of intravenous opioids after major cardiac procedures. The use of the VAS as an objective manner of testing postoperative pain proved the efficacy of this method. Moreover, nurses reported minimal opioid use. In fact most patients did not need any opioids at all. The relief of pain reported by nurses in charge of each patient was also significant. The patients implied in this study were free of disabling pain and the adverse effects resulting from it. All of them were able to easily breathe their way out of the ventilator and off the bed. None developed respiratory complications of any manner.The subcutaneous catheters proved easy to use and remove. There were no infections in all patients enrolled in the study. The catheters did not cause discomfort in any way. Surgeons were able to perform wound dressing changes easily while the catheters were in place and the nursing personnel did not have any difficulty dealing with the elastomeric pump or the device as a whole. In fact, the pump was filled in the operation room and followed the patient thereafter as a unit until it was removed on day four. Thus there was no addition to the usual patient care on behalf of the nursing personnel.Finally, the LOS was considerably reduced. This result matches the fast-tracking protocol widely accepted by cardiac surgeons and anaesthetists for cardiac surgical patients and clearly points the way traditionally opioid pain alleviation adversely affects this protocol.In conclusion, the continuous infusion of ropivacaine directly on the sternotomy wound with specially designed subcutaneous catheters has been proved effective in reducing postoperative pain in cardiac operations of most kinds. This method also improved many patient outcome variables especially time to ambulation and LOS and most of all patient satisfaction with their pain management. This non-opioid analgesic method facilitates the fast-tracking protocol after open heart surgery.IK placed most of the catheters, conducted the study protocol and drafted the manuscriptMA was the primary surgeon in many cases and placed most of the cathetersAD was the anaesthesiologist and prepared the Ropivacaine solutionsVP assisted in most operations and managed the postoperative follow up of the patientsNT assisted in most operations and managed the postoperative follow up of the patientsCC is the head of the department and was the primary surgeon in many cases


Of all patients with low back pain, 85% are diagnosed as "non-specific lumbar pain". Lumbar instability has been described as one specific diagnosis which several authors have described as delayed muscular responses, impaired postural control as well as impaired muscular coordination among these patients. This has mostly been measured and evaluated in a laboratory setting. There are few standardized and evaluated functional tests, examining functional muscular coordination which are also applicable in the non-laboratory setting. In ordinary clinical work, tests of functional muscular coordination should be easy to apply. The aim of this present study was to therefore standardize and examine the inter-rater reliability of three functional tests of muscular functional coordination of the lumbar spine in patients with low back pain.Nineteen consecutive individuals, ten men and nine women were included. . Two independent examiners assessed three tests: "single limb stance", "sitting on a Bobath ball with one leg lifted" and "unilateral pelvic lift" on the same occasion. The standardization procedure took altered positions of the spine or pelvis and compensatory movements of the free extremities into account. The inter-rater reliability was analyzed by Cohen's kappa coefficient (κ) and by percentage agreement.The inter-rater reliability for the right and the left leg respectively was: for the single limb stance very good (κ: 0.88–1.0), for sitting on a Bobath ball good (κ: 0.79) and very good (κ: 0.88) and for the unilateral pelvic lift: good (κ: 0.61) and moderate (κ: 0.47).The present study showed good to very good inter-rater reliability for two standardized tests, that is, the single-limb stance and sitting on a Bobath-ball with one leg lifted. Inter-rater reliability for the unilateral pelvic lift test was moderate to good. Validation of the tests in their ability to evaluate lumbar stability is required. Only 15% of patients with low back pain (LBP) are given a specific pathological diagnosis, the remaining 85% are diagnosed as "non-specific lumbar pain" -5. MuscuClinicians use a battery of different clinical tests to investigate muscular coordination of the lumbar spine -19. ThesPatients consulting a physiotherapist due to low back pain with or without referred pain in the lower limb, or for arm and/or shoulder pain were recruited from a private physiotherapy clinic in the south of Sweden. Inclusion criteria consisted of age group between 18–65 years and a good knowledge of the Swedish language. Exclusion criteria were pregnancy, visual analogue scale (VAS) > 70 mm, previous known trauma or operation of the lower extremity which could jeopardise the performance of the tests, and known neurological or rheumatological disease. Between each test the patients rated their pain on a VAS scale. The purpose of these ratings was to check that the score did not exceed 70 mm on the scale, which we considered too high and could potentially affect the performance of the next test.The raters were blinded as to what diagonoses the patients had. Patients with low back or arm and/or shoulder pain were included. The purpose of including patients with shoulder pain was to avoid the raters being biased and also to obtain a more even distribution of positive/negative findings . A list The assessment undertaken in this study consisted of in part a normal orthopaedic objective assessment. The aims, methods and procedures of the study were approved by the head of the clinical setting. In accordance with Swedish law, the study complied with the ethical principles of the Helsinki Declaration. All patients gave their written, informed consent before participation. To decline participation in the study or to withdraw consent to participate did not affect patients' right to further rehabilitation. Statistical analyses were made on group level and no single individual could be identified.The study was single-blinded, that is the raters were not informed of the patients' symptoms.The patients were examined by two experienced physiotherapists (JT and AJ), both trained in orthopaedic manual therapy and in The McKenzie method . Both phBefore each test, the patient was informed about the test procedure. This information was based on a standardized written protocol which was read by one of the physiotherapists. It was decided by randomization which physiotherapist should inform the patients about the performance of the tests. The same physiotherapist also demostrated how the tests should be performed. The randomization was done by computer. The tests were performed in the same order for all patients.Before the study began, the physiotherapists co-coordinated the evaluation of the tests on ten patients in order to improve concordance. The results of these tests were not included in this study of reliability.The inter-rater reliability was assessed for each test, at the same time, by the two physiotherapists. A study form was independently filled in by the physiotherapists. Before and after each test, the patients rated their pain from the low back, leg or arm/shoulder on a VAS scale. Before each test the physiotherapists asked the patients whether they scored >70 on the VAS scale, which was an exclusion criterion. After the tests had been completed the patients were examined and treated as in normal clinical practice.All the tests were started in the "neutral zone of the back" position, and therefore, the normal curve of the spine had to be identified ,11. In oFigures Negative if the spine was kept in its original vertical position for 20 s, and the pelvic crests were kept in their original horizontal plane for 20 s with no compensatory movements made by the contra-lateral leg or the arms. A change from the starting position was accepted as long as this position was quickly resumed.Positive if:• the spine deviated from the original vertical position and/or• the pelvic crests deviated from the horizontal plane and/or• compensatory movements were made by the contra-lateral leg or the arms and/or• two or more short changes from the starting position were made.Not valid if the patient did not manage to perform the test due to painThe patient sat on a Bobath ball one metre in front of a checked curtain so that one of the longitudinal lines of the curtain was in line with the spine. The raters were positioned about two metres behind the patient as close to the patients midline as possible. The raters were kneeling down so that the eyes of the raters were in a horizontal line with the patient's low back. The diameter of the ball was 0.65 m. However, for patients shorter than 1.60 m a ball 0.55 m in diameter was used and for patients taller than 1.90 m the diameter of the ball was 0.75 m. The dorsal sides of the patient's hands were loosely placed on his/her thighs. There was approximately 0.05 m between the feet, and the calves did not touch the ball. The patient was then asked to lift his/her foot and keep it about 0.05 m above the floor for 20 s Figure  and 2b. Negative if the spine was kept in its original vertical position for 20 s and if no compensatory movements were made by the lifted leg or by the arms. A short change from the starting position was accepted as long as this position was quickly resumed.Positive if:• the spine deviated from the original vertical position and/or• compensatory movements were made by the lifted leg or by the arms and/or• two or more short changes from the starting position were made.Not valid if the patient did not manage to perform the test due to pain.Figures The test was evaluated as:Negative if the imagined line between both superior iliac spines of the pelvis was in the horizontal plane for 20 s and the trunk was kept in line with the thigh of the supporting leg for 20 s. A short change from the starting position was accepted as long as this position was quickly resumed.Positive if:• the whole pelvis was lowered in the direction to the couch and/or• the iliac spine of the pelvis on the side of the lifted leg deviated from the horizontal plane and/or• compensatory movements were made by the lifted leg or by the arms and/or• two or more short changes from the starting position were made.Not valid if the patient did not manage to perform the test due to pain.The simplest way to study agreement between two raters is to calculate the percentage agreement or the absolute agreement. In order to account for the calculation of chance we used the kappa value . As the Each test was evaluated dichotomously: negative/positive. The inter-rater reliability was assessed by the percentage agreement and by Cohen's kappa . The perOf all the nineteen patients (ten men) that were included, 13 had low back pain and six had arm and/or shoulder pain. Their mean age was 42 years (± 12 yrs). The patients with low back pain rated their pain on an ungraduated 100 mm visual analogue scale (VAS) where 0 = no pain and 100 = worst pain . The meaEach patient carried out six tests, that is three for the left and three for the right side. Of all 114 tests that were evaluated only two were not valid due to pain. The results are presented in Table According to the criteria of Altman , the intThe present study showed that the single-limb stance and sitting on a Bobath ball with one leg lifted have a good to very good inter-rater reliability. The kappa value for unilateral pelvic lift was moderate to good. Despite the percentage agreement for this test (78% and 73% respectively) the raters disagreed on four and five tests out of 19 possible, which in our opinion is not an acceptable agreement. It might be possible to further adjust the standardization procedure for this test in order to improve to a more acceptable level.As the kappa value depends on the prevalence of findings in each category, it is difficult to make a direct comparison to different studies of clinical tests. Murphy reports a kappavalue of 0.72 for left leg and 0.76 for right leg for a hip extension test . Hicks rThe tests used in this study were measured from a neutral position of the spine in three different functional positions. They aimed at keeping the spine close to the neutral zone while maintaining the normal curvature of the spine through each test procedure ,11. An iPain-ratings in this study were generally not affected by the tests. The patients did not rate their pain after the unilateral leg lifting test, which was the last one. We regretted this, as both raters found that of all the tests this one provoked the largest pain response. In this study, a checked curtain was used as reference in order to standardize the starting position. In a clinical setting, other backdrops could be used. Before the study started, the raters practiced their routine on ten patients, who were not included in the present study. They found that the evaluation of lumbar stability depended on where the rater was standing relative to the patient. In order to register a changed position, it was important to stand exactly behind the patient, which was a problem when two raters made the evaluation at the same time. When evaluating the unilateral pelvic lift, it was important to stand on the same side as the supported leg and to be in line (eye level) with the patient's hip to be able to evaluate any tipping of the pelvis and at the same time to have some reference line beneath the patient by which to register any lowering of the pelvis.The Trendelenburg test was previously used to evaluate the strength of the abductor muscles of the hip ,20,27. TExercising on a Bobath ball is regarded as a progression in training programs to gain control of the spine , where tWith the unilateral pelvic lift, other functions are also evaluated. Reliability was poorer for this test which may have been due to the difficulty in making a precise evaluation of whether the pelvis was being lowered or not. This may depend on how the raters were standing relative to the patient. Many patients seemed to lack a coordinated low back with many quick turns of the pelvis which also jeopardised the evaluations. For some patients it was difficult to achieve a good starting position due to tight hip flexor muscles. These patients therefore started with the pelvis in a lower position. This test has earlier been used to evaluate muscular endurance . ShellenA weakness of this study is that the sample size was small which may affect the precision of the kappa value. Another weakness is that the evaluated tests are not validated. A strength of the study is that the standardization procedure, as performed in this study, has shown good to very good reliability between two raters for two out of three tests. Much effort was put into the standardization to simplify the evaluation of functional muscular coordination of the lumbar spine.The present study showed good to very good inter-rater reliability for two standardized tests, i.e. the single-limb stance and sitting on a Bobath-ball with one leg lifted. Inter-rater reliability for the unilateral pelvic lift test was moderate to good. Validation of the tests in their ability to evaluate lumbar stability is required.The authors declare that they have no competing interests.JT participated in the design of the study, participated in collecting the data, performed the statistical analyses, and drafted the manuscript. EH participated in the design of the study, the statistical analyses and in the progress and revision of the manuscript. Both authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Tennis elbow is a common musculoskeletal disorder; management options include physiotherapeutic, medical, surgical, and other forms of intervention. Some patients remain symptomatic despite best efforts. We present two patients who did not respond to medical and surgical treatments, and whose symptoms were relieved with duloxetine. This is the first report on the use of duloxetine to treat tennis elbow.Two mentally healthy young Asian women aged 32 and 27 years, each with tennis elbow of about 18 months duration continued to suffer pain despite treatment with analgesics, local steroid injections, physiotherapy, cryotherapy, ultrasound, and surgical release, among other interventions. Both showed substantial improvement within 4 to 6 weeks of receiving monotherapy with duloxetine 60 mg/day. Both were pain-free with continued treatment at a 6-month follow-up.Duloxetine may be a useful treatment option in patients with chronic tennis elbow, even those who have failed conventional medical, physiotherapeutic, surgical, and other forms of management. Lateral epicondylalgia or tennis elbow is a common cause of pain and disability; it often develops in non-athletes. It is characterized by pain and tenderness centered around the lateral epicondyle. The source of the pain was initially thought to be due to extensor carpi radialis brevis degeneration. However, it is now recognized that the lateral epicondyle, the annular ligament, the radial head and the capitellum may also contribute to the experience of pain in tennis elbow .Several factors have been implicated in the causation of tennis elbow. These include overuse of the affected limb, repetitive forceful movements, training errors, misalignments, flexibility problems, ageing, poor circulation, strength deficits and muscle imbalances ,3.Tennis elbow can be difficult to treat. The condition is prone to recurrence, and the symptoms may last for several weeks or months, with the average duration of a typical episode reported to be between 6 months and 2 years . Non-opeDuloxetine is an antidepressant which acts by serotonin and noradrenalin reuptake inhibition . DuloxetA 32-year-old woman, presented with symptoms of tennis elbow of the right limb of 18 months duration. She had been treated with analgesics, splint immobilization and rest, local steroid infiltrations, ultrasonic therapy and autologous blood infiltration over a period of 1 year. She had also undergone lateral tendon release 7 months earlier. A psychiatric evaluation was sought because of the unrelenting nature of the pain arising from the common extensor muscles of the forearm. Physical examination showed tenderness just distal and anterior to the lateral epicondyle along with pain with resisted wrist extension with elbow in full extension. Clinical interview identified no Axis I psychiatric disorder. The pain on the visual analogue scale (VAS) was about 70–75 mm, with 0 being none and 100 being maximum pain. The initial Nirschl stage was 5 [She was prescribed duloxetine in a dose that was increased to 60 mg per day over 5 days; analgesic treatment was stopped. She reported a gradual reduction in pain; VAS scores dropped to 40 after 3 weeks, and to 25 after 4 weeks. She was substantially pain-free after 6 weeks of treatment. The tests for elbow tendinosis, including resisted wrist extension and supination and 3rd digit extension, did not produce pain. The Nirschl stage was 2.A 27-year-old woman was diagnosed with right-sided tennis elbow of 18 months duration. She had been treated with analgesics, plaster immobilization, multiple steroid infiltrations, cryotherapy, ultrasonic therapy, and prolonged brace wear. She had experienced limited pain relief lasting for less than a fortnight on most occasions. Nirschl tendon release was done after the conservative methods failed. She experienced partial pain relief for 4 weeks but again developed pain. She was referred for a psychiatric evaluation but this did not reveal any Axis I psychiatric disorder. The pain on VAS was 65–70 mm with a Nirschl stage of 4.She was prescribed duloxetine 60 mg/day. After 4 weeks, the VAS score had dropped to 30. The tests for elbow tendinosis, including resisted wrist extension and supination and third digit extension, did not produce pain. The Nirschl stage was 2.Both patients continued with duloxetine to a 6-month follow-up, at which time VAS scores were recorded as zero.Chronic pain compromises quality-of-life and impairs work performance. While a cure may not be feasible, treatment efforts should aim for pain relief and improvement in the quality-of-life.Pain is transmitted from peripheral sites along two sets of afferent nerves, that is, the A delta and C fibers. These synapse in the dorsal horn of the spinal cord. Preliminary processing of pain information occurs here before transmission through ascending tracts to the thalamus and higher brain centers. Pain information however, can be modulated by the activity of descending inhibitory fibers passing from the brain to the spinal cord. The neurotransmitters primarily involved in the descending pathways, that is, norepinephrine and serotonin, act synergistically in reducing the transmission of pain information from the periphery to the central nervous system ,12. AnalDuloxetine may relieve pain in patients with chronic tennis elbow, including those who have failed to respond to medical, physiotherapeutic, surgical, and other interventions. The benefits of duloxetine and its impact on the pathology of the disorder merit investigation in prospective clinical trials.Written informed consent was obtained from both patients for publication of these case reports. Copies of the written consent are available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.ZAW reviewed the literature, and conceived of and drafted the manuscript; YHR performed the psychiatric assessment of the patients including the follow-up. SAD and MFB were responsible for the orthopedic assessment and revision of the paper. SS performed the psychological assessment of the patients. All authors read and approved the final manuscript.


Brief intervention programs for subacute low back pain (LBP) result in significant reduction of sick leave compared to treatment as usual. Although effective, a substantial proportion of the patients do not return to work. This study investigates predictors of return to work in LBP patients participating in a randomized controlled trial comparing a brief intervention program (BI) with BI and physical exercise.Predictors for not returning to work was examined in 246 patients sick listed 8-12 weeks for low back pain. The patients had participated in a randomized controlled trial, with BI (n = 122) and BI + physical exercise (n = 124). There were no significant differences between the two intervention groups on return to work. The groups were therefore merged in the analyses of predictors. Multiple logistic regression analysis was used to identify predictors for non return to work at 3, 12, and 24 months of follow-up.At 3 months of follow-up, the strongest predictors for not returning to work were pain intensity while resting , the perception of constant back strain when working , negative expectations for return to work , and having been to a physiotherapist prior to participation in the trial . At 12 months, perceived reduced ability to walk far due to the complaints , pain during activities , and having been to a physiotherapist prior to participation in the trial  were the strongest predictors for non return to work. At 24 months age below 41 years  was the only significant predictor for non return to work.It appears that return to work is highly dependant on individual and cognitive factors. Patients not returning to work after the interventions were characterized by negative expectations, perceptions about pain and disability, and previous physiotherapy treatment. This is the first study reporting that previous treatment by physiotherapists is a risk factor for long-term sick leave. This has not been reported before and is an interesting finding that deserves more scrutiny. Disability and work absence due to low back pain (LBP) present a major public health problem and high economical costs in western societies . The lonSeveral interventions have been identified to reduce complaints and disability due to LBP. Even the most efficient methods leave a number of patients without substantial relief, and being unable to RTW . The aimThe treatment program consisted of Brief Intervention (BI) or BI and a physical exercise program. BI is a light mobilization program where return to normal activity and work is the main goal of the intervention. Previous studies of BI for LBP have shown significant reduction of sick leave compared to treatment as usual -11. AlthPsychosocial risk factors, including emotional and social problems, disbelief in recovery, and fear-avoidance behaviour, have been shown to predict long-term LBP -16. Trea246 patients, 120 men (49%) and 126 women (51%), mean age 41.1 years (SD 10.7), sick listed 8 - 12 weeks for LBP participated in the trial  in the 5 neighbour communities of the spine clinic sent written information about the trial and invitation to participate in the study to patients sick listed 8 - 12 weeks, between 18 and 60 years, and diagnosed with one of the following ICPC-diagnoses; L02 (back pain), L03 (low back pain), L84 (back pain without sciatica), and L86 (sciatica). Copies of sickness certificates for 531 participants that had accepted the invitation were then sent to the spine clinic for evaluation for inclusion. 531 patients were referred to the spine clinic and evaluated for inclusion in the study. 133 were excluded before enrolment and 152 were excluded during the first and second visit at the spine clinic. Exclusion criteria were; pregnancy, recent low back trauma, cauda equina symptoms, cancer, osteoporosis, rheumatic low back disease, ongoing treatment for LBP by another specialist, and information from the general practitioner indicating forthcoming RTW  randomized into two groups, using concealed randomization procedures; BI (n = 122), which received no further treatment, and BI and a physical exercise program (BI/PE) (n = 124). There were no significant differences between the two groups on age, gender or other baseline characteristics. Patients in the BI/PE group participated in an exercise program , designed to "re-educate" the trunk muscle to its normal stabilizing role, improve balance, muscle co-ordination and proprioception [ randomizAll patients answered a number of standard validated Norwegian versions of questionnaires including pain, psychosocial and sociodemographic data. Questionnaires were filled out at the spine clinic at baseline, three months after the second visit, and one and two years after the initial granting of sick leave for both groups. The questionnaires were answered individually by the patients, and were independent of researcher and clinician influence. The following questions and questionnaires were considered to be potential predictors.Hopkin's Symptom Check list (HSCL-25) [Fear-Avoidance Beliefs Questionnaire(FABQ) [Subjective Health Complaint Inventory [Roland Morris Questionnaire [Brief Pain Inventory (BPI) was used to assess pain [COOPER job stress questionnaire [Psychological distress was measured by the HSCL-25) , which cre(FABQ) . The FABnventory . Subjectionnaire , where aess pain . Only siionnaire . The scaionnaire . CODE mePrimary outcome was sick leave (due to low back pain) based on register data from local insurance offices and self-report. Non RTW according to register data included patients on sick leave as well as rehabilitation and disability benefit, while non RTW according to the self-reported data was defined by a confirmative response to the question: "Are you sick listed now?". Sick leave status after one and two years were estimated within a timeframe of 14 days before and after the exact date of sick leave. This was done in order to account for patients being put off the sick list just before the date of sick leave, and patients being off the sick list for a few days before a new sick leave period. Data from the insurance offices and self-reported data showed perfect agreement. Information from the local insurance offices was missing on 15 patients, in these cases the self-report data was used to ensure fuller datasets.SPSS 14.0.2 was used for all the statistical analyses. Since there were no differences between the intervention groups at any follow-ups  the grouExpectations of RTW was divided into "positive expectations" (agreeing to the statement) and "none or negative expectations" (no opinion or disagreeing to the statement), and sleep problems due to pain was divided into "seldom or never" and "sometimes, often or all the time". Potential predictors were tested with simple logistic regressions. RTW versus non RTW after 3, 12, and 24 months were the dependent variables . All variables with p-values less than 0.01 in the univariate analyses were considered to be potential predictors and were included in the fully adjusted model. Gender, age, education, and treatment group were included as control variables. Stepwise logistic regression was performed to see if the results from the fully adjusted model were consistent. Only patients with complete data were included in the multiple regression models. No imputation methods were therefore applied on any of the single items. However, if subjects had less than 50% missing on a subscale, mean scores on other variables in the subscales were used to compute sumscores.All variables were dichotomized using median split. The study was approved by The Regional Ethical Committee and the Norwegian Social Science Data Services National Register of Data. All principles in the Helsinki declaration were followed. The participants were given declarations of voluntary participation with detailed information. Informed consent was signed by each participant with emphasize on the right to withdraw from the experiment at any time without any explanation.No significant differences were found between BI and BI plus exercise on RTW at 3, 12 or 24 months , and botNo significant differences were found in baseline characteristics or RTW between those included in the multiple regression models (complete datasets) and those excluded from the multiple regression models (not complete datasets).In the adjusted model for 3 months follow up, 72% (n = 176) of the participants had complete data and were included in the analyses. In the fully adjusted model, including possible confounders, pain intensity while resting (odds ratio (OR) = 5.6; 95% CI = 1.7-19.0), perception of constant back strain while working , negative expectations of RTW , and having been to a physiotherapist (PT) prior to participation in the trial  predicted non RTW at 3 months  of the participants had complete data and were included in the analyses. In the fully adjusted model, including possible confounders, perceived reduced ability to walk far due to the complaints , pain during activities , and having been to a PT prior to participation in the trial  predicted non RTW at 1 year  of the participants had complete data and were included in the analyses. Age below 41 years  was the only significant predictor for non RTW after 2 years table .Backwards stepwise regression was performed in order to test the models with higher power in the analyses. The results confirmed the results as shown in table The aim of this study was to identify predictors of non RTW after Brief Intervention (BI) and BI plus Physical Exercise at a spine clinic. High pain intensity while resting, the perception of constant back strain when working, negative expectations of RTW, and having been to a physiotherapist prior to participation in the trial, were significant predictors of non RTW 3 months after the second visit at the spine clinic. 12 months after initial sick leave, perceived reduced ability to walk far due to the complaints, pain intensity during activities, and physiotherapy prior to participation in the trial, were the strongest predictors for non RTW. Age was the only significant predictor of non RTW 2 years after initial sick leave.The results are in line with previous studies. Patients' own beliefs regarding RTW -26, patiThe surprising finding of this study was that previous treatment by a physiotherapist predicted non RTW. The type of physiotherapy treatment most frequently reported was passive treatments such as hot packs, massage, ultrasound etc table . We haveA limitation which applies for all prognostic studies is the possibility of omitting important predictors. Variables like work strain, or biological variables like genetics, were not included in this study and can not be ruled out as possible confounders. However, we know that although heavy work has been found to predict duration of sick leave , it seemMany theories have been suggested to explain differences in individual health. The recent Cognitive Activation Theory of Stress (CATS) combines physiological and cognitive explanations . AcquireOlder patients (above 41 years) were more likely to be back at work at 2 years follow up. Older individuals, still active in the labour market, might have established a positive response outcome expectancy, they have learned that they are successful. They might also have learned to cope with the complaints during the years, making them more robust than the younger patients. Patients with less ability to cope might have disappeared from the labour market at an early age, contributing to a "healthy worker effect" , leavingIt appears that return to work is highly dependant on individual and cognitive factors. Patients not returning to work after the interventions were characterized by negative expectations, perceptions about pain and disability, and previous physiotherapy treatment. Physical therapy as predictor of no return to work has not been reported before and is an interesting finding that deserves more scrutiny.The authors declare that they have no competing interests.EMH conceived of the study, and participated in its design and coordination. SER participated in the design of the study, performed the statistical analysis and drafted the manuscript. HRE participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/10/139/prepub


Passive suicidal thoughts are relatively common in patients with terminal cancer. There is a need for more information about the factors that influence these patients to desire death.To examine the prevalence of suicidal ideation among terminally ill cancer patients.Fifty-four terminally ill inpatients (27 men and 27 women) from the palliative care unit of the Oncology department of Kasturba Hospital, Manipal were evaluated on various rating scales for depression, hopelessness and suicidal ideation, and the correlation of suicidal ideation with medical symptoms such as pain, as well as awareness of the diagnosis and understanding of the illness.Most patients (79.7%) denied having suicidal thoughts or wishing for an early death; only 9.2% had severe suicidal ideation. Two patients (3.8%) with severe suicidal ideation had a past history of major depression. Factors such as the presence of pain, awareness of the diagnosis and understanding of the illness contributed to depressive mood states.Suicidal ideation and a desire for death appear to be linked exclusively to the presence of a mental disorder. In addition, poor pain control, and awareness of the diagnosis may also contribute to suicidal ideation. However, the epics mention the ending of one's life as justified under certain circumstances such as when a person is suffering from an incurable disease or intolerable pain. In ancient times, people who were too old to carry out their religious duties used to terminate their lives voluntarily by drowning, starvation, self-cremation (samadhi), etc.4Suicide rates tend to correlate with the degree of acceptance of suicidal behaviour in particular cultures. In India, for instance, religion forbids death by suicide and it is believed that one who commits suicide will not attain Some studies suggest that while relatively few cancer patients commit suicide, they are at increased risk for suicide.In a study of 44 terminally ill patients, 77.3% had never wished for death to come early. Three patients had been suicidal and 7 others had desired early death. All 10 patients who had desired death were found to be suffering from clinical depressive illness.9Another study examined 200 terminally ill inpatients by a semi-structured interview. Occasional wishes for death to come soon were reported by 44.5% of patients; 8.5% of the patients acknowledged a serious and pervasive desire to die. The desire for death was correlated with ratings of pain and low family support but most significantly with measure of depression. The prevalence of diagnosed depressive syndrome was 58.8% among patients with a desire to die and 7.7% among patients without such a desire.10There is a paucity of data on the incidence of suicidal ideation in terminally ill cancer patients. We investigated the occurrence of suicidal ideation/desire for death in this group to determine its association with the putative risk factors of depression, pain, awareness of the diagnosis, and the course and outcome of the illness.There is also a need for more information about the factors that influence terminally ill cancer patients to desire death, especially factors that might be remediable with medication and psychosocial interventions.13Seventy-six patients with a primary medical diagnosis of terminal cancer (life expectancy ≤6 months), were recruited from the palliative care unit of Kasturba Hospital, Manipal, India. Of these 76, 22 (28.9%) had to be excluded—7 (9.2%) had cognitive impairment, 6 (7.9%) had inability to communicate including impaired sensorium, 5 (6.6%) were physically weak or sick, and 4 (5.3%) died. Thus, the final group interviewed comprised 54 patients (27 men and 27 women). Diagnostic classification or treatment regimen was not a determining factor for selection. The study was approved by the ethics review committee of the hospital and all patients gave their consent to participate. Each patient underwent a semi-structured diagnostic interview leading to a DSM-IV diagnosis. In all cases the interview was conducted by the first author (KSL) who had been trained in the protocol. The psychological status of the patients was assessed through a series of psychiatric rating scales.This is a 21-item self-report inventory. Each item consists of four alternative statements that represent gradations of a given symptom rated in severity from 0 to 3. The instrument was either self-administered by the patient or read aloud by the examiner and rated. Symptoms such as anorexia, weight loss, insomnia, reduced energy and fatigue were taken as physical items which could be a part of any medical condition and hence excluded from the total score.This consists of 20 True–False statements to assess the extent of pessimism. Each of the 20 items score 1 or 0. The total score is the sum of the individual item scores. The possible range of scores is from 0 to 20. This scale was also either self-administered by the patient or read aloud by the examiner and rated.This scale quantifies the severity of current suicidal thoughts and wishes. It includes 19 items, each with 3 choices—0 (least severe), 1 (severe) and 2 (most severe). The total score is computed by summing up the individual item ratings; it can range from 0 to 38. The items quantify the frequency and duration of suicidal thoughts as well as the patient's attitude towards them. Subjective feelings of control regarding suicidal ideation are also assessed. The scale was completed by the examiner in a semi-structured interview with the patient.Assessment of the impact of medical factor (e.g. the presence of pain) on mental status: The intensity of pain was measured by the verbal rating scale comprising three descriptors-‘no pain’ or ‘least possible pain’, ‘pain controlled’, and ‘worst possible pain’.Awareness of the diagnosis: The following details were collected in a semi-structured interview.Patient's awareness of the diagnosis and understanding of the illness, details of its meaning, prognosis, course and outcome.What are the patient and the family being told?What and how much are they absorbing?Awareness of the diagnosis and understanding of the illness were graded as ‘present’, ‘partial/denied’, and ‘absent’.In the statistical analysis, unadjusted responses from the initial interview were used to determine the overall prevalence of suicidal ideation/desire-for-death phenomenon. Demo-graphic, psychiatric and medical correlates of suicidal ideation/desire for death were then examined. Descriptive statistics were generated for all the variables. Mean scores were computed for depression, hopelessness and suicidal ideation. ANOVA was done to compare the impact of medical variables such as pain, awareness of the diagnosis and the meaning of illness on the variables of depression, hopelessness and suicidal ideation on different patients.The sociodemographic profile of the study group is given in The duration of illness was 1–6 months in 61% of the patients; 6 months–1 year in 20.4%; and >1 year in the remaining. Of the men, 74.1% had a history of alcohol intake; about 45% of these men had dependence and the rest drank occasionally. The distribution of illness-related variables among the study group is given in The mean depression score in patients who were aware of the diagnosis was 21.7, whereas it was 20.8 in those who were not aware of the diagnosis. The degree of awareness of the diagnosis was significantly correlated with development of depression as well as hopelessness. The differences in the mean score of SIS were not statistically significant.In this study, 51.8% of the patients had pain. There were differences in the mean BDI, HS and SIS scores between the three groups on the variable of pain; these were statistically significant. The mean depression and hopelessness scores were higher in those patients in whom the pain was poorly controlled.It is evident from This study provides information about the occurrence of suicidal ideation in terminally ill cancer patients. A patient with terminal cancer goes through various emotional stages—denial, anger, bargaining, depression and finally acceptance. In the stage of depression one might experience hopelessness and fleeting suicidal thoughts. However, these reactions may be dependent on such physical and psychological variables as pain, awareness of the diagnosis, understanding of the meaning of cancer in terms of its course, prognosis and outcome, social support, previous coping style and financial standing. The site of illness and disability as a result of the illness might affect the mood of the patient.The robust association of suicidal ideation with current depressive symptoms leads to the hypothesis that suicidal ideation/desire for death may occur with greater frequency among patients who have increased vulnerability to depression as might be reflected in their psychiatric history. This hypothesis received partial support as only 2 of the 9 severely depressed patients had a past history of depressive episodes and others expressing a death wish had no past history of depressive episodes.Patients with terminal cancer develop suicidal ideation/ desire for death in different ways, and their experience helps to frame the terms of reference in planning various psychological interventions as well as in the euthanasia debate. In this study, a 60-year-old married woman with severe depression and hopelessness expressed repeated suicidal thoughts and pleaded for mercy killing. She had a past history of breast cancer and had undergone mastectomy. She later developed cancer of the oesophagus with metastasis. She had difficulty in swallowing, talked in whispers and wept incessantly whenever the examiner visited her. Her husband was always by her side and appeared caring and supportive. She reported that they were childless and no one would be affected by her death. She died 1 week later in the hospital. Two other patients  in their mid-forties had severe suicidal ideation. They had a past history of major depression and one of them was on treatment. Two other men in this group reported lack of financial support as a reason for suicidal ideation. Being the main bread-winners, their finances were affected, and they had unfulfilled commitments such as the marriage of a daughter, sick children to care for and no one else to take the responsibility of their wives and children after their death.Understanding and managing the problem of pain in cancer patients is of special importance. Pain is significantly associated with high levels of depression and anxiety. Chronic pain may be depression equivalent and may cause psychiatric syndrome. In this study about 51.8% of patients complained of pain which was distressing and 16.7% had a BDI score above 30. Depression, hopelessness and poorly controlled pain may be risk factors for suicide in patients with cancer.8karma, fate and destiny may be yet other reasons why, despite the worst life situations, people do not verbalize their death wishes. It should also be noted that all the patients had satisfactory social support networks, which might have facilitated coping with their crisis.It is interesting to note that about 79.7% of patients denied having suicidal ideation. This may be due to the fact that while many may harbour suicidal thoughts at some time or other in the course of their illness, they refrain from expressing suicidal ideation for fear of criticism from the family and treating team as death by suicide is stigmatized. Many were unaware of the concept of euthanasia and therefore did not ask about mercy killing. There also might have been some protective factors in the family and community at large due to which patients refrained from expressing suicidal ideation/death wishes. Belief in the theory of Patients who are suicidal require careful assessment to determine the underlying cause—whether it is a depressive disorder or an expression of the patient's desire to have ultimate control over the symptoms.


Morphine consumption can vary widely between individuals even for identical surgical procedures. As mu-opioid receptor (OPRM1) is known to modulate pain perception and mediate the analgesic effects of opioid compounds in the central nervous system, we examined the influence of two OPRM polymorphisms on acute post-operative pain and morphine usage in women undergoing elective caesarean delivery.-5) and weight-adjusted morphine (p = 6.6 × 10-5). There was also significant association of this OPRM variant and time-averaged self-rated pain scores (p = 0.024). OPRM 118G homozygotes used more morphine and reported higher pain scores than 118A carriers. Other factors which influenced pain score and morphine usage include ethnicity, age and paying class.Data on self-reported pain scores and amount of total morphine use according to patient-controlled analgesia were collected from 994 women from the three main ethnic groups in Singapore. We found statistically significant association of the OPRM 118A>G with self-administered morphine during the first 24-hour postoperative period both in terms of total morphine (p = 1.7 × 10Our results suggest that ethnicity and OPRM 118A>G genotype are independent and significant contributors to variation in pain perception and postoperative morphine use in patients undergoing cesarean delivery. Studies have consistently demonstrated the existence of individual differences for both clinical and experimental pain -3. TheseIn addition to pain sensitivity and tolerance, clinical studies indicate that there is extensive interindividual variability in drug response and voluntary use of analgesics ,10. For We have previously found an association of the OPRM 118A>G SNP with pain perception and the amount of morphine self-administered in Chinese patients undergoing the same surgical procedure . In anotThis study involved a prospective cohort of women undergoing elective caesarian section under spinal anesthesia at KK Women's and Children's Hospital. All study procedures were approved by the hospital institutional review board. Subjects were recruited consecutively over 28 months from May 2005 to August 2007. Written informed consent was obtained from the patients after the study was explained to them before the scheduled caesarean procedure.Data were collected on ethnicity, age, weight, height, duration of operation, and post-operative vital signs. Subjects were asked to state their ethnicity and that of their parents and all four grandparents. Information on previous lower segment cesarean section (LSCS), age, height and weight was obtained from case records. Before initiation of anesthesia, baseline blood pressure, heart rate, respiratory rate, and oxygen saturation by pulse oximetry were recorded. Intravenous access was then established with all parturients given 0.5 liter lactated Ringer's solution for prehydration. Spinal anesthesia was then induced with a standard single shot at L3-L4 or L4-L5 with the parturients in the lateral or sitting position. A 27-gauge pencil point needle was passed into the subarachnoid space and free flow of cerebral spinal fluid was ensured before the intrathecal dose of 2 ml of heavy bupivacaine 0.5%  and 100 μg of morphine was injected. Surgery was allowed to begin when sensory block to cold at patients' midline was detected at T4 level with the patients lying in the supine position with a 15° left lateral tilt.Only one patient had had "technical failure" due to unsuccessful attempts to obtain cerebral spinal fluid with the spinal needle. Patients who did not obtain sensory level of >T6 twenty minutes after the administration of spinal anesthesia were deemed to have a 'failed block'. Six were converted to general anesthesia due to such "failed block". All seven were withdrawn from the study. Antiemetics  were administered at the end of the surgery.On arrival at the post-anesthesia area, all patients received an IV patient controlled analgesia pump (PCA) . The PCA pump was set to deliver one mg IV bolus of morphine per demand with a lockout time of five minutes, without continuous background infusion. The maximum amount of morphine allowed was 10 mg/hour. The cumulative dose of morphine administered by each patient within every four-hour period was recorded until 24 hours post-operation. No other supplemental analgesics were given during the first 24 hours postoperative period.Seven patients who had PCA removed before 24 hours when the last three recordings were not zero, and one patient who misinterpreted the use of PCA pump were removed from the study. Another seven patients requested for withdrawal from the study because they did not want to continue with PCA.Other data recorded were nausea and pruritis on a severity scale of 0–3, 0 = none, 1 = mild, 2 = moderate, 3 = severe; vomiting as defined by the number of episodes; and respiratory depression as defined by a rate of < 8 and/or shallow breathing.At the postoperative recovery area and at four hourly intervals up to 24 hours counting from the time of administration of spinal anesthesia, subjects were asked to rate the degree of pain on the Visual Analogue Scale (VAS) consisting of numeric scale from zero to 10 points; with zero being "no pain" and 10 being "maximum pain".Patients who received nitrous oxide by inhalation and/or IV fentanyl of up to 100 μg were excluded from the study, as the use of intraoperative opioids and hypnotics could potentially affect pain scores and the use of PCA morphine postoperatively. Patients who were inadvertently prescribed and took any oral analgesic were also excluded from the analysis.At the time of establishing the mandatory intravenous access before surgery, three ml of blood was collected in EDTA tubes and stored. DNA was extracted in batches from frozen whole blood samples using the Gentra Puregene Blood Kit . DNA was checked for quantity and purity using the NanoDrop Spectrophotometer .The OPRM A118G polymorphism (rs1799971) was genotyped by the Taqman SNP Genotyping Assay ID C___8950074_1 . Amplification was performed in a volume of 12 μl containing 25 ng genomic DNA, Taqman Universal Polymerase Chain Reaction Master Mix, 60 nM of each probe, and 270 nM of each primer. Cycling and hybridization conditions were set according to manufacturer's instructions. The 50 cycles of denaturation and annealing/extension and post-polymerase chain reaction quantification of fluorescent intensity were performed using the Applied Biosystems 7300 Real-Time PCR System.The OPRM -172T>G promoter polymorphism (rs6912029) was genotyped by allele-specific PCR using primers CACAGAAGAGTGCCCAGTGA and GAGATACGCCAAGGCATCAGT followed by restriction with BSe8I at 60°C for hours. Following agarose gel electrophoresis, two bands (234 bp and 200 bp) would be observed for the T allele while the amplicon with the G allele would be unrestricted and remained as 434 bp.Summary statistics stratified by the genotypes of the OPRM118 locus were calculated for all variables. Normality for each variable was assessed using a Shapiro-Wilk test. Each variable with distribution that did not deviate from normality was summarized using the mean and standard deviation, and comparison across the three genotypes was performed with an analysis of variance (ANOVA). For variables with skewed distributions, the median and semi-interquartile range was calculated and comparison across the three genotypes using the Kruskal-Wallis rank sum test.Statistical significance for assessing Hardy-Weinberg equilibrium for the two OPRM polymorphisms was obtained using a Monte-Carlo permutation strategy. Multiple linear regression analysis correcting for race, age, BMI and average VAS pain score was performed to investigate the effects of OPRM polymorphisms on morphine intake per kilogram bodyweight. The amount of variance explained by each covariate was calculated by assessing the sums-of-squares decomposition in the regression. A separate multiple linear regression analysis was performed for each of the three ethnic groups, similarly correcting for age, BMI and average VAS pain score. Haplotypes for each sample at the two OPRM polymorphisms were statistically inferred using an Expectation-Maximization procedure, and haplotypic effects for the two OPRM polymorphisms were assessed. All analyses were performed using the statistical software R, and statistical significance was set at p < 0.05.A total of 1066 subjects were recruited. The procedure for some subjects did not meet study requirement and their data were removed. Among them there were 24 Chinese, 12 Malays, 11 Indians, 25 mixed ancestry or of races other than Chinese, Malays and Indians. Results from 994 subjects were included in the analysis. There were 620 Chinese (62.1%), 241 Malays (24.1%) and 137 Indians (13.7%). The mean age was 32.5 years (SD = 4.8), mean weight was 70.9 kg (SD = 11.1) and mean height 1.58 m (SD = 0.06). Six-hundred and ten were private or paying patients who paid for all surgical and hospitalization expenses fully while 384 were "non-private" patients who received co-payment from the government. For 33.6% of the patients it was the first caesarean delivery. Just over 50% had a prior caesarean delivery, 14.9% had two and 0.9% had three prior caesarean deliveries. Average duration of operation was 53.7 min (SD = 16.0). There was statistically significant difference between paying (47.9 ± 13.6 min) and subsidized class (63.1 ± 15.0 min).-7); allelic: p = 1.2 × 10-7, between Chinese and Indians , but not between Malays and Indians .The distribution of the genotype and allele frequencies for the A118G polymorphism (rs1799971) was significantly different between Chinese and Malays (genotypic: p = 1.0 × 10The average amount of morphine the patients administered on themselves through the PCA pump was 8.95 mg (SD = 9.59). Sixty-five patients did not use any, 129 patients used only one dose, while another 122 administered 2 doses. The highest amount recorded was 62 mg, followed by 55 mg. The rest were between three and 40 mg.Average VAS score was 0.594 (SD = 0.591). Two hundred and thirty-eight patients (23.8%) selected VAS score of zero for all six four-hourly time points indicating no pain at all during the first 24 hour post-operative period. The highest time-averaged VAS over the 24-hour period was 4.-5) and age (p < 10-3), with Indians and younger patients reporting higher maximum pain scores. For mean VAS scores, race (p = 2.1 × 10-7) and age (p = 0.046) remain significant factors. Paying class was marginally significant (p = 0.048) with private patients having lower mean scores.In a univariate analysis for maximum VAS scores, there was statistically significant association with both race (p = 4.2 × 10-16), followed by ethnicity (p = 2.5 × 10-14) with those of Indian ancestry using the most morphine. Other statistically significant factors were paying class (p = 3.7 × 10-6) and age (p = 5.5 × 10-4), with private patients and those older in age using less morphine.For weight-adjusted morphine usage, univariate analysis revealed that maximum VAS scores had the strongest association (p < 10-5) and weight-adjusted morphine (p = 6.6 × 10-5) (Table -3). There was also statistically significant difference at every time-point .For VAS scores, there was statistically significant association with 118 A>G polymorphism for the time-averaged VAS scores (p = 0.024) but not across all time-points  . Haplotypes consisting of the two polymorphisms were also assessed although this did not improve the association with the response variable significantly.-3) but not Malays (p = 0.085) and Indians (p = 0.804) for morphine usage . The trend was observed in both Malay and Indian groups  for all patients Table . This 11For OPRM -172 T>G, there was no statistically significant association between genotypes and nausea, number of vomiting episodes or pruritis for all patients or within any ethnic subgroup.-16), followed by ethnicity (p = 3.1 × 10-15) and OPRM 118 A>G (p = 5.2 × 10-5). If the p-value for the association with weight-adjusted morphine was corrected for OPRM 118 A>G, ethnicity is still a significant contributing factor (p = 1.1 × 10-10).In a multiple regression analysis, the most important factor contributing to bodyweight-adjusted morphine usage was maximum pain score (p < 10This study examined the effect of two polymorphisms within the OPRM gene on pain perception and morphine usage. The results showed that the 118G variant was associated with higher pain scores, higher morphine usage, and lower nausea score.Other studies on pain sensitivity have also found that carriers of 118G are more sensitive to electrical stimuli and chemically induced pain , and alsin vitro studies show that the there is lower expression of the receptor protein corresponding to the 118G allele [However, one study on labor pain showed that women carrying the 118G allele of OPRM were more sensitive to analgesic effect of intrathecal fentanyl . AlthougG allele -28.The allele frequencies for the 118G allele for each ethnic group were similar to what we have found previously with different sets of subjects from the same three ethnic groups . In the Due to the observed population difference and to rule out false association due to ethnic difference in allele frequencies, we have also analyzed the three groups separately. There was only statistically significant difference for Chinese but not the Malay and Indian subgroups. This could be due to the smaller number of subjects and the higher 118G frequencies for these two ethnic groups. Our sample size for Malays had 71% power to detect 20% difference in additive allelic effect, while our sample size for Indians had 66% power to detect 20% difference.We have previously reported on ethnic difference in VAS scores for this study group . With VAFor the OPRM promoter polymorphism, the TT group appeared to have the lowest average VAS scores. However, the number in this group was very small with only six Chinese, two Indians and no Malay having this genotype. Hence there was considerable uncertainty in the estimated medians. The potential importance of this SNP is uncertain at this point.Our results from a standardized acute post-operative pain model add to the evidence that OPRM 118 genotype influences the perception of pain and the consequent use of analgesia. We also found that ethnicity is an important factor in determining morphine requirement for post-cesarean analgesic. Identification of predictors could be important in the provision of post-surgical analgesic with morphine to provide adequate pain relief while minimizing the occurrence of side effects.The authors declare that they have no competing interests.ECT co-designed the study, supervised the genotyping and co-wrote the manuscript. ECPL designed the PCR-RFLP assay for the promoter polymorphism and performed all the genotyping. YYT did the statistical analyses. YL supervised the recruitment and co-designed the study and co-wrote the manuscript. HYL supervised the blood collection and DNA extraction. AS conceived the study, co-designed the study and co-wrote the manuscript.


This study examined the clinical results of surgical treatment using a mini-open muscle resection procedure under local anesthesia for intractable lateral or medial epicondylitis.Forty two elbows (41 patients) were treated surgically for lateral or medial epicondylitis. The indication for surgery was refractory pain after six months of conservative treatment, or a history of more than three local injections of steroid, or severe functional impairment in the occupational activities. The treatment results were assessed in terms of the pain using the visual analogue scale (VAS), Roles & Maudsley score, and Nirschl & Pettrone grade.p < 0.01): 0.3 at rest, 1.46 at daily activities, and 2.21 at sports or occupational activities. The preoperative Roles & Maudsley score was acceptable in 6 cases, and poor in 36 cases, which was changed to excellent in 23 cases, good in 16 cases, acceptable in 3 cases after surgery. According to the grading system by Nirschl & Pettrone, 23 cases were excellent, 18 cases were good, and the remaining 1 case was fair. Overall, 41 cases (97.6%) achieved satisfactory results. Postoperative complications were encountered in three cases. Subcutaneous seroma due to the leakage of joint fluid in two patients was managed by additional surgery and suction drainage, and resulted in a satisfactory outcome. One patient complained of continuous pain on occupational activity, but her pain at rest was improved greatly.The preoperative VAS scores of pain were an average of 5.36 at rest, 6.44 at daily activities, and 8.2 at sports or occupational activities. After surgery, the VAS scores improved significantly (The mini-open muscle resection procedure under local anesthesia appears to be one of effective methods for intractable lateral or medial epicondylitis. Lateral epicondylitis (tennis elbow) and medial epicondylitis (golfer's elbow) are the most common painful syndromes resulting from overuse of the elbow. Mechanical overload and repetitive stress on a tendon with a degenerative lesion are known to be the primary causes. Conservative measures using anti-inflammatory drugs, physical therapy, and local steroid injections can be the preferred options in the early stages. However, they produce unsatisfactory outcomes that can lead to chronicity and a pervasiveness of the symptoms in many cases. In addition, considering that they are work-related disorders, the patients cannot avoid uncomfortable experiences at work due to pain and low work capacity. Therefore, a surgical approach is indicated for the treatment of lateral and medial epicondylitis in patients unresponsive to long-term conservative treatment. The currently available surgical options are open, percutaneous, and arthroscopic. Each of these options is described as a successful procedure but the comparative benefits of these approaches have yet to be determined. Although Shin et al.This study evaluated the surgical outcome and efficacy of a mini-open muscle resection procedure under local anesthesia for lateral and medial epicondylitis in patients unresponsive to conservative treatment.The study population consisted of 41 patients (42 cases) who were treated with a mini-open muscle resection procedure under local anesthesia for lateral and medial epicondylitis at our hospital between February 2003 and June 2007. There were 28 females (29 elbows) and 13 males (13 elbows). The mean age was 47.5 years  and more than 50% of patients were aged between 40 - 49 years. Twenty-eight were right elbows and 14 were left elbows. The symptomatic elbow was on the dominant side except for 4 cases. There were 32 and 10 cases of lateral and medial epicondylitis. All patients were unilaterally affected except for 1 patient. When the patients were divided according to occupation, 17 were housewives, 21 were laborers, 2 were involved in sports activities, and 2 were office workers. The mean duration of morbidity was 28 months . An average of 4.2  local steroid injections were administered before surgery. The mean postoperative follow-up period was 13.4 months .The indications for surgery were as follows: more than 6 months of persistent symptoms despite the aggressive conservative treatments, such as rest, drug therapy, splinting, physiotherapy, and a history of more than 3 steroid injections for treatment, and functional impairment at work and home.All procedures were performed by a single surgeon (Y.M.K.) using a mini-open muscle resection procedure under local anesthesia, which is a modified version of the procedure reported by Nirschl.3)For lateral epicondylitis, the site of maximum tenderness over the lateral epicondyle was marked before, and an approximately 1.5 cm long skin incision was made under local anesthesia. The subcutaneous fat was held aside and the intermuscular septum was incised to allow palpation of the tip of the lateral epicondyle. The origin of the extensor carpi radialis brevis (ECRB), approximately 1cm anterior and distal to the tip, was detached from the bone using Bovie electrocautery . The degFor medial epicondylitis, the degenerative tissue at the origin of the common flexor was exposed and removed in a similar manner. The fascia of the common flexor was closed after multiple microfracturing of the cortical bone of the medial epicondyle.The elbow was immobilized in a long arm splint after surgery and joint movement within the comfortable range was allowed from the 1st postoperative day. Normal daily activities were allowed according to the level of pain. Progressive muscle strengthening exercises and sporting activities were allowed from the 3rd postoperative month.The pain was assessed preoperatively and postoperatively using a visual analogue scale  at rest, during daily activities, and during sports or work. The preoperative and postoperative VAS scores were compared to determine the improvement in pain.The Roles and Maudsley score and the Nirschl and Pettrone's grading systemp-value < 0.05 was considered significant.Statistical analysis was performed using paired t-test on SPSS ver. 10.0. A p = 0.007). The mean VAS score during daily activities improved from 6.44  preoperatively to 1.46  at the last follow-up (p = 0.002). The score during sports or work improved from 8.2  preoperatively to 2.21  at the last follow-up (p = 0.004). Overall, the level of pain improved significantly at rest, during daily activities and during sports or work  preoperatively to 0.3  at the last follow-up  of the 42 cases had satisfactory results: 23 (54.7%) cases were excellent, 18 (42.9%) were good and 1 (2.4%) was fair . With thThe postoperative complications encountered included two cases of subcutaneous seroma due to the leakage of joint fluid and one case of continuous pain. The former two cases, which were noticed after the skin suture was removed, were managed with revision under local anesthesia. The leaked fluid was wiped off and a suction drainage was inserted. Continuous drainage after reclosure of the fascia led to successful healing. Continuous postoperative pain was reported by a patient in whom the preoperative pain had been too severe to raise her arm. Although the pain improved after surgery, she informed us that a return to her former occupation (carrier) was not possible.Lateral and medial epicondylitis are syndromes that are characterized by local pain and tenderness over the elbow, which is the origin of the tendons that move the wrist and fingers. They are associated with housework, occupation and sporting activities, and cause great discomfort during daily activities. The cause of these syndromes is unclear but some suspected causesWith regard to the pathophysiology of epicondylitis, CyriaxLateral and medial epicondylitis are often treated with conservative measures, such as rest, medication, immobilization, physical therapy, and local steroid injection. Unfortunately, they recur in 12-30% of patients,Lateral epicondylitis has many possible causes and a number surgical treatment options. Among them, open ECRB release, percutaneous extensor tenotomy and arthroscopic ECRB release are currently the most preferred procedures with an 80-97% success rate.12)Good results were obtained by performing a resection of the denatured tissue after identifying the anatomical lesion at the origin of the ECRB or that of the common flexor through a minimal skin incision under local anesthesia. In addition, the procedure produced low levels of postoperative pain, a short hospital stay and rehabilitation period, and early return to daily activities. However, a randomized comparative study with a similar study population should be carried out because it was impossible to compare the three advantages of the procedure with other studies. In addition, lesions of the inside of a joint, such as a plica or synovitis, were not identifiable. Mucoid degeneration was observed and the deposition of steroid after the injection was observed during surgery in some cases.An improvement in the understanding of the disorder and in surgical techniques has led to the use of a smaller skin incision. However, the size of the skin incision was approximately 5-6 cm or was not even mentioned in most domestic studies. In addition, there was no information on the anesthetic method. Arthroscopy is one of the most common minimally invasive procedures, and can be performed under regional anesthesia. Therefore, it is believed that this method requires only an approximately 1.5 cm incision under local anesthesia without the need for hospitalization, and will be beneficial to patients in terms of avoiding general or regional anesthesia and reducing medical expenses.Surgical treatments often result in unsatisfactory outcomes but there are few papers describing the cause of such failures. According to Morrey,In this study, the complications after surgery included two cases of a subcutaneous seroma due to the leakage of joint fluid and a case of pervasive pain in the elbow. The former two were treated successfully with revision. In order to prevent the occurrence of such complications, care should be taken not to damage the articular capsule during the release of the ECRB. One patient, who could not return to work (carrier) due to pervasive pain, also stated that the preoperative severe intractable pain was reduced significantly.Verhaar et al.The limitation of this study was that an analysis was not made based on a comparison with other methods of anesthesia and surgical techniques, which were mostly heavier than the present method, in terms of intraoperative discomfort, postoperative pain, medical expenses, patient satisfaction, hospital stay, and rehabilitation period. Such comparisons will be performed in further studies.In conclusion, 41 (97.6%) out of 42 elbows with medial or lateral epicondylitis, which were unresponsive to long-term conservative treatments, were managed successfully with mini-open muscle resection procedure under local anesthesia. Overall, it is believed that this procedure is an effective treatment option that reduces the time and expense required for conservative treatments, allays the patient's concerns regarding anesthesia, and promotes a rapid return to work.


When conservative therapies for low back pain (LBP) are not effective, elective surgery may be proposed to these patients. Over the last 20 years, a new technology, disc replacement, has become increasingly popular because it is believed to maintain or restore the integrity of spinal movement and minimize the side-effects compared to fusion. Although disc replacement may relieve a patient from pain and related disability, soreness and stiffness of the lumbopelvic region seem to be common aftermaths of the surgery. This prospective case series was undertaken to identify and describe potential adverse events of lumbar spinal manipulation, a common therapy for low back pain, in a group of patients with symptoms after disc prostheses.Eight patients who underwent lumbar spine total disc replacement were referred by an orthopaedic surgeon for chiropractic treatments. These patients had 1 or 2 total lumbar disc replacements and were considered stable according to the surgical protocol but presented persistent, post-surgical, non-specific LBP or pelvic pain. They were treated with lumbar spine side posture manipulations only and received 8 to 10 chiropractic treatments based on the clinical evolution and the chiropractor's judgment. Outcome measures included benign, self-limiting, and serious adverse events after low back spinal manipulative therapy. The Oswestry Disability Index, a pain scale and the fear avoidance belief questionnaire were administered to respectively assess disability, pain and fear avoidance belief about work and physical activity. This prospective case series comprised 8 patients who all had at least 1 total disc replacement at the L4/L5 or L5/S1 level and described persistent post-surgical LBP interfering with their daily activities. Commonly-reported side-effects of a benign nature included increased pain and/or stiffness of short duration in nearly half of the chiropractic treatment period. No major or irreversible complication was noted.During the short treatment period, no major complication was encountered by the patients. Moreover, the benign side-effects reported after lumbar spine manipulation were similar in nature and duration to those frequently experienced by the general population. In industrialized countries, low back pain (LBP) is one of the most common heath problems, generating a great socioeconomic burden in the form of serious disability and work absenteeism -5. ApproIn the United States, it has been estimated that between 6 and 7.5% of chronic LBP patients undergo spinal surgery ,6. The mFor many years, vertebral fusion was considered to be the gold standard in surgery for disc degeneration . The maiIn the last 20 years, a new technology, disc replacement, has become increasingly popular  but remaClinical outcome measures, such as the Oswestry Disability Index (ODI), the SF-36 health questionnaire, the visual analogue scale (VAS), medication prescription and patient satisfaction, have been investigated in several clinical trials to assess disc replacement efficacy and safety ,27,28. ASpinal manipulation is one of the recommended conservative therapies for LBP -32. The Since disc prostheses are believed to restore normal segmental range of motion and reduce potential residual instability, patients with total disc replacement could probably be manipulated similarly to patients with nonspecific LBP by standard side posture spinal manipulation to alleviate residual pain. This prospective case series was undertaken to identify and describe potential adverse events of lumbar spinal manipulation in a group of patients with disc prostheses. We hypothesized that, after disc replacement, patients with residual, chronic LBP would present spinal manipulation side-effects similar to those generally described in a chronic LBP population.Maverick Lumbar Disc Model . However, despite this stability the patients involved in this study presented for chiropractic treatment with persistent, post-surgical, non-specific LBP or pelvic pain. Table Eight patients who underwent lumbar total disc replacement were referred by an orthopaedic surgeon (JFR) for chiropractic treatments. These patients had 1 or 2 total lumbar disc replacements and were considered stable according to the surgical protocol. Prosthesis stability was analyzed on antero-posterior and lateral radiographs at 8 weeks and on lateral flexion and extension radiographs at 12 weeks. The prosthesis in all patients was a metal-on-metal Patients were treated by 1 of the 2 practising chiropractors involved in the study, and only lumbar spine side posture manipulations were undertaken for standardization of the therapeutic procedure. After a brief neurological and orthopaedic examination was conducted to exclude the possibility of persisting neurological symptom, the segment to be manipulated by the chiropractor was identified using a combination of static and pain palpation (patients in prone position) regardless of disc prosthesis location. Both chiropractors performed the same sequence of examination, static and pain palpation prior to spinal manipulation. During the first chiropractic treatment, the patient was placed in a "preload" side posture position similar to the spinal manipulation procedure to evaluate if it was tolerated. Whenever the position did not yield any increase in lumbar pain level, a low-amplitude and high-velocity thrust was delivered at the painful segments, regardless of the disc prosthesis level. Patients were scheduled for 8 to 10 treatments at a frequency of twice a week . The totOutcome measures included the assessment of benign, self-limiting, and serious adverse events following low back spinal manipulative therapy using a customized questionnaire completed at the beginning of each consultation. This qualitative questionnaire has not been validated and was developed for this study. The ODI and the Fear Avoidance Beliefs Questionnaire (FABQ) were administered to respectively assess disability and fear avoidance belief about work (FABQ I) and physical activity (FABQ II). The psychometric properties of the ODI and FABQ (French versions) have been assessed recently, and both questionnaires present moderate validity as well as good reproducibility ,37. PainEight patients were included in this prospective case series. They all had at least 1 total disc replacement at the L4/L5 or L5/S1 level and described persistent post-surgical LBP interfering with daily activities. Mean baseline ODI score was 38.25 (2.0); mean pain score was 2.6 (1.1), whereas FABQ I (work) was 23.1 (16.4) and FABQ II  was 13.3 (12.3). In all patients, pain was increased by manual, static or dynamic palpation of the lumbar segments.The chiropractors were instructed to give between 1 to 10 lumbar spine manipulations. All of them were placed in a preload side posture position without any exacerbation of their pain. Spinal manipulation was considered successful when cavitation was audible or whenever the chiropractor was satisfied with the load applied and the resulting segmental motion .The most common adverse event of a benign nature was a slight increase in short-duration pain (less than 12 hours) in almost half of treatments administered but two patients in the trial reported severe back and leg pains after the first treatment. , positive straight leg raised test (radiculopathy at >70°) or organic dysfunction were noted. One of these patients presented non-organic signs on physical examination, characterized by a "give away reaction" during motor function testing, as well as generalized overreaction to physical assessment. The other patient was referred back to the orthopaedic surgeon after a trial of lumbar spine manipulation. The orthopaedic surgeon administered a local lumbar facet joint injection of anaesthetic and anti-inflammatory agents that led to significant symptom reduction. It is noteworthy that these 2 patients had higher scores on the ODI questionnaire (72 and 60), on the pain scale (4) and on FABQ (I: 42 and II: 24) before the intervention. High levels of pain, disability and fear avoidance beliefs have all been identified as risk factors for the development of chronic LBP or associated with poor prognosis ,40. We cSome patients will report residual, non-specific LBP after total disc replacement . In caseBy nature, broad conclusions and generalization from case series studies are limited. Interpretation of the study is limited by its small sample size and the absence of long term follow-up. Other common and especially uncommon adverse reactions may not have been detected because of such limitations. However, standardization of outcome measures, evaluation and intervention during this trial may have restricted potential biases. Future investigations should address the standardization of adverse reaction outcomes across patients but most importantly across studies. Moreover, the current trial included patients who received a particular disc prosthesis, and not all prostheses may be suitable for spinal manipulation. In all cases, the origin of post surgical LBP must be thoroughly assessed and underlying pathologies  should be ruled out by a specialist before any manual therapy is initiated. Finally, collaboration with surgeons is essential to determine safety of spinal manipulation procedures in this group of patients.Relationships between the best and worst outcomes of total disc replacement and several variables, such as gender, body mass index, occupation type, insurance type, surgery/prosthesis level and type, number of levels operated, smoker, back pain versus leg pain, previous surgery, radiographic placement, VAS scores, preoperative ODI scores and time off work before surgery, were studied recently ,45. TimeIn brief, although spinal manipulation only yielded modest pain and disability improvements during the short chiropractic treatment period, no major lasting complications were reported by the patients. Moreover, benign side-effects after lumbar spine manipulation were similar in nature and duration to those occurring in the general population. Clinical trials are needed to assess the safety and efficacy of spinal manipulation in patients with disc prostheses. Consultation with an orthopaedic surgeon should be essential prior to the initiation of spinal manipulative therapy in patient with disc prostheses until further research establishes effectiveness and safety.Written informed consent was obtained from the patients before the publication of this case series and any accompanying figure. A copy of the written consent forms was provided to the Editor-in-Chief of this journal.The authors declare that they have no competing interests.JOS and MDx were responsible for manuscript writing. JOS and MDt participated in the chiropractic treatments. JFR performed all clinical evaluations, surgery and postoperative follow-up. All authors have read and concur with the final manuscript. The article has not been submitted or published elsewhere.