It is a novel drug used for the treatment of postoperative pain with antihyperalgesic properties and a unique mechanism of action. Gabapentin and the related, more potent compound pregabalin have been shown to be beneficial in the treatment of neuropathic pain as well as postoperative pain following spinal surgery and hysterectomy. This study reviews five aspects of gabapentin: (1) chemical and structural characteristics; (2) pharmacokinetics and pharmacodynamics; (3) application in acute pain management; (4) adverse effects; and (5) drug safety. Overall, gabapentin has been reported to be a safe and efficacious drug for the treatment of postoperative pain.Gabapentin (1-aminomethyl-cyclohexaneacetic acid) is an amino acid that has the structure of the neurotransmitter  Primarily, three different classes of drugs are utilized for the treatment of postoperative pain . Unfortunately long-term clinical use of these agents is limited by their side effects. Gabapentin is a novel drug used for the treatment of postoperative pain with antihyperalgesic properties and a unique mechanism of action, which differentiates it from other commonly used drugs. Various studies have shown that perioperative use of gabapentin reduces postoperative pain.2-delta subunit of the dorsal horn neurons' voltage-dependent calcium channels, causing decreased calcium entry into nerve endings and thus decreased release of neurotransmitters. Other possible cellular mechanisms include the effects of gabapentin on NMDA receptors, sodium channels, monoaminergic pathways, and the opioid system  is a structural analog of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) . It is aof 10.70 . Gabapenof 10.70 , high peof 10.70 , and higA or GABAB receptors, does not block GABA uptake or metabolism, and has no direct GABAergic action [Though it is structurally similar to GABA, gabapentin does not bind to GABAc action . The mecc action . Becausec action .Gabapentin inhibits the tonic phase of nociception stimulated by formalin and carrageenan and in neuropathic pain models prevents mechanical and thermal allodynia and mechanical hyperalgesia . Though α2δ subunit of the voltage-dependent calcium channel, regulating the action of the calcium channels and neurotransmitter release [Gabapentin binds to the  release , 21, 22. release . Decreas release . These rOther effects of gabapentin that do not have major pharmacodynamic significance include slight reductions in the release of monoamine neurotransmitters  from mammalian brain tissue , 26 and Cmax) of 2.7 ± 2.99 mg per liter are reached in healthy volunteers approximately 3 hours after a single oral 300 mg dose [Cmax increases less than threefold due to the dose dependent saturable absorption of gabapentin [Administered orally, gabapentin is absorbed in part by diffusion and in part by the carrier-mediated, L-amino acid transport system . As a re mg dose . When thbapentin .μg per mL [Gabapentin has a high volume of distribution of 0.6–0.8 L/kg or 50–60 L in healthy volunteers , 32, 33 g per mL . Brain tg per mL . In ratsg per mL . The drug per mL .In contrast to many antiepileptic drugs, which are metabolized, gabapentin is not metabolized in humans and is eliminated solely by renal clearance. The drug is excreted unchanged in urine and undergoes first order kinetic elimination , 33. PlaGabapentin is unique among anticonvulsant drugs as it lacks hepatic metabolism, exhibits low protein binding, and does not induce or inhibit hepatic microsomal enzymes or inhibit the metabolism of other antiepileptic drugs , 34. No Ucak et al. evaluated the analgesic effects of perioperative gabapentin after coronary artery bypass graft (CABG) surgery with median sternotomy as well as internal mammary artery harvesting . They usZakkar et al. performed a literature search and identified five papers with the best evidence regarding the use of gabapentin to reduce the incidence of pain experienced by patients after thoracic surgery –46. TheyLee et al. explored the efficacy of using gabapentin (600 mg) 1 hour before the administration of anesthesia for thyroid surgery . He deteMisra et al. performed a study to investigate patients undergoing craniotomies and the efficacy of gabapentin plus dexamethasone on postoperative nausea and vomiting (PONV) and pain after craniotomy . PatientYu et al. performed a systematic review and meta-analysis to determine the efficacy of gabapentin in the management of postoperative pain after lumbar spinal surgery. They showed that oral gabapentin was efficacious in the management of postoperative pain at every time point during the first day after surgery and therefore is efficacious in reducing postoperative pain and narcotic requirements after lumbar spinal surgery .Ajori et al. performed a study investigating the preemptive use of gabapentin (600 mg) prior to abdominal hysterectomy and its influence on nausea and vomiting, and meperidine consumption . Pain waSiddiqui et al. performed a study investigating the effects of gabapentin (600 mg) orally 1 hour prior to surgery in patients with inflammatory bowel disease (IBD) undergoing major bowel surgery. This group found that a single preoperative administration of 600 mg gabapentin in patients undergoing major bowel surgery does not reduce postoperative pain scores, opioid consumption, or opioid-related side effects .Panah Khahi et al. explored the efficacy of preemptive use of gabapentin on reduction of postoperative pain in the first 24 hours after internal fixation of the tibia under spinal anesthesia . PatientGabapentin may have dose-limiting side effects, which could prevent some patients from achieving therapeutic plasma levels. Studies have reported no significant difference in the frequency of adverse events in patients receiving a higher dose as compared to those receiving a lower dose of gabapentin . The mosClivatti et al. performed a study looking at twenty-six randomized, placebo-controlled, clinical studies between 2005 and 2007 and evaluated the effects of gabapentin preoperatively (PRE Group) and pre- and postoperatively (PRE-POST Group) . The stuTuran et al. investigated the effects of gabapentin on acute postoperative pain and on morphine consumption in patients undergoing spinal surgery where 1,200 mg gabapentin was given 1 hour before surgery. The most common adverse effects of gabapentin observed during the study were dizziness and nausea but the number of incidences did not significantly differ from the placebo group and therefore no significant adverse effects were associated with a single oral dose of gabapentin . HoweverSen et al. showed that although the most common side effects after an elective hysterectomy were nausea and vomiting, there were no differences in the incidence of these side effects between the perioperative administration of a placebo, ketamine, and gabapentin . SimilarFurthermore, a study by Compton et al. evaluated the efficacy of gabapentin, a key agent for neuropathic pain, to reverse opioid-induced hyperalgia in methadone maintenance for the treatment of addiction patients . The twoA major complication that develops after the abrupt discontinuation of high-dose gabapentin used for the prevention of chronic postsurgical pain is withdrawal symptoms that clinically resemble alcohol or benzodiazepine withdrawal . Signs aGabapentin has been reported to be a well-tolerated and safe drug , 33, 63.Rowbotham et al. conducted a randomized controlled trial to determine the safety of gabapentin in reducing postherpetic neuralgia . In thisMcLean et al. performed a study which evaluated and demonstrated the tolerability and safety of gabapentin when used as an adjunctive therapy in doses required to achieve the most effective seizure control in patients with epilepsy . This stIn this study, McLean et al. showed that 48.3% of patients reported the occurrence of at least one adverse event and 36.4% of patients reported at least one associated adverse event . The mosA serious adverse event was defined as any event that was fatal, life-threatening, and permanently disabling, required or prolonged inpatient hospitalization, or was a congenital anomaly, cancer, or overdose and was reported in only 3.3% of patients . The mos1c levels from baseline to the termination of treatment in either group. As such, glycemic control was maintained during the study. Neurological examination data revealed no significant differences in the rate of disease progression and the proportion of patients with a change from normal or decreased at baseline to absent at study termination was similar between groups (less than 14% in each case) for the 3 sensory modalities tested . Dizziness and somnolence were the two adverse events reported to occur more frequently in the gabapentin group. Overall, this study showed that gabapentin monotherapy produced rapid onset of clinical meaningful pain relief with relatively minor and potentially avoidable adverse effects; in turn, this further supports the safety of gabapentin as described in the prior studies [Backonja et al. investigated the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy by titrating from 900 to 3600 mg per day or maximum tolerated dosage or placebo . The saf studies .Clinical studies have shown that gabapentin can reduce acute postoperative pain, decreasing the need for opioids. For example, a gabapentin dose of 1.2 grams per day 1 hour before surgery and for 2 days after CABG surgery showed that postoperative pain scores at 1, 2, and 3 days as well as the consumption of tramadol given as a rescue analgesic were significantly lower in the gabapentin group when compared to the placebo group . Additio


High-concentration-capsaicin-patches (Qutenza®) have been put on the market as a treatment for peripheral neuropathic pain. A minimum infrastructure and a determinate skill set for its application are required. Our aim was to assess the feasibility of treatment with high-concentration-capsaicin-patches in clinical practice in a variety of refractory peripheral neuropathic pain syndromes in non-diabetic patients.Observational, prospective, single-center study of patients attended to in the Pain Unit of a tertiary hospital, ≥18 year-old non-responders to multimodal analgesia of both genders. The feasibility for the application of capsaicin patch in clinical practice was evaluated by means of the number of patients controlled per day when this one was applied and by means of the times used for patch application.Between October 2010 and September 2011, 20 consecutive non-diabetic patients  with different diagnoses of refractory peripheral neuropathic pain syndromes, with a median (range) age of 60 (33–88) years-old were treated with a single patch application. The median (range) number of patients monitored per day was not modified when the capsaicin patch was applied [27 (26–29)] in comparison with it was not applied [28 (26–30)]. The median (range) total time to determine and mark the painful area was 9 (6–15) minutes and of patch application was 60 (58–65) minutes. No important adverse reactions were observed.High-concentration-capsaicin-patch treatment was feasible in our unit for the treatment of a population with refractory peripheral neuropathic pain. The routine of our unit was not affected by its use. Neuropathic pain management often involves the use of many therapeutic approaches  that are not free of side effects –7. In 20High-concentration capsaicin patches should be applied by a physician or by a health care professional under the supervision of a physician. Furthermore, specific skills and procedures should be applied according to the summary of the product . They inThis was an observational, prospective, single-center study of patients treated with the capsaicin patch in the Pain Unit. This study was based on the clinical practice without any modification. That is, the patients were administered the patches regardless of whether the study taking place. Therefore, this study simply took the opportunity to study their effects. This study was performed according to the stipulations of the Declaration of Helsinki and the level of protection of confidentiality concerning the protection of personal data as required by Spanish laws (LOPD 15/1999) was ensured. All patients gave their written informed consent for their medical information to be used for purposes of scientific research in accordance with the ethical committee of the participating site . The Ethical Committee approved the informed consent in September 2010.The capsaicin patch was applied following the instructions of the summary of product characteristics . MoreovePatients included in this study had to fulfill the following eligibility criteria: men or women, ≥18 years old with peripheral neuropathic pain, non-responders to multimodal analgesia and candidates to be treated with the capsaicin patch. No minimum VAS was required for inclusion. Patients with hypersensitivity to the active substance or to any of the excipients were not included.The following data were gathered: age, sex, diagnosis, previous analgesic treatments, pain intensity, localization and area of pain, concomitant pain medication, indicators of feasibility, health state and adverse events related to the capsaicin patch as well as the effectiveness of the capsaicin patch.The indicators used to assess the feasibility in clinical practice were “number of patients visited per day when the patch was applied” and “number of patients visited the same day of the previous week if the patch was not applied in the Pain Unit”. Likewise, as indicator of feasibility was used the times for patch application: “time to determine and mark the painful area”, “time of patch application” and “time to monitor”.The “number of the patients visited per day when the patch was applied” was defined as the total number of patients visited in the Pain Unit the day that capsaicin patch was applied and corrected by the number of doctors who attended patients that day. The “number the patients visited the same day of the previous week if the patch was not applied in the Pain Unit” was defined as the number of patients attended to in the Pain Unit the same day of the previous week that the capsaicin patch was applied and corrected by the number of doctors who attended patients that day. The previous week was chosen whenever no patient was treated with capsaicin patch.“Time to determine and mark the painful area” on the skin was defined as the total time (in minutes) needed by the physician to determine and mark the painful area. This variable includes: hair removal, washing and drying the skin, topical anaesthetic pretreatment and cutting the patch to match the size and shape of the treatment area. “Time of patch application” was defined as the total time (in minutes) from when the patch was applied until it was removed. “Time to monitor” was defined as the total time in minutes of monitored blood pressure from when the patient laid down on the couch until he/she was discharged from the unit.The tolerability and safety of capsaicin patch  was gathered. Likewise, the pain intensity and its evolution (at 2 and 12 weeks after the treatment) was evaluated by means of a Numerical Rating Pain Scale  at baseline (before applying the capsaicin patch treatment) and 12 weeks later (last visit). Furthermore, the pain intensity was also gathered by means of a verbal NRPS through a telephone control 2 weeks after applying the capsaicin patch. Likewise, the neuropathic pain was diagnosed by the validated Spanish versions of the DN4 with a score equal to or above 4 and by the Brief Pain Inventory (BPI). The health state was measured by means of the validated Spanish version of the EuroQol-5D  at baseline and 12 weeks later. Concomitant pain medications during the 12-week study were recorded.No formal sample size was performed. The sample size was defined as the whole population treated with the capsaicin patch in the first year available in our hospital.A descriptive analysis was performed to describe baseline population characteristics. Continuous variables were described as median (range: minimum-maximum) and categorical data were summarized as absolute frequency and percentages. As an exploratory analysis, the primary variable: the number of patients monitored per day in the Pain Unit when the capsaicin patch was or when was not applied was compared. The median and mean percentage changes in NPRS scores from baseline to 2 and 12 weeks later were calculated. The treatment success (responder) of the capsaicin patch was defined as a reduction of greater than 30% in pain intensity at 12 weeks from baseline. The percentage of responders and its corresponding 95% confidence intervals (95% CI) were calculated. The correlation between pain intensity evolution and health state was assessed. Data was recorded and analyzed using Microsoft Excel running on Windows XP .A total of 20 consecutive patients (7 men and 13 women), who fulfilled the inclusion and exclusion criteria, were treated with the high-concentration capsaicin patch between October 2010 and September 2011 (both included) in its first year of availability in our hospital. All these patients were included in this study and all of them gave their consent. The median (range) age was 60 (33–88) years-old. The median (range) of the history of pain treated with the patch was of 4 (0.6-14) years. The baseline characteristics of each patient included is shown in Table Prior to applying the capsaicin patch treatment, the diagnosis of peripheral neuropathic pain in non-diabetic patients was confirmed: post-herpetic neuralgia (6 patients), total knee arthroplasty post-surgical pain (3), painful scar , femoral cutaneous neuropathy , neuroma (3), complex regional pain syndrome (CRPS)-I after Colles’ fracture (1) and HIV-associated neuropathy 1). The median (range) DN4 score was 6 (4–10).All patients included had been treated with multimodal analgesia . Previous multimodal analgesia is shown in Table The capsaicin patch was applied to 20 consecutive patients without problems who were candidates for treatment (applicability 100%).The median number of patients monitored per day was not modified when the capsaicin patch was applied [27 (26–29)] in comparison with when the capsaicin patch was not applied [28 (26–30)]. The frequency for patients treated with the capsaicin patch was more or less every 2 weeks and only 2 patients were treated in the same week on only one occasion. Only in one case two patient were treated in two consecutive weeks and in the same day of the week, being the reference day the two same days of the previous week (two different weeks) when capsaicin was not applied.The median (range) total time to determine, mark the painful area and apply local anesthetic was 9 –15 minutPain during the capsaicin patch application (15 patients) was the most frequently reported adverse event. The pain intensity (NRPS) scored between 1 and 3. Only six (30%) patients required the administration of oral NSAIDs. Erythema on the area where the capsaicin patch was applied was reported in 9 (45%) patients, and ice was administered to 4 (20%) patients to reduce the sensation of heat. Pruritus was reported in 1 (5%) patient.No alteration in the electrocardiogram register after capsaicin patch application was found. A slight increase in blood pressure  was observed in the first fifteen minutes of capsaicin patch application. This increment in blood pressure was neither statistically nor clinically significant.All patients were pre-treated with a topical anesthetic cream  prior to application of a high-concentration capsaicin patch to reduce application related discomfort. The body areas treated were: thorax (7 patients), knee (3), thigh external side (2), leg external side (1), groin (1), foot (2), left flank (1), finger (2) and wrist (1).The median (range) pain intensity at baseline was 8 (4–9) [mean (sd): 7.5 1.7)] and it was 7 (0–9) [mean (sd): 5.8 2.6)] at 12 weeks from the capsaicin patch treatment. The overall median (range) percentage of the reduction in pain scores after 12 weeks was 13% : 23% (32)]. Eight  out of 20 treated patients were considered responders (≥30% of reduction from baseline): 4 (57%) out of 7 men and 4 (31%) out of 13 women. In the group of responder patients, the median (range) percentage of the reduction in NPRS pain scores was 56% (38%-100%) [mean (sd): 62.1 (21–0)], and in non-responders 11%  [mean (sd): 3.2 (13.6)]. Based on the responder definition of a pain reduction ≥50% from baseline, 5  out of 20 patients treated with a high-concentration capsaicin patch [1 (14%) man and 4 (31%) women] were achieved a pain reduction ≥50% from baseline (Table .6] at 12.7] and iConcomitant pain medications during the 12 weeks of study are summarized in Table The median (range) health state (EuroQol VAS) at baseline was 50 (20–90) [mean (sd): 50.8 (22.0)], and the descriptive system scored is shown in Table This observational, prospective 12-week study reports novel data on the feasibility  of the high-concentration capsaicin patch in patients who did not respond to multimodal analgesia. One of the most important reasons for performing this feasibility study was to identify both real and potential problems that may be encountered in applying this new treatment (capsaicin patch) routinely in the clinical practice. Our pain unit has three treatment rooms, three consultations rooms, and we work altogether with two specialized pain nurses leading to a flexible work minimizing the negative impact of the treatment application. During the consultation clinic the physician could develop the normal activity because the nurses were trained in performing this procedure including the patient monitoring.It is remarkable that no more than one patient was treated with a capsaicin patch per day and it was only in 1 week that the capsaicin patch treatment was applied to two patients. The aforementioned along with the small sample size may affect the interpretation of the feasibility data. However, the results suggest that the use of high-concentration capsaicin patch in our pain unit of a tertiary hospital may not have a relevant organizational impact insofar as the burden of visited patients was not affected the work-force. Thus, it can be carried out as planned within the estimated times.The use of high-concentration capsaicin patches requires organization –10. ThisIn spite of the time required to manage this treatment, capsaicin patch application time did not affect the number of patients treated per day in our Pain Unit. The capsaicin patch was not a difficult treatment to manage and it might be an alternative in patients with peripheral neuropathic pain and multimodal analgesia non-responders.Another objective of this feasibility study was to convince us of the treatment’s value. Conclusions on the effectiveness of capsaicin patch could not be drawn due to the study design, the low number of patients included and to the variability of indications of peripheral neuropathic pain tested. To our knowledge, limited or no evidence based on clinical trials is available on the efficacy of the capsaicin patch for peripheral neuropathic pain different from post-herpetic neuralgia and HIV-associated neuropathy in non-diabetic patients , 12 or iThe capsaicin patch was well tolerated. As expected, the most commonly reported adverse reactions were local transient pain at the application site, erythema and pruritus.At this point, it is worth mentioning that in our patients topical anaesthetic pretreatment was only applied for a time less than 60 minutes as specified in the Summary of Product Characteristics. In no case was it necessary to remove the patch before time. To manage the acute pain during the application of the capsaicin patch, oral analgesics (NSAIDs) and local cooling (ice) were administered in 30% and 20% of the patients, respectively. In fact, short-acting opioids, as recommended in the summary of product characteristics, were not necessary.This study has limitations that should be considered before drawing any conclusion. The study design  is not ideal for evaluating the impact of the capsaicin patch in clinical practice or for evaluating efficacy. The small sample size could lead to underestimating or overestimating the results obtained. In fact, this study was planned as exploratory. Data concerning the time of the analgesic treatment before inclusion in the study was not collected, and this might be affected the effectiveness. The evolution of pain was only based on 3 controls . In this vein, when the study was planned, it was thought that the moment of pain intensity control (between 8:00 am to 3:00 pm) could not be standardized. In order to minimize the effect of variability at the moment of gathering the pain intensity, this one was based on the worst pain in the last 24 hours. Likewise, in our pain unit, the interventional procedures are performed twice a week in the operating theatre but on different days from capsaicin patch application. Hence, the feasibility results may not be applicable in hospitals with different organizational structure.Data from this study provides evidence that the high-concentration capsaicin patch treatment was feasible in the pain unit of a tertiary hospital for the treatment of a variety of refractory peripheral neuropathic pain syndromes in a population of non-diabetic patients. The routine in our unit was not affected by its use. Nevertheless, pharmaco-economic studies are necessary to validate the feasibility of the capsaicin patch. No important adverse events were gathered.


Arterial punctures for assessment of arterial blood-gases can be a painful procedure. Lidocaine can be used to reduce pain prior to needle insertion but it is not a widely accepted practice. The purpose of this study was to determine whether a large size needle induces more pain compared to a smaller size needle for radial arterial puncture and to assess the anxiety associated with radial arterial punctures.We conducted a prospective, double-blind, randomized, controlled, monocentric study including all outpatients who had a planned assessment of arterial blood gas analysis. Patients were randomized to have the arterial puncture performed with a 23 or a 25 G needle. The main judgement criteria was pain during arterial puncture. Visual analogue scale for pain (VAS-P) and visual analogue scale for anxiety (VAS-A) were used to assess pain and anxiety during radial arterial puncture.p: 0.369, p<0.0001). There was a correlation between the pain experienced by patients and the anxiety experienced in anticipation of another arterial puncture .Two hundred consecutive patients were randomized. The 25 G needle was as painful as the 23 G needle . Time for arterial puncture was longer with the 25 G needle than with the 23 G needle . There was a correlation between the level of anxiety prior to the arterial puncture and the pain experienced by the patients (The use of 23 G needle allows quicker arterial sampling and is not associated with increased pain and symptoms. Anxiety was correlated with the pain experienced by patients during arterial punctures.NCT02320916Clinicaltrials.gov:  Arterial blood-gas (ABG) measurements are the gold standard to evaluate pulmonary gas exchange . HoweverCapillary sampling of arterialised blood taken from the earlobe is another technique to assess pulmonary gas exchange. This technique is less painful than arterial puncture without subcutaneous anaesthesia . CapillaThe aim of the present study was to compare the pain experienced during arterial punctures performed with a 25 G or 23 G needle. The secondary endpoints were the characterization of the pain and the anxiety associated with the arterial punctures.We conducted a monocentric, prospective, randomized, double-blind study.All consecutive outpatients who had planned assessment of arterial blood gas as part of their routine clinical care in our Respiratory Department between April 11 and May 25, 2013, were asked to participate in the trial. Written and oral information was provided to all the patients. They were then asked to provide written informed consent for their participation in the study. Exclusion criteria included patients under the age of 18, inability to provide consent, or the presence of a contraindication to arterial punctures based on the American Association of Respiratory Care Guidelines ) or a 25 G needle (5.21 mm [0–18.49 mm]) (p = 0.53) . There wp: -0.244, p<0.001).Arterial punctures took significantly more time when using the 25 G needle (42 s [35–55 s]) compared to the 23 G needle (33 s [24.5–35 s]) (p = 0.002) . There wp: 0.369, p<0.001). In the overall study population, the anxiety experienced by the patients with respect to future arterial punctures was correlated with the pain experienced during the arterial punctures . In the overall study population, there was a correlation between the anxiety experienced with respect to future arterial punctures and the level of anxiety experienced prior to the arterial punctures    . In the p<0.001) . In the  <0.001) . While tOur study showed that needle gauge has no significant impact on the pain experienced by patients during arterial punctures and that the use of small gauge needles lengthens the time required for the arterial punctures by about 10 s. Our study also provided more detailed informations on the type of pain experienced by patients and its correlation with anxiety.Arterial blood pressure is correlated with the filling time of syringes with 23 G needles . While wLike previous interventional studies on pain associated to ABG, our study did not find any difference in the level of pain between each group. Interestingly, the level of pain experienced in our study is lower than the level of pain described in the literature. Indeed, the level of pain assessed was 6.63 and 5.21mm in each group. This level of pain is lower than the ones that have been reported in previous works in the placebo groups: 30.1  and 23.8To the best of our knowledge, our study is the first to assess the impact of anxiety on the pain experienced by patients during arterial punctures. Several studies have reported a correlation between anxiety and pain in other settings ,23. Our As pain management is now a cornerstone of the care that has to be provided to patients and as pulmonary gas exchange assessment remains central to manage patients with breathing disorder, we think further research should be led in that field. As they often tend to have repeated ABGs, patients in acute respiratory failure are of special interest. Indeed, rather than a precise isolated value, the kinetic of their gas exchange is a more relevant information as it guides physicians’ treatment. In that perspective, non-invasive tool such as transcutaneous capnography or electrical impedance tomography could be of particular interest.Our study had several limitations. First, it was conducted in a single center with nurses experienced in performing arterial punctures and with patients in a steady state. We cannot thus extrapolate our results to patients with acute respiratory failure and to patients in whom arterial punctures would not be performed by experienced nurses. However, our study reproduced the daily clinical practice of chest physicians. Second, most of the patients had already experienced arterial punctures in the past. This may explain why the level of pain observed in our study was lower than in previous studies.Our study showed that pain associated with arterial puncture is not correlated with needle gauge and that anxiety is correlated with pain. We recommend the use of 23 gauge needles since they require less time than 25 gauge needles to perform the procedure. We also recommend that patients should be reassured prior to the arterial puncture. Further studies should be conducted to identify novel strategies to reduce the level of pain experienced by patients undergoing arterial punctures.S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(PDF)Click here for additional data file.S1 ImagePatients were installed on the right of the curtain and inserted their wrist between the curtains. Nurses were installed on the left of the curtain and performed the arterial puncture as well as the record the duration of the sampling using the chronometer.(TIFF)Click here for additional data file.


Contemporary therapies for metastatic castration-resistant prostate cancer (mCRPC) have shown survival improvements, which do not account for patient experience and health-related quality of life (HRQoL).This literature review included a search of MEDLINE for randomized clinical trials enrolling ⩾50 patients with mCRPC and reporting on patient-reported outcomes (PROs) since 2010.n=5 trials) and Brief Pain Inventory Short Form  questionnaires. The published data indicated that HRQoL and pain status augmented the clinical efficacy data by providing a better understanding of treatment impact in mCRPC. Abiraterone acetate and prednisone, enzalutamide, radium-223 dichloride and sipuleucel-T offered varying levels of HRQoL benefit and/or pain mitigation versus their respective comparators, whereas three treatments  had no meaningful impact on HRQoL or pain. The main limitation of the data were that the PROs utilized were not developed for use in mCRPC patients and hence may not have comprehensively captured symptoms important to this population.Nineteen of 25 publications describing seven treatment regimens  met the inclusion criteria and were critically appraised. The most commonly used measures were the Functional Assessment of Cancer Therapy-Prostate (Recently published randomized clinical trials of new agents for mCRPC have captured elements of the patient experience while on treatment. Further research is required to standardize methods for measuring, quantifying and reporting on HRQoL and pain in patients with mCRPC in the clinical practice setting. Generally, PSA level should be <0.5 ng ml−1 after radiation therapy and <0.2 ng ml−1 after a radical prostatectomy,2 and occurrence of two consecutive PSA level elevations is often considered biochemical recurrence or progression to stage D1.5 disease. Biochemical recurrence develops in ≈10% of low-risk and up to 60% of high-risk prostate cancer patients after external beam radiation therapy6 and in 20–30% of patients after radical prostatectomy9 despite use of ADT.Prostate cancer is the third most commonly diagnosed malignancy in the United States (after breast and lung), with an estimated 220 800 new cases and 27 540 deaths in 2015.10 and the death of >50% of patients within 3 years with historical standard therapies.15 This end of the disease continuum is termed metastatic castration-resistant prostate cancer (mCRPC), defined by cancer progression despite a testosterone level of <50 ng dl−1 (<1.7 nmoll−1).16Once prostate cancer has become metastatic, ADT is deployed and is highly effective, eliciting a response in most cases; however, resistance inevitably develops, resulting in transition to a lethal castration-resistant phenotype, affecting 10–20% of prostate cancer patients within 5 years,10 where HRQoL is considered a multidomain phenomenon capturing an individual's perceived mental, emotional, physical and social well-being over time.18 The first treatments approved by the US Food and Drug Administration for mCRPC management focused on the palliative benefits of pain control achieved by mitoxantrone, strontium and samarium.21 In 2004, docetaxel became standard of care after two phase III trials demonstrated a survival benefit over mitoxantrone.13 Data from one of these trials13 showed that global HRQoL improved from baseline to 6 months in patients receiving docetaxel despite similar rates of pain relief in both groups,22 suggesting that pain relief is only a component of HRQoL in mCRPC, as fatigue and physical function (upon which pain can have an impact) are also major contributors. Certainly, asymptomatic patients are more likely to have worsening HRQoL after cytotoxic chemotherapy treatment,23 and this risk must be weighed against potential benefits.The natural history of mCRPC can involve worsening symptomatology represented by a progressive decline in health-related quality of life (HRQoL) and worsening pain,31 Median overall survival (OS) among patients with nonvisceral mCRPC who received immunotherapy with sip-T was 25.8 versus 21.7 months in the placebo group.26 In patients with mCRPC before and after chemotherapy, respectively, targeted therapy with abiraterone acetate plus prednisone ,31 enzalutamide ,30 and radium-223 dichloride 32 all increased OS relative to control. Additional cytotoxic therapy with cabazitaxel was found to extend OS (15.1 vs 12.7 months) in men whose mCRPC had progressed after docetaxel therapy, when compared with the prior palliative standard of mitoxantrone.33 The life-extending noncytotoxic therapies in particular have potential to have a favorable impact on patients' HRQoL and pain and may strike a better balance between cancer control and toxicity.Since 2010, a fundamental shift has occurred in the mCRPC treatment landscape with the arrival of immunotherapy (sipuleucel-T (sip-T)), agents targeting androgen signaling , and a bone-targeting radiopharmaceutical (radium-223 dichloride), which extend survival when utilized before or after docetaxel chemotherapy.34 The US Food and Drug Administration defines a PRO as ‘any report of the status of a patient's health condition that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else.'17 PRO instruments typically include information about HRQoL, symptoms, function, satisfaction with care or symptoms, adherence to prescribed medications or other therapy, and perceived value of treatment.18 In the prostate cancer setting, multiple instruments have included specific symptoms relevant to the disease , the most widely used being the multidimensional Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, which indicates a worsening or improving HRQoL when the total score changes by at least 6–10 points on a 0–156 scale.35In response to the Prostate Cancer Clinical Trials Working Group 2 proposed principles of conduct for phase II and III mCRPC trials, the clinical trials of these new therapies evaluated patient-reported outcomes (PROs) to ensure that the overall efficacy and safety profiles of new therapies reflect patient experience and perceptions.Here we review PRO data from clinical trials of patients with mCRPC reported since 2010 in order to contextualize the overall impact of new treatment modalities from the patient's perspective, and in so doing, guide patient-centered care, clinical decision-making, and health policy decisions.To review clinical trials reporting PROs in patients with mCRPC, we conducted two separate searches of the US National Library of Medicine National Institutes of Health Medline database for full articles published between January 2010 and April 2015. We first created a database of all randomized, controlled trial articles in mCRPC using the following Boolean search term strategy: (prostate cancer) AND (castration-resistant OR hormone-refractory OR androgen independence) AND (randomized OR randomised). A second search was conducted as follows: (prostate cancer) AND  OR pain OR fatigue OR weight loss. Both searches were limited to articles published in English and combined to create the full data set of potentially eligible articles. Additional references were identified from bibliographies of published articles.We screened the title and abstract of each retrieved article for relevance against predefined inclusion criteria: clinical studies in mCRPC with a sample size ⩾50. We qualitatively reviewed full text articles for final inclusion and assessment based on the following endpoints of interest: change from baseline in PRO scores; time to improvement or deterioration in a PRO measure; and proportion of patients with improvement or deterioration in a PRO measure.41 Nineteen publications describing seven treatment regimens  were reviewed  Short Form .45 Three of the trials did not use an HRQoL instrument and only used pain instruments.47 These trials and one other collected data regarding use of analgesics, specifically opiate medications.49 Conversely, two trials did not use a dedicated pain instrument and used an HRQoL instrument only.51 The PREVAIL study  pain-related items, which complemented utilization of the BPI-SF.52 Patient-reported fatigue was reported in three studies: one utilized the Brief Fatigue Inventory (COU-AA-301)53 and the others utilized the fatigue symptom scale questionnaire of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30.51 Studies reporting FACT-P total and PCS scores included items addressing fatigue but, to date, no results have been published on fatigue domains of FACT-P scores specifically.Across the 10 clinical trials, 7 different patient-completed questionnaires measuring HRQoL and/or pain were used. All PROs had demonstrated reliability, had been subject to validation processes, were responsive to change in health state, and had well-established psychometric characteristics although the Pain Index has not been subject to same validation processes as far as we are aware . In the IL study  used twoMost studies reported time-to-event analyses  by use of Kaplan–Meier survival analysis and/or the proportion of patients with clinically meaningful improvement in a PRO score. Changes from baseline in mean scores for a particular PRO measure were not reported routinely.54 Patient compliance rates with PRO questionnaires were high during both studies.57Two registrational, placebo controlled, phase III studies of abiraterone acetate in mCRPC examined HRQoL and pain in patients progressing after docetaxel chemotherapy (COU-AA-301) and before docetaxel chemotherapy (COU-AA-302) despite ongoing ADT.55 Changes in estimated FACT-P total score from baseline to week 112 favored the abiraterone acetate plus prednisone arm over the placebo plus prednisone arm throughout the study (104 to 50 points vs 104 to 30 points).55 Median times to deterioration in FACT-P total score and PCS, as defined in 55 Additionally, median time to improvement in fatigue intensity  was shortened in the abiraterone acetate plus prednisone arm.53 Greater proportions of patients in the abiraterone acetate plus prednisone arm than placebo plus prednisone arm reported improvements in FACT-P total and PCS scores .53In COU-AA-301, patients had mean baseline FACT-P total scores approximating 108 of the maximum possible score of 156, indicating that these patients had a moderate level of HRQoL impairment.S scores , as wellS scores . Similar56 The BPI-SF pain data from COU-AA-301 showed a clear benefit in the abiraterone acetate plus prednisone arm, as evidenced by longer median times to first deterioration in worst pain and pain interference, where progression on both pain outcomes was confirmed at two consecutive follow-up visits (P=0.0018) and interference  was shorter in the abiraterone acetate plus prednisone arm than placebo plus prednisone arm. A greater proportion of abiraterone acetate plus prednisone than placebo plus prednisone recipients reported clinically meaningful palliation of worst pain intensity (45% vs 29% P=0.0005) and pain interference (60% vs 38% P=0.0002). Median duration of worst pain intensity palliation was also longer in the abiraterone acetate plus prednisone arm than placebo plus prednisone arm .56Patients enrolled in COU-AA-301 were considered mildly symptomatic based on a median BPI-SF question 3 score of 3 .p visits . This st57 Patients who received abiraterone acetate plus prednisone had lower risks for and longer median times to first deterioration in FACT-P total score and PCS scores than patients who received placebo plus prednisone .31In COU-AA-302, baseline FACT-P total scores averaged ≈122, indicating a patient population with a better HRQoL than the COU-AA-301 population.ednisone . A signintensity .28 Media58The FACT-P and BPI-SF completion rates were high throughout both registrational phase III studies of enzalutamide versus placebo, AFFIRM (following chemotherapy) and PREVAIL (chemotherapy-naive).P<0.001).35 In addition, significant treatment differences at week 25 favoring enzalutamide over placebo were evident for mean changes from baseline across all FACT-P subscale and index scores.35 Median times to deterioration in FACT-P total and PCS scores were longer in the enzalutamide arm than placebo arm .58 Enzalutamide was associated with a 44% reduction in risk for pain progression relative to placebo on FACT-P item 4 in AFFIRM (58 Of 64 patients (5%) who were evaluable for pain palliation assessments, 22 (45%) of 49 patients receiving enzalutamide reported pain palliation at week 13 versus one (7%) of 15 receiving placebo (difference 38% P=0.0079). A smaller proportion of patients had BPI-SF pain progression in the enzalutamide arm than in the placebo arm (28% vs 39% P=0.0018).58In AFFIRM, enzalutamide was associated with change from baseline to week 13 improvements in mean scores of the FACT-P item 4 , BPI-SF pain severity and BPI-SF pain interference , FACT-P PCS  and EQ-5D visual analog scale  scores measured at week 61.52 Median times to deterioration in FACT-P total and PCS scores were longer in the enzalutamide arm than placebo arm  and EQ-5D VAS .52The PREVAIL patient population had not yet been burdened by significant disease-related symptoms, but nevertheless had mild HRQoL impairment at baseline as evidenced by median baseline FACT-P total scores of 121  in the enzalutamide arm and 122  in the placebo arm.cebo arm , as wereP<0.0001).52 Significantly more enzalutamide patients than placebo patients had an improvement at any time during the study in all FACT-P subscale scores  and PCS (55% vs 34%) scores , as welle scores .P=0.0025) and interference  measured at week 25 favored enzalutamide over placebo.52 A lower proportion of enzalutamide patients than placebo patients reported progression of worst pain (29% vs 42% P<0.0001) and average pain severity (28% vs 44% P<0.0001) at week 13, but not week 25. Only the comparison on pain interference progression retained statistical significance in favor of enzalutamide at week 25 (23% vs 29% P=0.0195).52 Median times to progression in BPI-SF worst pain, average pain severity, and pain interference were significantly longer in the enzalutamide arm than placebo arm . Clinically meaningful improvements in FACT-P total score also favored radium-223 dichloride over placebo .47The ALSYMPCA trial compared the effects of radium-223 dichloride with placebo in mCRPC patients with symptomatic bone metastases who had either received docetaxel or were not planning to receive it.26 The original study design specified time to disease-related pain as a coprimary endpoint , but this endpoint was eliminated at enrollment.46 Results were released summarizing time to development of disease-related pain  in a post hoc pooled analysis of three randomized phase III trials of sip-T in men with asymptomatic or minimally symptomatic mCRPC with an expected survival of ⩾3 months.46 Time to disease-related pain was not significantly prolonged in the sip-T arm (P=0.038).46 The HR for time to disease-related pain in the IMPACT study was 0.80 . 46The IMPACT trial studied the role of the immunotherapy sip-T in the treatment of mCRPC patients with an expected survival of ⩾6 months.ip-T arm  but time33 The pain response rate (7.7% vs 9.2% P=0.63) and median time to pain progression  using the McGill–Melzack present pain intensity instrument  receiving either docetaxel alone or with estramustine had an improvement in their pain as measured by EORTC QLQ-C30, and 20% had an improvement on the more detailed BPI.49A phase II trial in Italy randomized 95 mCRPC patients to either docetaxel plus estramustine or docetaxel alone. There were no significant changes from baseline in EORTC QLQ-C30 total scores in either arm during treatment; however, only 59 of 95 patients completed both baseline and first post-treatment questionnaires at week 6, limiting the conclusions that can be drawn from this data set.51 Patients were randomized to receive either mitoxantrone, vinorelbine or etoposide. The primary endpoint was palliative benefit rate, defined as pain control without disease progression; HRQoL was a secondary endpoint and was measured with EORTC QLQ-C30 plus EORTC QLQ-PR25  was 8 months with abiraterone acetate plus prednisone57 and the placebo-adjusted delay in deterioration of the FACT-P PCS pain-related score was 6 months with enzalutamide.52 Aside from delaying cancer-related symptoms associated with disease progression, these agents are associated with postponement of cytotoxic chemotherapy and its attendant toxicities. For men with symptomatic osseous metastatic disease, radium-223 dichloride offered HRQoL improvement and appeared to slow the subsequent decline in HRQoL when added to standard therapy.We now have a far better basis for explaining to patients with mCRPC what they can expect as they initiate a new systemic therapy. For patients who have recently progressed to castration resistance and are either asymptomatic or minimally symptomatic, oral hormonal agents abiraterone acetate plus prednisone and enzalutamide offer a means to delay deterioration in HRQoL  by ≈4 months59 The overall impact of corticosteroids remains poorly defined, especially as many corticosteroid-related toxicities are related to cumulative doses and duration of corticosteroid use increases as life-extending therapies are applied earlier in the treatment paradigm. Thus, careful consideration of the risk-benefit ratio of corticosteroids in mCRPC patients is appropriate; however, we found little exploration of independent effects of corticosteroids on HRQoL and pain palliation in the publications we reviewed.Direct comparisons of the palliative effects and HRQoL impacts of the new agents for mCRPC treatment are not possible, as no head-to-head studies have been performed. One clinical issue that further complicates comparison of HRQoL data is the role of corticosteroids. Among agents currently used in mCRPC, corticosteroids are given routinely or required in conjunction with docetaxel, abiraterone acetate, cabazitaxel, and mitoxantrone, but are not required with enzalutamide or radium-223 dichloride. It is noteworthy that median time to mean pain intensity progression on the BPI-SF among chemotherapy-naive patients who received placebo plus prednisone in COU-AA-302 was 18.4 months, whereas in PREVAIL it was 5.5 months among patients who received placebo only. Other interstudy methodological factors, such as different methods by which a progression was defined and analyzed, likely explain such a large difference in this pain metric. Corticosteroids have known palliative effects but are associated with some risks that may impact HRQoL, including development of thrush, insomnia and fat deposition.et al.60 used patient interviews to generate a list of 16 issues and outcomes that are most important to mCRPC patients, and included items such as PSA anxiety, urinary obstruction/frequency, and change in self-image, which are not well represented in FACT-P and EORTC QLQ-30 questionnaires. Lack of consistency in applying PRO instruments creates further variability. For example, COU-AA-301 and AFFIRM both used the FACT-P and BPI-SF instruments, but the study methods differ in areas such as frequency of PRO assessments and definition of outcomes. In COU-AA-301, patients were only considered eligible for improvement in HRQoL if their baseline FACT-P total score was ⩽122, whereas in AFFIRM, all patients were considered eligible for improvement in HRQoL regardless of baseline FACT-P score. In addition to establishing standard time points and ‘response' or ‘progression' benchmarks, reporting time-linked outcomes, such as time to pain palliation or duration of pain palliation, and analyzing symptomatic and asymptomatic patient populations separately are needed in order to produce more clinically relevant data.Contextualizing HRQoL and pain palliation results is made difficult because of the inconsistency in methodology for evaluating these parameters. Most HRQoL instruments commonly used in mCRPC trials were not designed specifically for an mCRPC population. Consequently, these instruments may focus on issues more relevant to prostate cancer patients treated for localized disease and may not capture all major factors that drive HRQoL for men with metastatic disease. For example, Eton et al.61 observed a cohort of 280 mCRPC patients for up to 9 months in the clinical practice setting and found that their deterioration in HRQoL was more rapid than that described in major clinical trials, suggesting that clinical trial data may underestimate HRQoL challenges faced by real-world mCRPC patient populations. This also implies that the quality and depth of HRQoL data collected in a trial depends heavily on the approach used to gather it. More prospective observational data with serial HRQoL assessments is required to elucidate disparities between clinical trial and real-world settings regarding patient well-being. Although HRQoL instruments can be incorporated into practice,62 the manner in which HRQoL data from clinical trials are presented must be better standardized and reported in a way that lends itself to incorporation into everyday practice.Another difficulty in understanding the impact of therapies on disease burden and HRQoL in mCRPC comes from translating clinical trial data into real-world practice, as confounding issues relating to study design, patient selection, therapeutic implementation and healthcare delivery contribute to an efficacy-effectiveness gap. Patients enrolled in clinical trials may be healthier than average mCRPC patients, with fewer of the medical comorbidities often found in an older patient population. Patients with mCRPC in clinical trials may also have a lower burden of illness over the course of their disease. Sullivan Validating the implementation of PRO questionnaires in the clinical practice setting is required to ensure that information is captured accurately and without bias. Yet systematic collection of PRO data in routine clinical practice requires time and effort, placing a burden on patients, families, and clinical staff. In addition, although HRQoL instruments such as FACT-P and EORTC QLQ-C30 are validated for use in research, their utility in general clinical practice is unclear. Ultimately, once a practice completes PROs, clinicians will need tools to view sequential HRQoL information in parallel with the rest of the medical record so that these data can be interpreted in the context of the patient's treatment plan and cancer control. Applications that help clinicians explain to patients the impact of therapy on HRQoL, ideally with graphical depiction, will be helpful in stimulating dialog about the overall value of treatment.Since 2010, mCRPC has seen an increasing number of therapeutic options. When considering a specific treatment decision, a clinician must balance the potential HRQoL improvement that could result from disease control with potential HRQoL decrements related to adverse effects associated with treatment. To give context to the relative impact of treatments on HRQoL and pain, it is critical to understand the underlying disease burden in mCRPC patients and to standardize methods for measuring and quantifying HRQoL and symptom assessments. Active treatment with noncytotoxic agents, abiraterone acetate plus prednisone and enzalutamide, and radium-223 dichloride and sip-T, is associated with varying levels of improvement in HRQoL and pain status, but direct comparisons between treatments are not possible. As patients progress to mCRPC and receive life-extending therapies, PROs that are subject to validation processes in the clinical practice setting will be required to monitor their experiences with the disease and its treatment.


The prevalence of chronic postoperative pain after cardiac surgery has been reported from 17% to 56%.We aimed to compare the prevalence of postoperative pain between patients who had undergone CABG using the internal mammary artery (IMA) and those who had undergone other cardiac surgeries including CABG using the saphenous vein or cardiac valvular surgeries.In this cohort study, medical records of 188 patients were evaluated and divided into two equal groups (94 in each group); patients who had undergone CABG using the IMA (IMA group) and those who had undergone other cardiac surgeries using the saphenous vein or other cardiac valvular surgeries (non-IMA group). The patients' data were recorded in a self-structured questionnaire and then phone interviews were performed 3 months after the operations regarding the rate of postoperative pain. The severity of chronic pain was rated based on the numerical rating pain scale.The two groups differed significantly regarding the prevalence of pain (P = 0.023). In the IMA group, 83 (88.3%) patients experienced pain lasting for more than three months compared to 71 (75.5%) patients in non-IMA group. The two groups differed significantly with respect to the severity of chronic pain after cardiac surgery via sternotomy (P = 0.001). The groups did not differ significantly regarding the effects of chronic pain on their sleep, referral to a physician, and drug consumption to alleviate their pain. The IMA group experienced more complications at work and during their occupational activity.The rate and severity of chronic pain after cardiac surgery via sternotomy was higher in patients undergoing CABG with separation of IMA for revascularization. According to the International Association for the Study of Pain (IASP), chronic pain is a pain without any determined biological rate which persists after the normal rehabilitation period of a tissue for about three months . DespiteCardiac surgery is a potentially stressful process for patients since they are afraid of the final outcome of surgery, and believe that if they survive, sustained postoperative pain would affect and limit their routine life . SimilarConsidering the importance of this issue, we aimed to compare the prevalence of postoperative pain between the two groups of patients; patients who had undergone CABG using the IMA (IMA group) and those who had undergone other cardiac surgeries including CABG using the saphenous vein or cardiac valvular surgeries (non-IMA group) to understand, follow, and treat factors leading to chronic postoperative pain.In this cohort study, medical records of 188 patients referred to Nemazee and Shahid Faghihi Hospitals, Shiraz, Southern Iran during 2010-2012 were evaluated and divided into two equal groups (94 in each group); patients who had undergone CABG using the IMA (IMA group) and those who had undergone other cardiac surgeries including CABG using the saphenous vein or cardiac valvular surgeries (non-IMA group). The patients were in classes II and III of the American Society of Anesthesiologists (ASA) physical status class. The sample size was calculated using previous studies  as 94 patients in each group. The patients' data were recorded in a self-structured questionnaire and then phone interviews were performed regarding the rate of postoperative pain. The interviews were performed by an anesthesiology resident three months after the operations. The severity of chronic pain was rated based on the numerical rating pain scale (NRS) on a scale of 0-10 . General anesthesia was induced using the standard narcotic-based protocol for all the patients: midazolam, fentanyl, morphine, sodium thiopental for anesthesia induction and pancuronium for paralysis and maintained with isoflurane and fentanyl. Otherwise the patient was excluded. The sternum was incised using classic midline sternotomy in all patients and hypothermia during operation was in the range of 34-36 °C. Pain management was similar for all patients (diclofenac suppository and/or intravenous pethidine) in ICU. We included 25-65 year-old patients who had undergone cardiac surgery via sternotomy at least three months prior to the study, with an ejection fraction of more than 40%. The exclusion criteria were as follows: redosurgery, kidney and liver failure, malignant neoplasms, alcoholism, chronic psychological problems needing medication, ICU stay of more than 5 days due to respiratory complications and wound infection, addiction, and death. Patients with incomplete records or those unwilling to cooperate or were unreachable phone interviews were also excluded and replaced. Data was analyzed using SPSS software, version 19 . Chi-square, T-tests and Pearson’s correlation coefficient were used where necessary.The mean ± SD ages of the participants in the IMA and non-IMA groups were 54.5 ± 7.3 and 46.28 ± 14.2 years (range: 25-65 years), respectively. The patients’ demographic variables are summarized in We found that chronic pain after cardiac surgery was more prevalent in the IMA group 88.3%) than the non-IMA group (75.5%). This percentage was considerably higher than other related studies, which could be attributed to different surgical techniques during sternotomy and separating the IMA, duration of operation, patient's position, and postoperative acute pain management. In previous studies, chronic postoperative pain after cardiac surgery through sternotomy has been reported as 30% % than th, 10. FacThis study had some limitations such as incomplete patients' records, lack of patient’s cooperation, and being unable to reach patients. In conclusion, the rate and severity of chronic pain after cardiac surgery via sternotomy was higher in the IMA group compared to the non-IMA group. It is necessary to present methods to reduce chronic pain in such patients , 16.


The aim of this clinical investigation was to compare the level of discomfort reported by patients during the removal of orthodontic metallic brackets performed with four different debonding instruments.p = 0.05), and the data were analyzed using the BioEstat 5.0 software .The sample examined in this split-mouth study comprised a total of 70 patients (840 teeth). Four different methods of bracket removal were used: lift-off debonding instrument (LODI), straight cutter plier (SC), how plier (HP), and bracket removal plier (BRP). Prior to debonding with all experimental methods, the archwire was removed. Before appliance removal, each patient was instructed about the study objectives. It was explained that at the end of debonding in each quadrant, it would be necessary to assess the discomfort of the procedure using a visual analog scale (VAS). This scale was composed of a millimeter ruler scoring from 0 to 10, in which 0 = a lot of pain, 5 = moderate pain, and 10 = painless. The level of significance was predetermined at 5 % (The pain scores with SC were significantly higher than in all other methods. There were no significant differences between HP and BRP pain scores, and the LODI group showed the lowest pain scores. Statistically, significant differences were observed in the ARI between the four debonding methods.The biggest limitation of this study is that each tooth was not assessed individually.Patients reported lower levels of pain and discomfort when metallic brackets were removed with the LODI. The use of a straight cutter plier caused the highest pain and discomfort scores during debonding. Despite all recent developments in dentistry, patient’s complaints of pain or discomfort are commonly registered after different types of dental treatments and orthodontic therapy is not an exception , 2. The Orthodontic patients may experience pain not only during the phase of active treatment but also during the removal of fixed appliances . VariousIn an attempt to fill this gap in the literature, the aim of this clinical investigation was to compare the level of discomfort reported by patients during the removal of orthodontic metallic brackets performed with four different debonding instruments and to verify the integrity of the enamel after debonding.Before data collection began, the project was sent for approval by the research ethics committee of Southeast Bahia State University, and it received a favorable report (number 405.944). The sample examined in this split-mouth study was collected from a single private practice and included patients who had fixed orthodontic appliances removed in both arches. The inclusion criteria were the presence of an Angle class I malocclusion and permanent teeth, except the third molars. Conversely, patients requiring extractions or presenting teeth with restorations on the buccal surface were excluded from the study. The sample comprised a total of 70 female patients (840 teeth). The mean age at the time of debonding was 31 years and 10 months, ranging from 14 years and 3 months to 45 years and 11 months. All patients or their legal guardians signed an informed consent prior to initiating their treatment.All fixed appliances were bonded and removed by the same orthodontist, and the same brand and model of stainless steel brackets were used on all patients (Standard Edgewise 0.022 × 0.030 in.) . Prior to bonding, the buccal surface of all teeth was pumiced with a mixture of pumice and water on slow speed, enamel was conditioned with a self-etching primer , and the same resin composite  was used in all patients following the manufacturer’s instructions.Before appliance removal, each patient was instructed about the study objectives. It was explained that at the end of debonding in each quadrant, it would be necessary to assess the discomfort of the procedure using a visual analog scale (VAS). This scale was composed of a millimeter ruler scoring from 0 to 10, in which 0 = a lot of pain, 5 = moderate pain, and 10 = painless. Prior to debonding, the order and the debonding method for each quadrant were randomly selected. The teeth evaluated in this study were canine and premolars because their brackets were exactly the same.Four different methods of bracket removal were used Fig. . The firThe amount of composite remaining on the enamel surface was examined immediately after bracket removal. The patients were instructed to rinse with a solution containing fuccina  for better identification of residual composite adhered to the tooth. A portable electron microscope  was used to evaluate the adhesive remnant index (ARI) Fig.  23]. Th. Th23]. p = 0.05), and the data were analyzed using the BioEstat 5.0 software .For descriptive analysis of pain scores and ARI values, mean and standard deviations were calculated. The differences registered for all debonding methods were compared with the Friedman test followed by the Wilcoxon test to compare pairs. The level of significance was predetermined at 5 % (Figure Statistically significant differences were observed in the ARI between the four debonding methods Fig. . CompariThe search for ways to reduce patient’s pain and discomfort during different dental procedures has been a concern in contemporary dentistry , 22. TheThe results of this study showed significant differences on the patient’s discomfort between the four debonding methods. In general, the use of LODI caused lower levels of pain or discomfort to remove the brackets when compared to the other methods. Furthermore, the use of the SC was the method that presented the highest discomfort for the patients. This finding corroborates with previous clinical reports , 29, as The reasons that justify the different results found between the methods studied are unknown. However, the direction of the debonding force may influence the degree of discomfort during the removal of metallic brackets .According to Williams and Bishara , the dirThe discomfort felt in the premolars and canines were recorded in this study. This was an attempt to better standardize the sample. Primarily, because the brackets used for both teeth were identical. Secondly, because the type of tooth appears to influence on the threshold of pain, since the biggest complaints have been previously reported during incisor debonding . This maThe four methods of debonding were also assessed for their damaging potential to the enamel surface. A crucial point for this evaluation is the line of adhesive fracture during bracket debonding. According to Artun and Bergland , the enaA portable electron microscope was used to evaluate the ARI, which due to its reduced dimension could be introduced directly into the oral cavity. After debonding and prior to microscopic evaluation, the enamel was stained with fuccina to facilitate the composite visualization and quantification.The results of this study showed significant ARI differences among the four debonding methods tested. Despite these statistical differences, HP, LODI, and BRP showed clinically similar results, showing on average, approximately half of the enamel surface with remaining adhesive Fig. . HoweverTherefore, when compared to the other methods tested, the use of SC seems to be far from the ideal debonding method, since it has greater potential to cause enamel damage which caused greater patient discomfort. Furthermore, if bracket rebonding is required, the use of SC may also not be considered the method of choice for removal of the brackets since another study , 15 repoPatients reported lower levels of pain and discomfort when metallic brackets were removed with the lift-off debonding instrument.How plier and bracket removal plier generated intermediate and similar levels of patient discomfort.The use of a straight cutter plier caused the highest pain and discomfort scores during debonding.The ARI scored with all four debonding methods were not significantly different.According to our findings, it can be concluded that:


In stroke patients without pain, lower trapezius had furthermore a significantly earlier onset in comparison to stroke patients with shoulder pain . Serratus anterior also showed a significantly earlier offset in stroke patients with shoulder pain in comparison to controls (p = 0.01) and stroke patients without pain (p < 0.001). Analysis of muscle recruitment patterns indicated that for full range tasks, stroke patients without pain used early and prolonged activity of infraspinatus. In stroke patients with shoulder pain, recruitment patterns were characterized by delayed activation and early inactivity of serratus anterior. These timing results can serve as a reference frame for scapular muscle timing post-stroke, and when designing upper limb treatment protocols and clinical guidelines for shoulder pain after stroke.This study aimed to characterize scapular muscle timing in stroke patients with and without shoulder pain. Muscle activity of upper trapezius, lower trapezius, serratus anterior, infraspinatus, and anterior deltoid (AD) was measured  in 14 healthy controls (dominant side) and 30 stroke patients (hemiplegic side) of whom 10 had impingement-like shoulder pain. Participants performed 45° and full range anteflexion, in two load conditions. The impact of group, anteflexion height, load condition, and muscle was assessed for onset and offset of the different muscles relative to the onset and offset of AD, using a 3 (group) × 2 (height) × 2 (load) × 4 (muscle) mixed model design. Recruitment patterns were additionally described. Across all load conditions and groups, serratus anterior had a significantly earlier onset and, together with lower trapezius, a significantly later offset in 45° compared to full range anteflexion tasks ( Shoulder pain is a common complication after stroke, affecting one-third of stroke patients in general. It not only negatively impacts on a patient’s independency level and functional ability but also impedes a successful rehabilitation  and were considered eligible for participation in case they 1) were at least 6 weeks after a first time stroke ; (2) had mild to moderate upper limb motor impairment , prior to study participation.Scapular muscle activity was recorded using surface electromyography  at the hemiplegic side. Following muscles were measured: upper trapezius , lower trapezius (at one-third of the line between trigonum scapula and T8 processus spinosus), serratus anterior (anterior to the latissimus dorsi at the level of the scapular inferior angle), infraspinatus , and AD   was attached to the participants’ wrist (average weight 1.15 kg). A bar was placed in front of the patient at 45° of anteflexion to give visual information about the correct anteflexion height for this task. Participants were instructed to start with the elbow fully extended and thumb pointing upward, and to maintain this positioning during the anteflexion. To ensure correct task performance and a proper pace of task execution , each participant was given some practice trials.From the recorded trials, only the middle 10 repetitions were selected for data-analysis, as these were considered free from initiation or completion strategies. Raw EMG data were first high-pass filtered with a sixth-order Butterworth filter of 20 Hz to avoid movement and cardiac artifacts, and subsequently rectified and filtered with a low-pass filter (cut-off frequency of 45 Hz) to smooth the data. Both filters were implemented as bidirectional filters to reduce the phase error.Onset of muscle activity was defined as an increase in muscle activity of more than two SD on top of the mean baseline activity (as recorded for 10 s prior to movement start) for at least 50 ms. Muscular offset was reached when the recorded activity was lower than the mean baseline activity plus two SD for at least 50 ms . Afterwards, sequences of recruitment were further explored for each task at the level of the individual subject within each group. Given that the sampling rate of the EMG-signal was set at 2000 Hz (which implies a time resolution of 0.5 ms), time intervals could theoretically be measured with an accuracy of 1 ms. Even though bidirectional filters were used to reduce timing errors, an uncertainty error of 4 ms was taken into account. Therefore, the accuracy for determining the onset time was estimated at 10 ms, meaning that the difference in timing between two muscles within one individual had to exceed 10 ms to represent real difference in recruitment timing.Differences in onset and offset timing between groups , anteflexion heights , load conditions , and muscles  were analyzed using a 3 (Group) × 2 (height) × 2 (load) × 4 (muscle) Mixed Model  and muscle (p < 0.0001), and a significant interaction effect for height × muscle (p = 0.02) were observed for onset and offset.A significant main effect for height . Only serratus anterior and lower trapezius (both heights), and serratus anterior and infraspinatus (45° task) did not differ significantly from each other. Post hoc analysis further indicated that only serratus anterior had a significant earlier onset in 45° compared to full range tasks (p < 0.0001).Post hoc analysis of the height × muscle interaction effect for offset indicated that, over all load conditions and groups, all muscles had a significantly different offset (p < 0.005) except for infraspinatus and upper trapezius (both heights). This analysis also showed that only serratus anterior and lower trapezius had a significant earlier offset in full range compared to 45° anteflexion tasks (p < 0.001).group × muscle interaction effect was also found for onset and offset. Post hoc analysis for onset firstly indicated that, over all tasks, lower trapezius had a significant earlier onset in stroke patients without pain than in stroke patients with shoulder pain (p = 0.04). Second, for each group, all muscles showed a significantly different onset (p < 0.001), except for (1) infraspinatus and serratus anterior in controls, (2) infraspinatus and lower trapezius, and serratus anterior and lower trapezius in stroke patients without shoulder pain, and (3) serratus anterior and lower trapezius in stroke patients with shoulder pain.A significant Post hoc analysis for offset indicated that, over all tasks, serratus anterior had a significant earlier offset in stroke patients with shoulder pain compared to controls (p = 0.01) and stroke patients without shoulder pain (p < 0.001). Furthermore, all muscles showed a significantly different offset for every group (p < 0.001), except for (1) infraspinatus and serratus anterior, and infraspinatus and upper trapezius in controls, (2) infraspinatus and upper trapezius in stroke patients without shoulder pain, and (3) serratus anterior and lower trapezius, and infraspinatus and upper trapezius in stroke patients with shoulder pain.p < 0.001).In controls and stroke patients with shoulder pain, upper trapezius was activated first during each task, while lower trapezius was activated last. In stroke patients without shoulder pain, upper trapezius was also active first, but lower trapezius was activated last only during the 45°, unloaded task. In all other tasks, serratus anterior was activated last in this group. The difference in onset between upper trapezius and lower trapezius, and upper trapezius and serratus anterior was significant across all groups and tasks . Recruitment patterns based on average group data are visualized for every task in Supplementary Material .In every group, lower trapezius was also the first muscle that was inactive and upper trapezius the last. Only in stroke patients with shoulder pain, during the 45° tasks, serratus anterior was inactive first (in the loaded condition together with lower trapezius), while in the full range loaded task infraspinatus was inactive last. The difference in offset between upper trapezius and lower trapezius, upper trapezius and serratus anterior, and lower trapezius and infraspinatus was significant across all groups and tasks  and 73% (loaded) of controls, in 67% (unloaded) and 31% (loaded) of stroke patients without shoulder pain, and in 38% (unloaded) and 22% (loaded) of patients with shoulder pain. Infraspinatus was active before or together with AD in 45% (unloaded) and 31% (loaded) of controls, in 65% (unloaded) and 45% (loaded) of stroke patients without shoulder pain, and in 80% (unloaded) and 60% (loaded) of stroke patients with shoulder pain.Concerning For full range anteflexion tasks, serratus anterior activated before or together with the AD in 39% (unloaded and loaded) of controls, in 17% (unloaded) and 33% (loaded) of stroke patients without shoulder pain, and in 10% (unloaded and loaded) of patients with shoulder pain. Infraspinatus was active prior to or together with AD in 36% (unloaded) and 21% (loaded) of controls, in 70% (unloaded) and 42% (loaded) of stroke patients without shoulder pain and in 50% (unloaded) and 30% (loaded) of stroke patients with shoulder pain.offset timing during the 45° anteflexion tasks, serratus anterior was inactive before or together with the offset of AD in 55% (unloaded and loaded) of controls, in 28% (unloaded) and 35% (loaded) of stroke patients without shoulder pain, and in 50% (unloaded) and 67% (loaded) of patients with shoulder pain. Infraspinatus was inactive before or together with AD in 66% (unloaded) and 54% (loaded) of controls, in 32% (unloaded) and 45% (loaded) of stroke patients without shoulder pain and in 50% (unloaded) and 60% (loaded) of stroke patients with shoulder pain.For In full range tasks, serratus anterior was inactive before or together with the offset of AD in 77% (unloaded) and 69% (loaded) of controls, in 69% (unloaded) and 58% (loaded) of stroke patients without shoulder pain, and in 100% (unloaded) and 90% (loaded) of patients with shoulder pain. Infraspinatus stopped before or together with AD in 50% (unloaded and loaded) of controls, in 26% (unloaded) and 39% (loaded) of stroke patients without shoulder pain and in 80% (unloaded) and 70% (loaded) of stroke patients with shoulder pain.When moving the arm, our muscles exhibit a feed-forward or anticipatory control activity to ensure that the scapular position is adapted to the humeral position. As such, the scapula serves as a stable base for arm anteflexion. Motor control of the shoulder relies on a synchronized activation of the upper trapezius, lower trapezius, and serratus anterior (Inman et al., Across all tasks, we found a delayed onset for lower trapezius in stroke patients with shoulder pain as compared to stroke patients without shoulder pain. Inspection of the individual recruitment patterns further indicated that, especially in the low anteflexion tasks, a high percentage of stroke patients with pain had no or a delayed serratus anterior onset. This was not seen in controls or stroke patients without pain. Serratus anterior was moreover earlier inactive in stroke patients with shoulder pain compared to controls and stroke patients without shoulder pain, across all tasks. This was also confirmed in the inspection of individual recruitment patterns, i.e., more stroke patients with shoulder pain showed inactivity of serratus anterior before the offset of AD, compared to the other two groups. The alterations in stroke patients with shoulder pain are quite similar to the delayed serratus anterior and lower trapezius onset (Moraes et al., In contrast to our hypothesis and other studies who reported alterations in timing of lower trapezius and serratus anterior during loaded arm anteflexion in healthy persons and persons with impingement (Phadke and Ludewig, The lack of uniform data on muscle recruitment patterns in healthy controls and persons with impingement in previous literature (De Baets et al., A limitation of the current study is that we only included stroke patients who had developed the ability to move outside the synergetic pattern and to perform analytical anteflexion movements. As a consequence, results should not be generalized to patients who move in the abnormal, stereotypical pattern of elbow flexion with shoulder abduction–extension-external rotation, or elbow extension with adduction–flexion-internal rotation (Twitchell, Current study results paved the road to gain a deeper understanding on alterations in recruitment and the emergence of compensatory strategies in the scapular and glenohumeral stabilizers post-stroke. We identified the presence of compensatory motor control of infraspinatus during arm anteflexion in stroke patients without shoulder pain. Our results furthermore indicated that stroke patients with shoulder pain should relearn scapular motor control, mainly of the serratus anterior and lower trapezius to address the scapular setting and to restore dynamic stability while doing arm movements. Future treatment guidelines for scapular motor control and shoulder muscle strengthening should moreover consider the impact of a task demand, i.e., reaching height. As important stabilizers are already active in low anteflexion tasks to perform a scapular setting, this task is deemed highly suited for the training of temporal muscle timing early after stroke when patients may still have mobility problems in higher degrees. Motivating patients to perform arm anteflexion tasks in higher degrees in occupational or physical therapy should be done cautiously and only after a good control of scapular setting and rotation in lower anteflexion tasks has been established.This knowledge has the potential to offer a useful way for clinicians to prescribe appropriate therapeutic management strategies and for researchers to enhance knowledge in relation to this clinical challenge.All authors met following criteria: substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.http://www.frontiersin.org/Journal/10.3389/fnhum.2014.00933/abstractThe Supplementary Material for this article can be found online at Click here for additional data file.


Corticoids have potent anti-inflammatory effects, which may help in relieving pain and dysfunction associated with lumbar canal stenosis. We assessed the effectiveness of a decreasing-dose regimen of oral corticoids in the treatment of lumbar canal stenosis in a prospective, double-blind, randomized, placebo-controlled trial.2 at L3/L4, L4/L5, and/or L5/S1on magnetic resonance imaging; and claudication within 100 m were electronically randomized to an oral corticoid group (n = 31) or a placebo group (n = 30). The treatment group received 1 mg/kg of oral corticoids daily, with a dose reduction of one-third per week for 3 weeks. Patients and controls were assessed by the Short Form 36 Health Survey, Roland–Morris Questionnaire, 6-min walk test, visual analog scale, and a Likert scale. All instruments showed similar outcomes for the corticoid and placebo groups (P > 0.05). Obese patients exhibited more severe symptoms compared with non-obese patients. L4/L5 stenosis was associated with more severe symptoms compared with stenosis at other levels.Sixty-one patients with lumbar canal stenosis (50–75 years; canal area < 100 mmThe oral corticoid regimen used in this study was not effective in the treatment of lumbar canal stenosis. Symptomatic lumbar canal stenosis is characterized by degenerative alterations in several structures of the vertebral segment, including the zygapophyseal joint, flavum, articular capsule, and intervertebral disc. These alterations decrease the vertebral canal area, resulting in pressure on the neural structures that is As the population ages, the number of symptomatic patients is expected to increase. Indeed, symptomatic lumbar canal stenosis is the primary reason for surgical treatment of the spine in patients over 60 years of age. TreatmeBecause spinal stenosis most frequently affects the elderly, a patient group with a high surgical complication rate, an oral regimen can dramatically improve overall treatment safety. To this end, we assessed the efficacy of oral corticoids for the treatment of lumbar canal stenosis.This prospective, double-blind, randomized controlled study was approved by the research ethics committee of Universidade Federal de Sao Paulo (CEP 1892/10). Sixty-one patients were electronically randomized to the drug treatment or placebo control group. Opaque envelopes were used to ensure the secrecy of the allocation. The drug treatment group was administered corticoids at 1 mg/kg/day with a one-third dose reduction per week. The control group was administered placebo for the same period. All patients were assessed at four time points during the study: baseline (T0), at the end of treatment , and at 6 and 12 weeks after study initiation . All patients were permitted paracetamol (750-mg tablets) up to 3 times a day as a rescue analgesic. Total paracetamol intake and response were also assessed. The patient and the assessor were blinded to treatment.All patients were assessed by the following instruments: canal area calculation; a 10-cm visual analog scale (VAS) for pain; the Roland–Morris Questionnaire for function; the 6-m2 in at least one of the levels assessed  by the Hamanishi technique[Inclusion criteria were the presence of claudication within less than 100 m and the presence of at least two of the following lower limb symptoms: pain, weakness, burning, tingling (associated with or independent of lower back pain), and a vertebral canal area of <100 mmThe exclusion criteria were as follows: decompensated diabetes mellitus, systemic hypertension, decompensated cardiopathy, systemic diseases affecting the lower limbs, neuromuscular diseases, use of corticoids in the past 3 months, previous lumbar or thoracic surgeries, cognitive deficits that compromise the capacity to understand or interpret the questionnaires, spondylolisthesis (except degenerative), degenerative scoliosis with a Cobb angle of >10°, degenerative pathologies in the hip or knee that can interfere with gait, and a history of total or partial arthroplasty in the hip and/or knee joint.The canal area was calculated on the basis of maximum anteroposterior (a) and mediolateral (b) area using magnetic resonance imaging (MRI). After calculating these values, they were individually divided by 2 and multiplied by π as show in the following formula:The constant is 0.8 when the canal is circular, 0.7 when the canal is elliptical, 0.6 in the presence of facetary compression, and 0.5 when the compression is caused by the disc and facets.The sample size was chosen to yield a statistical power of 80% and a α of 5% when comparing VAS scores between groups, assuming a group standard deviation of 2 cm and a minimum mean intergroup difference of 2 cm. We used Student’s t-test to compare continuous variables with a homogenous distribution across groups. Generalized linear models and unbalanced 2-factor ANOVA were used to test the temporal effect of medication and interaction between the test period and medication. Tukey’s test was used for 2 by 2 comparisons between time period and medication for the measurement points. Pearson’s correlation analyses were performed to assess the relationships among clinical variables. In all statistical tests, P-values of <5% were considered statistically significant.All 61 eligible patients, including 31 in the corticoid group and 30 in the placebo group, completed the study. There were no group differences in female: male ratio and there were no significant differences in height and weight between groups for the males and females. The mean and standard deviation for age was 58.23 (6.38) in the corticoid group and 58.33 (6.19) in the control group. Regarding BMI the mean and standard deviation for the corticoid group and control group was 25.97 (5.16) and 27.90 (4.53) respectively, and no difference were found between groups.The mean and standard deviation of the stenosis at the three levels assessed, namely L3/L4, L4/L5, and L5/S1, are presented in Table The VAS scores for pain suggested a mild improvement in both groups at T3, as indicated by the lower scores compared with those at baseline (T0); however, these scores increased thereafter, with no significant change across test periods between groups Table .The Roland–Morris questionnaire was administered at baseline (T0), after the 3-week drug/placebo trial (T3), and at 6 and 12 weeks after study initiation   and the control group intake was 19.63 (11.29) and no significant difference was observed between groups (p = 0.94).The Likert-type scale, wherein patients were instructed to document how they were feeling after treatment  also indicated no significant benefits of corticoids.The body mass index (BMI) show a low correlation with VAS for pain,  Roland Morris scores , six minute walk test  and SF-36 . Showing that increase in BMI did not lead to more pain or poor function and quality of life.Regarding the canal area we found a low correlation between lumbar canal stenosis at L3/L4 and more paracetamol consumption  and pain subscale of SF-36  showing that smaller canal area at L3/L4 leads to pain increase and makes patient’s to consume more analgesic medication.Stenosis at L4/L5 shows a low correlation with VAS for pain (r = 0.28 and p = 0.027), showing that patients with stenosis at L4/L5 level have worse pain.The oral corticoid regimen tested in this study provided no significant pain relief or benefits to motor function in patients with lumbar canal stenosis. The primary structures contributing to the decrease in spinal canal area and many of the symptoms of spinal stenosis are the intervertebral disc, zygapophyseal joint, flavum, and venous plexus. HoweverIn this study, the area of stenosis did not influence evolution of the disease, and similar to the findings of Zeifang, we found no relationship between the distance walked and canal area. Also, in accord with our study, Thornes et al. found thOur study included cases of degenerative spondylolisthesis, all between L4/L5. This eventually causes stenosis of the cauda equina roots,16. In tThis study attempted to identify an effective oral medication regimen for the management of spinal stenosis, while maintaining safety by using a decreasing-dose regimen. While this treatment appeared safe, with no obvious adverse events, it was not effective for pain or movement deficits. The effectiveness of corticoids in providing relief from this syndrome has been tested several times, most often when applied locally, and the clinical response has been highly variable,19-26. CObesity, often due to a sedentary lifestyle, is associated with loss of sagittal balance, changes in muscle strength, and a greater weight load on vertebral discs, all of which are likely to exacerbate degeneration. These patients are more susceptible to painful conditions and generally carry a poorer prognosis for most diseases. In this study as well, we found that patients with a higher BMI were more symptomatic, suggesting that weight loss is one safe noninvasive therapy that may improve symptoms and possibly obviate the need for surgery.The structures compression in lumbar canal stenosis leads to two changes: one caused by mechanical compression and another by venous dilatation and the venous blood retention can lead to local vascular inflammation and subsequent pain. These changes can cause neuropathic pain that can recruit inflammatory mediators enhancing the inflammation component. Probably the mechanical compression and edema during gait are the main causes of pain and inflammatory component is only a secondary adjunct in this disease. We assuStudies showing no effect of these potent anti-inflammatory drugs on stenosis symptoms suggest that inflammation is not important for symptom expression and that mechanical and anatomical alterations are more likely explanations. However, we do not know how effective this particular dose regimen was at decreasing inflammation around the stenosis sites; therefore, we cannot exclude a beneficial effect of other more efficacious and tolerable anti-inflammatory drugs.This placebo-controlled study indicates that a tapering regimen of oral corticoids, starting at 1 mg/kg daily, is not effective regarding pain, function, quality of life, analgesic consumption or satisfaction with the treatment in patients with lumbar canal stenosis when compared to placebo. Obese patients with lumbar canal stenosis show more pain or poor function and quality of life. Lumbar canal stenosis at L3/L4 leads with more analgesic consumption as compared with stenosis in other levels and lumbar canal stenosis at L4/L5 is more painful as compared with stenosis in other levels.• The use of oral corticoids is not effective in the treatment of lumbar canal stenosis.• Obese patients with lumbar canal stenosis show more pain or poor function and quality of life.• Lumbar canal stenosis at L3/L4 leads with more analgesic consumption as compared with stenosis in other levels.• Lumbar canal stenosis at L4/L5 is more painful as compared with stenosis in other levels.The authors declare that they have no competing interests.LCLR held the inclusion of patients, study design, statistical evaluation and formatting article. JN worked in study design, participated in its coordination and helped to draft the manuscript. All authors read and approved the article.