ERB) and 16 patients (840 fields throughout treatment) treated with a hydrogel spacer (GEL) without an ERB. Patient shifts were recorded before and after each treatment field, correlated with a treatment time, using x‐ray imaging and implanted fiducial alignment. For each shift, recorded in X, Y, and Z, a 3D vector was calculated to determine the positional change. There was a statistically significant difference in the mean vector shift between ERB (0.06 cm) and GEL (0.09 cm), (P < 0.001). The mean includes a large number of zero shifts, but the smallest non‐zero shift recorded was 0.2 cm. The largest shifts were, on average, in the Z direction (anterior to posterior). The average Z shift was +0.02 cm for both ERB and GEL. There was no statistical difference between ERB and GEL for shifts greater than 0.3 cm (P = 0.13) or greater than 0.5 cm (P = 0.36). For treatment times between 5 and 9 min, a majority of shifts were less than 0.2 cm, 85.9% for ERB and 73.2% for GEL. There was a significant positive correlation between the vector shifts and field time for both ERB  and GEL . We have shown that prostate motion is clinically comparable between an ERB and a hydrogel spacer, and the time dependencies are similar. A large majority of shifts for both ERB and hydrogel are well within a typical robust planning margin. For GEL patients, we chose to maintain slightly larger planning margins than for ERB due to already improved rectal sparing with GEL.The purpose of this study was to evaluate intrafraction prostate motion in patients treated with proton therapy and an endorectal balloon or a hydrogel spacer using orthogonal x‐rays acquired before and after each treatment field. This study evaluated 10 patients (662 fields throughout treatment) treated daily with an endorectal balloon ( Prostate motion is typically a function of bladder and rectal filling, and will vary day‐to‐day and during treatment. Most commonly, patients are aligned using implanted fiducials in the prostate. These fiducials can be aligned using orthogonal x‐rays and checked periodically throughout daily treatment, to evaluate prostate motion. In proton therapy, prostate cancer is traditionally treated utilizing an endorectal balloon. The benefit of an endorectal balloon is improved prostate stability and consistent rectal filling. There are several studies validating prostate motion with an endorectal balloon.In April of 2015, a hydrogel spacer, SpaceOAR  was approved by FDA for use in prostate radiation treatment. Since that time, this gel spacer has been utilized in several treatment modalities, including proton therapy. The hydrogel spacer is implanted between the prostate and the anterior wall of the rectum, providing additional separation and potentially improving high dose rectal sparing.It is clinically important to understand the effect of a hydrogel spacer and empty rectum on prostate motion during treatment, because this motion defines planning target margins and image guided radiation therapy (IGRT) protocols. Modern radiation therapy is moving toward hypofractionation and smaller PTV margins.The effect of a hydrogel spacer on prostate motion has been studied previously, comparing patients treated with gel and with an empty rectum without gel. One study utilized Calypso and found that the intrafraction motion is unaffected by the presence of the hydrogel.The purpose of this study, therefore, was to evaluate intrafraction motion of the prostate in patients treated with proton therapy and an endorectal balloon or a hydrogel spacer implant using orthogonal x‐rays acquired before and after each treatment field.2This study evaluated 26 patients; 10 of whom were treated daily with an endorectal balloon (ERB) and 16 were treated with hydrogel spacer implant (GEL) without an ERB.2.AOur fiducial and hydrogel implant procedure has been described elsewhere and is summarized, as follows.A single radiation oncologist performed all hydrogel and fiducial placements. There were no instances of rectal needle penetration and all procedures were performed without complications.2.BOn the day of the treatment planning CT (TPCT), patients were instructed to drink a certain volume of water at a known time before the TPCT, to ensure bladder fullness and reproducibility. All GEL patients were instructed to perform a fleet enema the morning of the TPCT. ERB patients had a 60 cc RadiaDyne endorectal balloon placed in their rectum and the balloon was filled with water. All patients were simulated supine, with a vacuum bag and knee immobilization. All patients also underwent MRI scans on the same day as the TPCT for improved target visualization. MRI scans were also useful for visualizing the hydrogel spacer.The TPCT and MRIs were fused, based on fiducials, to allow for target and hydrogel contouring on the TPCT. For all patients, the clinical target volume (CTV) for low risk patients included only the prostate, as visualized on MRI and CT fusion; the CTV for intermediate risk included the proximal and medial 1 cm of the seminal vesicles on the first phase of the treatment with a subsequent boost to CTV2, defined as the prostate. For ERB patients, the planning target volume (PTV) is an expansion of the CTV, 0.3 cm posteriorly and 0.4 cm elsewhere. For GEL patients, the planning target volume (PTV) is an expansion of the CTV, 0.5 cm posteriorly and 0.6 cm elsewhere. Increased margins were utilized for GEL patients due to the lack of a priori motion data. Additionally, because the rectum was displaced away from the prostate due to the hydrogel implant, larger margins did not necessarily provide additional high dose to the rectum. In addition, the PTV Evaluation  structure is an expansion of the PTV, 0.5 cm in the direction of the beams. For each plan in this analysis, lateral beams were utilized. PTV_Eval was used for inverse planning to increase dose range laterally, which improves dose coverage and overall plan robustness.Treatment was planned using the RayStation planning system with the following objectives and dose constraints: For target coverage, 95% of the PTV was to receive 100% of the prescribed dose and 100% of the PTV was planned to receive a minimum of 95% of the prescription dose. Generally, 99% of the CTV received 100% of the prescription dose. We have previously documented the ability to reach a rectum V90% of ≤1% using pencil beam scanning proton therapy and SpaceOAR with the margins and expansions described above. Therefore, our rectum OAR constraint was routinely set at V90% ≤1% for GEL patients and ≤10% for ERB patients, while maintaining target coverage priority. Each patient in this study was treated with two opposing lateral fields. Each patient underwent a robust evaluation by a medical physicist, analyzing the effects of patient motion in all directions, 3 degrees of roll, 3 degrees of yaw, and 2.5% + 0.1 cm range uncertainty. For ERB patients, the patient was shifted 0.3 cm in all directions, GEL patients were shifted 0.5 cm in all directions. Under all perturbations, the prostate CTV must maintain V100% ≥95%. Typical dose distributions are shown for both ERB and GEL in Fig. 2.CFor daily treatment, the patient was set up in the treatment position based on lasers and patient tattoos. The patient was then imaged using two orthogonal x‐rays. On the DRR, each fiducial had a 0.2 cm expansion created, known in‐house as the “grape”. In this study, the patient's shifts were recorded before and after each treatment field, correlated with a treatment time, in order to determine the amount of motion within each treatment time. This data was assessed using x‐ray imaging and fiducial alignment. Therapists were instructed to record the amount of shift necessary, in X, Y, and Z, to return each fiducial to within its respective “grape”. In order to treat, all 3 of the patient's fiducials must align within the respective grape. The shifts prior to field 1 were not recorded and were considered to be the zero point. Therapists did record the time at which the first images were acquired.Following the patient's first treatment field, the patient was imaged again. Both pre‐ and post field images are shown in Fig. At our center, we have two treatment rooms with a gantry and one treatment room with a fixed beam. In the gantries, the gantry was rotated 180 degrees between treatment fields. For the fixed beam room, the treatment table was rotated 180 degrees between fields. Following gantry or table rotation, the patient was imaged again and the necessary shifts and time point were recorded. These were the “Pre Field 2” shifts and time. At this point, the table was translated to return the fiducials to the center of the grapes. The second field was delivered and the patient was imaged a final time. These were the “Post field 2” shifts and time. The necessary shifts were recorded but not applied. For all images, if the fiducials were still in the grapes, even marginally, a zero shift was recorded.2.DThe patients were separated in to ERB and GEL, to evaluate the difference in intrafraction motion. For each fraction, the time during field 1 and field 2 were calculated. The intrafraction motion for each field was defined as the shift values recorded for the post field images. The Pre Field 1 shifts were assumed to be zero and not recorded. The Pre Field 2 shifts were recorded but not analyzed. Because the fiducials were aligned within the grapes before each treatment field, the post field shifts indicate the motion that occurred during each field. For each shift, recorded in X, Y, and Z, a resultant 3D vector was calculated to determine the 3D positional change. This is referred to as the vector analysis. We also evaluated the average changes in X, Y, and Z, referred to as the directional analysis. This allowed us to determine if one group showed prevalence in one shift direction over another. Finally, we were interested in the correlation of time with shift magnitude, e.g., does a longer treatment time lead to larger shifts.The vector shift distributions were not normally distributed, so they were analyzed using non‐parametric statistics with medians and interquartile ranges. Due to a non‐normal distribution, the time correlation was analyzed using non‐parametric Spearman's rho correlations.33.AP < 0.001). Figure Ten ERB patients were analyzed for a total of 662 fields. Sixteen GEL patients were analyzed for a total of 840 fields. There was a statistically significant difference in the mean vector shift between ERB (0.06 cm) and GEL (0.09 cm), (It should be noted that the mean shift includes a large number of zero shifts (83% for ERB and 69% for GEL). The smallest non‐zero shift recorded was 0.2 cm, which is the threshold distance of the “grape”.3.BThe largest shifts were, on average, in the Z direction (anterior to posterior). The average Z shift was +0.02 cm (anterior) for both ERB and GEL when evaluating both positive and negative shift values. When evaluating the absolute values of the shifts, Z remained the largest shift, at 0.03 cm for ERB and 0.06 cm for GEL.Table A scatter plot was also created for the individual shifts, evaluating X, Y, and Z, shown in Fig. 3.CDuring this study, we used a robust evaluation tolerance of 0.5 cm for GEL, therefore, we chose to evaluate patients who had a vector shift or directional shift that exceeded this value. The total number of fields with a vector shift exceeding 0.5 cm was 19 of 662 fields for ERB (2.9%) and 21 of 840 fields for GEL (2.5%).P = 0.13) or greater than 0.5 cm (P = 0.36).We also evaluated the vector shift distribution difference between ERB and GEL for vector shifts greater than 0.3 cm (ERB robust) and greater than 0.5 cm (GEL robust). There was no statistical difference between ERB and GEL for shifts greater than 0.3 cm , i.e., unidirectional shifts. In GEL patients, shifts in more than one direction within the same field were identified in three fields, for a total of 16 shifts in 13 of 840 fields (1.5%).3.DField 1 was evaluated separately from field 2 and it was found that, on average for ERB, field 1 had a longer time  and larger average vector shift . For GEL, field 1 had a longer treatment time  and the average vector shift was the same (0.09 cm). The longer field 1 time is due to the time required for initial alignment of the patient. On a daily basis, therapists first align the patient using tattoos and lasers. Field 1 will typically require more images and longer imaging time to move the patient from the initial alignment point to the treatment location. Ideally, the final image before treating field 1 would have been used as the Pre Field 1 time, but for convenience and consistency, therapists recorded the time of the first image for each field. For field 2, the patient is already within a few millimeters of the treatment location, so the imaging time is shorter.r = 0.2, P < 0.001) and GEL . A histogram of the distribution of shifts with respect to time is shown in Fig. The average time per field was 7 min for ERB and 5 min for GEL. For each fraction, the time per field correlated with a vector shift. For ERB and GEL, a majority of the field times were between 5 and 9 min. In this time period, a majority of the shifts were less than 0.2 cm, 85.9% for ERB and 73.2% for GEL. There was a significant positive correlation between the vector shifts and field time for both ERB (4This study identified a mean vector shift of 0.06 cm for ERB and 0.09 cm for GEL. While this is statistically different, it is not clinically relevant since both values are less than the minimum robust evaluation tolerance of 0.3 cm. When evaluating shifts greater than 0.3 cm and greater than 0.5 cm, there is no longer a statistical difference in the vector shifts between ERB and GEL. On rare occasions, there were shifts greater than 0.5 cm for both ERB and GEL patients, which indicates that the need for imaging between treatment fields remains. Our data has shown, however, that the likelihood of several large shifts, i.e. greater than 0.5 cm, for a single patient is low.For smaller shifts, less than 0.3 cm, GEL has more non‐zero shifts than ERB. This indicates that the prostate is more likely to move over a short distance with GEL than with ERB. Based on this data, we felt comfortable reducing our posterior PTV expansion margin from 0.5 cm to 0.4 cm for GEL patients. However, we chose to maintain the 0.6 cm GEL expansion in all other directions since it does not include biologically critical tissues. Additionally, because the GEL is proven to improve rectal sparing over ERB, we did not feel the need to reduce the posterior margins to match the 0.3 cm ERB expansion. Even with a larger posterior PTV expansion, the GEL rectal sparing is still superior to ERB.For both ERB and GEL, there is a tendency to have increased shifts with increased treatment time. A majority of our patients, for both ERB and GEL, were treated within 5–9 min. Within this time block, small GEL shifts were statistically higher than ERB shifts. However, similar to the overall shifts, the values were statistically relevant, but not necessarily clinically relevant. The ERB mean shift was 0.03 cm and the GEL mean shift was 0.07 cm. While the GEL shift magnitude is twice as large as ERB, the shifts are sub‐millimeter and well within the robust tolerance. For times greater than the average, there is no difference between GEL and ERB. This indicates that the effect of rectal filling does not seem to have a significant effect on prostate motion during the treatment time.5For patients undergoing proton radiation therapy for prostate cancer, prostate motion with a hydrogel spacer is clinically equivalent to motion with an endorectal balloon. We have shown that the mean shifts are clinically comparable between an endorectal balloon and a hydrogel spacer, and the time dependencies are similar. A large majority of shifts for both balloon and hydrogel are well within a typical robust CTV margin. For GEL patients, we chose to maintain slightly larger planning margins than for ERB due to already improved rectal sparing with hydrogel.Authors have no conflicts of interest to disclose.


To explore the safety and efficacy of the selective 5-serotonin and norepinephrine reuptake inhibitor duloxetine hydrochloride and alpha-adrenergic receptor blocker  doxazosin mesylate-controlled tablets in the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).P < 0.05). The SF-MPQ score in the doxazosin group decreased to 1.80 ± 1.29, 2.66 ± 1.57, and 3.24 ± 1.67 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the doxazosin group decreased to 2.24 ± 2.17, 4 ± 2.11, and 4.90 ± 2.62 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the sertraline group was 9.76%, 36.59%, and 63.41% after 1, 3, and 6 months, respectively. The SF-MPQ score in the sertraline group decreased to 1.76 ± 1.28, 3.07 ± 2, and 3.93 ± 2.53 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the sertraline group decreased to 3.56 ± 4.11, 5.73 ± 5.26, and 7.27 ± 6.50 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the duloxetine group was 36.36%, 88.64%, and 88.64% after 1, 3, and 6 months, respectively. The SF-MPQ score in the duloxetine group decreased to 3.61 ± 2.54, 6.05 ± 3.66, and 7.41 ± 4.26 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the duloxetine group decreased to 3.14 ± 3.28, 6.93 ± 3.90, and 9.43 ± 4.67 after 1, 3, and 6 months, respectively (P < 0.05). There were significant differences in the reduction of the NIH-CPSI score and the SF-MPQ score between the duloxetine group and the sertraline group and between the duloxetine group and the doxazosin group (P < 0.01). There were significant differences in the reduction of the HAD score at 3 months between the duloxetine group and the doxazosin group, and there were significant differences in the reduction of the HAD score at 6 months among the groups (P < 0.05). The incidence rates of adverse reactions in the duloxetine group, the sertraline group, and the duloxetine group were 29.5%, 17%, and 7.3%, respectively, with adverse events ranging from mild to moderate.In all, 150 patients were enrolled and 126 patients completed the study . This was an open randomized 6-month study. CP/CPPS patients who met the diagnostic criteria were randomized into 3 groups. The patients in the duloxetine group received doxazosin 4 mg + duloxetine 30 mg once a day, and the dosage of duloxetine was increased to 60 mg after a week. The patients in the doxazosin group received doxazosin 4 mg once a day. The patients in the sertraline group received doxazosin 4 mg + sertraline 50 mg once a day. National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, the short-form McGill Pain questionnaire (SF-MPQ), and the hospital anxiety and depression scale (HAD) were applied for evaluations during follow-up of 1, 3, and 6 months after treatment.There were slight positive significant correlations between NIH-CPSI scores and HAD scores, moderate positive significant correlations between the quality of life (QOL) and SF-MPQ, and slight positive significant correlations between HAD and QOL. The effective rate in the doxazosin group was 4.88%, 19.51%, and 56.10% after 1, 3, and 6 months, respectively (There was a clear relationship between the extent of pain and mental factors in CP/CPPS with the main symptom of pain. Doxazosin combined with duloxetine exhibited good safety and efficacy in the treatment of pain disorder in CP/CPPS. With the change of seasons or course of disease, the extent and characteristics of the pain can fluctuate or change. The symptoms that last more than 3 months in the past 6 months, with or without various voiding symptoms and sexual dysfunction. Many treatment methods, such as antibiotics, alpha-blockers, and nonsteroidal anti-inflammatory drugs, have been used widely in the treatment of CPPS but showed low efficiency; particularly in the treatment of the pain of CPPS, the efficiency was limited and temporary. The physical discomfort and great economic burden caused by recurrent and incurable diseases cause serious damage to the patient's quality of life (QOL).More than 90% of symptomatic patients have chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with the main symptom being pain in the pelvic region. Antidepressant drugs directly or indirectly have effects on opioid, histamine, cholinergic, 5-serotonin, and other receptors or ion channels to exert their analgesic effect. Several randomized, double-blind, placebo-controlled studies have confirmed that tricyclic antidepressants such as amitriptyline have good analgesic effects. Duloxetine hydrochloride is a new selective 5-serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant drug with good efficacy and tolerability in treating a variety of types of chronic pain and is a recommended first-line drug by the International Association for the Study of Pain for chronic pain syndromes such as diabetic peripheral neuropathic pain, postherpetic neuralgia, and fibromyalgia. Duloxetine hydrochloride combined with the alpha-blocker doxazosin was used for the treatment of chronic pain in CPPS, and the control groups were a doxazosin group and a sertraline  group to explore its safety and efficacy.Since the tricyclic antidepressants were found to have antidepressant properties, many antidepressant drugs have been used in the treatment of chronic pain.22.1This was a prospective, open label study with 3 phases. Phase I is a week-long screening and enrollment period. Phase II is the treatment period, which will last for 6 months. The eligible patients will be randomly divided into 3 equal-sized groups through a voice telephone system aided by computer. The groups are a doxazosin group (doxazosin 4 mg qd), a doxazosin + sertraline group , and a doxazosin + duloxetine group . Phase III is the withdrawal period, which lasts for 2 weeks. The patients who completed the treatment will move into this period. The purpose of the withdrawal period is to reduce the incidence of withdrawal reactions, and the dosage will be reduced gradually until the withdrawal is complete. The patients in the 3 groups will be followed up at 1, 3, and 6 months to assess efficacy and safety.The experimental design was developed according to the moral principles and implementation of the Declaration of Helsinki. The Peking Union Medical College Hospital Ethics Committee requires informed consent for the experiment, and there are no experiments performed before receiving signed informed consent. Informed consent was obtained from all individual participants included in the study.2.2 and NIH-CPSI pain score should be ≥4 points.Those male patients aged above 18 years and diagnosed with CP/CPPS in the Department of Urology in our hospital with discomfort or pain symptoms in the pelvic area for at least 3 months will be enrolled. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score should be ≥15 points,The main exclusion criteria are as follows: treatment with doxazosin or other alpha-adrenergic receptor blockers for CP/CPPS or for any other reason in the past; urinary tract infection ; genital herpes in the past 3 months; 5α-reductase inhibitor for 3 months in the past year; unilateral testicular pain without pelvic area symptoms; urinary or reproductive system cancer; inflammatory bowel disease; active urethral stricture; prostate or bladder operation history; neurogenic bladder; or the usage of a strong P-3A4 enzyme inhibitor  or erythromycin. Those patients with mania, bipolar disorder, psychosis, or who were identified as a suicide risk by researchers were excluded. In addition, those patients who used monoamine oxidase inhibitors or who had liver disease or other serious diseases in the 2 weeks before screening were also excluded.2.3The subjects were enrolled from January 2011 to January 2012, and the last follow-up time was July 2012. A total of 150 patients were enrolled under the criteria, and all patients were randomly divided in to 3 treatment groups, the doxazosin group, the sertraline group, and the duloxetine group; there were 50 patients in each group. A total of 24 patients did not complete the experiment , and the main reasons were adverse drug reactions in 8 patients ; poor efficacy in 9 patients ; and loss to follow-up in 7 patients .2.4 The total possible score on the NIH-CPSI scale is 43 points, and it takes into account 3 major symptoms: pain , urination , and adverse effect on QOL (0–12). In the short-form McGill pain questionnaire (SF-MPQ), the total scores are 0 to 45 and include sensory 0 to 33 and affective 0 to 12 descriptors; the higher the score, the more severe the pain. The hospital anxiety and depression scale (HAD) was also utilized .The main index was the NIH-CPSI score. The curative index required that the NIH-CPSI score improved by ≥ 25% and decreased by at least 6 points, as recommended by Nickel et al.2.5Adverse events are briefly reviewed according to the toxicity standard and organ system. The toxicity effects of each subject and each system are evaluated, and each system of each participant is evaluated as 1 adverse event. If a particular participant has multiple adverse events in the same organ, the most serious events will be recorded. The adverse events in each experimental group were evaluated.2.6P < 0.01 is considered highly significantly different, and P < 0.05 is considered significantly different.IBM SPSS Statistics software is utilized for statistical analysis. Single factor analysis of variance is used for the index comparison among the 3 groups, and the assumption of homogeneous variance for the LSD method is used for multiple comparisons. T tests of paired sample indexes are used for the comparison of indexes are different time points. Bivariate correlation analysis is used for the analysis of SF-MPQ, NIH-CPSI, and HAD. Pearson analysis is used to calculate the correlation coefficient. A 2-sided significance test is used; 33.1The baseline data of the patients in the 3 groups are shown in Table 3.2There was a slight positive and significant correlation between the total NIH-CPSI score and the HAD score, the HAD score increased with the increase of the NIH-CPSI score Fig. . There w3.3The effective rates of doxazosin at 1, 3, and 6 months after treatment were 4.88%, 19.51%, and 56.10%, respectively; the effective rates of sertraline were 9.76%, 36.59%, and 63.41%, respectively; and the effective rates of duloxetine were 36.36%, 88.64%, and 88.64%, respectively. The effective rates and changes of NIH-CPSI are shown in Table P < 0.01), but there was no significant difference between the sertraline group and doxazosin group .The NIH-CPSI scores decreased gradually with prolonged treatment, and the duloxetine group had the largest reduction and the highest efficiency at each time point; the doxazosin group had the smallest reduction, and the reduction in the sertraline group was intermediate. There were significant differences between the duloxetine group and sertraline group and between the duloxetine group and doxazosin group at each time point (3.4P < 0.01) , while there was no significant difference between the sertraline group and the doxazosin group .There were significant differences in the decline of McGill Pain scores between duloxetine group and sertraline group and between the duloxetine group and the doxazosin group at each time points in 1, 3, and 6 months (3.5P < 0.01). There were no significant reductions in HAD score for any group at 1 month. After 3 months, There were no significant differences between the duloxetine group and sertraline group (P = 0.166) or between the sertraline group and the doxazosin group (P = 0.051), but the HAD score improved significantly in the duloxetine group compared with the doxazosin group (P < 0.01). The HAD score improved significantly in the duloxetine group compared with the sertraline group (P = 0.042), in the sertraline group compared with the doxazosin group (P = 0.029), and in the duloxetine group compared with doxazosin group after 6 months (P < 0.01). The changes in HAD scores are shown in Table There was significant improvement between groups at 1, 3, and 6 months compared with the baseline after treatment . The occurrence rate of nausea and vomiting was 15.91% in duloxetine group, which was significantly higher than that in the other 2 groups, and some patients were unable to tolerate the adverse reactions. Details of common types and frequencies of adverse effects are shown in Table 4 studied 38 patients with CP/CPPS by randomized controlled methods and used NIH-CPSI, International Index of Erectile Function-5 (IIEF-5) questionnaires, the Hamilton Anxiety Scale (HAM-A), and the Hamilton Depression Scale (HAM-D) as the evaluation tools. Patients in group 1 received tamsulosin (0.4 mg/d), saw palmetto (320 mg/d), and duloxetine (60 mg/d), and the patients in group 2 received tamsulosin (0.4 mg/d) and saw palmetto (320 mg/d). The NIH-CPSI score and subscores improved significantly compared with baseline after 16 weeks, while the patients in group 2 only showed significant improvement in NIH-CPSI and urinary evaluation score. Significant improvements in the NIH-CPSI pain subscore, the NIH-CPSI QOL subscore, and the NIH-CPSI total score were observed in patients in group 1 compared with those in group 2 (P < 0.01), together with a significant improvement in HAM-A and HAM-D scores (P < 0.01). By contrast, our study had larger sample size, longer observation time and used the McGill Pain score as an additional pain assessment tool.In our study, a prospective and randomized trial was designed to explore efficacy and safety by comparing the SNRI drug duloxetine hydrochloride and the SSRI drug sertraline hydrochloride combined with doxazosin in the treatment of pain disorder in CP/CPPS, and the results were also compared with the commonly used alpha-blocker doxazosin mesylate in CP/CPPS. Giannantoni et al,15 Our study showed that there was a slight positive and significant correlation between the NIH-CPSI score and the HAD score and between the HAD and SF-MPQ. There was a significant positive correlation between the HAD and QOL, which indicated that the extent of pain in CPPS with pain as the main symptom was closely associated with mental factors, and mental factors are emerging as the most important factors affecting the QOL.The deterioration of psychoemotional status frequently accompanies urologic symptoms and pain in patients with CP/CPPS; chronic pain and depressive symptoms in patients with CP/CPPS, alone or in combination, are associated with a risk of diminished physical functioning and deterioration of QOL. Li et al studied the efficacy of 4 alpha-blockers, including prazosin hydrochloride, terazosin hydrochloride, phenoxybenzamine hydrochloride, and doxazosin mesylate in the treatment of CP/CPPS using a randomized controlled study in which the control group did not receive an alpha-blocker, and the curative effect was statistically significant. Cheah et al observed 86 CP/CPPS patients treated with terazosin for 14 weeks using a random, placebo-controlled method, and terazosin significantly improved the NIH-CPSI score, pain score, urinary symptoms, and QOL score. A large randomized, multicenter, double-blind, placebo-controlled study selected 272 CP/CPPS patients who had never had alpha-blockers before. The patients received alfuzosin treatment for 12 weeks, but alfuzosin did not show obvious advantages compared with placebo in the NIH-CPSI score and its 3 subscores. Based on the effective index being a reduction of more than 6 points, the present study showed that the NIH-CPSI score did not improve significantly 1 and 3 months after doxazosin treatment, but it improved significantly after 6 months. SF-MPQ and HAD scores improved to a certain degree without significant differences. This result indicated that alpha-blockers could relieve the symptoms of CP/CPPS to some degree, but the therapeutic effect was not significant. Further treatment methods should be explored.In recent years, alpha-blockers have been widely used in the treatment of CP/CPPS and are regarded as a basic drug for CPPS. The mechanism of alpha-blockers may lie in the following 2 aspects: Firstly, the continuous and frequent contraction of the bladder neck and prostate smooth muscle, regulated mainly by alpha-adrenergic receptors, may be one of the mechanisms of CP/CPPS, and alpha-blockers can relax the prostate, urethra, and bladder smooth muscle tissue. Secondly, the excitement of alpha-adrenergic receptors in the central nervous system can delay pain relief in CP/CPPS, and alpha-blockers can reduce the neuroinflammation in the lower urinary tract. In a randomized, placebo-controlled study, 14 male patients with chronic pelvic pain received 26 weeks of treatment with sertraline 50 mg daily. The results showed some improvement in symptoms but were not significantly different. Our study indicated that there were no significant differences in NIH-CPS scores or SF-MPQ between the sertraline combined with doxazosin group and the doxazosin group at 1, 3, and 6 months, and there was no significant difference in HAD scores at 1 and 3 months, but there was significant difference at 6 months.The mechanism of antidepressant drugs on chronic pain is direct action on neurons for pain and indirect improvement of depression, anxiety, and other emotional disorders, thereby improving the experience of pain and the ability to cope with pain. An epidemiological survey of chronic pain has clearly suggested that depressive symptoms and pain experience are closely related, especially in chronic pelvic pain. Some scholars believe that nervous people, with physiological and genetic origins of anxiety, are easier to diagnose with the presence of anxiety, depression, and other affective disorders induced by chronic pain.,23 5-HT and NE nerve conduction abnormalities play an important role in the pathogenesis of severe depression, and they often coexist with CP. Serious depression in patients often presents with painful physical symptoms, such as headache, backache, and chronic pelvic pain, and duloxetine can markedly relieve the pain of severe depression with somatic symptoms.Our study indicated that there was significant improvement in the NIH-CPS score, SF-MPQ, and HAD after treatment with the new antidepressant duloxetine hydrochloride combined with doxazosin after 1, 3, and 6 months. In addition, the improvement was also significant compared with doxazosin and sertraline group. There is now evidence that 5-hydroxytryptamine (5-HT) and norepinephrine (NE) regulate pain through endogenous descending pain inhibitory pathways, and their dysfunction is a potential mechanism in patients experiencing pain. Antidepressant drugs are used for many chronic pain syndromes through adding 5-HT- and NE-mediated neurotransmission. Previous studies have shown that the double effect of inhibition of 5-HT and NE mediated by antidepressants is clearly superior to single receptor therapy. Duloxetine hydrochloride is a powerful 5-HT and NE reuptake inhibitor with a relatively balanced affinity for 5-HT and NE, and animal experiments have shown that duloxetine lacks an obvious affinity for cholinergic, adrenergic, and opiate receptors, and its analgesic effects on neuropathic pain are better than those of venlafaxine, amitriptyline, and other antidepressants.The dosage, course of treatment, and possible adverse reactions were communicated to the patients and adjusted before treatment, and a few patients chose other treatment methods because of adverse reactions after this communication. The majority of patients in the sertraline group had mild and tolerable adverse reactions, such as dizziness, nausea, vomiting, and constipation after 2 to 3 days, which disappeared gradually in 5 to 7 days. In the duloxetine group, there was nausea, vomiting, constipation, and lethargy, and we used the so-called “sandwich” method, that is, administration during a meal significantly reduced the incidence of gastrointestinal reaction. Most adverse events were transient and mild, weakened gradually, and disappeared in approximately 1 week.,25 and the present study recommend that the indications for the use of antidepressants in the treatment of pain disorders in CPPS are as follows: First, the disease is associated with obvious anxiety, depression, and other psychological symptoms, and cognitive behavior therapy is invalid. Second, the main symptom is persistent or recurrent pain, and the use of alpha-blockers and galenical drugs was invalid, seriously affecting the QOL of the patients.Antidepressant drugs are mainly used for mental disease, and they are still in the exploratory stage for the treatment of CP. We should strictly control the indication of treatment, obtain the informed consent of patients and strictly follow-up to facilitate timely adjustment of the treatment scheme. Literature reviews and the effective rate in the sertraline and duloxetine groups in this study was >30%, which confirmed the effectiveness of the treatment.This study also has limitations. First, the samples were small in the 3 groups, which may have had adverse effects on the determination of results. Second, a placebo group was not established because of patient compliance and ethical constraints in 6 months in real clinical practice, which might have a certain bias on the interpretation and safety assessment. Previous studies have shown that the efficiency of placebo in CP/CPPS is up to 30%, CP/CPPS is caused by a variety of pathogenic factors, and a single treatment method is unlikely to be satisfactory; a variety of drugs and/or the combined application of various methods is rational. The SNRI drug duloxetine hydrochloride combined with the alpha-blocker doxazosin was safe and effective in the treatment of pain disorder in CP/CPPS, which is useful information in the treatment of CP/CPPS, and more exact curative effects need to be confirmed by more rigorous clinical studies.Duloxetine has been widely used in chronic pain, especially in neuropathic pain, but reports are rare for the treatment of CP/CPPS. With respect to chronic pain, especially for neuropathic pain, the therapeutic efficacy for 1 type of pain is not exactly the same as for another type of pain. However, the efficacy of first-line drugs that have been confirmed in 1 or more types of pain may be reasonable for another type of pain, and the drugs that are needed in clinical practice should exhibit satisfactory efficacy.


Delayed diagnosis of ectopic pregnancy (EP) is responsible for maternal morbidity and mortality. Our objective was to develop and validate decision rules for the diagnosis of EP, in patients in their first trimester of pregnancy with symptoms, based solely on a self-assessment questionnaire.From September 2006 to March 2008, 574 patients, who have consulted for acute pelvic pain at the gynecologic emergency department (ED) of five hospitals, completed a Self-Assessment Questionnaire for Gynecological Emergencies (SAQ-GE). We included for our study only women in their first trimester of pregnancy experiencing acute pelvic pain and/or vaginal bleeding who were hospitalized (262 patients). Two-thirds of patients were selected to derive the SAQ-GE EP score which was built on multiple logistic regression. One third of patients were used for internal validation.Five variables were independently and significantly (p<0.05) associated with EP: no frequent need to change sanitary towels , duration of bleeding > 24 hours , pain during coughing , brown discharge  and unilateral pelvic pain . The SAQ-GE ectopic pregnancy score was based on these five criteria with values ranging from 0 to 100. The low-risk group of EP (score<25) had a sensitivity of 95.9% 95% CI  and an LR− of 0.2 95% CI [0.1–0.5]. The high-risk group (score>70) had a specificity of 97.4 95% CI [90.9–99.7] and a LR+ of 12.3 95% CI [3.0–49.8]. The percentages of EP observed in the validation sample were: 0% in the low-risk group and 88.9% in the high-risk group.These prediction rules that classify patients in a low-risk or high-risk group may prove useful for triaging pregnant women in their first trimester with symptoms before complementary exams. In the United States, ectopic pregnancy (EP) is diagnosed in 0.6% to 2.1% of all pregnancies .At present, the diagnosis of EP is made by laparoscopy, which is the gold standard, or by an algorithm combining transvaginal ultrasound (US) and serial serum human chorionic gonadotrophin (hCG) determination ,5. In thTriage on the admission to ED by non-clinicians, based only on questioning, could be useful to help identify patients with EP, who should then be given transvaginal US and quantitative hCG measurement as a priority. Clinical prediction models for diagnosing EP have already been developed ,9 but thThe aim of this study was to construct a clinical decision rule solely based on the SAQ-GE for identifying patients with a high probability of EP in the gynecologic ED, among pregnant women experiencing early pregnancy symptoms such as acute pelvic pain and/or vaginal bleeding.The study was approved by the French Department of Higher Education and Research (n°06.336) and by the French National Committee for Information Technology and Individual Liberties (n°906253).The construction of the SAQ-GE is described in detail elsewhere . It was From September 2006 to March 2008, all voluntary patients aged 18 years or more consulting for acute pelvic pain at the participating gynecologic EDs were asked to complete the 89items of the SAQ-GE. The patients were enrolled at five gynecologic EDs in the Paris greater metropolitan region . Patients with a history of chronic pelvic pain, no knowledge of French, psychiatric or neurologic diseases were excluded. The ED staff proposed the SAQ-GE to the patients who self-completed it before the initial consultation with the gynecologist and if necessary after appropriate pain management. The nurses then collected the completed questionnaires. They were then anonymized.For our study we included only pregnant women in their first trimester of pregnancy experiencing acute pelvic pain and/or vaginal bleeding who were admitted to the hospital from the gynecological ED. The pregnancy was diagnosed using a urine pregnancy test for every patient who was not aware of their pregnancy, on arrival at the gynecological ED.The reference standard for the diagnosis of EP was through laparoscopy. Each patient operated had operative and pathological reports that confirmed the diagnosis.In the absence of surgery, the diagnosis of EP was made by a non-surgical algorithm ,6 based The first two-thirds of patients who attended a gynecologic ED were used to derive the clinical decision model (training sample) and the remaining third of patients was used for validation .2 test) test as appropriate. We converted variables associated with the presence of EP at a threshold of p<0.10 into dichotomous variables using receiver operating characteristic (ROC) curves. The diagnostic performance of each of these variables (p<0.10) was assessed on the basis of sensitivity (Se), specificity (Sp), positive likelihood ratio (LR+), negative likelihood ratio (LR−) and diagnostic odds ratio (DOR).First, we carried out univariate analysis comparing patients from the training sample with EP and IUP for each variable of the SAQ-GE, using a quantitative (Student's t-test) or qualitative . Variables were selected by a backward, stepwise procedure from those associated with EP in the univariate analysis at a threshold of p<0.10. Adjusted diagnostic odds ratios (aDOR) were calculated with their 95% confidence intervals (95% CI). The stability of each predictive variable in the model was tested using a bootstrap procedure . The perNext we built a score by rounding up the β coefficients from the multivariate analysis to generate a simple scale . MissingWe classified patients as at high risk or low risk of EP by choosing two threshold values of the score to make two classifications, one with sensitivity > 95% and LR+ > 4.0 (rule out) and the other with specificity > 90% and LR− <0.25 (rule in) .Finally, the score was applied to the validation sample. The sensitivity, specificity, LR+ and LR- of the score and the observed probabilities of EP in the high-risk and the low-risk groups were compared with those obtained from the training sample.Statistical analyses were performed using STATA 13.0 .During the study period, 574 patients completed the SAQ-GE . Among tVariables of the SAQ-GE associated with EP in the univariate analysis (p<0.1) were evaluated for their diagnostic performance. Their Se, Sp, LR+, LR- and DOR are shown in The multiple logistic regression analysis identified five variables independently and significantly (p<0.05) associated with the diagnosis of EP: no frequent need to change sanitary towels , duration of bleeding > 24 hours , pain during coughing , brown discharge  and unilateral pelvic pain  . All of The SAQ-GE EP score was given by the following equation: Score = (no frequent need to change sanitary towels×30)+(duration of bleeding>24 hours×25)+(pain during coughing×15) +(brown discharge ×15)+ . The ROCWe then defined a low and high-risk group of EP :Patients with a score<25 were defined as a low-risk group. A threshold score value of 25 produced a sensitivity of 95.9% 95% CI [89.8–98.9] and a LR− of 0.2 95% CI [0.1–0.5]Patients with a score>70 were defined as a high-risk group. A threshold value of 70 produced a specificity of 97.4 95% CI [90.9–99.7] and a LR+ of 12.3 95% CI [3.0–49.8]The score was calculated for the patients in the validation sample. The low-risk group had a sensitivity of 100% and an LR- of 0. The high-risk group had a specificity of 93.1% and an LR+ of 3.9. The sensitivity, specificity, LR+ and LR- in the validation sample were in the expected range. The observed percentages of EP were: 0% in the low-risk group and 88.9% in the high-risk group .We have developed the first decision rule for triaging patients for EP among pregnant patients hospitalized for acute pelvic pain and/or vaginal bleeding entirely based on a self-assessment questionnaire designed for gynecological emergencies. The clinical model is based on five simple “Yes or No” items, namely: no frequent need to change sanitary towels, duration of bleeding > 24 hours, pain during coughing, brown discharge and unilateral pelvic pain. The clinical decision rule is obtained after combining these items into a score. A score < 25 puts patients in a low-risk group of EP with a sensitivity of 100%, a LR- of 0 and a probability of EP of 0%. A score > 70 puts patients in a high-risk group with a specificity of 93.1%, a LR+ of 3.9 and a probability of EP of 88.9%.A major strength of our study is the original design of the standardized questionnaire based on self-assessed experience of pain in patients presenting with acute pelvic pain. This differs from using history-taking, which is based on the physician’s perceptions of symptoms and experience. Indeed, the interpretation of history-taking, which necessitates practitioner experience, may be subject to interobserver variability due to cognitive bias . With thFurthermore, the five criteria of our score have good face validity because it was built with common-sense criteria for practitioners involved in gynecological emergencies. They also have good physiopathological plausibility. The pain during coughing, which is a sign of peritoneal irritation, suggests an EP complicated with a hemoperitoneum . The uniThe major limitation of our study is that we did not include all patients who consulted at a gynecologic ED for acute pelvic pain and/or vaginal bleeding but included only hospitalized patients. This choice was made to limit the potential diagnostic bias consecutive to patients’ loss of follow-up. However, this recruitment strategy may have created a referral bias, in that we included more patients with more severe pathologies. In fact all patients presenting an EP were hospitalized whether they had medical or surgical treatment. On the other hand, patients presenting an IUP were not all systematically hospitalized. Hospitalized patients with IUP may be only those with a more serious condition along with those for whom the initial diagnosis between IUP and EP was difficult (including PUL before definitive diagnosis). This explains the high prevalence of ectopic pregnancy in our study. Differential diagnosis between EP and the more symptomatic IUP is difficult and is of major interest. Even in this selected population, our score is highly discriminant and useful for triaging patients.Lastly, we performed no cross-validation study with an independent sample. Consequently there is a risk that we overfitted the data when we developed the decision model . To safeCurrently, there is no clinical decision rule based solely on questioning for triaging for EP among patients in their first trimester of pregnancy with acute pelvic pain and/or vaginal bleeding. Calculation of the SAQ-GE EP score needs no physical examination nor complementary exams. It could be implemented by non-clinicians for every pregnant patient with acute pelvic pain and/or vaginal bleeding on admission to the gynecologic ED.The future validation of the simplified version of the SAQ-GE and the decision rule for triaging patients for EP among pregnant patients needs to be carried out in general EDs. The validation of the SAQ-GE EP score needs to be performed on all pregnant patients with acute pelvic pain and/or vaginal bleeding, regardless of whether or not they are hospitalized. After this validation of the score in the general population with future studies, we could even extend its application to general ED, general practitioners or, with the burgeoning new technologies, it could even be used by patients themselves with a host terminal or a touch pad.All women pregnant in their first trimester of pregnancy experiencing symptoms must have physical examination and complementary exams by a physician. However, depending on the risk groups, the appropriate timing and place to do these exams will be different. Thus, patients classed as at high-risk by the decision rule should see a doctor without delay to have transvaginal US and quantitative HCG measurement in a center open 24 hours a day, seven days a week. On the other hand, when patients are classed as at low-risk complementary exams are still necessary but they are not an emergency.S1 Table(XLS)Click here for additional data file.


The provision of written information is a low-cost and readily available intervention that has been found to reduce pain and anxiety in a variety of clinical settings. The current study was undertaken to determine if information provision may improve patients’ experience during conventional electrodiagnostic studies.128 participants were recruited from a tertiary teaching hospital who were referred for electrodiagnostic studies. They were randomized into 2 groups where the intervention group was provided with written information about the electrodiagnostic testing. Patients were invited to complete a questionnaire that included pain and anxiety using a visual analogue scale (VAS) following the testing. All participants underwent nerve conduction studies (NCS) whilst a subset also underwent subsequent needle electromyography (EMG).Those who received information had a statistically significant lower perception of anxiety during NCS, whilst only females who received information had a statistically significant lower perception of pain to both NCS and EMG.The provision of written information can reduce the degree of pain and anxiety experienced during electrodiagnostic testing.Improving patient comfort and tolerability during electrodiagnostic testing may have practical implications towards more reliable and accurate results obtained from such investigations that may in turn improve patient diagnosis and management. Due to the nature of electrophysiological evaluations, most patients express a degree of discomfort, pain and anxiety, with pain being the most common complication. This is well tolerated by most patients, however in some patients, poor tolerance may limit the validity and accuracy of the test by restricting the extent of the study and hence the diagnostic utility of these evaluations , 2. ThisVarious interventions have been studied to increase tolerability of electrodiagnostic studies, particularly for pain related to needle electromyography (EMG). These include pharmacological interventions such as vapocoolant spray, eutectic mixture of local anaesthetics , ibuprofProviding information that includes both sensory (sensations that will be experienced) and procedural (the sequence of events) aspects of the procedure a patient will be undergoing has been found to be beneficial in reducing stress and pain –13 in a This prospective study recruited patients whom were referred for outpatient NCS/EMG testing at a tertiary teaching hospital from October 2015 to December 2016. Participants were referred to the electrophysiology clinic for a wide range of provisional clinical diagnoses. These included most commonly entrapment neuropathies such as carpal tunnel syndrome, ulnar or peroneal neuropathy; peripheral neuropathy; radiculopathies; motor neuropathies or neuronopathies; and myopathy.Inclusion criteria were: age between 18–80 years inclusive, English literacy (sufficient for comprehension of information pamphlet and questionnaire), willingness to participate in the study, no active psychiatric illnesses or cognitive decline, and not taking anti-neuropathic agents or psychotropic drugs.Patients who met the above criteria were randomized on the day of testing by using a table of generated random numbers adapted from Pocock , where tA total of 214 patients were initially recruited for the study over a one year period. Subsequent exclusions during data analysis were made based on the above-mentioned inclusion criteria or the questionnaire not being completed correctly. A total of 128 participants were included in the final data analysis and this was reached by further exclusion criteria . AmongstInformation was provided in the form of a 2 sided pamphlet informing patients about what to expect for the nerve conduction study, answering basic questions such as what the study would consist of, what patients needed to do during the test, what the test would feel like, how patients could prepare for the test, what to do if their symptoms were to get better before the test, how long the testing would take and whether it was safe if they had a pacemaker. On the second page, patients were informed that needle EMG may be performed subsequently and similarly, answered questions such as what it was, how many muscles would need to be tested, how they could prepare for it, what it would feel like, what they should expect after testing and when results would be received .Electrodiagnostic examination was performed by skilled examiners guided by senior clinicians. Examiners who performed the study were blinded to the assignment of information. Examiners provided a standard introduction and brief explanation regarding the testing procedure to all patients prior to the commencement of the electrophysiological testing. In addition, all patients were also given the opportunity to ask questions regarding the testing procedure.All patients underwent NCS with or without subsequent EMG depending on the clinical indication. Electrical stimulation required for the NCS was standardised with the minimum stimulus required for an adequate examination as with typical studies. Immediately after the examination, patients who were eligible for the study completed a 2-page questionnaire in which they indicated their level of pain and anxiety experienced using separate 100 mm lines representing pain experienced during NCS, anxiety experienced during NCS, pain experienced during EMG and anxiety experienced during EMG, if applicable. The 100 mm line represented the visual analogue scale (VAS) scale (where 0 = no pain/anxiety on one end and 100 = worst pain/anxiety that they have ever experienced). The VAS scale, which is used as the primary outcome measure in this study, has been validated as a measure of the magnitude of experimental pain and anxiety –27.The questionnaire included a secondary outcome measure of the experience of undergoing the study in relation to their expectation of the study. Further questions were whether they received information or had obtained information from other sources, whether they would have preferred to have received information, and the level of satisfaction with the electrodiagnostic examination. .The study received approval from the New South Wales Health South Eastern Sydney Local Health District Human Research Ethics Committee and written consent was obtained from all participating individuals.Data analysis was performed using IBM SPSS 23 statistical package. The Student's t-test was used when the distribution of data in both intervention and non-intervention groups were normally distributed, while the Mann-Whitney U test was performed when the data groups were non-normally distributed. The data is expressed as mean ± Standard Error of the Mean (SEM) and the p-value cut off of less than 0.05 was considered statistically significant. The planned comparisons between the gender subgroups also utilized the Student’s t-test or Mann-Whitney U test where appropriate. The Pearson chi-square test was used to study the differences in participant characteristics such as gender. It was also used to study the categorical data indicating patients’ experience after undergoing the test in relation to their expectation in the intervention group compared to the non-intervention group. Correlation analyses were performed using Spearman rank test.Overall scores for anxiety in the NCS cohort were found to be significantly lower (p = 0.04) in the intervention group (14.53±2.44mm) than in the non-intervention group  and non-intervention group (25.30±2.44mm) in the NCS cohort did not differ significantly (p = 0.15). Further gender subgroup analysis was performed but there were no significant differences in pain scores amongst males in the intervention group (22.56±3.03mm), compared to those in the non-intervention group . However, amongst females, NCS pain scores were found to be significantly lower (p = 0.033) in the intervention group (19.15±3.60mm) compared to the non-intervention group  or anxiety p = 0.65) levels were demonstrated for the intervention and non-intervention groups in the subgroup of patients that underwent needle EMG testing. However, when further subgroup analysis by gender was performed, a significant information effect (p = 0.024) was found in females in the level of pain perceived during the EMG testing. Those who received information had significantly lower levels of pain (13.75±2.71mm) compared to those that did not (54.63±13.37mm) . Furthermore, females were significantly more likely to want the provision of information than men (p = 0.014).This is the first study utilizing a randomized control design in a large cohort of patients examining the effect of the provision of written information on the perceived levels of pain and anxiety during conventional electrodiagnostic testing. The use of VAS in retrospective pain assessments have been found to accurately reflect patients' pain experience during the procedure  and up tThe results of the current study demonstrated that compared with patients who were not provided with information, those who were provided with information showed a significant reduction in the anxiety levels perceived during NCS. It is interesting to note that for patients who received information compared to those who did not, there was a trend of reporting the study experience as being better than expected rather than worse or the same as expected. This is in keeping with previously reported data demonstrating that the amount of presented information allowed an increase in the perception of patient control that ultimately assisted in the management of acute procedural pain –33.In females a reduction in pain levels was previously observed during NCS and EMG testing , 21. WhiThe reduction in EMG pain perceived in females who received information compared to their male counterparts is consistent with the suggestion that there are gender differences in responses to non-pharmacological interventions such as cognitive intervention  for expeA much smaller sample of patients was collected for needle EMG compared to NCS and may represent a potential limitation of the study. The relative number of patients who went on to have EMG was small in our cohort as many of the referrals were for CTS, ulnar neuropathies, peripheral neuropathies, which in most clinical circumstances would not require needle EMG subsequent to the diagnostic NCS. Study group numbers for comparing pain in females during EMG was also small, however, it should be noted that means of groups were reflective of group perceptions. Future studies that are able to recruit larger numbers for needle EMG patients may be of benefit to corroborate the current findings.In conclusion, the provision of written information as a simple intervention to reduce subsequent pain and anxiety experienced during electrodiagnostic studies is effective, practical and easily implemented. Prior information is particularly effective in improving the tolerability of the study for females. This has important practical implications as improved tolerance to the testing may facilitate improved reliability and accuracy of electrodiagnostic results as well as allowing for more thorough testing which may in turn result in improved diagnosis and management for patients.S1 FileThose participants whom were randomized to received written information were provided with this in print.(PDF)Click here for additional data file.S2 FileAll participants whether provided with written information or now prior to the electrophysiological testing, were asked to complete the study questionnaire if they consented to take part in the study.(PDF)Click here for additional data file.


Nonspecific low back pain is characterized by a wide range of possible triggering and conserving factors, and initial screening needs to scope widely with multilevel addressment of possible factors contributing to the pain experience. Screening tools for classification of patients have been developed to support clinicians. The primary aim of this study was to assess the criterion validity of STarT Back Screening Tool (STarT Back) against the more comprehensive Örebro Musculoskeletal Pain Questionnaire (ÖMPSQ), in a Norwegian sample of patients referred to secondary care for low back pain. Secondary aims were to assess risk classification of the patients, as indicated by both instruments, and to compare pain and work characteristics between patients in the different STarT Back risk categories.An observational, cross-sectional survey among patients with low back pain referred to outpatient secondary care assessment at Trondheim University Hospital, Norway. Cohen’s Kappa coefficient, Pearson’s r and a Bland-Altman plot were used to assess criterion validity of STarT Back against ÖMPSQ. Furthermore, linear regression was used to estimate mean differences with 95% CI in pain and work related variables between the risk groups defined by the STarT Back tool.A total of 182 persons participated in the study. The Pearsons correlation coefficient for correspondence between scores on ÖMPSQ and STarT Back was 0.76. The Kappa value for classification agreement between the instruments was 0.35. Risk group classification according to STarT Back allocated 34.1% of the patients in the low risk group, 42.3% in the medium risk, and 23.6% in the high risk group. According to ÖMPSQ, 24.7% of the participants were allocated in the low risk group, 28.6% in the medium risk, and 46.7% in the high risk group. Patients classified with high risk according to Start Back showed a higher score on pain and work related characteristics as measured by ÖMPSQ.The correlation between score on the screening tools was good, while the classification agreement between the screening instruments was low. Screening for work factors may be important in patients referred to multidisciplinary management in secondary care. Low back pain is the leading cause of years lived with disability globally , 2. In aManagement guidelines suggest that patients seeking care for nonspecific and uncomplicated low back pain should be offered treatment in primary care . On the There are data suggesting that in general, previous management for patients with low back pain have failed to address its multifactorial nature and accordingly not contributed significantly to patients’ improvement in the long term . Part ofThe primary aim of this study was to assess the criterion validity of the STarT Back Screening Tool against the Örebro Musculoskeletal Pain Screening Questionnaire in a Norwegian sample of patients with low back pain referred to assessment at a university hospital. Secondary aims were to assess risk classification of the patients, as indicated by both instruments, and to compare pain and work characteristics between patients in the different STarT Back risk categories.An observational, cross-sectional survey was performed in an outpatient multidisciplinary clinic for musculoskeletal pain in Trondheim University Hospital, Norway.The study sample was patients referred for secondary line management because of low back pain. The inclusion criteria were as follows: Referred from their physician, manual therapist or chiropractor in the primary health care system with low back pain for more than 6 weeks. Exclusion criteria were age under 18, insufficient language capabilities, malignant disease, and unresolved social security or insurance problems.Background variables included age, gender, marital status, country of birth, educational level, and work status. Participants that were not out of work, sicklisted or on work assessment allowance were classified as employed. We defined people with any percentage of sickleave as sicklisted. Information on other diseases category was also collected, including headache, pulmonary disease, coronary disease, hypertension, diabetes and an open category for diseases specified by the participants.STarT Back screening tool contains nine questions, and was developed based on prognostic factors for longstanding disability due to low back pain [ack pain . The queack pain .Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) was developed to assist health care providers in assessing risk of developing a persistent back problem. Originally it was aiming at predicting risk for work absenteeism due to sickness [sickness . The scosickness , 21 and sickness . The quesickness . Lower csickness . Therefothe mean ÖMPSQ score with 95% confidence interval (CI) according to STarT Back total score  based on STarT Back and ÖMPSQ was assessed by Cohen’s Kappa coefficient. The calculations were done for the overall study population, but since some of the items of the ÔMPSQ are work related, we also estimated the agreement in risk classification for patients who were classified as workers. We also calculated ore Fig. . Since tnt ≥0.60 . The perRisk classification of the patients, as indicated by both instruments was described by a classification table. Finally, we used linear regression to estimate mean differences with 95% CI in pain and work related variables between the three risk groups defined by the STarT Back tool. Non-normally distributed variables were analyzed using non-parametric Mann-Whitney U test and results presented as differences in median values between risk groups.A total of 300 patients received the study questionnaire, and 199 (66%) returned it. After excluding 17 persons due to incomplete answers or age below 18 years, 182 patients (61%) were available for statistical analysis. Among those, 73% were employed, mean age was 48 years (SD = 15), and 51% were men . The Bland Altman plot  and 34.1 (STarT Back) percent of the respondents had low risk for longstanding disability due to low back pain. Clinical guidelines recommend secondary care referral when management needs are too complex for primary care management . In geneTo our knowledge, no studies have compared scores and classification by these two screening instruments in patients referred to secondary care. On the other hand, the predictive value of both instruments in secondary care has been evaluated. An Australian study concluded that the instruments add no further value over and above clinical judgement , and a DThis is a cross-sectional study, and it cannot evaluate the predictive value of the screening instruments. The response rate was 66% and we cannot rule out that the study participants were different from the non-responders. Consequently, the results may not automatically be generalisable to the population of patients referred to the multidisciplinary clinic. Missing responses on some items may have introduced bias. To compensate for missing on the work items, supplementary analyses were performed to compare whole-sample results to results from analyses restricted to patients in work.The results from the present study do not suggest that the risk classification by STarT Back is comparable to risk classification by ÖMPSQ for patients referred to secondary care for low back pain, though the instruments’ scores correlated well. This study also suggests that around one third of the patients referred to secondary care will be classified low risk according to these primary care screening tools. The results do not support the applicability of StarT Back screening tool as decision support in Norwegian secondary health care. This may be due to differences in timing of testing, clinical setting, and study sample compared to the original target group for screening. The results also indicated that the working items in ÖMPSQ may be central when addressing psychosocial load in working patients.STarT Back scores correlated well to scores on ÖMPSQ, while classification agreement between the instruments was low in patients referred to multidisiplinary secondary care for low back pain. Patients classified as high risk by STarT Back reported more challenges connected to work on ÖMPSQ sub-items.


Objective Rectus muscle reapproximation at cesarean delivery (CD) is performed frequently by some obstetricians; however, the effect on postoperative pain is unclear. To this end, we investigated whether rectus muscle reapproximation increases postoperative pain.Materials and Methods This is a prospective, double-blind, randomized controlled trial of women undergoing primary CD with singleton or twin pregnancy at >35 weeks' gestation. Women were randomized to rectus muscle reapproximation with three interrupted sutures or no reapproximation. Exclusion criteria were prior cesarean, prior laparotomy, vertical skin incision, active labor, chronic analgesia use, allergy to opioid or nonsteroidal anti-inflammatory drugs, and body mass index ≥ 40. Intra- and postoperative pain management was standardized within the study protocol. The primary outcome was a combined movement pain and opioid use score averaged over the 72-hour study period, called the Silverman integrated assessment. Movement pain scores were assessed at 24, 48, and 72 postoperative hours.Results In total, 63 women were randomized, of whom 35 underwent rectus muscle reapproximation and 28 did not. Demographic and obstetric variables were similar between groups. Silverman integrated assessment scores during the 72-hour postoperative period were higher in the rectus muscle reapproximation group . Operative times were similar between groups , and there were no surgical complications in either group. Maternal satisfaction with analgesia at 72 hours was high in both groups .Conclusion Rectus muscle reapproximation increased immediate postoperative pain without differences in operative time, surgical complications, or maternal satisfaction. Benefits of rectus muscle reapproximation should be weighed against increased postoperative pain, and analgesia should be planned accordingly. Cesarean delivery (CD) is the most common surgical procedure performed in women in the United States, with nearly 1.3 million CDs performed in 2013.Given the potential for rectus muscle reapproximation to reduce adhesions but insufficient short-term postoperative data, we assessed whether rectus muscle reapproximation at CD increases postoperative pain and analgesic use in a prospective, double-blind, randomized controlled trial.This study is a prospective, double-blind, randomized controlled trial conducted at Lucile Packard Children's Hospital at Stanford between September 2006 and July 2013. Women undergoing scheduled primary CD who were not in labor and consented to the trial were randomly assigned to receive rectus muscle reapproximation versus no reapproximation.Inclusion criteria were women older than 18 years with a singleton or twin pregnancy at ≥35 weeks' gestation and with American Society of Anesthesiologists (ASA) class 1 or 2. The exclusion criteria were active labor, chronic analgesia use, vertical skin incision at cesarean, allergy to opioid or nonsteroidal anti-inflammatory drugs (NSAIDs), prior laparotomy, and class III obesity (body mass index ≥ 40). Randomization was conducted through sequentially numbered opaque envelopes generated by a study nurse in blocks through a random numbers table, in a 1:1 ratio.Surgical techniques at CD were standardized within the study and included closure of the parietal peritoneum and two-layer uterine closure. For women randomized to rectus muscle reapproximation, surgeons were instructed to place three vertical midline interrupted sutures to reapproximate the rectus muscles. Suture type was initially standardized to 2–0 chromic catgut; however, after poor recruitment of surgeons willing to comply with this initial requirement, Monocryl (Ethicon) was also allowed. Surgeons were instructed not to discuss randomization group in the operating room so that the patient remained blinded to group assignment. All surgeries were performed by an attending physician and a resident physician.In our institution, surgeons nearly universally perform a low-transverse skin incision using a Pfannenstiel approach, with a combination of sharp and blunt dissection to open the abdomen. The rectus muscles are dissected off the fascia, and the muscles are separated in the midline by pulling. The pyramidalis muscles are not routinely separated from the rectus sheath, unless the surgeon determines a need to create more room.Intraoperative analgesia was standardized to spinal anesthesia using intrathecal bupivacaine 12 mg, fentanyl 10 mcg, and morphine 200 mcg. Postoperative pain management was standardized to scheduled ibuprofen 600 mg or, if the patient was unable to tolerate oral medications, ketorolac 15 mg intravenous every 6 hours, and, as needed, one to two tablets of either oxycodone 5 mg with acetaminophen 325 mg or hydrocodone 5 mg with acetaminophen 500 mg for breakthrough pain management. Postoperative pain scores were assessed per routine postpartum care by the patient's nurse; patients with pain scores ≤4/10 received one tablet of the narcotic, and patients with pain scores >4/10 received two tablets every 4 hours as needed. Patients with pain unresponsive to the aforementioned treatment could receive intravenous morphine boluses as necessary.Verbal numeric pain scores were assessed through in-person interview in the hospital by a member of the study team at 24, 48, and 72 hours after surgery, and by telephone at 6 weeks postpartum. Women were asked to rate their pain using a 0 to 10 pain scale at rest and with movement, with 0 being no pain and 10 being the worst pain imaginable. To assess pain with movement, patients who were lying down at the time of the assessment were asked to sit up, and patients sitting at the time of the assessment were asked to stand. Maternal satisfaction with pain management was measured at 72 hours on a scale of 0 (completely unsatisfied) to 100 (completely satisfied). All members of the study team who conducted the VPS interviews were blinded to the randomization group.Total opioid use was determined by converting administered doses of oral hydrocodone or oxycodone to “intravenous morphine milligram equivalents” using a standardized relative-potency conversion scaleThe primary outcome was the Silverman integrated assessment pain score, an approach that allows researchers to account for both the pain score and analgesic use as a single outcome measure following surgical procedures.αof 0.05). Data were analyzed by intention to treat, and the primary outcome of combined pain scores and analgesic use was analyzed using the Silverman integrated assessmentt-tests, Mann–Whitney U test, and Pearson's χ2were applied as appropriate to analyze demographic and secondary outcome data. Normal distribution of data was determined using visual inspection, QQ plots review, and Kolmogorov–Smirnov test. The study was approved by the Stanford University Medical Center Institutional Review Board and was registered in ClinicalTrials.gov (NCT00505362).An a priori sample size calculation based on previous institutional data estimated that we required 112 patients to show a 30% difference in pain scores when rectus muscle reapproximation was performed .Silverman integrated assessment scores during the 72-hour postoperative period were higher in the rectus muscle reapproximation group .Operative times and surgical and infectious complications were similar between groups . There Our study suggests that rectus muscle reapproximation at primary CD results in increased Silverman integrated assessment scores during the first 72 postoperative hours. Increased postoperative pain with movement has been suggested as a reason some obstetricians avoid rectus muscle reapproximation,rectus,cesarean, andpainfrom 1960 to 2016 did not identify any related studies.The evidence base to assess rectus muscle reapproximation is quite limited. In 2012, Encarnacion and Zlatnik concluded in a review of evidence-based CD that additional research is needed to assess rectus muscle reapproximation as no studies on the practice could be identified.The frequency with which rectus muscle reapproximation is performed at CD in the United States is unknown. Rectus muscle reapproximation was performed among 24% of CDs at a single U.S. hospital in the previously mentioned study of rectus muscle reapproximation and adhesions.Our study highlights the importance of using a tool such as the validated but not widely used Silverman integrated assessment to assess pain and opioid use, as it accounts for critical interactions between two commonly used endpoints in surgical pain studies, the pain score and opioid use, which could skew study outcomes.Our study protocol standardized factors that could affect postoperative pain. Study participants received consistent intraoperative anesthesia, standardized postoperative pain management, and similar surgical techniques to reduce the number of potentially confounding variables and to isolate the effect of rectus muscle reapproximation on pain. As most surgeons in our institution use a Pfannenstiel skin incision and frequently a combination of blunt and sharp dissection to open the abdomen, it would have been impossible to quantify the degree to which each was used, which is why we chose a randomized study design. Closure of the parietal peritoneum has been shown to increase immediate postoperative painWe excluded patients with factors that may independently influence postoperative pain or surgical complications, including labor, chronic analgesia use, vertical skin incision at cesarean, prior laparotomy, and class III obesity. We made some assumptions where literature is absent about which factors alter pain: we included women carrying a singleton or twin gestation and excluded women delivering prior to 35 weeks' gestation in case potential emotional strains of an unexpected preterm birth influence perception of pain.Women who underwent rectus muscle reapproximation were more likely to have a placental abnormality as the indication for CD, and were less likely to be parous or have breech presentation. Whether these differences in obstetric characteristics mattered to the primary outcome is unknown.We encountered several challenges in running this study. Enrollment was slow. Our limited inclusion of only women undergoing a primary CD, not in labor, without prior laparotomy and without class III obesity contributed to slow enrollment. Furthermore, we standardized surgical techniques to reduce the number of potentially confounding variables and failed to anticipate that due to this some surgeons preferred not to enroll their patients. In an attempt to increase acceptance of our study by surgeons, we removed the requirement for use of 2–0 chromic catgut for rectus muscle reapproximation that some obstetricians found objectionable. There are no data suggesting that suture type alters pain when used in the abdomen, and because the study was randomized, we do not feel that this change introduced bias. Our group sizes were different despite 1:1 randomization. Early in the study, our randomization box, which was kept in a shared room and contained sequentially numbered cards, was moved and several cards were lost. We monitored that all remaining cards were opened in the correct order following this event, and verified that all surgeons complied with randomization throughout the study. However, our final group sizes were consequentially imbalanced at 28 and 35 patients, respectively. Finally, some patients were reluctant to enroll in an interventional trial where the outcome involved an assessment of pain.Due to slow enrollment, we closed our study prematurely, after 6 years and before the target sample size was obtained, to minimize potential confounding effects inherent to a prolonged enrollment period such as changing surgical practices, suture preferences and patient population.Nonetheless, we felt the results of this study are important to present. Rectus muscle reapproximation is not uncommon, yet data regarding postoperative pain and surgical outcomes are limited. Despite the premature termination of our study and our relatively small final patient numbers, we found a difference in combined pain and opioid use, and our post hoc power calculation revealed that we had 80% power to identify a 30% difference in Silverman integrated assessment scores between groups likely due to a better than expected effect size in the study. Our a priori power calculation was based on institutionally derived data estimates prior to starting the study due to the lack of literature on which to base it, and appears to have underestimated the effect size and therefore overestimated of the numbers needed to conduct this study.Despite our study limitations, we feel that our rigorous methodology, with careful standardization of intra- and postoperative pain management and standardization of surgical techniques, enhanced our ability to isolate and assess rectus muscle reapproximation and its impact on postoperative pain and analgesic use. We used a standardized assessment of pain scores based on in-person pain assessment that considered movement as well as rest pain at standardized postoperative time points. Standardized analgesic pain management protocols also allowed for accurate assessments of postoperative opioid use.Our results suggest that rectus muscle reapproximation modestly increases short-term postoperative opioid use and movement pain among women undergoing primary CD. Operative time, surgical complications, and maternal satisfaction do not appear to be impacted by rectus muscle reapproximation. The benefits described with rectus muscle reapproximation such as less adhesions, should be weighed against the potential for a modest increased postoperative pain and corresponding opioid use.


To compare post-operative pain relieving effect of topical diclofenac 0.1% versus ketorolac 0.5% in Corneal Collagen Cross Linking (CXL) for patients diagnosed with keratoconus.This randomized controlled trial was carried out for six months from October 2016 to March 2017. We included young patients having keratoconus with k-readings greater than 47D and central corneal thickness more than 400 microns. All the patients received single dose one drop of topical diclofenac 0.1% to (Group-A) and ketorolac 0.5% to (Group-B) 30 minutes in advance of the corneal collagen cross linking (CXL) procedure. The CXL was performed with topical 0.1% riboflavin eye drops in 20% dextran as a photo sensitizer. After 36 hours of the CXL procedure, the postoperative intensity of pain was assessed verbally by patients with the help of visual analog scale (VAS) numbers from zero to five where 0 designated no pain & 5 symbolized worst pain.The study comprised sixty eyes of forty one patients. Out of total 16 were male while 25 female patients. The mean age of the patients was 24.27 ± 2.93 years (range 20 to 29 years). In the conclusive analysis, diclofenac 0.1% was used on 30 patients in Group-A and ketorolac 0.5% on 30 subjects in Group-B. Pain relieving scores in Group-A (diclofenac 0.1%) was 2.57 ± 0.67 while in Group-B (ketorolac 0.4% treated arm) was 3.20 ± 0.61.Topical diclofenac 0.1% is statistically comparable to topical ketorolac 0.5% in precluding severity of pain after corneal collagen cross linkage operation. Keratoconus affects both the sexes equally and its onset of generally occurs at puberty.Customary CXL-procedure familiarized by Wollensak and colleagues recommended a short duration refractive surgical technique comprised of mechanical peeling of corneal epithelium around 7mm diameter with use of 0.1% isotonic riboflavin solution in 20% dextran as a photosensitizer.8Non-steroidal anti-inflammatory drugs (NSAIDs) are quite well known to exercise potent anti-inflammatory and analgesic effects. There is evidence that non-steroidal anti-inflammatory (NSAIDs) preparations are administered topically before refractive surgery as they lower down post-surgical intensity of pain and photophobia.12Armed Forces Institute of Ophthalmology is a tertiary care center with well-equipped and state of the art refractive surgery department. To best of our knowledge in the field of refractive surgery, no study has yet been conducted at the national level to differentiate topical ketorolac with topical diclofenac in terms of post CXL pain relief. Therefore, we designed this study to compare the usefulness of a single dose of topical diclofenac 0.1 % and ketorolac 0.5 % with each other in the preclusion of post-CXL pain and discomfort.This was a randomized control clinical study conducted at the Armed forces institute of ophthalmology (AFIO) Rawalpindi between October 2016 and March 2017. This single-station and single surgeon prospective randomized study comprised of male and female patients between 16 to 35 years of age, included by non-probability consecutive sampling suffering from significant keratoconus with k-readings greater than 47D and central corneal thickness more than 400um. The subjects with any previous history of ocular surgery, acute corneal hydrops, dense corneal ectasia, corneal opacity, any history of hypersensitivity against the NSAIDs or use of topical/systemic anti-inflammatory medications within two weeks before surgery were excluded from the study. The study protocol was approved by the Ethics/Research Committee of Armed Forces Institute of Ophthalmology (AFIO) Rawalpindi. All registered subjects signed a written informed consent. A total of 60 eyes of 41 patients were investigated in this study. All eyes that underwent CXL between October 2016 and March 2017 were scrutinized. The pre-operative assessment included un-corrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA) and detailed examination of anterior and posterior segments with slit lamp. Investigations such as corneal topography  and ultrasound pachymetry were performed. The enrolled patients were randomly divided into two groups and assigned to two arms of drug regimen. Group-A to Diclofenac 0.1% and Group-B to Ketorolac 0.5%.The first arm Group-A received one drop of diclofenac sodium 0.1%, and the second arm Group-B received one drop of ketorolac 0.5% thirty minutes before surgical intervention by a qualified and trained coordinator. Under sterile conditions CXL was performed as a day care procedure. Lids and skin scrub was done with 5% povidone-iodine solution. Topical akinesia was induced by using proparacaine hydrochloride 0.5% ophthalmic drops. A central 7 mm round corneal deepithelialization for efficient penetration of riboflavin through exposed corneal stroma was performed with the help of sterile blunt spatula. Riboflavin 0.1% in 20% dextran was administered topically every two minutes for 30 minutes. Slit lamp examination was performed to confirm riboflavin absorption throughout the corneal stroma and anterior chamber. Riboflavin saturation in corneal stroma ensures the formation of free radicals whereas riboflavin shielding in anterior chamber sub serve protection of deeper ocular structures such as the corneal endothelium. UVA radiations were delivered using (CCL-365) corneal cross-linking system at a distance of 5-6 cm from cornea for 30 minutes at power settings of 3mW/cm2 (Standard Dresden Protocol). Bandage soft contact lens was placed at the end of procedure for three days till complete reepithelialization of cornea. All the operated patients were informed of how to evaluate their post-operative ocular discomfort and subjectively report to the concerned. After 36 hours of CXL procedure, the postoperative intensity of pain was assessed verbally by patients with the help of verbal rating scale (VRS) numbers from zero to five where 0 designated no pain & 5 symbolized worst pain. In a much selected patients with post-operative worst pain oral analgesics were advised.Statistical Package for Social Sciences (SPSS) version 16 was used for data analysis. Descriptive statistics were used to calculate mean and standard deviation for quantitative. Variables like age, pain. Frequencies & percentages were presented for qualitative variable like gender. To measure difference of mean pain between two groups (Group-A = Diclofenac and Group-B = Ketorolac), independent sample t-test was utilized-value ≤ 0.05 was considered as a significant measure.Sixty eyes were included in this study, divided into two groups of thirty each. About 66.7% were right eyes and 60% of the participants of study were females. Mean age was 24.27 ± 2.93 years. Both the groups were comparable in terms of gender and age. Total of 33 eyes experienced very mild grade pain (30 in diclofenac group vs. 3 in ketorolac group) after a mean duration of 5.00 ± 1.4 hours after surgery  Fig.1mild after a mean duration of 5.32 ± 2.22 hours  In all the sixty eyes, pain was graded as intermediate grade, after mean duration of 6.50 ± 0.70 hours post op in Diclofenac group versus 30 eyes progressing to intermediate pain in ketorolac group earlier than diclofenac group (5.90 ± 1.44 hours). None of the patient in diclofenac group progressed to severe degree of pain while 3 patients reported it after a mean of 6.33±0.57 hours in ketorolac group. Only in two patients pain progressed to The only proven treatment that halts progression of Keratoconus is Corneal crosslinking (CXL).16El-Harazi SM and Kim SJ in their studies also observed significant regression in post-operative anti-inflammatory effect in subjects using preemptive NSAIDs.17There are many techniques and methods for management of postoperative pain; of these, pre-operative approach in the use of NSAIDs for inducing analgesia is of great interest. Presumptive use of NSAIDs is quite efficacious in the first post-operative day to control pain and discomfort.18In this study, it was also observed that pain free interval after CXL was longer in diclofenac group (7.20+1.06 hours) as compare to ketorolac group (3.43+1.25 hours). However, this pain relief interval is statistically insignificant (P = 0.14)and the duration is much less than what has been claimed by Hang JP et al, who claimed this to be 24 hours.Maurin et al. studied pain perception in Epi-off versus Epi-on CXL using iontophoresis and found out statistically less pain in later as compared with earlier. Ghanem et al studied relation of age and pain perception and found out a statistically significant difference between pain perception between the two age groups.It has small sample size and short-term follow-up. The short term and long term snags of CXL like, temporary corneal haze, corneal infection, and prolonged post-CXL ocular pain and discomfort were not considered. Further additional work is required for pre-operative analgesia in ophthalmic surgical procedures to overcome early and prolonged post CXL pain related hazards in the management of progressive keratoconus.We concluded that topical diclofenac 0.1% is comparable with topical ketorolac 0.5% in releieving postoperative pain following CXL surgery.MS: Conception and Data collection.MSK: Designed and drafting the manuscript. AH: Conception and Design. MAY: Final review. MI: Final approval of the manuscript.