BackgroundDespite the increased use of electronic medical records (EMRs) in past years, the recording of clinically useful baseline pain information may still be lacking. An educational effort targeted at the acute pain service and reinforced by electronic prompting may be an effective way to promote electronic documentation of relevant pain metrics. The objective of this study was to assess whether an educational effort with electronic prompting in the EMR promotes the documentation of baseline pain scores and preoperative opioid use by an acute pain service (APS).MethodsA total of 98 patients were included in this study: 49 in the study group and 49 in the control group. The study group consisted of patients who underwent knee and hip arthroplasties after the institution of a multimodal analgesia educational program that also incorporated an electronic prompt to promote behavior change. Primary outcomes were the frequency of documentation of baseline pain scores and preoperative opioid use.Resultsp = 0.0001). Preoperative opioid use was recorded in 24% of APS documentation within the control group, but this increased to 73% after the educational intervention (p = 0.0001). Documentation of resting pain scores on the day of surgery also increased from 59% to 87% (p = 0.0014).After the implementation of the education initiative, 67% of the patients had baseline pain scores recorded in the preoperative APS documentation, compared to 20% in the control group (ConclusionsThe introduction of a multi-dimensional educational effort focused on baseline pain metric recording within the context of an analgesic change of practice increased assessment of both baseline pain and preoperative opioid use by APS. These results can be applied to other settings in which a focused change of practice is required and an electronic medical record already utilized. The presence of electronic medical records (EMRs) has become almost ubiquitous over the course of the past decade. Specific to perioperative medicine, EMRs have become integral to accurate documentation of patient vital signs and medication administration, as well as capable data repositories and tools to investigate perioperative outcomes. Despite these advantages, an EMR system is only as useful as the data contained therein and the initial input of a patient’s relevant health variables is critical. Several recent investigations suggest that prompts in the EMR encouraging healthcare providers to record a particular data point may be influential on behavior and may even have a role in the accuracy and reducing documentation errors -4. Within the realm of perioperative pain management, the accurate recording of analgesic metrics such as pain scores, functional status, and opioid use is critical to providing personalized and effective analgesic interventions. In the context of postoperative analgesia, an important data point that is sometimes overlooked or not recorded in preoperative documentation is a patient’s baseline pain score. Some evidence suggests that the higher the patient’s preoperative pain level, the more likely the patient will have postoperative pain that will be difficult to control or will develop chronic pain -7. FurthThe University of Florida - Jacksonville Institutional Review Board approved this study. In this retrospective chart review, the two study groups were:· Intervention group: consisted of patients undergoing total hip or knee arthroplasties after August 3, 2015, the first surgical date after the educational effort and implementation of the multimodal analgesic guideline.· Control group: an equivalent cohort matched for age, American Society of Anesthesiologists (ASA) classification, and surgery type who underwent hip or knee arthroplasty prior to August 3, 2015.To increase the homogeny between the two study groups, exclusion criteria for initial review were age less than 18 years, bilateral surgery, fracture as preoperative surgical diagnosis, placement of antibiotic spacer, and preoperative patient refusal for regional anesthesia.A total of 152 patient charts were reviewed for this study. In total, 54 patients were excluded secondary to administration of one or more of the non-opioid analgesics (in the control group), clinical contraindication to one or more of the non-opioid analgesics or the peripheral nerve block. A total of 98 patients were therefore included in this study. A chart review consisted of recording the following information: age, gender, American Society of Anesthesiologists (ASA) score, site of surgery, whether primary or revision surgery, documentation of preoperative baseline pain score and opioid use, regional anesthetic technique employed, administration of acetaminophen, celecoxib, and gabapentin, and postoperative static and active pain scores.Pre-implementation educationAs a component of the multimodal arthroplasty guideline, all clinical members of the anesthesia APS  participated in a pre-implementation educational program. With regard to the current study, the purpose of this educational effort was to introduce and reinforce the concept and benefits of multimodal analgesia and more surgery-specific pain data recording. Specific aims with regards to the current study were to 1) promote a more thorough preoperative review of patient pain history, 2) encourage documentation of preoperative baseline pain scores and opioid use, and 3) reinforce postoperative pain score recording. The educational effort consisted of three sessions: one grand rounds lecture, one online module, and one separate review session with residents, who would be the primary individuals evaluating patients and documenting outcome metrics  pain scores at the surgical site (at rest and with motion), 2) ambulatory opioid analgesics, if any, and 3) dose and frequency of those analgesics if applicable. These variables were obtained by directly asking patients the following questions:· On a scale from 0 to 10 (0 being no pain and 10 being worst pain imaginable), how much pain do you currently have in your operative knee/hip at rest? With motion?· During the past week, what opioid medications have you taken for pain on a daily basis?· What dose of that opioid do you take and how many times a day?Outcome measuresPrimary outcomes were the frequency of assessment of 1) preoperative pain scores and 2) preoperative ambulatory opioid use as documented in the APS consult note. Preoperative opioid use was defined as a patient taking oral morphine, oxycodone, hydromorphone, methadone, or hydrocodone daily for the week prior to surgery, or a fentanyl transdermal patch for at least one week prior to surgery. Secondary outcomes included frequency of documentation of actual intake of preoperative opioid , and frequency of recording of postoperative pain scores (at rest and with motion) by APS on surgical follow-up. Administrations of non-opioid analgesics and peripheral nerve catheter use were also assessed. The use of these multimodal analgesic approaches was considered as consistent with the program guideline if the patient received a peripheral nerve catheter and all three non-opioid analgesics in the preoperative bay and these analgesic methods were continued on postoperative day (POD) 1.Statistical analysist-tests were used for quantitative variables; χ2 analysis was utilized for nominal variables.Based on an estimated rate of baseline pain score and preoperative opioid use assessments of approximately 20% given current clinical practices prior to the establishment of the multimodal approach, we estimated that to detect a 30% change in incidence , at least 38 patients would be required in each group. Statistical analysis was conducted using AcaStat . Two-tailed unpaired p = 0.027).Baseline patient characteristics are shown in Table Primary outcomesp = 0.0001). Of those patients whose baseline pain score was assessed, there was no significant difference in the baseline pain score before (7.70 ± 1.89) and after (7.52 ± 1.54) multimodal guideline implementation (p = 0.75). Preoperative opioid use was recorded in 24% of APS documentation within the control group, but this percentage increased to 73% after the educational intervention (p = 0.0001).Primary outcomes are shown in Table Secondary outcomesp = 0.35). Among these patients, 68% of control patients had 24-hour preoperative opioid intake documented, compared to only 20% of study patients (p=0.0001). Regarding documentation of POD 0 and POD 1 resting and active pain scores by APS, only documentation of resting pain scores on POD 0 resulted in a statistically significant difference between the two groups . Use of multimodal analgesics was 100% for acetaminophen, 88% for celecoxib, and 98% for gabapentin after the introduction of the analgesic guidelines. Peripheral nerve catheter use (rather than single shot nerve blockade) did not increase significantly . Approximately 10% of patients in the control group were found to have no sensory deficit in the recovery area and thus were classified as “failed block”.Secondary outcomes are also shown in Table p = 0.0001; 30% vs 74%, p = 0.0004, respectively), consistent with general results.As more patients in the protocol group underwent primary arthroplasty, outcomes were re-examined within this sub-population Table . Rates oIn our study, the use of a multifaceted educational program that included didactic instruction and electronic prompting emphasizing documentation of baseline pain characteristics in the EMR was associated with a significant increase in recording of both baseline pain scores and opioid use. This finding is in agreement with previous research which suggests that both educational efforts and electronic prompting are effective in causing behavior change -4,13. ItWith regards to our patient population, the establishment of this multimodal analgesic guideline: 1) revealed that patients undergoing arthroplasties at our institution had a fairly high baseline pain score (>7/10), and 2) suggest that almost three-quarters of our hip and knee arthroplasty patient population may use opioid medication on a regular basis prior to surgery. Knowledge of these high preoperative pain scores and rates of use of opioid analgesics is very useful for the analgesic management of patients after major surgery such as arthroplasty for two reasons. First, the accurate assessment of preoperative pain scores provides a relative framework within which to build both clinician and patient expectations, which can affect post-surgical outcome . A patiep < 0.001). The reasons for this decrease in recording of this information are unclear but may be secondary to 1) a significantly smaller number of patients (n = 10) that were confirmed to be using opioids preoperatively in the control group compared to those in the intervention group (n = 25); 2) a need for further, more targeted educational reinforcement for obtaining this particular parameter or 3) an overall need for deeper cultural change with respect to the significance of this data. We believe that obtaining a relative idea of the amount of opioid, if any, that a patient is consuming prior to undergoing a major operation is important as this variable can influence the patient’s postoperative risk profile as well as directly affect intraoperative and postoperative analgesia.Despite the improvement in recording the baseline preoperative opioid use, the recording of the actual amount of preoperative opioid analgesic consumed by patients in a 24-hour period did not improve and in fact worsened after the educational intervention  had clinicians been exposed to any other educational interventions on the same topic previously? and 2) did social pressure rather than the intervention cause a behavior change? For the first point, no other concurrent educational intervention or hospital policy was implemented or ongoing six months prior to or during the implementation of our educational/clinical protocol. While it may be possible that some clinicians had previously had some education on this topic, the use of multimodal analgesia and a comprehensive peri-operative pain documentation approach was not commonplace in our practice, and thus any previous exposure is unlikely to have influenced the observed results. Regarding social pressure, while this is certainly a possibility, we believe that such social pressure would arise as a consequence of the study intervention, and thus still be attributed to the educational/electronic prompting system. Therefore, we believe that overall the change in behavior as indicated by an increase in the documentation was, in fact, a result of the efforts described in this study.Lastly, the reason for a 10% incidence of "failed block" in the control group (compared to 0% in the study group) is unclear. We speculate that the decrease in block failure after the study intervention was related to an educational component that encouraged assessing sensory deficit soon after peripheral nerve blockade, but this explanation assumes that no other change in clinical practice occurred.In conclusion, the introduction of a multi-dimensional educational effort for the implementation of a multimodal analgesic guideline increased assessment of both baseline pain and preoperative opioid use by the acute pain service. These results can be applied to other settings in which a focused change of practice is required and an electronic medical record already utilized. Future studies should be done to further examine and prospectively verify and supplement these results.


This study aimed to assess whether urethral pain can be alleviated by urination in male patients undergoing flexible cystoscopy.Ninety-six male outpatients undergoing flexible cystoscopy were randomly divided into two groups. Patients in the test group urinated during flexible cystoscopy, whilst patients in the control group received no instructions to do so. All patients received 10 mL of 2% lidocaine gel prior to assessment. Using 0 (no-pain) to 10 (unbearable severe pain) pain scores (VAS), we assessed patient discomfort prior to anesthesia gel perfusion (baseline), during gel perfusion, during cystoscope insertion through the urethra, and 15 min post-examination analysis. The entire protocol was completed by a single doctor in our Department of Urology.P = 0.001). No significant differences between other evaluation points were observed between groups.The groups showed no statistical differences regarding age or examination time. During cystoscope insertion, the test group recorded significantly lower pain scores 2 (IQR 1–3) - compared to the control group 3 (IQR 2–3), (Urethral pain can be significantly alleviated by urination in male patients undergoing flexible cystoscopy through the urethra.Registry name: Clinical study of urination action to relieve urethral pain associated with flexible cystoscopy.Registration number: ChiCTR-INR-17013294Date of Registration: 2017-11-08 Cystoscopy is one of the most important tools for disease diagnosis in urology. Since its inception in 1984, flexible cystoscopy has been the procedure of choice for this purpose. Compared to rigid cystoscopes, flexible cystoscopy has the advantage of no blind areas, small damage, clear vision and a low requirement for body positioning. During analysis, the cystoscope must pass through the urethra to reach the bladder resulting in contact with the urethra mucosal membranes, leading to discomfort and pain. Patients receiving this procedure are thus often stressed, have increased heart rates and elevated blood pressure .Methods to alleviate pain in patients undergoing flexible cystoscopy have been widely investigated. Local anesthesia is a widely used analgesic method in flexible cystoscopy. Its analgesic theory is to inject anesthetic and penetrating drugs into the urethra to block the nerve located under the mucosa, thus playing the role of anesthesia. Local anesthetics are mostly gelatinous mixtures of anesthetics and lubricants, such as lidocaine gel, bupivacaine gel, tetracaine gel, etc. These anesthetic gels can not only play an anesthetic role in the urethra but also have lubrication. Lidocaine is currently the most widely used local anesthetic. However, recent studies have shown that lidocaine gel has no obvious advantage over urethra pain control compared with ordinary gel, and may cause additional pain and discomfort –5. In adWe believe that defining the specific site of urethral pain caused by cystoscopy can help us control the pain more effectively. Chen  and TaghWe thus assumed that during the course of flexible cystoscopy, if the patient is urinating according to defined instructions, the external sphincter can relax, thereby reducing urethral pain during cystoscope insertion. Based on this hypothesis, we designed a prospective, randomized, controlled trial in which we assessed the levels of pain in patients instructed to urinate during flexible cystoscopy.The trial was conducted between December 2017 and April 2018 in the Beijing Tongren Hospital in Beijing, China. The study was approved by the ethics committee of the Beijing Tongren Hospital, Capital Medical University  and registered at chictr.org.cn , prior to patient recruitment. The study was conducted according to common standard guidelines for clinical trials  revised version, Somerset West, Republic of South Africa, 1996) [Male patients were admitted to our clinic for flexible cystoscopy. All patients were over 18 years old. Exclusion criteria included any analgesic used within 24 h of the study period, known urethral stricture, previous history of urethral dilation, acute urinary tract infection, indwelling urethral catheter, and existing urethral pain  Patients, as well as those who are unable to cope with pain assessment due to mental disorders.Patients were screened by the chief physician of the outpatient clinic. Use a computer  to build a random number table, then randomly divide patients into two groups. The randomisation was carried out by an independent researcher who was not involved in the subject-recruitment process. The sealed opaque envelopes were used to ensure concealed allocation. Intervention participants in the trial knew the patient’s grouping, and information collectors did not know the patient’s grouping.We performed a prospective, randomized, controlled trial designed to compare pain scores between patients in experimental- and controls groups. Patients in the test group urinated during flexible cystoscopy. Patients in the control group received no instructions during the procedure. During examination, 10mls of 2% lidocaine gel was injected into the urethra and the penis was clamped for 10 min. A flexible cystoscope was passed through the urethra into the bladder for examination. All cystoscopies were performed by an experienced urologist. Flexible cystoscopy instruments included digital camera (Olympus OTV-S7), color video monitor (Olympus OEV-191H) and 16F flexible cystoscope (Olympus CYF-5A).The patient was taken supine position during cystoscopy. Routine disinfection. During examination, 10mls of 2% lidocaine gel was injected into the urethra and the penis was clamped for 10 min. The procedure of the control group was as follows: the examiner lifted the penis with his left hand, inserted the front end of the flexible cystoscope into the urethra with the help of his left thumb and index finger, and held the mirror with his right hand. The thumb controlled the adjusting lever. With the help of water flow, the examiner observed the urethral side entry mirror under video surveillance. Stay 1–2 s when seeing the external urethral sphincter and entered the bladder under direct vision. In the experimental group, the examiner lifts the penis with his left hand, inserts the front end of the flexible cystoscope into the urethra with the help of his left thumb and index finger, holds the mirror with his right hand, and controls the control lever with his thumb. With the help of water flow, the examiner observed the urethral side entry mirror under video surveillance. Stay for 1–2 s when seeing the external urethral sphincter and ask the patient to urinate. Then entered the bladder under direct vision.Patient histories were collected prior to operation. During cystoscopy, an experienced urologist nurse recorded the pain score according to the patient’s assessment before aesthesia gel perfusion (baseline), anaesthetized gel perfusion, cystoscopy insertion into the urethra, and 15 min post-examination analysis. Patients were asked to cross a line in a 10 cm region with 0 at one end of the transverse line indicating no pain; and 10 at the other end indicating a sharp intense pain.Before the experiment, researchers collected general information about patients, including age, height, weight, and underlying diseases.n = 48 per group); recognizing a potential loss of analytical power due to patient withdrawal from 10%.We used the result of Taghizadeh as the pain score of our control group, 2.82 ± 1.2VAS . A minimp-value less than 0.05 was considered to be statistically significant.SPSS20.0 software was used for all data analysis. Data are expressed as mean ± standard deviation (SD), median and interquartile range (IQR) for variables that do not follow a normal distribution, or frequencies for categorical data. Normally distributed continuous variables were compared between the two groups using a two-sided t-test, with chi-square tests for categorical variables and with non-parametric Wilcoxon test for not normally distributed continuous variables. A P = 0.815). Study groups did not differ in demographics, co-morbidities. The mean examination times were 3.42 ± 0.64 mins for the test group and 3.54 ± 0.71 mins for the control group, which did not significantly differ (P = 0.371).The trial included 96 patients (48 cases in each group). As shown in Table P = 0.761 & P = 0.661, respectively). Upon comparison of the scoring when the cystoscope was inserted, the score of the test group was 2 (IQR 1–3) compared to 3 (IQR 2–3) for the control group, which was significantly lower (P = 0.001)  was observed in either group . When the two groups were compared after gel perfusion and 15 min following examination, no significant differences were observed  to 2 (IQR 1–3), This study has the following advantages: In addition to prospective, random controls, all operations were performed by the same highly skilled physician, thus maintaining consistency. Secondly, the characteristics of the two study groups were similar and both groups underwent comparable examination times. Thus, bias and other confounding factors were reduced to a minimum. The limitations of this study included the uncertainty that patients in the control group displayed no autonomous urination. In addition, apart from the subjective pain score, we had no objective evidence that the external urethral sphincter relaxed. Future studies should employ external urinary sphincter electromyography to ensure an objective evaluation of our study findings.In summary, we suggest that during male cystoscopy, patient urination represents a means of reducing pain levels during the examination.


To evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with RA who had an inadequate response to csDMARDs.Patients in SELECT-NEXT, a randomised controlled trial, were on a background of csDMARDs and received upadacitinib 15 mg and 30 mg or placebo daily for 12 weeks. PROs included Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration and severity of morning (AM) joint stiffness, Short Form 36 Health Survey (SF-36), and Work Instability Scale for RA (RA-WIS). Least squares mean (LSM) changes were based on mixed-effect repeated measure models. Percentages of patients reporting improvements ≥ minimum clinically important differences (MCIDs) and scores ≥ normative values and number needed to treat (NNT) were determined; group comparisons used chi-square tests.P < 0.05) in PtGA, pain, HAQ-DI, FACIT-F, duration and severity of AM stiffness, SF-36 (PCS and 6/8 domains), and RA-WIS at week 12. Significantly, more upadacitinib-treated patients  reported improvements ≥ MCID in PtGA, pain, HAQ-DI, FACIT-F, AM stiffness, SF-36 (PCS and 4 or 7/8 domains), and RA-WIS and scores ≥ normative values in HAQ-DI, FACIT-F, and SF-36 (PCS and 4 or 5/8 domains). For most PROs, the incremental NNT with upadacitinib to report clinically meaningful improvement from baseline ranged from 4 to 8 patients.Data from 661 patients were analysed. Compared with placebo, patients receiving upadacitinib reported statistically significant improvements (both doses, Upadacitinib 15 mg or 30 mg daily for 12 weeks resulted in significant and clinically meaningful improvements in global disease activity, pain, physical function, fatigue, duration and severity of AM stiffness, HRQOL, and work instability among csDMARD-IR patients with RA.NCT02675426. Retrospectively registered 5 February 2016.Clinicaltrials.gov,  Rheumatoid arthritis (RA) is a chronic, inflammatory, and destructive joint disease that is associated with substantial clinical burden . Pain, fJanus kinase (JAK) inhibitors are a class of orally administered targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) that have recently received regulatory approval and are under evaluation in randomised controlled trials (RCTs) for the treatment of RA –23. UpadClinicalTrials.gov, NCT02675426) were reported previously [Full details of the study design of SELECT-NEXT  and the patient’s assessment of pain were measured using visual analogue scales (VAS) of 0 to 100 mm, with higher scores indicating greater disease activity and worse pain. Reductions of ≥ 10 mm in both PtGA and pain scores are the minimum clinically important difference (MCID). Physical function was assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI) , 27, witP values were analysed using a mixed-effect repeated measures model with unstructured variance-covariance matrix including treatment, visit, treatment-by-visit interaction, and prior bDMARD use as fixed factors and baseline value as a covariate. The assumptions of linear regression were checked and met for all outcomes included in the study except for AM stiffness duration and EQ-5D-5 L. Linear regression models were implemented for the analysis of AM stiffness duration and EQ-5D-5 L outcomes for consistency; given the large sample size, estimates are unlikely to be biassed. The results were expressed as least squares mean (LSM) changes. The baseline values and LSM changes for SF-36 domains were transformed based on the mean and standard deviation of the 1998 general US population. Analyses were performed in the full analysis set of all randomly assigned patients who received at least one dose of study drug.Changes from baseline at weeks 4 and 12, 95% confidence intervals, and nominal P < 0.05 was considered significant.The percentages of patients reporting improvements in PRO scores from baseline to week 12 ≥ MCID or scores ≥ normative values (age- and gender-matched for SF-36 only) at week 12 were compared between active treatment groups and placebo. Non-responder imputation was used when PRO data were missing. Comparisons between active treatment groups and placebo were made using chi-square tests. For each PRO, the incremental numbers needed to treat (NNTs) to achieve clinically meaningful improvements from baseline (≥ MCID or MID) were calculated as the reciprocal of the response rate differences between the active treatment groups and placebo. Times to response from baseline to week 12 were assessed for pain, HAQ-DI, and AM stiffness using Kaplan-Meier analysis. Median times to response were calculated for each dose group; comparisons between the groups used log-rank tests. A total of 661 patients with active RA were randomised and treated ; of these, 618 (93%) completed the placebo-controlled 12-week period . Baseline characteristics were balanced across the 3 groups  LSM changes from baseline to week 12 were reported with both upadacitinib 15 mg and 30 mg compared with placebo for all PROs (P < 0.001) except SF-36 MH with 15 mg, and SF-36 MCS, RE, and MH with 30 mg  from baseline were reported as early as week 1 for PtGA , pain , HAQ-DI , AM stiffness severity , and AM stiffness duration .Statistically significant LSM changes  more upadacitinib-treated (15 mg and 30 mg) patients reported improvements ≥ MCID in PtGA, pain, HAQ-DI, FACIT-F, duration and severity of AM stiffness, RA-WIS, SF-36 PCS, and SF-36 MCS (15 mg only) and seven of eight SF-36 domains with 15 mg and four of eight SF-36 domains with 30 mg .P < 0.05) in HAQ-DI, FACIT-F, and SF-36 PCS with both upadacitinib doses versus placebo. Across SF-36 domains, the percentages of patients reporting scores ≥ normative values at 12 weeks ranged from 18% (RP) to 40% (RE) with upadacitinib 15 mg and 20% (RP) to 40%  with upadacitinib 30 mg, compared with 8% (RP) to 34% (RE and MH) with placebo, statistically significant (P < 0.05) in PF, RP, BP, and VT for both upadacitinib doses and GH with 30 mg  for SF-36 PCS in the upadacitinib 30-mg group to 89 (41%) for SF-36 MCS in the upadacitinib 30-mg group . There appears to be little difference in the treatment responses between the upadacitinib 15-mg and 30-mg doses, consistent with the reported primary efficacy results . Most PRAssessing the effect of upadacitinib on pain, physical function, fatigue, and AM stiffness is important because these outcomes directly impact HRQOL by reducing patients’ ability to perform daily activities and providing barriers to maintaining employment –44. The This RCT has several strengths of note. Several validated PROs reflecting different aspects of the patient experience were assessed in this study. The analyses performed in this study were comprehensive in nature as they not only examined the changes from baseline but also the proportion of patients reporting improvements ≥ MCID/MID criteria and population norms as well as the time to response for important patient-centric outcomes, such as pain and physical function. The use of MCID or MID criteria to measure response provides a context of how clinically meaningful these improvements are from a patient’s perspective. In addition, assessing the proportion of patients with improvements that reach normative values is a more stringent assessment criterion than MCID, and our results show that a statistically significant proportion of csDMARD-IR patients with RA reported this level of improvement with upadacitinib treatment.This RCT also has limitations to be considered when interpreting the results. PROs were collected at fixed visits; therefore, responses were unavailable at other time points; however, differences in the outcomes occurred early and were maintained at week 12. The generalisability of these results to patients with milder disease may be limited because patients had moderately to severely active disease at enrolment. The method used to impute missing data (non-response imputation) assumes that missing PRO scores are associated with non-responses, which are stringent conditions and may underestimate the true rate of response.Upadacitinib 15 mg and 30 mg daily resulted in rapid and clinically meaningful improvements in the outcomes important to patients including disease activity (per PtGA), pain, physical function, fatigue, HRQOL, AM stiffness, and work instability among csDMARD-IR patients with RA.


Pain response rates are equivalent after single 8 Gy and fractionated palliative radiation therapy for bone metastases. Reirradiation remains more frequent after a single fraction, although this does not simply reflect pain recurrence. Given the possible role of stereotactic radiation therapy in providing durable pain control, measures of durability are required. Net pain relief (NPR), the proportion of remaining life spent with pain response, may provide this. This study assesses the use of NPR as an outcome measure after palliative radiation therapy for bone metastases.This is a secondary analysis of data collected in the Dutch Bone Metastasis Study, a randomized trial comparing palliative radiation therapy delivered as 8 Gy in a single fraction and 24 Gy in 6 fractions. NPR was assessed by survival cohorts, treatment regimen, and primary diagnoses. The consequences of missing data upon the use of NPR in future studies were considered within sensitivity analyses.P = .004). Differential willingness to reirradiate may be influencing this outcome. When response beyond reirradiation was included, this difference was not seen .Patients whose pain improved after palliative radiation therapy experienced improvement for 56.6% of their remaining lives. Missing responses in questionnaires mean the range of uncertainty in NPR is 36.1% to 62.1%. When response beyond reirradiation was excluded, NPR after treatments of single-fraction 8 Gy and 24 Gy in 6 fractions was 49.0% and 56.5%, respectively (Patients who responded to conventional radiation therapy experienced improved pain control for approximately half of their remaining life. NPR may provide valuable information in assessing pain response durability. Missing data are, however, inevitable in this population. This must be minimized and the consequences recognized and reported. Additionally, reirradiation protocols and the frequency and duration of trial follow-up may have a significant impact upon this outcome, requiring careful consideration during trial design if NPR is to be used in future studies. Patients who respond to palliative radiation therapy for bone metastases can expect improved pain for approximately 50% of their remaining life. Net pain relief, although rarely reported, can provide valuable information about response durability. This is particularly important when assessing stereotactic radiation therapy outcomes. Limited trial follow-up, long intervals between questionnaires, and missing data may result in significant uncertainty. This latter must be minimized and clearly reported, and its consequences must be assessed where net pain relief is considered.Palliative radiation therapy for painful bone metastases, alongside analgesia, is the standard of care. Multiple studies have compared different dose fractionation schedules. Response is assessed as the proportion of individuals gaining an improvement of at least 2 points on a 0 to 10 point numerical rating scale without concurrent increase in opioids.4In attempting to quantify response durability, studies routinely report reirradiation rates in the absence of difficult-to-collect longitudinal response data. Twenty percent reirradiation rates are seen after single-fraction treatment compared with 8% after multiple-fraction regimens.8International consensus endpoints have increased homogeneity in bone metastasis trial conduct and reporting. These recognize the potential of net pain relief (NPR) as a possible outcome measure to assess response durability.Although the Dutch Bone Metastasis Study (DBMS) was performed in the late 1990s, the study collected weekly and subsequently monthly response questionnaires on pain and quality of life after radiation therapy.The data used in this analysis were collected by the DBMS group. Details of the study methods have previously been published14For the present analysis, patients were grouped according to their primary tumor into 4 groups: breast cancer, prostate cancer, lung cancer, and all other diagnoses. Baseline characteristics were described for the study population. Survival was defined from the start of radiation therapy. Survival cohorts were identified as individuals surviving <6 weeks, 6 to 12 weeks, 12 to 24 weeks, 24 to 52 weeks, and >52 weeks. Individuals censored at trial closure had unknown survival time. Median survival was calculated using the Kaplan-Meier method.• Initial analyses included only individuals with known survival time who were known to have responded to treatment. This determines observed NPR in responders. This was assessed by survival cohort, diagnosis, and treatment regimen.• Subsequently, this analysis was reproduced including patients with known survival time, but who were not known to have experienced a response to treatment. This provides overall expected NPR for all patients.• Those individuals censored at trial closure and known to have responded were then considered separately because their response duration beyond trial closure was not known.The patient's pain response at each questionnaire was classified using International Consensus endpoints,t test in individuals with known survival time.Mean cqaNPR for different treatment regimens was compared using 2-sided Student's • cqaNPR assumes that response in unobserved questionnaires was as seen in the observed questionnaires (as detailed earlier). This includes response beyond reirradiation.• NPRa: All unobserved questionnaires were assumed to represent an NR state (worst case estimate).• NPRb: Unreturned questionnaires were assumed to represent response (an anticipated overly optimistic scenario).• NPRlv: A last-value-carried-forward approach was used to replace the missing values. In this analysis, an individual's last known pain state was assumed to persist until the next known state or death. NR is assumed before the first known response after radiation therapy.Studies investigating interventions in patients near the end of life often have significant amounts of missing data.Finally, the consequences of excluding all responses beyond reirradiation were assessed . The exclusion of these responses provides an assessment of response durability in the absence of reirradiation.A total of 1147 patients were included in the study cohort . Survival time was known in 849 patients (74%) . The median survival after radiation therapy was 29.6 weeks (26.3-32.9) in the whole population  and 18.9 weeks (16.9-20.3) in those who died during trial follow-up. The most common diagnoses were breast (39.2%), lung (24.5%), and prostate (23.2%) cancer. Breast and prostate cancer were more frequent in the survivors beyond study closure. Median baseline pain score was 7 with 26.7% of patients taking strong opiates .P = .191)  (n = 539), including all responses beyond reirradiation. cqaNPR was higher in those known to have experienced a CR compared with PR . cqaNPR appeared higher in those with very limited survival, namely 66.4%  versus 54.4% in long-term survivors , although significantly more data were missing in the short survival cohort, making these results difficult to interpret a and 2b. = .191) . Patient = .191) .Fig. 2CoIn patients alive at study closure who responded to treatment, cqaNPR was 66.3% higher than in those with known survival time (56.6%) a and 2b.2d P = .001]).One hundred and three (12.1%) patients had no observed response assessment after treatment. Median survival of this group was 7.86 weeks . In the population who were observed until death, 3760 questionnaires were missing (31.0%). Missing data were more common for patients with limited observed survival . In individuals who returned at least 1 posttreatment questionnaire, 38.7% of questionnaires were missing in nonresponders whereas 21.6% were missing in responders. Fewer data were missing after single 8 Gy treatment  with known survival time returned enough questionnaires to allow assessment of more than 90% of their remaining life. The median survival of this group was 33.0 weeks; 101 individuals (87.8%) were responders, of whom 48 (41.7%) were complete responders (compared with 17.4% CR in those with <90% time observed). In responders in this cohort the mean cqaNPR was 55.7%.P = .004])  c.Durability of pain control is an important outcome for patients undergoing palliative radiation therapy for painful bone metastases.In this study, patients who responded to palliative radiation therapy gained improved pain control for 56.6% of their remaining life (cqaNPR). No difference was seen in cqaNPR after single- and multiple-fraction palliative radiation therapy in responders (55.5% vs 57.5%), although a significant difference was seen when response beyond reirradiation was excluded (49.0% vs 56.5% respectively). Although statistically significant, it is unclear if this latter difference is of sufficient scale to be clinically relevant given the recognition that reirradiation is not a simple reflection of pain; therefore, this outcome is likely to be confounded by differential willingness to re-treat between the treatment arms.Although appealing in its potential to offer valuable information about response durability, we demonstrate that challenges exist in the use of NPR as an outcome measure.Despite being a well-conducted study, significant numbers of questionnaire responses are missing, as is anticipated in studies investigating palliative interventions.By reporting both intention to treat and assessable responses, existing studies recognize the impact of missing data (due to death and incomplete data).NPR, as measured here, recognizes that patients’ symptoms may fluctuate,Patients who responded and were alive at trial closure experienced higher NPR than those observed until death (cqaNPR of 66.3% vs 56.6%). It is not possible to determine whether this difference reflects the nature of the censored group  or the fact that the observations included were relatively closer to treatment, possibly not including the point of pain recurrence. With well-balanced treatment arms, this may not be a problem, but differing follow-up periods with variable time points for response assessment will limit comparability of NPR between studies. This has implications for the use of NPR in stereotactic radiation therapy studies, as benefit may be anticipated to be greatest in patients with longer survival who are more likely to be censored at trial closure.A further limitation of the NPR outcome is that a returned questionnaire is assumed to be representative of the entire period since the previous questionnaire. Questionnaires, however, focused upon an individual's worst pain over the preceding week because robust capture of experienced pain can only be achieved over short periods in cancer patients.• Specific efforts, beyond those already in place, are required to minimize missing data .• The collection of outcomes using digital platforms has been shown to be feasible and beneficial in advanced cancer and might enable capture of weekly outcomes to reduce uncertainty in the measurement of NPR.• The use of cohort multiple randomized controlled trial designs could be considered to aid recruitment and gain follow-up information for a cohort receiving standard treatment. The challenges of this in a population with limited prognosis may, however, be significant.28• Robust reporting of the extent of missing data and sensitivity analyses will be required to allow comparisons of NPR both within and between trials.• Although assessing NPR in all patients (both responders and nonresponders) provides an important sensitivity analysis, the increased uncertainty introduced by including nonresponders can be avoided by assessing this outcome only in responders. The question answered by these 2 results differs and given the overall aim of comparing treatment efficacy, it may be necessary to accept (and recognize) this uncertainty.Unfortunately, missing data during follow-up are inevitable in this patient population and will remain a limitation of NPR as an outcome measure, particularly in subgroups where missing data are more prevalent . Caution is required in interpreting outcomes in these groups. These uncertainties should not, however, prevent the use of NPR as an outcome measure in future trials, although they have implications for trial conduct and reporting:Despite comparable response rates after fractionated and single-dose treatments for patients with painful bone metastases, the justification offered for fractionated radiation therapy is often response durability, as measured by reirradiation rates.NPR might address these concerns; however, given the inevitability of missing data in palliative care studies, variable frequency of pain assessment, and practicalities of trial duration, uncertainty in the measurement of NPR is significant. Consensus guidelines should consider its incorporation and provide methodological and reporting recommendations to minimize these limitations. If this can be achieved, NPR may provide valuable information within trial information about an outcome of clear importance to patients.NPR provides useful additive information next to response percentages when interpreting outcomes of trials treating patients with painful bone metastases.


Objective: The present study aimed to compare the efficacy of naproxen patches in pain control during orthodontic tooth separation, by means of visual analogue scale (VAS) and interleukin 1β (IL-1β) levels in gingival crevicular fluid (GCF). Pain related to orthodontic tooth movement is common and cause dissatisfaction and discomfort. t-tests and two-way repeated measures ANOVA analysis of variance with a significance level of 0.05 were applied.  In this split-mouth triple-blind clinical trial, with 40 patients following separation, 5% naproxen or placebo patches were randomly placed on the upper right or left first molars every 8 hours. Pain intensity scores were determined after 2 and 6 hours, sleep time, 24 hours, days 2, 3 and 7 by the patients using a 100-mm VAS ruler. IL-1β levels in GCF were evaluated by ELISA at baseline, 1 and 24 hours and 7 days. Paired samples p< 0.0001) and IL-1β levels (p= 0.047) between naproxen and placebo groups. Lower pain scores were reported for the patients using naproxen patches at all time points, except 1 hour after separation. IL-1β levels were lower for the patients using naproxen patches only 1 hour after separation (p= 0.047). The peak of pain scores and IL-1β levels were calculated at 24 hours. A total number of 30 patients  finished the trial. Significant differences were found in pain scores (In the light of VAS scores and IL-1β levels, naproxen patches reduced the pain caused by separator placement. Ischemic regions in the periodontal ligament (PDL) and mild transient pulpal inflammation are among these mechanisms.,Interleukin 1β (IL-1β) is an inflammatory mediator that can be released as a response to the substance P-Prostaglandins, which are inflammatory mediators necessary for OTM, are among probable pain stimulators,-Several medications and other approaches such as low level laser therapy, chewing gum, local prescription of gels and patches, vibratory and transcutaneous electric nerve stimulationThis triple blind split-mouth randomized controlled clinical trial was performed on patients referred to the orthodontic department  for fixed orthodontic treatment in 2016. Study protocol was according to CONSORT statement 2010, and was approved by the ethical committee of the university. Also, informed consent was taken from all included patients.α=1.96 and Zβ=0.84. Sample size was increased to 40 patients in order to increase study power and considering probable dropouts.Adult patients (age ≥ 18 years) who needed banding of upper first molars for fixed orthodontic treatment were enrolled consecutively from study population. The inclusion criteria were: generally healthy patients, no periodontal or endodontic disease, presence of bilateral first and second maxillary molars and second maxillary premolars, tight posterior teeth contacts with no spacing, presence of antagonist teeth without posterior open bite, and no psychologic or mental disorder. Patients who did not participate in the follow up sessions, had no pain on both sides, took systemic or topical painkillers except prescribed patches, removed separators, did not used patches as prescribed, and did not fill VAS questionnaire on time or lacked cooperation were excluded. The sample size of 23 was calculated to find 1 unit difference with 1.1 unit standard deviation between two groups and considering α=0.05, β=80%, ZNaproxen patches were prepared using solvent casting method: 2.5% HPMC and 1% PVL were used for adhesion to the oral mucosa; also, 4% propylene glycol was used for ligation of naproxen, and 0.25% aspartame was used to sweeten the patches. Ingredients plus naproxen  were solved in chloromethane and alcohol solvents with 2:1 ratio and kept under fume hood for 72 hours. In order to evaporate the remaining solvents, the fabricated patches were dried for one more week in the room.The proper size of the patches was determined following try and error method: 0.5 x 1.5-cm patches seemed to be the most appropriate size for adhesion and remaining in place. Two sets of patches were prepared and coded: one set contained 5% naproxen, and the other set without naproxen (placebo). The patches and their packages were visually similar and only a code was written on each package. So, neither the examiner nor the patient were aware of the type of the patches (double blind). Maxillary first molars were separated from adjacent teeth using elastic separators . One package of each set was given to the patient. Then, the patient was instructed to place one patch from one of the packages on the attached and free gingiva of maxillary first molar of one side and one patch from the other package on the other side molar. The sides were randomly selected using coin flip method. Patient’s age, gender as well as code of the patch used on each side were recorded. The patients were instructed to place the patch on the gingiva, press it and hold it for 20 seconds every 8 hours for 7 days. There was no limitation for eating and drinking. Also, the patients were instructed to use painkillers if they had intolerable pain.The patients were instructed to record the pain they felt on each side after 1 and 6 hours, at night, 24, 48 and 72 hours and 7 days, based on a 100-mm VAS ruler. A questionnaire including 21 VAS rulers and instruction were given to the patients. Zero indicated no pain, while 100 showed the most severe pain.Levels of IL-1β in GCF was measured at the time of tooth separation (baseline) and after 1 and 24 hours and 7 days, using ELISA. First, GCF was collected from distobuccal and mesiobuccal sulcus of maxillary first molars using paper cones  size 30 after isolation with cotton roll. For this, paper cones were inserted 1 mm into gingival sulcus for 60 seconds. Then, paper cones were transferred to sterile 1.5-ml µtubes containing 200 µl phosphate buffered saline for couple of minutes followed by 10-minute centrifuge at 3000 rpm at 4°C. Finally, the supernatant fluid containing GCF proteins was transferred to another sterile µtube, which was frozen at -70°C. Commercial ELISA kit  was used to measure the levels of IL-1β in the GCF samples, following manufacturer’s instructions. Briefly, the kit micro-wells including human anti-IL were rinsed twice with 400 µl PBS. Then, 50 µl buffer and 50 µl of each sample plus 50 µl Biotin-conjugated anti-human IL added to each well and incubated for 2 hours at room temperature. The wells were rinsed 3 times and received 100 µl Streptavidin-HRP enzyme and incubated one more hour. Again, the wells were rinsed and 100 µl substrate was added to each well and incubated for 10 minutes. Finally, 100 µl stop solution was added to each well and color to the wells containing IL, which turned yellow. Optical density was read using ELISA reader  at 450 wavelengths. Finally, density of IL-1β (pg/ml) was determined using standard absorbance values .t-test was applied. To evaluate association of pain scores and levels of IL-1β, Pearson correlation coefficient and regression model was used.The results of pilot study were compared using repeated measure ANOVA. A two-way repeated measure ANOVA was used to analyze the effect of study group, time, as well as pain scores or levels of IL-1β. To compare patients pain scores or IL-1β levels at each time point between the two groups, paired samples All statistical analyses were performed using SPSS computer software , with a significance level of 0.05, by an expert who was blind to the allocated groups (triple blind).A total of 40 patients  were enrolled in the study, out of which 10 patients were excluded. The reasons for exclusion were: no regular use of the patches (2 patients), lack of pain at both sides (7 patients) and use of painkiller during the experiment (1 patient). Therefore, a final number of 30 patients  with a mean age of 27.47±4.08 years (22 to 40 years) finished the study.p< 0.0001), time (p< 0.0001) and their interaction (p= 0.005) had a significant effect on the pain scores. Comparison of the mean pain scores at each time point between two groups revealed significantly lower pain score at naproxen group at each time point (p< 0.05) except at 1 hour after separation (p= 0.792).The mean and standard deviation (±SD) of pain scores based on VAS at different time points in both groups are shown in p= 0.29).There was no difference in the mean pain scores between males and females (p= 0.047), time (p< 0.0001) had a significant effect on the levels of IL-1β. However, their interaction was not statistically significant (p= 0.3). Comparison of mean levels of IL-1β at each time point between two groups revealed that only 1 hour after separation naproxen group had significantly lower levels of IL-1β, compared to placebo group; while the difference at other time points was not significant (p> 0.05).The mean and standard deviation of levels of IL-1β at different time points in both groups are demonstrated in p= 0.92).There was no difference in the mean IL-1β levels between males and females (p= 0.04 and r = 0.374) and a negative correlation between them in naproxen group after 7 days (p= 0.03 and r = -0.395) (Pearson correlation coefficient showed significant positive correlation between pain scores and IL-1β levels in control group after 1 hour ( -0.395) .Linear regression model revealed that each 10 unit increase in IL-1β levels is related to 2 unit increase in the pain scores. Therefore, the following formula could be used to show correlation between pain scores and IL-1β levels: Pain (VAS) = 1 ± 0.2 IL-1β (pg/ml),NSAIDs are appropriate choices for pain management during orthodontic treatment, as the pain is related to combination of pressure, ischemia and inflammation.,NSAIDs could have various complications-,,Comparison of mean pain scores between the two groups showed significantly lower pain in the naproxen group at every time point, except 1 hour after separation. These results are in agreement with some previous studies.,,,-,,,,The results of the current study showed that the mean pain score in both groups reaches its peak after 24 hours and then decrease until 7 days. It seems that the most prominent inflammatory responses during OTM happen during the first day.-The pain model and assessment of pain using VAS are common methods in orthodontic literature. Placement of elastic separators move the teeth and can cause various degrees of pain. Compared to archwire activation, placement of separators allows more control on the confounding factors.,,,,It has been revealed that IL-1 levels increase during experimental tooth movement, reaching its peak after 1 day and recovering to the normal value during 1 week.The pain scores in the naproxen group were lower than placebo groups at all time points from 6 hours to 7 days after separation. However, the difference was not significant after 1 hour.Levels of IL-1β was lower in naproxen group at 1 hour after separation, but no difference was found at later time points until 7 days. Lack of strong correlation between pain scores and IL-1 levels indicates that there is a need for other biologic indicators of pain intensity during OTM.As the highest pain intensity was recorded one day after separation and naproxen patches were effective in pain relief, it could be concluded that naproxen patches could be administered specially at the first days after orthodontic separator placement.This study showed that locally administered naproxen patches with lessened dosage can successfully relief pain and there is no need for systemic usage of the drug.


Although there have been many studies about lumbar and cervical ablation procedures, few studies have been performed in the thoracic region. To evaluate the clinical results of a percutaneous disc decompression device in patients with radicular symptoms and/or dorsal pain due to thoracic disc herniation.Eleven patients with thoracic disc herniation and/or degenerative discs  who did not respond to conservative treatments were undergoing ablation and compression procedures. Pain and radicular symptoms consistent with the thoracolumbar region were confirmed via abnormal magnetic resonance imaging findings after detailed anamnesis and physical examination. All patients were evaluated before and 1, 3, 6, and 12 months after treatment using the visual analog scale score. The patient satisfaction scale was used to evaluate the level of patient satisfaction at the end of the treatment at 12 months.The median visual analog scale score was 7.00±0.45 points before treatment and 2.73±0.65 points at 12 months post-procedure and were statistically significant (p<0.001). The results of pairwise comparisons using the Bonferroni Corrected Wilcoxon Signed-Rank test showed that there were statistically significant differences. The mean visual analog scale score at the beginning (7.00±0.45) was significantly higher than the mean score of other months. Postoperative improvement was significant with a 99% confidence interval. No complications that may cause permanent damage occurred.Percutaneous disc decompression is an effective and safe procedure to treat pain caused by lower thoracic intervertebral disc disease, which did not respond to conservative treatments. Thoracic disc herniation is a rare disease with an incidence of 1/1,000,000 per year . In the In 75% of thoracic disc herniation patients, the affected level is below T8 and is mostly at T11-T12 .Patients with thoracic disc herniation may have a wide variety of symptoms; the most common is continuous or intermittent back pain which is usually described as burning or stabbing ,8. DepenTM  has been introduced to treat degenerative discs. It has a wheel-shaped knob that can be rotated to provide the desired angle and be controlled within the disc and has a conductive electrode accessible to the back tear ring of the desired region  applications in patients with lower radicular symptoms and/or dorsal pain due to thoracic disc herniation who did not respond to conservative methods.Despite studies about lumbar and cervical ablation procedures, few studies have been performed in the thoracic region. To evaluate the clinical results of percutaneous disc decompression  on the 10 cm line between the “no pain” anchor and the patient’s mark, providing a range of scores from 0-100: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm) .Patients were asked the following four questions to determine their level of satisfaction 12 months after the procedure (North American Spine Society).1. Very good: The procedure met my expectations.2. Good:  I didn’t get as much improvement as I expected, but I can do the same for the same result.3. Moderate: I didn’t get as much improvement as I expected, but I wouldn’t do the same for the same result.4. Bad: I am the same or worse than before.All patients were evaluated before and 1, 3, 6, and 12 months after treatment using the visual analog scale score. The Patient Satisfaction Scale was used to evaluate the level of patient satisfaction at the end of the treatment at 12 months.Patients were permitted extensive walking, standing, and sitting down. They were instructed to avoid heavy lifting, forward skin bending or crushing. After 10-14 days, lightly working and home exercise with gentle flexion and extension were allowed.Data analysis was performed by ‘SPSS for Windows 21’ package program. Descriptive statistics were expressed as the mean ± standard deviation for variables with normal distribution, median (minimum-maximum) for variables with non-normal distribution, and number of cases and percentage (%) for nominal variables. The difference between the distributions of visual analog scale scores measured at different times was evaluated using the Friedman test. The Bonferroni Corrected Wilcoxon Signed-Rank test was used for multiple comparisons. For pairwise comparisons, the adjusted type 1 error level was accepted as 0/0.05 (0.05/10).The power for non-parametric tests could not be calculated . Since tEleven patients, 7 males and 4 females, were included in the study and were aged between 35 and 65 years. Nine patients had middle thoracic axial, and 2 had radicular pain whereas 4 patients had thoracolumbar disc degeneration and/or 7 had disc herniations at T10-T11 and T11-T12 levels, 8 patients had middle lumbar axial pain, and 3 had mild radiculopathy . None ofst, 3rd, 6th, 12th months  were statistically significant (p<0.001). The results of pairwise comparisons using the Bonferroni Corrected Wilcoxon Signed-Rank test showed that there were statistically significant differences between the scores at the beginning and the 1st, 3rd, 6th, and 12th months . The mean visual analog scale score at the beginning (7.00±0.45) was significantly higher than the mean score of other months  and the 1r months .Kendall’s W value was calculated as 0.759 for the visual analog scale score. It has a great magnitude of effect according to Cohen’s criteria because 0.759 is greater than 0.5. This result is clinically significant.When evaluated by patient satisfaction score at 12 months, 3 patients selected very good, 6 patients selected good, and 2 patients selected moderate. Overall, 82% rated the procedure as very good or good, and no patient rated it as worse .Initially, our patients’ visual analog scale scores were 7.00±0.45 points and then they were 2.73±0.65 points at 12 months. When compared with initial values, the visual analog scale scores of patients significantly decreased by 85%. According to the HMS survey, we achieved a value of 82% patient satisfaction. No complications occurred, and all patients were discharged the same day as the intervention.Haufe et al.  reportedHellinger et al.  performeTM. Kim et al. (Lee et al.  evaluatem et al.  studied TM electrode tip is effective for a successful outcome. In addition, therapeutic efficacy is significantly related to both patient selection and practitioner experience in all similar procedures. In conclusion, we propose that percutaneous ablation decompression L’DISQTM treatment may have an analgesic effect in select patients with thoracic disc herniation and discogenic/radicular pain.We suggest that the correct approach to reach the target level with proper control of the L’DISQ


The purpose of this study was to describe the incidence, management and impact of pain on behavior and delirium in hospitalized older adults living with dementia. This was a descriptive study using baseline data from patients in the first cohort of the Fam-FFC study which evaluates the impact of a family-engaged function-focused care intervention in hospitalized patients with dementia. The majority of the sample was female (70%) and black (80%) with a mean age of 82.5 (SD=8.9). Pain (PAINAD) was reported by 36% of the patients; 42% of those demonstrating pain were prescribed analgesics. Controlling for age, gender and baseline cognition, pain was significantly associated with behavioral and psychiatric symptoms of dementia  and delirium severity . Results suggest the need for pain assessment and individualized treatment plans to promote comfort and decrease behavioral and delirium symptoms in hospitalized persons with dementia.


Non-pharmacological treatment options are non-invasive electrical stimulation with either transcranial direct-current stimulation or repetitive transcranial magnetic stimulation which both require further evaluation in regard to applicability. Surgical options remain a valid choice for patients not responding to medical treatment and include Gasserian ganglion percutaneous techniques, gamma knife surgery, and microvascular decompression. There is continual effort to improve these techniques and predict the outcome for better patient selection.Despite recent advances in understanding and treating trigeminal neuralgia, its management remains a considerable challenge. Better classification of different types of facial pain and the identification of prognostic factors for different treatment options lead the way toward better quality of life for the individual patient. Although the principles of treating trigeminal neuralgia remain basically the same, antiepileptic drugs, muscle relaxants, and neuroleptic agents are widely used medical treatment options. They were not originally developed for treating trigeminal neuralgia. Carbamazepine was studied in adequate placebo-controlled clinical trials in the 1960s and is still considered the most effective drug. Among emerging treatment options currently under clinical investigation are local botulinum neurotoxin type A injections and a novel sodium channel blocker (CNV1014802) that selectively blocks the Na The revised ICHD-III  classifies TN as classic  TN without or with concomitant persistent facial pain2. TN caused by trauma, tumor, herpes zoster, or multiple sclerosis is classified as secondary painful trigeminal neuropathy. A slight hyperesthesia or hypoesthesia, either of which is often present, is now in line with the classic TN diagnosis2.Trigeminal neuralgia (TN) is defined by the International Headache Society as a “unilateral disorder characterized by brief electric shock-like pains, abrupt in onset and termination, and limited to the distribution of one or more divisions of the trigeminal nerve”2. An involvement of the ophthalmic nerve may be associated with other differential diagnoses such as severe unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and luckily is present in less than 5% of cases3. Typical TN attacks usually last between 1 second and a few seconds. TN may also occur in clusters of different duration and intensity lasting up to 2 minutes. The attack is followed by a short refractory period in many patients, during which a new attack cannot be evoked by further stimulation4. In between paroxysms, patients are usually pain-free; however, in some patients, a dull, concomitant background pain may persist2. Pathophysiological mechanisms explaining this concomitant pain are missing, but it seems to be associated with a poor medical and surgical outcome8. Although many patients respond to first-line therapy initially, most treatment approaches tend to lose efficacy over time, so new and innovative treatment options are warranted. Many patients will receive surgery after their medical treatment failed, whereas others require medical treatment after the long-term efficacy of surgery slowly deteriorates.TN typically starts in the second or third branches of the trigeminal nerve9, which results in serious impairment of their individual daily function and their quality of life. Reduced measures of daily functioning, quality of life, well-being, sleep, mood, and overall health status correlated with pain severity10. In 34% of patients with TN, even employment was impacted. Depression is quite frequent in this patient population. Moderate to severe pain was reported by up to two thirds of patients within the previous 24 hours10. Owing to difficulties in properly assessing the burden of disease, a recent study evaluated the validity of a revised version of the Penn Facial Pain Scale (Penn-FPS-R), which focuses on the patients’ health-related quality of life. The Penn-FPS was introduced as a supplement to the Brief Pain Inventory Pain Interference Index (BPI-PII) and was revised to include a total of 12 items with more TN-specific additions such as “biting and chewing”, “self-care” , and “temperature change” . Besides the usefulness of the questionnaire, this study revealed a high burden of disease with an average mean pain of 6.85 (standard deviation of 2.34) on a 0- to 10-point numerical rating scale despite adequate treatment attempts in the majority of included patients11.Severe attacks may cause an inability to speak or eat. Many patients contemplate the constant fear of pain that may return at any time even between attacks12, which is more difficult to treat14. Routine head imaging with magnetic resonance imaging (MRI) can detect structural causes in as many as 15%  of patients excluding those with microvascular conflict. The blink reflex and other trigeminal reflex tests have a high accuracy to identify patients with STN. Five independent studies showed a pooled sensitivity of 94% (95% CI 91–97%) and a pooled specificity of 87% (95% CI 77–93%). Evoked potentials were unable to sufficiently distinguish classic TN from STN 16.A correct diagnosis is the paramount factor for adequate treatment and thus a good outcome. Differentiating trigeminal autonomic cephalalgias  and other craniofacial pain syndromes or persistent idiopathic facial pain is very important, as treatment is fundamentally different. Patients with first-division trigeminal pain only may have symptomatic TN (STN) 16. Moreover, a large imaging study of 135 patients with TN showed the presence of neurovascular conflict (NVC) on the symptomatic and the asymptomatic side . Severe NVC was more frequent on the symptomatic side compared with the asymptomatic one . The most common causes for severe neurovascular contact were arteries in 98% of cases17. NVC causing atrophy or displacement of the nerve (or both) was highly associated with pain on the symptomatic side of patients with classic TN in contrast to NVC in general, according to this study17. A more recent study reported that neurovascular contact with morphological changes to the nerve as detected by 3-Tesla MRI and male gender was associated with better outcome following microvascular decompression surgery18. Excellent outcome and concomitant persistent pain, current age, or disease duration were not correlated18. Outcome after microvascular decompression surgery was only slightly worse; recurrence rates were 9.23% in the age group younger than 65 years and 13.33% in the group older than 65 years19. However, long-term outcome was determined by concomitant pain as these patients developed TN recurrence in 60.3% following microvascular decompression surgery whereas patients without concomitant pain did not show signs of recurrence in 91.8% within a mean follow-up period of 20.6 months20. Depression and anxiety, along with a deterioration in quality of life, are common in patients with TN21. About 2% of patients with multiple sclerosis were reported to have symptoms similar to those of patients with TN3. TN commonly runs in families, but there have been reports of an increased risk in people living in the same household, which suggests that environmental factors may influence the disease23. Genetic variants of TN were also suggested in two investigated families: autosomal dominant in one family and autosomal recessive in the other24.MRI plays a major role in the pre-surgical assessment in order to determine the presence of microvascular conflict. Specificities and sensitivities are variable  between studies and this is probably related to different MRI sequences used in different investigationsv1.7 sodium channel over the different tested subtypes  for the depolarized and resting states. Sodium channel blocking quantity increases in parallel to increased stimulation frequency of Nav1.7 and of Nav1.2 and Nav1.6. BIB074 preferentially targets and inhibits higher frequencies (10 Hz and more) induced during seizures or by noxious stimuli25.A novel substance finished its phase II trial last year with promising results. BIB074  is a new state-dependent sodium channel blocker with potency and selectivity of the Na26. A 21-day open-label treatment period using BIB074 150 mg three times per day (tid) was followed by randomization into a double-blind treatment phase of 28 days with either placebo or BIB074 150 mg tid only in those patients who showed a successful treatment response within the final week27. The others were considered non-responders and dropped out of the study in order to go back on their previous TN medication. Thirty percent or more reduction in pain severity as well as a 30% reduction in numbers of paroxysms relative to the run-in period was defined as treatment response. Sixty-seven patients were included in the study and 69% completed the open-label phase to enter the double-blind phase.A novel randomized withdrawal design was used in the phase II study in order to show its efficacy27. The results are quite promising, but it should be remembered that the patient numbers were low and there was a short evaluation period, so this novel therapeutic option must prove its efficacy over time. A multicenter and international phase III study by Biogen is planned.BIB074 was able to reduce the number of paroxysms and the overall pain severity in all primary and secondary outcomes but missed statistical significance in its primary endpoint. A reduction of the number of paroxysms by 60% compared with 12% for placebo was demonstrated, and pain severity decreased by 55% compared with 18% under placebo treatment. The primary endpoint was treatment failure rate of 33% with BIB074 compared with 65% with placebo and a satisfactory separation of both conditions on the Kaplan–Meier time to relapse. BIB074 was well tolerated and no serious adverse events related to the drug were reported. The adverse event profile was comparable to that of placebo in the double-blind phase of the study28. Significant symptom relief following BoNT-A injections was shown in a small uncontrolled clinical trial (N = 13). BoNT-A was administered at a mean dose of 3.22 units/cm2 subcutaneously directly in the painful area of the face. The treatment effect of BoNT-A slowly faded after 60 days29. A randomized, placebo-controlled, double-blind study investigated 84 patients with classic TN treated with 25 U or 75 U of BoNT-A: placebo (n = 28), BoNT-A 25 U (n = 27), BoNT-A 75 U (n = 29). The duration of the study was 8 weeks. Pain severity, efficacy, and side effects were the endpoints of the study. Significant reduction of pain was shown on a visual analogue scale with both the 25 U and 75 U groups compared with placebo after 1 week, which remained stable for the whole study period. Responders among the 25 U group (70.4%) and 75 U group (86.2%) were more common compared with placebo (32.1%) at week 8. No difference between the 25 U and 75 U groups was detectable. Patient Global Impression of Change (PGIC) showed that 66.7% (25 U group) and 75.9% (75 U group) of patients reported “much improved” or “very much improved” pain symptoms but that only 32.1% of the placebo patients stated this outcome. Only mild or moderate side effects were documented30. The authors of a recent comprehensive meta-analysis showed a pooled reduction of −3.009 points on a 0 to 10 verbal rating scale  after treatment with BoNT-A and confirmed moderate evidence for the efficacy of BoNT-A31. These promising findings will have to be confirmed by additional controlled clinical trials in order to recommend the use of BoNT-A for the treatment of TN32.Botulinum neurotoxin type A (BoNT-A) was effective in the treatment of TN in recent studies. The pharmacological mechanism remains unresolved but includes the local release of anti-nociceptive neuropeptides such as glutamate, substance P, and calcitonin gene-related peptide (CGRP) in order to reduce central and peripheral sensitization33.Pharmacological and surgical treatment options are numerous, widely used, and not seldom efficacious . Medical16. Even though CBZ has stronger evidence37, OXC is generally considered to be better tolerated38. Second-line therapy includes add-on therapy with lamotrigine (400 mg/day)39, change to lamotrigine monotherapy, or the use of baclofen (40–80 mg/day)40. Pimozide (4–12 mg/day) is seldom in clinical use. Different antiepileptic drugs were investigated in open-label studies with small patient numbers. Efficacy was described for clonazepam, pregabalin, gabapentin, phenytoin, topiramate, valproate, and tocainide (12 mg/day)41.Carbamazepine (CBZ) (200–1200 mg/day) and oxcarbazepine (OXC) (600–1800 mg/day) should be considered first-line therapy, according to commonly accepted treatment guidelines42, peripheral nerve stimulation44, and invasive motor cortex stimulation45 and non-invasive cortex stimulation47. Patient self-conducted motor cortex transcranial direct-current stimulation (tDCS) showed excellent efficacy on pain reduction in patients with classic TN. Ten patients received daily stimulation over the course of 20 minutes for a total of 2 weeks with anodal (1 mA) or sham tDCS over the primary motor cortex (M1) in a double-blind, randomized, crossover design. Pain intensity was the primary outcome variable on a verbal rating scale (0–10). Anodal tDCS resulted in a 29% reduction of pain intensity after treatment (P = 0.0008). Reduction in attack frequency was also observed but did not reach statistical significance. No relevant adverse events were reported. Anodal tDCS over the course of two weeks may become a valuable treatment option for patients otherwise unresponsive to standard medical treatment8.Neuromodulation offers an alternative worth considering for patients whose neuropathy pain is refractory to pharmacotherapy. Central and peripheral neuromodulation are available, but the clinical evidence base is very limited. Options include electrical Gasserian  ganglion stimulation48. A different investigation included 12 patients who failed surgery with intractable TN, out of which 58% reported more than 30% reduction of pain intensity following rTMS49.Repetitive transcranial magnetic stimulation (rTMS) is also a relatively novel technology introducing the possibility of testing the responsiveness of patients with trigeminal neuropathic pain to invasive epidural cortical stimulation. In 24 patients, TN was treated with daily 20-Hz motor cortex stimulation over the course of five days. Ratings of pain decreased by 45% for at least 2 weeks50. TN surgical management is either ablative (destructive) with the intentional destruction of sensory function of the trigeminal nerve or non-destructive with mere decompression of the trigeminal nerve and preservation of its normal function.Medical treatment-refractory patients with a minimum of two adequately dosed recommended TN medications, including CBZ, are candidates for surgical treatment. The patients’ symptoms, not any neuroimaging investigations, are the most relevant factor for this decision21, followed by dysesthesias (6%), corneal numbness with risk of keratitis (4%), and anesthesia dolorosa (4%). Gasserian ganglion treatments are generally minor, overnight procedures with very low mortality16.Percutaneous techniques to the Gasserian ganglion are all destructive and consist mainly of percutaneous glycerol rhizolysis, radiofrequency thermocoagulation, and balloon compression. Pain relief was reported by 90% of patients undergoing these procedures. Approximately 68 to 85% of patients remain pain-free after 1 year but this deteriorates to 54 to 64% after 3 years and only 50% are still pain-free after 5 years. Sensory loss (50%) is the most common side effect with high impact on quality of life for these patients16. Quality of life improves by 88%21. However, gamma knife surgery is quite expensive, limiting its more widespread usage. This makes it a treatment reserved for patients unfit to bear conventional surgery or with blood coagulation disease or medication .Gamma knife surgery uses a focused radiation beam to sever the trigeminal root in the posterior fossa. Sixty-nine percent of patients were reported to remain pain-free 1 year after gamma knife surgery without additional medication. After 3 years, this was down to 52%. Pain relief may require up to several weeks (mean of 1 month) in order to develop. Sensory complications were reported in 6% of patients with a delay of up to 6 months, including paraesthesias in 6 to 13%, and facial numbness in 9 to 37% that may improve with time16.The most sustained pain relief was reported following microvascular decompression surgery. Ninety percent of patients had initial pain relief. More than 80% were still pain-free 1 year after surgery and this fell to 75% after 3 years and 73% after 5 years. However, it is a major surgical intervention including craniotomy in the posterior fossa to reach the trigeminal nerve. Mortality rates range from 0.2 to 0.5% on average, and about 4% of patients have serious adverse events such as infarcts, hematomas, or cerebrospinal fluid leakage. The most frequent complications are aseptic meningitis (11%), hearing loss (10%), and sensory loss (7%)52 and the improvement of common surgical techniques55. A huge number of studies were conducted in this regard over the past several years, but most of them remain on a descriptive level unable to unveil evidence-based comparisons and therefore inspire only indirect recommendations. It remains to be determined what the right timing for surgical intervention is56. Some experts recommended early surgical referral of patients unresponsive to first-line medical treatments, whereas other experts require at least two different drugs (including CBZ) alone and in combination medical therapy before even considering surgery. Supporting final evidence for either of the two options is still missing. It seems reasonable to refer patients unresponsive to medical treatment for surgical intervention without a long delay.Recent studies focused on the long-term evaluation of different surgical treatmentsTreatment of TN is still challenging, as individual responses to different therapeutic options may vary considerably. Only a few available therapy options have confirmed efficacy fulfilling current standards for evidence-based medicine. However, novel therapeutic options are on the rise; for the first time, substances are in clinical testing on larger patient populations specifically for this very disabling but rare disease. Outcome predictors and risk factors for treatment failure are being systematically assessed more and more so that an individual patient-guided treatment decision can be made. The continual effort by clinicians, researchers, and the pharmaceutical industry may soon provide therapeutic options that are more tolerable, more specific, and more efficient for patients with TN.