Sciatica is a condition that is characterised by radicular pain in the leg and primarily caused by a herniated lumbar intervertebral disk. In addition to leg pain, patients can experience back pain, leg numbness and leg weakness resulting in decreased productivity and social activity. The majority of sciatica cases recovers spontaneously and therefore patients are initially treated conservatively with oral pain medication. However, some patients experience intractable pain that severely impedes them and no consensus exists on the optimal conservative treatment to reduce this discomfort in the acute phase of sciatica. The aim of the TEIAS trial is to assess the effectiveness, cost-effectiveness and predictive capability on patient outcome of transforaminal epidural injection (TEI) compared to treatment with standard pain medication.This study is designed as a prospective, open-label, mono-centered, randomized controlled trial. Patients that visit their general practitioner with complaints of radicular leg pain and meet the selection criteria are asked to participate in this study. Eligible patients will be randomized to treatment with TEI or to treatment with standard oral pain medication. Treatment of TEI will comprise lidocaine with methylprednisolone acetate for L3 and below and lidocaine with dexamethasone above L3. A total of 142 patients will be recruited and follow-up will occur after 1, 2, 4, 10 and 21 weeks for assessment of pain, functionality, patient received recovery and cost-effectiveness. The primary outcome will be the average score for leg pain at 2 weeks. For this outcome we defined a clinically relevant difference as 1.5 on the 11-point NRS scale.Adequate conservative treatment in the acute phase of sciatica is lacking, particularly for patients with severe symptoms. Focusing on effectiveness, cost-effectiveness and predictive capability on patient outcome of TEI will produce useful information allowing for more lucid decision making in the conservative treatment of sciatica in the acute phase.NCT03924791 on April 23, 2019.This trial is registered in the ClinicalTrials.gov database under registry number  Sciatica is a condition that is characterised by radicular pain in the leg and generally caused by a herniated lumbar intervertebral disk. The herniated disk exerts pressure onto a lumbar nerve root that follows its way into the sciatic nerve. In addition to leg pain, this can lead to back pain, muscle weakness or muscle numbness resulting in decreased productivity and social activity –5. This The prognosis of sciatica is favourable since the majority of cases recovers spontaneously. Therefore, patients are initially treated conservatively with standard oral pain medication unless cauda equine syndrome or progressive paresis is reported. Those groups of patients are directly referred to the neurologist or neurosurgeon. An earlier RCT demonstrated that surgical therapy resulted in a similar outcome compared to conservative therapy at 26 weeks follow-up and 40% of the patients assigned to the conservative group crossed over to the surgical group with a mean delay of 15 weeks . Due to Transforaminal epidural injections (TEI) therapy might be the answer as it is postulated to have an analgesic and anti-inflammatory effect which can last several days to weeks. Analgesics and/or corticosteroids are deposited through a transforaminal approach in close proximity of the affected nerve root. Theoretically, this treatment would enable the patient to remain physically active while awaiting spontaneous recovery. Although its use is widespread, some patients experience a beneficial effect while others report no effect at all or only initial pain relief followed by recurrence of pain after several hours, days or weeks , 12. In Due to limited literature on TEI in patients with acute sciatica, it is still unclear whether TEI is a more (cost-)efficacious type of conservative treatment than oral pain medication in the acute phase. It remains difficult to differentiate between responders and non-responders and suggestions that response to TEI can be a predictor for long-term patient outcome require further research –14. ThisThe TEIAS  Trial is designed as a prospective, open-label, mono-centred, randomized controlled trial. Eligible patients will be randomized to treatment with TEI (intervention group) or to treatment with standard oral pain medication (control group). Patients will be followed for a total of 21 weeks.The aim of the TEIAS Trial is to determine whether transforaminal epidural injections are a more efficacious treatment to alleviate symptoms in patients suffering from acute sciatica than the current standard treatment with oral pain medication.The average score on leg pain at 2 weeks after treatment with TEI compared to usual conservative care.The primary objective is to estimate:2.The duration of effect from TEI;3.The percentage of patients that have experienced a satisfactory decrease in leg pain and increase in functionality at 4 weeks after treatment with TEI compared to usual conservative care;4.The response to TEI at 2 weeks as a predictor of leg pain at 14–16 weeks and 26 weeks after onset of symptoms;5.The correlation between response in leg pain, functionality and patient satisfaction at 1 week and at 2 weeks after randomization and at 10 and 21 weeks after randomization;6.The correlation between baseline data and responders and non-responders to TEI after 2 weeks;7.Cost-effectiveness of TEI to alleviate symptoms for acute sciatica;Secondary objectives are to estimate:This study will take place at the Spaarne Gasthuis (SG), Hoofddorp and Haarlem, the Netherlands in cooperation with researchers from the Department of Neurosurgery, Leiden University Medical Center (LUMC), Leiden, the Netherlands. Patient recruitment will occur at general practitioner offices that are part of the GP collective Haarlemmermeer and Kennemerland which embodies a total of 185 GP’s. Patient inclusion will continue until the target sample size has been reached.Patients suffering from acute sciatica that visit their general practitioner will be referred for participation in this study if they have a Numerical Rating Score (NRS) for leg pain of 6 or more on a 11-point scale and symptom duration of 3–8 weeks. Patients are contacted by the study investigator and inclusion and exclusion criteria are checked to determine whether the patient is eligible. Furthermore, it will be ascertained that the patient has access to e-mail in order to fill in the digital questionnaires at home. If patients are willing to cooperate and submit their informed consent to the researcher, they are referred to the neurosurgeon. The neurosurgeon will examine the patient and if the neurosurgeon is convinced that the patient is suffering from sciatica, the patient is enrolled by the researcher and randomized to receive TEI from the anaesthesiologist or to continue usual conservative care . A complete description of inclusion and exclusion criteria can be found in Table If the patient is eligible and decides to participate, block randomization in a 1:1 allocation ratio will determine which treatment the patient will follow. Randomization is done by using web-based randomization algorithm software . Details on blocking of randomization are unavailable to the researcher that will perform allocation. Consequently, baseline data will be collected, questionnaires will be filled in and the patient will receive instructions for follow-up questionnaires to be filled in at home. If the patient is randomized to the intervention group, the injection will be received within 4 working days after randomization. Level of injection will be determined by the anaesthesiologist although the neurosurgeon can advise. Patients from the control group will receive oral pain medication according to the care of their GP. Patients will be evaluated at baseline and after 1, 2, 4, 10 and 21 weeks. A schematic overview of the trial is shown in Fig. Patients that are randomized to the TEI group can receive additional injections if deemed profitable by the anaesthesiologist but an injection is only repeated after a certain time interval according to anaesthesiology guidelines for usual care. For all injections, details on timing, frequency and prevailing complications will be gathered.Patients allocated to the intervention group will receive TEI within 4 working days after randomization. Before this procedure, the patient will undergo an X-ray of the lumbar spine in order to identify any spinal abnormalities that may complicate the treatment. Administration of TEI will be performed by an experienced anaesthesiologist. The patient will lie in a prone position on the table. The skin is sterilized with chlorhexidine. Under X-ray guidance using the “tunnel vision” technique the needle is placed via a transforaminal approach in close proximity of the nerve root and contrast agent is injected to confirm correct positioning of the needle. In accordance with current Dutch anaesthesiologic guidelines, injections at L3 and below will contain 1,5 ml lidocaine 2% and 40 mg methylprednisolone acetate whereas injections above L3 will contain 1,5 ml lidocaine 1% and 10 mg dexamethasone. This is due to the possibility that particulate steroids like methylprednisolone acetate can occlude arterial blood vessels and result in an infarction of the spinal cord, the brain stem, cerebrum or cerebellum and therefore injections above L3 contain a non-particulate corticosteroid . After tThe current standard for conservative care in patients with sciatica during the first 14 to 16 weeks is oral pain medication. Patients randomized to the control group can use over the counter medication or pain medication prescribed by the GP according to national guidelines. Use of pain medication will be recorded through the web-based questionnaires. If deemed necessary, the GP can additionally prescribe physiotherapy.If leg pain remains severe at 2 weeks after randomization, the patient is allowed to deviate from the study protocol. The GP can refer the patient to the neurologist and the patient can be offered surgery if applicable. An NRS for leg pain of 4 or higher makes the patient eligible for surgery if the patient requests surgery. Patients are still encouraged to postpone surgery till 14–16 weeks after onset of pain. This decision is made using Shared Decision Making and it is possible that the patient is operated before this time point. However, patients that are randomized cannot receive surgery within the first two weeks, unless cauda equine syndrome or progressive paresis is reported. It is expected that during these two weeks the transforaminal epidural injection will have its effect.Intake of oral pain medication is allowed in addition to assigned treatment. Since it is a randomized controlled trial, it is reasonable to expect that participants in both treatment arms will demonstrate comparable variation in oral pain medication.Study parameters are assessed at baseline by a researcher and consequently by patients through online questionnaires at home. Data on the administration of TEI is collected by the anaesthesiologist. A summary of all study parameters and correlating follow-up moments can be found in Table The primary study parameter, NRS leg pain, will be measured at all follow-up visits: at baseline and at 1, 2, 4, 10 and 21 weeks after randomization. NRS leg pain will be scored on a 0 to 10-point scale with increments of 1 point and patients are not entitled to see pain scores from previous follow-up moments. Each patient will score the NRS leg pain based on the mean leg pain over the past week.NRS back pain will be scored at all follow-up visits: at baseline and at 1, 2, 4, 10 and 21 weeks after randomization. NRS back pain will be measured on a 0 to 10-point scale with increments of 1 point and patients are not entitled to see pain scores from previous follow-up moments. Each patient will score the NRS back pain based on the mean back pain over the past week;The Oswestry Disability Index (ODI) will be measured to assess the functionality of the patient directed at walking and daily activities. The ODI will be scored on a 0 to 50-point scale at all follow-up visits: at baseline and at 1, 2, 4, 10 and 21 weeks after randomization. Patients are not entitled to see ODI scores from previous follow-up moments;Perceived recovery will be measured using the Likert scale. This is a 7-point scoring scale that ranges from ‘completely recovered’ to ‘worse than ever’. The Likert score will be determined at baseline and at 1, 2, 4, 10 and 21 weeks follow-up;As an indicator for the patients’ perspective on his or her health state, EuroQoL Visual Analogue Scale (EQ-VAS) will be determined using a 0 (as bad as death) to 100-point scale  with increments of 1 point. This will be measured at baseline and at 2, 10 and 21 weeks follow-up;Data on timing of the injection (days after randomization), frequency of the injection, NRS leg pain after injection, prevailing complications and certainty of the anaesthesiologist that the patient is suffering from sciatica and that the injection has been administered at the correct lumbar level will be gathered during the total follow-up period of 21 weeks;For the economic evaluation (CEA), the five-level EuroQoL (EQ-5D) will be used. This questionnaire measures five aspects: mobility, self-care, daily activities, pain/discomfort, and anxiety/depression. The EQ-5D scores will be assessed at baseline and at 2, 10 and 21 weeks follow-up. In addition, cost diaries will be filled out by the patient at 10 and 21 weeks after randomization. Health care utilization including physiotherapy, visits to GP and specialists, nursing care and medication, patients costs, and absenteeism will be evaluated;In order to assess functionality, perceived recovery, perceived general well-being and cost-effectiveness secondary study parameters will be measured.Data will be gathered using Castor EDC, a web-based secured data-capture platform . This digital system will give each patient an untraceable ID. Only the main investigator, an independent monitor from the LUMC and the Inspection Healthcare and Youth (IGJ) will have access to the key that links these IDs to the patient’s personal details. All data will be safeguarded and stored for 15 years after end of study. Patients will fill in digital questionnaires for all follow-up moments at home using the link they received in an e-mail. When the questionnaire is completed, it will automatically be processed in Castor EDC. Only members of the research team, an independent monitor from the LUMC and the Inspection Healthcare and Youth (IGJ) will have access to the final dataset.It is hypothesized that patients in the intervention group will have a mean NRS for leg pain of 4.0 on a 11-point scale at two weeks after treatment with TEI and patients in the control group will have a mean NRS for leg pain of 5.5 two weeks after randomization. Based on literature review, a difference of 1.5 points on the NRS scale will be considered clinically relevant and a standard deviation of 2.6 is considered , 16. TogAll study parameters will be analysed according to the intention-to-treat (ITT) principle.Demographic data on age, gender, length, weight, tobacco exposure, alcohol abuse, history of previous radicular symptoms in the legs and usage of pain medication will be reported using mean and standard deviation or median and ranges if distribution is skewed. Presuming distribution is normal age, length and weight will be compared between groups using t-tests. Gender, tobacco exposure, alcohol abuse, history of previous radicular symptoms in the legs and usage of pain medication will be assessed using the Chi-square test.The primary study outcome, the average score on the NRS leg pain scale at two weeks, will be compared between groups utilizing the unpaired t-tests.The average score on the NRS leg pain scale at 4 weeks will be compared between groups utilizing the unpaired t-tests.The absolute decrease of NRS leg pain, NRS back pain, ODI and increase of EQ-5D will be analysed using t-tests for the period from baseline to 2 weeks follow-up and from baseline to 4 weeks follow-up;Perceived recovery Likert scores will be dichotomized: 1–2 will be considered a success and 3–7 will be considered no success. Consequently, data will be compared using the Chi-square test at 2 and 4 weeks after randomization or injection to 10 and 21 weeks after randomization;The success data from the 2-week follow-up will be correlated to the success data at 14 weeks and 26 weeks using Chi-square tests to make predictions. In order to correlate 2-week and 4-week success data to the absolute data for NRS leg pain, NRS back pain, ODI and EQ-5D at 10 and 21 weeks, logistic regression analysis will be used;Baseline data will be correlated to the 2-week success data after treatment with TEI using t-tests for numerical variables and Chi-square test for categorical variables;The cost-effectiveness analysis will be evaluated from a healthcare perspective (the costs per extra patient with symptom relief) and a cost-utility analysis from a societal perspective ). Both analyses will be trial-based, with a time horizon of 21 weeks. Use of health care and productivity will be valued according to the Dutch guidelines. QALYs will be assessed as the area under the utility curve based on the Dutch tariff for the EQ-5D. For sensitivity analysis, QALYs will be determined using the VAS for quality of life with power transformation. The average costs and patient outcome will be compared according to intention-to-treat, using net-benefit analysis, and using multiple imputation to account for missing data;Subjects can withdraw from the study at any time for any reason without consequences and will not be replaced. Subjects that refuse TEI after randomization to the TEI group, will be considered as cross-over subjects. Patients that withdraw during the study will be considered lost-to-follow-up patients. The study investigator can decide to withdraw a subject for urgent medical reasons.Data monitoring will be performed by an independent monitor from the LUMC twice per year and will oversee the handling, safeguard and storage of data in accordance with the LUMC protocol and Good Research Practice (GRP) guidelines. No data monitoring committee is involved since TEI is considered usual care and risks are considered to be moderate.Adverse events (AEs) are defined as any undesirable experience occurring to a subject during the study, whether or not considered related to TEI. All adverse events reported spontaneously by the subject or observed by the investigator or his staff will be recorded. Adverse events from treatment with TEI are rare. The most common AEs reported in literature are transient exacerbation of pain (2.4%), pain at site of injection (1.1%) and accidental dural puncture (2.3%) .ToetsingOnline to the accredited Medical Ethics Committee (MEC) that approved the protocol within one week of first knowledge of SAEs that result in death or are life threatening followed by a period of maximum of 8 days to complete the initial preliminary report. All other SAEs will be reported within a period of maximum 15 days after first knowledge of the events.Serious adverse events (SAEs) are defined as any untoward medical occurrence or effect that result in the subject’s death or is life threatening, require hospitalisation or prolongation of existing inpatients’ hospitalisation, result in persistent or significant disability or incapacity, is a congenital anomaly or birth defect or any other important medical event that did not result in any of the outcomes listed above caused by medical or surgical therapy, but could have been based upon appropriate judgement by the investigator. Elective hospitalization will not be considered as a serious adverse event. SAEs are reported by the investigator through the online web portal All AEs will be followed until they have subsided or until a stable situation has been reached. Dependent of the kind of event, additional tests or medical procedures may be required for follow-up, and the subject may be referred to the general practitioner or a medical specialist.In literature arachnoiditis and ‘nervous system disorder’ have been described as major complications. Despite the lack of exact data, these complications are considered to be rare .The investigator will annually submit a summary of the progress of the trial to the accredited MEC. Information will be provided on the date of inclusion of first subject, total number of subjects included to that point, total number of subjects that have completed the trial, serious adverse events, other problems and amendments. Additionally, the independent data monitor and the Inspection Healthcare and Youth (IGJ) will have access to interim analyses.In case the study is ended prematurely, the sponsor will notify the accredited MEC within 15 days, including the reasons for the premature termination.The results from the TEIAS Trial will be published in international peer reviewed neurological and neurosurgical related journals. Results will be presented at national and international spine and pain congresses. Furthermore, the results can influence the usual care in the Netherlands and will subsequently be offered to be considered by (inter) national guideline-authors for treatment of sciatica.The current guidelines on treatment of sciatica state that a period of conservative therapy up to 14–16 weeks is preferred and these guidelines are based on the results from the Sciatica trial by Peul et al. During this trial, 40% from the group that received continued conservative care crossed-over to the surgical group with a mean delay of 15 weeks . The TEIFor the TEIAS study it is presumed that eligible patients will have an average duration of symptoms of 5 weeks when randomized to either the treatment arm or control arm. Therefore, follow-up at 10 weeks will correspond with the 14–16 week time point from the Sciatica trial. In the same manner, the 21 week follow-up moment will be similar to the 26 week time point in the Sciatica trial at which surgical intervention did not yield a superior patient outcome compared to conservative therapy. Therefore, the short-term effect of TEI will be evaluated at 1, 2 and 4 weeks and long-term evaluation will be performed at 10 and 21 weeks.The burden from the pain and resulting immobility during the acute phase of sciatica have been a challenge and an adequate routine treatment strategy to alleviate symptoms during this period of ‘wait-and-see’ is lacking. TEI has often been proposed as an option to reduce pain and inflammation caused by mechanical compression of the nerve root and literature has demonstrated this treatment to be efficacious in part of the sciatica patients –21. HoweA Dutch study by Spijker-Huiges et al. investigated the effect of epidural steroid injections containing 80 mg of triamcinolone in normal saline in acute sciatica patients (2–4 weeks of symptoms) . They coDue to the pragmatic nature of this study patients suffering from sciatica are directly referred by the GP to the anaesthesiologist without interference of any type of imaging. With the current organization of usual care it takes several weeks before the patient has visited the neurologist, undergone MRI examination and received TEI. In order to minimize this waiting time only a neurosurgeon will shortly examine the patient before inclusion to confirm that the patient is suffering from sciatica. This means that determination of the herniated disc level is based on medical history taking and physical examination. The neurosurgeon will advise the anaesthesiologist on the affected nerve root level, but if a disagreement exists the anaesthesiologist has the final decision on the level to be treated. In order to determine whether uncertainty with regard to the level of injection may play a role in the effectiveness of TEI the anaesthesiologist is asked to express his confidence in the correctness of the diagnosis and of the treated disc level.An interesting feature of TEI that has only been studied before to a limited extent is its predictive capability on long-term patient outcome. In theory, if such predictive power of TEI exists, patients that will not do well on the long term based on the short-term effect of TEI can be offered surgery at an earlier time point. For instance, a patient could become eligible for surgery after two weeks based on the two-week TEI outcome and would not have to wait until the 14–16 week time point. Joswig et al. addressed this predictive feature in a prospective study . The resThe trial is conducted according to the protocol, version 4.0 (14 February 2019). Recruitment of participants is intended to start June 2019 and is expected to be completed no later than July 1, 2020.


Abnormal vaginal bleeding is one of the most frequent problems found in gynecology. Endometrial histopathology is needed for definite diagnosis. It was obtained either from endometrial tissue sampling or from standard uterine curettage. Office endometrial tissue sampling is an easy and low morbid procedure. It is usually associated with pain and discomfort. Topical anesthetic agent is needed for pain relieving. This study was conducted in outpatient gynecology clinic, Thammasat University Hospital, Thailand. It was a double blind randomized controlled trial. A total of 140 participants were enrolled in study and control group. Each group consisted of 70 cases. Study group received topical spray of 10% lidocaine (40 mg) before endometrial aspiration. Topical spray of 0.9% normal saline was performed in control group. Novak curettage was an application for endometrial tissue obtaining in this study. Visual analog scale (10cm-VAS) was used for pain evaluation. Demographic character of both groups showed no statistical difference. The percentage of participants who had severe pain (VAS≥7) during tenaculum application and Novak curettage insertion and during procedure were 28.5% (20/70) versus 12.9% (9/70), 55.7% (39/70) versus 38.5% (27/70), and 78.5% (55/70) versus 60% (42/70) in control and study group, respectively. Both groups had no significant differences of postoperative pain at 15 minutes and 2 hours. This study indicates that topical lidocaine spray can relieve pain during endometrial tissue sampling. Abnormal vaginal bleeding is a common presenting complaint of women aged 35 years or more at the gynecology clinic. It is a major cause of distress for patients as well as a sign of a serious gynecological condition. The causes of abnormal vaginal bleeding most commonly include endometritis, endometrial hyperplasia, myoma uteri, adenomyosis, and endometrial cancer. Therefore, it is important to find the cause of abnormal vaginal bleeding by pathological examination of the endometrial tissue.The endometrial tissue can be obtained from either sharp or negative pressure aspirator. The instrument available includes Endocell®, Pipelle®, Karman®, or Novak. The Novak curettage is considered to be available tool for endometrial biopsy as it is quick and easy to use. The Novak endometrial curette is reusable and obtains an adequate amount of tissue for pathological examinations, even while the patient has bleeding. No need for sedation or analgesia was used before the procedure. It is made of stainless steel and comes in various sizes ranging from 1 to 4 mm in diameter [Lidocaine, an amide group local anesthetic drug , acts byEndometrial biopsy can cause patients moderate-to-severe pain during the procedure . The stuThe objective of our study was to investigate the analgesic effect of lidocaine spray on the patient's perception of pain during endometrial biopsy. The focus group is women aged 35 years or more with abnormal vaginal bleeding.Pain score was categorized in two groups, mild-moderate and severe. Mild-moderate pain is defined as a pain score of 0 to 6. Severe is defined as a pain score of 7 to 10. The results of both groups were calculated by chi-square test.This randomized controlled trial was conducted at the outpatient clinic, Department of Obstetrics and Gynecology, Thammasat University Hospital, Pathum Thani, Thailand, between February 2017 and January 2018. The approval from the Ethics Committee on Clinical Research of Faculty of Medicine, Thammasat University, was obtained prior to the study (MTU-EC-OB-2-145/59) (TCTR20170117001). The inclusion criteria included patients 35 years or over who presented with abnormal vaginal bleeding at the gynecology outpatients department between the specified period. Patients who had a history of abnormal coagulopathy were currently taking medication affecting coagulation, were allergic to lidocaine, were pregnant, had current pelvic infection, had cervical stenosis, and had known cases of abnormal uterine structure were excluded from the study.After personal counseling and filling the inform consent, a total of 140 participants were randomly assigned into a study and control groups using a computer-generated random number chart with a random block of four. Random allocation was done before curettage. The study group consisted of 70 participants. Patients in this group received 4 puffs (40 mg) of 10% lidocaine spray, prior to endometrial biopsy with the Novak curette. The control group (n=70) received 4 puffs of 0.9% normal saline.Two spray bottles of similar external appearances were prepared and numbered; one of the bottles contained normal saline, while the other contained 10% lidocaine. An envelope containing the medication number on its cover was opened by the responsible nurse to reveal the randomization and the trial medication was given accordingly. The patients, nurses, and gynecologists who were involved in the procedure were blinded.Four puffs of the spray containing either normal saline or 10% lidocaine were applied on the cervical surface 3 minutes before starting the procedure. After tenaculum application, the Novak curette was inserted through cervical os, and negative pressure was created via a 10-ml-syringe. Endometrial tissue was collected by aspiration and rotation at 3, 6, 9, and 12 o'clock. The patients were then asked to rank their pain on a 10 cm VAS score, from 0 (no pain) to 10 (worst pain). Six different times of pain evaluation were before the procedure, after speculum insertion, after tenaculum application and insertion of Novak curettage, during the procedure, at 15 minutes, and 2 hours after the procedure. After the procedure, if adverse outcome was immediately reported, patients would be kept in observation for 60 minutes.Statistical Analysis. ThePearson chi-square test and Fisher exact test were used to compare pain score in both groups. The Student t-test was used to analyze the demographic data. The statistical package for the social science  for Windows version 17 was used for data analysis. Statistical significance refers to p–value < 0.05.One hundred and forty participants were assessed for eligibility. The age of the participants ranged from 37 to 67 years. Demographic characteristics of patients in both groups were comparable in age, body weight, height, BMI, parity, number of vaginal deliveries, number of abortions, and age of their last child. There were no statistically significant differences of any of the demographic data between both groups . PredispAll procedures were successfully completed without any severe complications or serious adverse reaction, hypotension, or syncope. Out of the 140 patients, 12 and 9 participants experienced mild complications in control and study groups, respectively, with no statistical significance. Mild complications included abdominal pain and vasovagal reaction such as nausea or dizziness. No further treatment was needed . Average p<0.05. The ratio percentage of participants reporting severe pain between placebo and lidocaine spray treated groups during tenaculum placement, Novak curettage insertion, and tissue aspiration were 28.5 versus 12.8, 55.7 versus 38.5, and 78.5 versus 60, respectively, as seen in Pain scores collected during the procedure are presented in On the other hand, there were no statistically significant differences in the number of patients in the severe pain group between the placebo and the intervention arm at 15 minutes and 2 hours postoperatively. The number of participants in both study and control group in severe group at the end of procedure reduced from 55 and 42 to 8 and 7 at 15 minutes and to 3 and 1 at 2 hours, respectively.Abnormal uterine bleeding is an important issue in women aged 35 years or more. It is crucial to provide abnormal uterine bleeding patients with a definitive diagnosis, which can be obtained by endometrial biopsy. The endometrial biopsy can be performed in either an outpatient or an inpatient setting.Outpatient-based endometrial biopsy can be performed by using many devices. The advantages of using these devices are that they do not require the use of general anesthesia. As a result, it is important to minimize the patient's pain and discomfort during the procedure by using other forms of analgesia. Cervical pain transmitted via the pelvic splanchnic nerve to central nervous system. Many local anesthetics and oral analgesic drugs were experimented to help reducing pain during endometrial biopsy , 8.In the present study, lidocaine spray application at cervix significantly reduced pain during tenaculum application. The use of lidocaine spray has been previously studied during multiple gynecological procedures, with positive results. Karasu et al. showed that the use of lidocaine spray during IUD insertion reduced pain during both tenaculum application compared to placebo and paracervical block. Paracervical injection of lidocaine during IUD insertion only blocked the pain during IUD insertion period . Karasahp<0.05).Aksoy et al.  reportedOur study was performed pain evaluation in different stage of procedure. The result showed a significant reduction in pain score during tenaculum application and insertion of Novak curette and during tissue aspiration. Contrast to Aksoy's study, our postoperative pain was no statistically significant between both groups. We think that the similarity of pain level between both groups might be due to the short efficacy of lidocaine spray last for 10-15 minutes.The 10 cm VAS system was used in this study to obtain a pain score at various points during the procedure. The pain score was then grouped into either mild-moderate (0 to 6) or severe (7 to 10) pain. This study showed that the number of patients in the severe pain group was significantly lower in the intervention arm using lidocaine spray compared to placebo in three measurements, during the application of the tenaculum and the insertion of the Novak curette and during tissue aspiration. Therefore, the application of lidocaine spray significantly lowered the overall pain the patient experienced during the procedure compared to placebo group (p<0.05). The operators recorded higher satisfaction performing the procedure in patients of the treated group. This might be from the fact that patients with lidocaine spray experienced less pain during the entire procedure.The main limitation in this study was a subjective concept of pain among different patients . Pain peOur study sought to reduce pain during outpatient-based endometrial biopsy which might lead to better patient experience, reduce anxiety, and produce an overall better outcome. Our study showed that the application of topical lidocaine spray significantly reduced pain during the procedure when compared to placebo. Lidocaine spray has an advantage when compared with paracervical block, no risk of lidocaine intravasation, infection, or bleeding. It is easily to administer, worthily with cost-effectiveness, and comfortable. So, lidocaine spray is a suitable analgesic option during endometrial biopsy.


The incidence of cancer pain increases in discharged patients because of discontinued standard treatments and reductions in medication adherence. Motivated by the need for better pain management in discharged patients, we developed a mobile phone app (Pain Guard) to provide continuous treatment information and feedback to discharged cancer patients suffering from pain.The aim was to design, construct, and test the Pain Guard app in patients managing cancer pain, evaluate the total remission rate of pain and the improvement in quality of life (QoL) to improve pain management for cancer pain patients, and assess patient acceptance of the app.This randomized controlled double-arm study involved 58 patients with cancer pain symptoms. Participants were randomly assigned to a group receiving care through the Pain Guard app (n=31) or to a control group (n=27) who received only traditional pharmaceutical care. In a pretest, participants were rated using a baseline cancer pain assessment and QoL evaluation. During treatment, the consumption levels of analgesic drugs were recorded every week. After a 4-week study period, another round of cancer pain assessment and QoL evaluation was conducted. The system’s usability, feasibility, app compliance, and satisfaction were also assessed. Our primary outcome was remission rate of pain, and secondary outcomes were medication adherence, improvements in QoL, frequency of breakthrough cancer pain (BTcP), incidence of adverse reactions, and satisfaction of patients.P<.001). The frequency of BTcP in the app group was considerably lower than that in the control group (P<.001). The rate of medication adherence in the trial group was considerably higher than that in the control group (P<.001). Improvements in global QoL scores in the trial group were also significantly higher than those in the control group (P<.001). The incidence of adverse reactions in the trial group (7/31) was lower than that in the control group (12/27), especially constipation, with significant differences (P=.01). The 31 participants in the trial group completed a satisfaction survey regarding Pain Guard: 23 (74%) indicated that they were satisfied with receiving pharmaceutical care by Pain Guard, 5 (16%) indicated that they were somewhat satisfied, 2 (6%) indicated neutral feelings, and 1 (3%) indicated that they were somewhat dissatisfied; no participants indicated that they were very dissatisfied.All participants (N=58) successfully completed the study. There were no significant differences in baseline pain scores or baseline QoL scores between groups. At the end of the study, the rate of pain remission in the trial group was significantly higher than that in the control group (Pain Guard was effective for the management of pain in discharged patients with cancer pain, and its operability was effective and easily accepted by patients.Chinese Clinical Trials Registry ChiCTR1800016066; http://www.chictr.org.cn/showproj.aspx?proj=27153 Pain has been defined as the fifth vital sign following body temperature, pulse, respiration, and blood pressure . PreviouIn 2011, the Chinese Ministry of Health initiated the Good Pain Management Ward Program to improve the management of cancer pain in hospitalized patients . DespiteAccording to data from the China Internet Network Information Center, as of June 2018, the number of mobile internet users in China had reached 788 million, and 98.3% of them used mobile phones to access the internet . The useAlthough there are 165,000 medical and health apps , most of these apps are not scientifically validated . In a reConsidering these points, we developed a mobile phone app, known as Pain Guard. With the existing medical system and insufficient medical resources in China, a pain management app can be useful and appreciated by patients and health care professionals, making it a good choice for the management of cancer pain in our country ,15. The The Pain Guard app includes two opening screens: one opens to medical staff (the therapeutic interface) and the other opens to patients (the patient interface). The app in our study was designed to operate on the Android and iOS mobile operating systems to achieve an affordable, portable, and easy to use environment for patients. A total of 30 senior domestic pharmacy experts, clinical experts, nursing experts, and psychologists were included in the design process.We used the Delphi method  to desigThe therapeutic interface of the Pain Guard App was designed for checking a patient’s medical history, which was recorded by the system, and for providing real-time patient consultation . Note thThe patient interface of the app consisted of nine modules: self-evaluation, reminders, reports, records, real-time medication consultation, musical soothing treatment, pharmaceutical moments (a module for educating patients), team expert introduction, and my center .This module consisted of two parts: daily cancer pain assessment and breakthrough cancer pain (BTcP) assessment. The pain diary  was a quThis module was designed to remind patients to perform a BTcP reassessment and to view their examination and medication schedules so that they would remember to take their pain medicine on a regular basis .This module was designed so that patients could see their pain status and treatment history .This module was designed to enable patients to take photos of their inspection reports to be forwarded to the pain management team . These rThis module was designed to facilitate a real-time consultation session on pain management between the patient and the cancer pain management team .This module consisted of a questionnaire and an intelligent filter push function. The content of the questionnaire and recommended music catalog were formulated by the Delphi expert correspondence method. A total of 56 sounds were selected: 20 nature, 10 piano music, 5 harp music, 5 easy-listening music, 5 Chinese music, 5 religious (Christian) music, and 6 religious (Buddhism) music. These sounds could be used free of charge. According to a brief questionnaire, the system would suggest music playlists and links to help patients relieve tension and anxiety, raise the threshold of pain, and increase comfort levels .This module was designed to provide pharmacological knowledge for patients’ self-learning, including information on antitumor drugs, analgesic drugs, and adverse reaction prevention .This module was designed to survey satisfaction, collect feedback from patients for further improvement of the app, and to provide instructions for the usage and version information of the app .An experiment was designed to test the effectiveness of Pain Guard on cancer pain management. The experiment involved two groups: a Pain Guard trial group and a control group.After obtaining consent from all participants, clinical pharmacists conducted a standardized education session to teach the participants how to operate the mobile phone, use Pain Guard, properly assess pain, and use the rating system. The participants in the study group were asked to complete initial and final pain assessment questionnaires and QoL questionnaires on the mobile phones provided to them. Participants were encouraged to use Pain Guard as much as possible to record their pain status, at least once every day for 4 weeks.The control group received conventional pharmaceutical care. Initial and final pain and QoL assessment data were collected. Before the patient was discharged from the hospital, the clinical pharmacist conducted detailed medication education  and asked the patient to attempt to maintain a paper version of the pain diary.The participants had to meet the following screening criteria: (1) able to read Chinese and use a mobile phone, (2) aged between 18 and 75 years, (3) diagnosed with cancer and had self-reported cancer pain within a month before the study, and (4) could understand the study process and evaluation, agreed to participate in the trial, and signed the informed consent form. Exclusion criteria included (1) severe cognitive impairments; (2) hepatic insufficiency , or renal insufficiency (serum creatinine ≥2.5 × ULN); (3) inability to complete the pain assessment; (4) participation in any other investigational therapies or other study protocols that may have an impact on pain intensity, which were the main outcomes of this study; (5) history of drug abuse, addiction, or severe alcoholism; and (6) opioid allergy.The primary objective was to assess the effectiveness of pain management with Pain Guard. The secondary objectives were to evaluate the feasibility and changes in the quality of patients’ lives, user satisfaction, incidence of adverse reactions, and medication adherence when using Pain Guard.All participants were asked to complete a general information questionnaire regarding pain management and assessment. A baseline pain assessment was conducted using an NRS in both groups. Furthermore, a baseline QoL evaluation was conducted using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 in both groups. At the end of the trial, the pain assessment and QoL evaluation were repeated in both groups. Medication adherence was calculated by comparing the patient’s daily dose with the physician’s prescription and medication cycle . The conThe feedback on Pain Guard was designed to evaluate satisfaction with the system. The questionnaire was completed by participants at the end of the study. Overall satisfaction ratings were displayed by a certain number of stars. The number of stars was on a scale of 1 to 5, with 1 star being the worst and 5 stars being the best. The data generated after the survey were used to evaluate patient satisfaction with Pain Guard. The questionnaire also contained an open-ended question in which participants were encouraged to give any other suggestions regarding improvements to Pain Guard.P<.05), so the nonparametric test was used. The Wilcoxon-Mann-Whitney test was used to analyze differences in remission rate of pain, BTcP, medication adherence, and QoL between the trial and control groups.Due to the nature of this pilot work and the sample size, only limited statistical analyses were performed. Outcome evaluators were blinded to the data collection. The data were processed by using the R Statistical Software Package 3.5.1 , and were tested for normality by using the Shapiro-Wilk test. Notably, the mean values of several groups were not normal distributed  were enrolled. All patients underwent treatment in which analgesia principles, titrations, maintenance, and safety for the conversion or rotation of drugs strictly followed the National Comprehensive Cancer Network Adult Cancer Pain Guidelines. A randomization scheme was generated by independent statistical personnel using a computer. All participants were then randomly assigned into two groups: the Pain Guard study group (n=31) and the control group (n=27). The study group had 14 (45%) females; the control group had 6 (22%) females. The participants’ demographic information, as well as their disease characteristics, are summarized in P<.001). The remission rate of pain was significantly different in the Pain Guard versus control group . The medication adherence of patients in the Pain Guard group was median 100 (IQR 98-100) compared with median 75 (IQR 62-89) in the control group, which was significantly different (P<.001).We found no significant difference in the baseline pain scores between the two groups . Over thP>.05). The study group, compared with the control group, scored significantly higher in nine QoL dimensions: cognitive functioning , emotional functioning , social functioning , sleeping disturbances , nausea and vomiting , constipation , fatigue , pain , and global QoL . In the other dimensions, there was no significant difference. The total number of participants who completed the entire questionnaire was 58 (100%) at baseline and 58 (100%) at 4 weeks.The results shown in The occurrence of adverse reactions , recordeAn evaluation was conducted to measure the participants’ satisfaction with the Pain Guard app. Regarding their satisfaction, 23 (74%) participants in the trial group indicated they were very satisfied, 5 (16%) were somewhat satisfied, 2 (6%) were neutral, 1 (3%) was somewhat dissatisfied; none were very dissatisfied. Overall, the data suggest a high level of user satisfaction with Pain Guard.This study aimed to provide continuous professional treatment for patients with pain after discharge from hospital to improve QoL. We built a seven-module app with the following five functions: (1) patients can report pain status, adverse drug reactions, and physical status at any time; (2) the management team can intervene and treat the patients, according to their reports, in a timely manner; (3) re-evaluation and medication reminders are available; (4) medication education is provided to patients; and (5) music therapy treatment can be administered in the patient’s own home. Through a 4-week clinical trial investigating cancer pain management through Pain Guard, it was confirmed that Pain Guard significantly reduced the frequency of BTcP and improved pain relief and medication adherence in study participants with few adverse reactions. The satisfaction survey found that participants’ acceptance and satisfaction with the app were high.The cancer pain management team consisted of clinical pharmacists, physicians, and senior nurses. When the patient comes in for a consultation, the clinical pharmacist acted as the spokesperson for the pain management team. Simple problems were solved by the pharmacist, whereas complex problems were referred to the team by the pharmacist, and the corresponding expert would respond to the questions by consulting the patient’s medical records. The pharmacist was in charge of communicating the solution to the patient.Approximately 70% of patients with cancer pain are undertreated internationally  because Pain Guard was developed as a multidimensional tool, not only for real-time pain assessment but also for real-time drug adverse reaction treatment assessments and real-time messaging consultations. Such a mechanism enabled the team to convey clinical assistance and interventions to the patients. The Pain Guard app allowed patients to be able to instantaneously assess and report pain; thus, the team was able to provide prompt advice, which was not traditionally possible. From our study, the frequency of BTcP in the Pain Guard group was less than the control group. Through this app, BTcP could be reported in real time, standard treatment could be continued after the patient had been discharged, and the symptoms of cancer pain could be steadily controlled. Assessing adverse effects can lead to quicker responses, thus lowering levels of inconvenience experienced by patients . The incAccording to our hospital’s investigation, cancer patient’s lack of pain knowledge can lead to poor control of cancer pain . In the Music interventions may have a beneficial effect on anxiety, pain, fatigue, and QoL in people with cancer . FurtherAccording to a brief Music Therapy Self-Rating Scale , based oOur app establishes a pain case system such that the patient’s pain treatment information is available through a shareable information warehouse. The information warehouse collects basic information regarding patients, history of pain, history of treatment, and user feedback. After the patient is discharged from the hospital, authorized physicians and pharmacists can review the patient’s history of pain management at any time and location. Thus, the pain management team can rapidly and effectively manage the patient’s pain situation and achieve a seamless connection with the hospital.Because this was a pilot study, illustrative data analysis from the small sample collected over 2 months could only show apparent trends in the management of patients with cancer pain outcomes from baseline to poststudy.Pain Guard succeeded in connecting hospital staff with discharged patients using a low-cost, conveniently implemented system to facilitate real-time pain recording and timely intervention among Chinese cancer patients. Pain Guard effectively enhanced the management of patients with cancer pain at home, reduced adverse reactions, improved patient medication adherence, and improved patient’s QoL. In addition, the software operability was effective and easily accepted by patients.


Background: Many challenges encounter the endodontist, especially when dealing with necrotic teeth with chronic periapical lesions. Postoperative pain may be induced following conventional endodontic therapy and total eradication of the bacteria is almost unachievable even with recently available techniques. In recent years, diode laser usage in the endodontic field has gained acceptance. Thus, this study aimed to investigate the ability of the diode laser (DL) to decrease postoperative pain and achieve root canal sterility.Methods: 56 patients with anterior teeth with chronic periapical lesions in upper anterior teeth were randomly divided into two groups (n = 28). All patients were treated with two visits of conventional root canal treatment with ProTaper Universal. The DL group: root canals were irradiated with 200 µm fiber optic at both visits; the control group (Endo): the DL fiber was placed in root canal with no activation. Bacterial samples were collected from all the cases at each step of the treatment. Pain levels were evaluated using a numerical rating scale preoperatively, and after 6, 12, 24, 48 hours and 7 days. Bacterial count was used to detect both aerobic and anaerobic bacterial load. Results: The qualitative pain scores revealed statistically significant lower pain levels in the DL group compared with the Endo group at all time intervals (P<0.001), except preoperatively where there was no significant difference. There was a statistically significant lower bacterial count for both aerobic and anaerobic bacteria in the DL group compared with the Endo group in both S3 samples (after laser application) and S4 samples  (P<0.001).Conclusion: The 980 nm diode laser may be a successful adjunct to conventional endodontic treatment of necrotic cases with chronic periapical lesions in terms of postoperative pain and root canal disinfection.  Trail registration: PACTR201511001275414 (date: 23rd September 2015) There are two main complicating factors preventing achievement of this goal: the complicated anatomical root configuration and the special characteristics of the resident bacterial flora, which makes it sometimes inaccessible even with recent available armamentarium2. In recent years, intracanal laser irradiation has been used in root canal preparation3, gaining acceptance for its disinfection ability as adjunct to the conventional mechanical instrumentation and irrigation protocols available5. It was also reported that the use of laser therapy may result in decreased postoperative pain6. Recently, the diode laser (DL) 980 nm was introduced and its use in root canal disinfection was established4.The therapeutic goal of endodontic treatment in cases of necrotic teeth with chronic periapical lesions is the creation of a sterile, bacteria-free environment in the tooth and at the apex, including the periodontal tissue and the surrounding apical boneThis study aimed to evaluate the ability of the 980 nm DL to reduce the post-operative pain and intracanal bacteria when compared with conventional endodontic treatment.This study is a parallel randomized controlled trial, with an allocation ratio of 1:1 and a superiority framework.This study was approved by the Research Ethics Committee of the Faculty of Oral and Dental Medicine, Cairo University (15-9-19).This article was written in concordance with the CONSORT checklist 2010 .Patients received in the outpatient clinic of the Endodontic Department, Faculty of Dentistry, Cairo University in the duration between March 2016 and March 2017 were invited to participate. In total 56 participants were included in the study after fulfilling the inclusion criteria and after signing an informed consent.Inclusion criteria: Adult patients with average age between 18 and 35 years; medically free patients; patients suffering from necrotic pulp in maxillary central incisors permanent teeth with: closed apex, associated with or without sinus tract, radiographic evidence of periapical radiolucency; patients with healthy dental and periodontal status; positive patients’ acceptance for participation in the study.Exclusion criteria: Illiterate patients; pregnant woman ; patients having systemic disorder; teeth that have: open apex, extra coronal restorations, greater than grade I mobility, pocket depth greater than 4 mm, non restorable tooth, previous endodontic treatment; patients taking analgesics 12 hours before the intervention; patients who had received antibiotics in the last month; patients with acute pain at the time of intervention.et al. in 2006. To compensate losses during the follow-up this number should be increased to 56 patients . Sample size was calculated using G* Power program (2).To assess DL versus conventional endodontic regarding the postoperative pain, an independent t test was done. It was estimated that a total of 50 patients would be required for the detection of a difference between groups using a two-tailed α of 0.05 and a power of 0.80 if the absolute difference in periapical lesions is 0.37 mm with SD 0.46 as reported in MarkovickAll patients were treated by a single endodontic over two visits after signing an informed consent.First visit. At the first visit, all patients recorded their pain level preoperatively using a numerical rating scale . The teeth were locally anaesthetized 1. An access cavity was performed. Patency of the root canal was obtained using stainless steel hand k- files size #15 . The root canals were irrigated with 1 ml sterile saline solution. The first microbial samples (S1) were collected to assess the initial colonizers of the root canals using 3 sterile paper points which were inserted into the root canal for 1 min each with pumping movements. They were immediately placed inside sterile tubes containing a reduced transport medium of thioglycolate. Working length was determined using an electronic apex locator ), then confirmed with intraoral periapical radiograph. Mechanical preparation was performed with the ProTaper Universal Ni Ti system up to #F4 file for all the cases. In total 10 ml of 2.5% sodium hypochlorite was used for irrigation between each file and the next using a 25-gauge needle. 5 ml of 17% EDTA  was used at the end of the procedure to remove the smear layer. 5 ml of saline solution was the final irrigant used to neutralize all the previously used solutions. The second microbial samples (S2) representing the antibacterial effect of the mechanical preparation were obtained with the same procedure as the (S1) samples.Before isolation, antisepsis of the oral cavity was performed by rinsing for 1 min with 10 mL chlorhexidine gluconate mouth wash 0.2 %. The teeth were properly isolated with rubber damAccording to the randomization and sequence generation, the patients were allocated into two groups (n = 28/group). Experimental (DL) group: Root canals were irradiated with 980 nm diode laser coupled with optical fiber 200 µm  with setting 1.2-watt power, in pulsed mode. The irradiation protocol was a 5 sec irradiation followed by a 10 sec pause, which constituted one lasing cycle. The lasing cycle was performed four times for each tooth. The tip was positioned 1 mm short of the apex. This was followed by activation during which it was slowly dragged at a speed of approximately 2 mm/ sec in a way that the root canals were irradiated from the apical to the coronal portion, in a helicoidal movement touching the canal walls. This was done to ensure equal diffusion of light inside the root canal lumen (l lumen . The thiControl (Endo) group: Conventional endodontic treatment as above, after which the fiber optic was placed inside the root canals without activation (placebo) with no bacterial sample collected at this stage.At the end of the first visit a piece of sterile cotton was placed in the pulp chamber and all teeth was dressed with intermediate restorative material (IRM) as a temporary filling Second visit. At the second visit, one week later; the canals of both groups were accessed under rubber dam. Canals were irrigated with 1 ml sterile saline solution. The fourth microbial samples (S4) were taken to assess the recolonization of the bacteria and were collected from both groups. The same procedures of the first visit, the intracanal irradiation for the DL group and placebo for the Endo group was performed. The fifth microbial samples (S5) were collected to assess the status of root canal just before the obturation.th day. Patients were referred for final restorations. Any patient who reported the intake of an analgesic during this period was excluded from the study.Each root canal was obturated with the modified single cone technique using the ProTaper Universal gutta-percha points size F4 and gutta-percha points size 25  as auxiliaries with ADSEAL resin-based root canal sealer . All the teeth were restored with IRM as a temporary filling. At the end of the second visit, all patients were instructed to record pain level on the pain scale chart after 6, 12, 24 and 48 hours and after 7 days. The patients were instructed to submit the pain scale charts after the 7The NRS consisted of a line anchored by two extremes "No pain" and "the worst pain". The patients were asked to mark the chart at the point that represented their level of pain from 0 to 10.Pain level was assigned to one of 4 categorical scores: No pain (0), Mild (1–3), Moderate (4–6) and Severe (7–10).2. Once the samples arrived to the microbiology department, Cairo University, the tubes containing the thioglycolate (transport medium)  with the paper points were placed in microcentrifuge and vortexed for 30 sec. 100 µl aliquots of the vortexed samples were placed in a new sterile tube containing 1 ml of thioglycolate to obtain 1/10 concentration to assess the microbial load of common aerobes and anaerobes found in each root canal. However, no attempt was made to identify the specific microbial flora during the process. The effect of the treatment in each group, the mechanical preparation (S2), the Diode laser irradiation (S3) in the DL group only, the bacterial recolonization (S4) and the bacterial count just before obturation (S5), were compared.The bacterial count method was usedAerobic bacterial culture: 50 µl of these diluted samples were transferred to BHI agar plates  and cultured under aseptic conditions, followed by incubation at 37o C for 24 hours for the aerobic bacteria. The number of bacterial colonies in each plate was counted and reported as colony forming units per milliliter (CFU/ml).Anaerobic bacterial culture: The other 50 µl of these diluted samples were transferred to BHI agar plates under aseptic conditions, the agar plates were placed in an anaerobic sealed jar with Gas-Pak (Gas-Pak system)  and anaerobic indicator  were incubated for 48 hours at 37o C. Eventually, the number of bacterial colonies in each plate was counted and reported as CFU/ml.Double blinding was implemented in this study by the assessor and the statistician concerning evaluation of the post-operative pain intensity and microbiological evaluation. However, single blinding was implemented only by the statistician concerning the results of periapical lesion size. The blinded assessors were asked to fill a chart for each outcome with the number corresponding to each patient without knowing which group the participants were related to.http://www.random.org/) in the Center of Evidence Based Dentistry, Cairo University. The table was kept with the assistant supervisor. Four-folded numbered papers were packed in opaque sealed envelopes to be chosen by the patients after entering the study. The opaque envelopes contained the numbers of each random sequence to assign the patient to either the experimental (DL) or control group (Endo).A random sequence was generated by computer software . As data related to patients’ age and bacterial colony formation were parametric, significance of the difference between both groups was evaluated using unpaired t test. Chi square test was used to compare the qualitative pain scores. The level of significance was set at P<0.05.In total, 56 patients were included in the study. A CONSORT flow diagram can be seen inDemographic data, age and gender, had no significant difference between the two groups , and at 48 hours and 7 days , while preoperatively there was no statistical significance difference (P=1.0) . The resFull de-identified data for each participant, including demographic data, pain scores at all time intervals, and bacterial count of both aerobic and anaerobic bacteriaClick here for additional data file.Copyright: © 2018 Morsy DA et al.2018Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).This study aimed to evaluate the ability of the 980nm diode laser to decrease postoperative pain and disinfect the root canal and to evaluate whether the diode laser could be a successful adjunctive aid to conventional endodontic treatment.7. Among the various lasers, diode lasers are the most frequently used8. The active medium of the 980 nm diode laser is a solid-state semiconductor made of indium, gallium and arsenide. Diode lasers have several advantages: extreme compactness, affordability, ease of operation, simple setting-up, versatility and small size8. Diode wavelengths are highly absorbed in hemoglobin and melanin and have little absorption in dental hard tissue. They are also highly absorbed by water9, which provides the laser with the advantage of acting selectively and precisely8.Over time, various laser types have been developed and are used in different dentistry fields10. The temperature on the root canal walls rapidly decreases as the intracanal irradiation with the activated 200 µm fiber-optic is directed from apical to coronal direction rapidly. Thus, guaranteeing that the surrounding tissue is only marginally affected and damage of periodontal tissues or the underlying bone should not be expected9.In the present study, the intracanal irradiation was done using the pulsed mode to decrease the risk of thermal damage on external root surface and thus decrease the postoperative pain and favor healing of periapical area7. Garcezet al.11 achieved higher antimicrobial effect when they used the optical fiber in disinfection of the root canal. Diode lasers have demonstrated excellent clinical benefits12.The 980 nm diode laser use an optical flexible fiber 200 µm to deliver the beam to the target area, probably distributing homogenously the light inside the root canal for a more efficient photoreactionet al.13, reported that, the NRS has greater sensitivity to change in pain intensity. Amelia and Barbara14 reported that the NRS represents interval levels so it can provide data for parametric analysis.In this study, the NRS scale was used to record postoperative pain. Jamisonet al.15 and Pawaret al.16, who reported that the use of diode laser in root canal irradiation showed significantly lower pain at 8, 24, 48 hours and 7 days postoperatively when compared to conventional treatment. Tuneret al.17, found that, usually after conventional RCT of chronic cases, which is the situation in this trial, the case become acute when the process of healing starts, thus patients are at risk of experiencing postoperative pain which was not the situation in the DL group. The exact mechanism by which the use of laser results in decreasing post-operative pain is still unknown. Some authors proposed some mechanisms by which the diode laser relieves pain: Pawaret al.16 and Bjordalet al.18 found that the diode laser acts on chronic pain and has an anti-inflammatory effect by decreasing PGE2, bradykinin, histamine, acetyl choline and serotonin, also the diode laser was proved to decrease the production of substance P. Our results concerning postoperative pain in the cases of chronic apical periodontitis, when treated with diode laser, showed promising results.The results of this study showed that the DL group had statistically significant lower pain levels than the Endo group at all tested time intervals . These results are in accordance with the findings of Berk19. Thus, in this study the effect of the treatment on both the aerobic and the anaerobic bacterial count were assessed following the same methodology of Garcezet al.20 and Bonsoret al.2. This technique was selected due to its ability to detect exclusively the viable bacteria and also the correlation proved previously, by many studies22, between negative cultures at time of obturation and more favorable treatment outcomes.It is generally accepted that the development of periapical diseases are pathologic features of polymicrobial bacterial infection and its components which stimulate bone resorption22. Our findings are in accordance with the findings of Garcezet al.11 and Gutknechtet al.4, who found that the use of diode laser resulted in significant decrease of the intracanal bacterial load. The high antibacterial effect of diode laser may be explained by the fact that the near infrared lasers are absorbed to small extent by dentin. This is important for the efficient disinfection as the laser is not absorbed by the superficial dentin but rather penetrates deep into the intertubular dentin1. Vaarkampet al.23 and Odoret al.24 provided an explanation for this way of light propagation, as they described the ability of enamel prisms and dentinal tubules to act as an optical fiber and thus allowing the diode laser to be more effective in deep layers of dentin. According to Gutknechtet al. in 20089, the ND: YAG, 810 nm diode laser and 980 nm diode laser are the only wavelengths that showed high transmission through hydroxyapatite and water. Thus, it can be used successfully for the disinfection of root canals.In this study, the antibacterial results showed statistically significant lower bacterial count in the S3 samples of DL group than the S2 samples of both groups. It also showed significantly lower bacterial recolonization in S4 samples of the DL group than the Endo group. The S5 samples of the DL group resulted in significantly lower bacterial count than the Endo group, which may favor the treatment outcomes25 talk about a permanent destruction of the cell membrane, which is commonly in correlation with direct heat having an impact on the bacteria. The diode laser exerts a photo-thermal effect on the bacteria26. It also, exerts a photo-disruptive effect on the unreachable bacteria26.Diode laser radiation has a bactericidal effect by altering the bacterial cell wall. Microbiologistset al.4 demonstrated that diode laser light can penetrate up to >1000 μm into the dentin. Thus, it can be an effective means for disinfection of the root canal system together with conventional biomechanical instrumentation reaching areas, which were considered earlier non-reachable. GuteknechtThis study is a randomized clinical trial conducted on a relatively big sample size patients, in real clinical settings and was conducted efficiently. It proposes an alternative way for treatment of necrotic teeth with chronic periapical lesions efficiently and without postoperative pain.The following limitations should be considered: this study didn’t evaluate if there is a difference between single visit or two visit approach when the intracanal diode laser is used on postoperative pain and bacterial count of necrotic teeth with chronic periapical lesions.in vivo and immunological studies are needed to identify the exact mechanism by which the intracanal Diode laser resulted in decreasing postoperative pain.FurtherIntracanal diode laser irradiation has the ability to decrease the postoperative pain experienced after conventional root canal treatment in cases of necrotic teeth with periapical lesions. Implementation of suitable wavelengths, together with conventional methods of cleaning and shaping, can effectively sterilize the root canals, dentin and periapical area and decrease the bacterial recolonization. Thus, based on the findings of this study, it may be concluded that the 980 nm diode laser can be used as an adjunct to conventional endodontic therapy. The data referenced by this article are under copyright with the following copyright statement: Copyright: © 2018 Morsy DA et al.Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).https://doi.org/10.5256/f1000research.16794.d22435127F1000Research: Dataset 1. Full de-identified data for each participant, including demographic data, pain scores at all time intervals, and bacterial count of both aerobic and anaerobic bacteria. , Introduction: There is a lack of information about the previously performed studies. The authors should clearly and briefly describe the existing studies, which have been done so far. Why did the authors perform this study? Which gaps was/were exist in the field of postoperative pain evaluation when diode lasers are used? What was the Null hypothesis? All should be described in the Introduction. The power analysis is adequate.Methods: Allocation concealment and sequence generation were described adequately. Results: Demographic and baseline characteristics  of the patients can be showed in one Table so that Table 1 and Table 2 can be removed.Discussion: In the Discussion, the second paragraph is unnecessary. It can be completely removed and can be add to the Introduction.I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. 1). In this way, the authors need to make clear in the introduction what is the innovation that this manuscript presents.There are many recent published papers that report the clinical efficacy of diode laser in endodontic treatment , while Tables 4 and 5 do not explain what upper and lower case letters refer to.This is a well-written and well-conducted article with clear problem and objective. For indexing, it is suggested some changes, described below:I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. After reviewing the manuscript entitled 'Posteroperative pain and antibacterial effect of 980nm diode laser versus conventional nedodontic treatment in necrotic teeth with chronic periapical lesions:A randomized control trial', I have found that it is such an outstanding article overall. It provides a comprehensive examination of a complex subject; providing new options in treatment of such an inevitable problem. A detailed description of the manuscript will be as follows:Introduction: which was a well-written and covering more than enough of the relevant theoretical data of literature.Aim of the study: Here the author stated the objectives and goals of the study in an appropriate manner.In the Methods: the author gave a detailed description of the employed methodology of the investigation. It was very well elaborated and relevant to the aim of the study.Results: The results were well organized into different categories; this section included tables and charts. All of which help the reader get a clear detailed insight of the different aspects occurring within the two groups of patients.Discussion: the author in this chapter was successful in showing logical overall arguments and used appropriate number of bibliography sources. This shows that the author developed a deep understanding of the theoretical knowledge and the discussed problems.Conclusion: The manuscript provides a relevant summary of the subject, methodology and results.References: They were organized and included a lot of recent publications. Generally, this manuscript meets all the basic requirements of good research and demonstrates coherence between theoretical position, problem presented and the methodology appointed. The author showed in this manuscript a significant level of understanding and analytical ability. I find the work innovative and recommend indexing it.I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


Sufficient pain control and rapid mobilisation after VATS are important to enhance recovery and prevent complications. Thoracic epidural analgesia (TEA) is the gold standard, but failure rates of 9–30% have been described. In addition, TEA reduces patient mobilisation and bladder function. Subpleural continuous analgesia (SCA) is a regional analgesic technique that is placed under direct thoracoscopic vision and is not associated with the mentioned disadvantages of TEA. The objective of this study was to assess surgical feasibility, pain control and patient satisfaction of SCA.n = 23). Pain scores  and patient satisfaction  were collected on postoperative day (POD) 0–3. Secondary outcomes were the period of urinary catheter use and period to full mobilisation.Observational pilot study in patients who underwent VATS pulmonary resection and received SCA  and was successful in all patients. Pain scores on POD 0–3 were 1.2 (SD 1.2), 2.0 (SD 1.9), 1.7 (SD 1.5) and 1.2 (SD 1.1) respectively. On POD 0–3 at least 79% of patients were satisfied or very satisfied on pain relief and mobilisation. The duration of subpleural continuous analgesia was 4 days . Urinary catheters were used zero days  and full mobilisation was achieved on POD 2 .Subpleural continuous analgesia in VATS pulmonary resection is feasible and provides adequate pain control and good patient satisfaction.This pilot study was not registered in a trial register. Sufficient pain control and rapid mobilisation after video-assisted thoracoscopic surgery (VATS) are important to improve recovery and prevent postoperative pulmonary complications . ThoraciThese disadvantages supported the development of other regional techniques for pain management. Single-shot thoracic paravertebral blockade, intercostal nerve blockade and serratus anterior blocks have been shown to be safe and effective for pain management after VATS , 7–9. ReSubpleural continuous analgesia (SCA) is a regional multilevel intercostal analgesic technique to control postoperative pain using a subpleural catheter placed under general anaesthesia and direct thoracoscopic vision. It does not influence mobility, bladder function or blood pressure. Jung et al. retrospectively compared SCA with intravenous patient controlled analgesia for pain management after VATS pulmonary resection and found average pain scores  higher than 3 on postoperative day (POD) 0–2 . The effSubpleural continuous analgesia is feasible, provides adequate pain control and has good patient satisfaction in patients after VATS pulmonary resection.We performed an observational pilot study in a Dutch teaching hospital . 23 consecutive patients who underwent VATS pulmonary resection and had an indication for TEA  between April and September 2018 were included and received SCA for pain management instead of TEA. The pain scores and postoperative outcomes of SCA patients were compared to a historical group to benchmark our results. Since this was an observational pilot study we were not aiming to prove non-inferiority or even superiority of either technique. The historical group contained 23 consecutive patients who underwent VATS pulmonary resection and received TEA between April and September 2017.Primary outcomes were surgical feasibility, pain control and patient satisfaction on postoperative day (POD) 0–3. Secondary outcomes were length of hospital stay, chest tube drainage and urinary catheter use, incidence of postoperative hypotension and degree of postoperative mobilisation.To assess surgical feasibility the duration of placement (minutes) and success of placement were collected. A numeric rating scale (NRS 0–10) was used to assess the level of pain in rest, while coughing and while moving. In addition, the necessity for intravenous and oral analgesics and the presence of postoperative nausea and vomiting were registered. Patient satisfaction on pain relief and mobilisation was measured on a 5-point Likert scale .For secondary outcomes we collected length of postoperative hospital stay (days), length of chest tube drainage (days), the length of urinary catheter use (days) and the incidence of postoperative complications . To examine hypotension we collected the lowest reported blood pressure in the morning, afternoon and evening on POD 0–3. Postoperative mobility was scored as the maximum achieved score on a non-validated 6-point scale . Pain control, patient satisfaction and mobility scores were assessed on the recovery room (only pain scores), at the evening after surgery and in the morning, afternoon and evening on POD day 1 and 2 and in the morning and evening on POD 3. In order to describe the use of SCA we collected details on the SCA catheter placement ) and possible complications in the postoperative period . Finally, we collected the following data from the electronical medical records: age, gender, length, weight, blood pressure at the pre-operative visit, American Society of Anaesthesiologists (ASA)-classification, indication for surgery , surgical details .In the historical TEA group prospectively collected pain scores on POD 1–3 were available. The baseline characteristics and postoperative outcomes data were collected retrospectively from the electronical medical records.Results were reported according to the Strengthening the Reporting of Observational studies in Epidemiology guidelines for observational studies . The meaPerforation of the parietal pleura during the placement of the subpleural catheter could have led to a decreased analgesic dose around the intercostal nerves due to leakage of analgesics into the pleural cavity. Therefore, we divided the SCA patients in a perforation and no perforation group and compared baseline characteristics, surgical details and pain scores between these groups.p = .05. All calculations and statistical analysis were done using the Statistical Package for Social Sciences, version 22.0 .Descriptive data were presented as means (with standard deviation (SD) and/or range) or medians (with interquartile range (IQR) and/or range) depending on  distribution of data. Categorical data were presented as counts and percentages. Categorical data were compared by the Chi-square test, whereas numerical data were compared by the unpaired T-test or Mann-Whitney U test depending on  distribution of data. We calculated 95% confidence intervals (95%-CI) around proportions using the Wilson interval . All perAll patients received general anaesthesia using propofol, sufentanil and rocuronium for induction and either propofol or sevoflurane for maintenance of anaesthesia (at the discretion of the anaesthesiologist). After surgery patients received additional analgesics according to the analgesic pain relief ladder; oral paracetamol (standard dose of 4000 mg per 24 h) with additional nonsteroidal anti-inflammatory drugs  and if necessary morphine or morphine equivalent .The multi-orifice 25 cm length On-Q local anaesthetic infiltrating catheter  was placed intraoperatively under direct thoracoscopic vision by one of two lung surgeons . After general anaesthesia and endotracheal intubation the patient was positioned in the lateral decubitus position with the affected side up. Access to perform was achieved by either uni- or multiportal incision(s). The pain catheter was inserted dorsally and at least two costal levels caudally of the most caudal placed incision which is generally made in the 8th intercostal space. After skin incision we searched for the subpleural space using blunt dissection under direct thoracoscopic vision Fig. , image 1n = 4) or conventional (n = 19) VATS. 18 Patients (78%) underwent an anatomical resection  and in the remaining five patients a large wedge was resected. We did a lobe-specific mediastinal lymph node dissection in 16 patients (70%). All patients received one chest tube for postoperative drainage , 74% males) were included for analysis. The primary surgical technique was either uniportal  and was successful in all patients. The mean pain score in rest on the recovery room was 1.1 (SD 1.2) and on the evening after surgery it was 3.1 (SD 2.0). On POD 1–3 the mean pain scores in rest were 2.0 (SD 1.9), 1.7 (SD 1.5) and 1.2 (SD 1.1) respectively. The mean pain score in rest on POD 1–3 together was 1.6 (SD 1.3)  with a period of chest tube drainage of 2 days . The period of urinary catheter use was 0 days . At the pre-operative visit none of the patients suffered from hypotension with a mean MAP of 100 mmHg (SD 12). Hypotension during the first three postoperative days was seen in only one patient (5%). SCA patients were able to walk to the bathroom without help on median POD 1 . Walking around the ward without help was median possible on POD 2 . Postoperative complications occurred in seven patients (30%) (Table n = 11) and the pleural perforation group (n = 12) in left or right sided surgery, duration of the placement of the pain catheter, mobilisation and pain scores in rest, while coughing or while moving on POD 0–3.The duration of subpleural continuous analgesia was 4 days . One patient reported deafness of the skin around the location where the catheter was inserted. Leakage of local anaesthetic from the skin insertion place of the pain catheter occurred in 6 patients (23%). We saw no other SCA-catheter related complications or ropivacaine related systemic side effects. Minor perforation of the parietal pleura during placement of the catheter occurred in 12 patients (52%). None of these patient had abundant drain production and no additional interventions were required to repair the perforations. We found no significant differences between the no pleural perforation group (p = 0.01) (Table p = .78) (Table p = .04), while the pre-operative MAP was comparable between groups . The length of hospital stay  and chest tube drainage  were similar to SCA patients. The period of urinary catheter use was 2 days  which was significantly longer compared to patients with SCA . Postoperative complications occurred in seven patients (30%) with SCA and six patients (26%) with TEA (p = .74)  Table . Signifi8) Table . HypotenSufficient pain control after VATS enables adequate breathing and early mobilisation hereby reducing postoperative complications and enhance recovery. Our results suggest that subpleural continuous analgesia in VATS pulmonary resection is feasible and provides adequate pain management and good patient satisfaction.To the best of our knowledge no consensus on optimal postoperative pain management after VATS is achieved in current literature. A review of enhanced recovery after thoracic surgery (ERATS) protocols strengthened the lack of unambiguity. The five included protocols all used different techniques for postoperative pain management: oral, intravenous, intercostal, paravertebral and epidural anaesthesia . The useUrinary catheters could be another cause of restricted postoperative mobilisation. Its use combined with TEA is however common practice in most hospitals. A prospective study showed significant post-void residuals in patients with thoracic epidural analgesia . In a raSufficient pain management allows patients to mobilize. Insufficient pain control by epidural or local analgesia could be compensated by additional oral or intravenous analgesics. However, since opioids and NSAIDs have certain disadvantages it is important to minimalize the use of these drugs. SCA patients had a higher opioid consumption on POD 1 and 2. These results are in concordance with current literature where slightly higher additional analgesic use is described in continuous local analgesia groups versus TEA-groups in thoracic surgery , 24. HowPlacement of the SCA catheter was easy and safe. Placement of the catheter took an average of 11 min resulting in a non-significant prolonged operation time in SCA patients. We noticed a very steep learning curve since the placement of the first 12 catheters took an average of 14 min versus 8 min in the last 11 catheters.The main benefits of SCA compared to TEA and other regional analgesic techniques  were fast placement under direct thoracoscopic vision and no need of additional equipment or specialized staff (beside the catheter). In addition, patients benefit from the placement of the analgesic catheter under general anaesthesia compared to possible stressful awake placement of a thoracic epidural catheter or awake percutaneous regional analgesic techniques . Lastly,The main limitations of our study were the observational character and the small sample size. This may have led to an underestimation of differences among TEA and SCA due to insufficient power. Since the primary objective was feasibility, pain control and patients satisfaction of SCA the results of the comparison with the historical group should be interpreted with care.The results and limitations of our study and the lack of consensus in current literature strengthen the need for prospective, randomised research on the most (cost-)effective technique of postoperative pain management after VATS pulmonary resection. Results of future research may aide in optimizing patient care and improve ERATS protocols.Subpleural continuous analgesia in VATS pulmonary resection is feasible and provides adequate pain control and good patient satisfaction.