To evaluate the effectiveness and feasibility of high-intensity focused ultrasound (HIFU) for the treatment of bone metastases. A single-center prospective study was made involving 17 consecutive patients with symptomatic bone metastases. Patients were treated by Focused Ultrasound (FUs) performed with magnetic resonance (MR) guidance. Surgical treatment or radiotherapy treatment was not indicated for patients who underwent FUs. Lesions were located in the appendicular and axial skeleton and consisted of secondary symptomatic lesions. The clinical course of pain was evaluated using the Visual Analog Scale (VAS) before treatment, at 1 week, and at 1 month after treatment and the Oral Morphine Equivalent Daily Dose (OMEDD) was also recorded. We used Wilcoxon signed rank test to assess change in patient pain (R CRAN software V 3.1.1).p = 2.9.10–4), and pre-procedure and 1 month post-procedure (p = 3.10–4). The proportion of responders according to the International Bone Metastases Consensus Working Party was: Partial Response 50% (8/16) and Complete Response 37.5% (6/16).We observed a significant decrease in the pain felt by patients between pre- procedure and 1 week post-procedure (HIFU under MR-guidance seems to be an effective and safe procedure in the treatment of symptomatic bone lesions for patients suffering from metastatic disease. A significant decrease of patient pain was observed.NCT01091883. Registered 24 March 2010. Level of evidence: Level 3. For 50 years, high-intensity focused ultrasound (HIFU) has been a subject of interest for medical research . HIFU trThanks to Magnetic Resonance Imaging (MRI) guidance, real-time thermal feedback of heated zones makes it possible to ablate targeted tissue in real time without damaging normal structures. The precision of the technique and the immediate feedback obtained make it an attractive and safe alternative to surgical or radiation therapy for both benign and malignant tumors . ClinicaPain due to bone metastases is a common clinical problem in cancer patients . The priMagnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has recently emerged as an effective treatment option for painful bone metastases by means of periosteal nerve-ending ablation. However, there exist few articles in the literature related to HIFU for this indication , 16–19.The objective of our study was to describe our experience in the treatment of painful bone metastases using volumetric MR-HIFU ablation and to assess the technical feasibility and safety of the procedure .We present a prospective observational study on 17 consecutive patients  suffering from symptomatic bone metastases of the appendicular skeleton. From October 2012 to March 2018, 17 patients with metastatic disease were enrolled. Most patients were suffering from intense inflammatory pain, often associated with mechanical pain and disability for walking or standing, depending on the localization of lesions. The lesions were located in the appendicular skeleton, involving the tibial diaphysis (two cases), femoral diaphysis (two cases), iliac bone (four cases), clavicle (one case), scapula (one case), humerus (one case), and in the axial skeleton, involving the ribs (six cases). All patients had exhausted maximum radiotherapy and analgesic treatment options for their painful bone metastasis.For inclusion, the pain arising from the lesion had to be self-rated by the patient as ≥5 on an 11-point numeric visual analog scale (VAS) from 0 (no pain) to 10 (worst imaginable pain) . ExclusiPretreatment magnetic resonance imaging  was available for all patients in order to confirm the location of the bone metastases. MR images were evaluated by a radiologist with 10 years’ experience to determine treatment accessibility of the target lesion. Final treatment eligibility was determined in a multidisciplinary setting. The MRI protocol included T1-weighted (T1W) turbo spin echo (TSE) and T2-weighted (T2W) sequences in two orientations and fat-suppressed T1W (SPIR) sequences in two orientations after intravenous administration of gadobutrol, a gadolinium-based contrast agent . Approval was obtained from the institutional review board of the Centre Antoine Lacassagne  and written informed consent for the treatment and for the use of their anonymized data for this study was obtained from each patient.Treatments were performed by an interventional radiologist (with 5 years’ experience) using the MR-HIFU system . All procedures were performed under general anesthesia.Patients were placed in a prone or supine position depending on the lesion location in order to be as close as possible to the transducer for optimal treatment. After identification of the target lesion, sonications were delivered to the patient, with a number of sonications depending on the lesion size, and were adjusted in real time using temperature control at the lesion site Fig .Fig. 1LoThe number of sonications delivered in our study ranged between 8  and 27 (biggest lesion). The duration of each sonication was 15 s. The average duration of the entire procedure was 2 h.An immediate post-operative MRI was made at the end of each procedure to evaluate bone metastasis destruction, including T1-weighted fat-suppressed sequence after gadolinium injection. The non-enhanced area after treatment corresponded to the necrotic zone.A prospective follow-up was done, consisting of post-operative evaluations at 1 week and at 1 month to assess the pain felt by the patients. Quantification of pain was made by each subject on an 11-point numeric visual analog scale (VAS) with values from 0 to 10 (where 10 indicates the strongest pain ever experienced and 0 indicates absence of pain) and was supervised by an independent evaluator. Pain evaluation was made specifically on the anatomical site treated by focused ultrasound . A difference in VAS > 2 points was considered a clinically significant result . We alsoPartial response was defined as either a ≥ 2-point decrease in VAS at the treated site with no increase in OMEDD or as an OMEDD reduction of 25% or more from baseline without an increase in pain. Complete response was defined as a pain score of 0 at the treated site with no simultaneous increase in OMEDD. Pain progression was defined as a ≥ 2-point increase at the treated site with stable OMEDD or an increase of 25% or more in OMEDD compared with baseline with the pain score stable or 1 point above baseline . A cliniP < 0.05 was considered statistically significant. Confidence intervals were computed by bootstrapping data. Statistical analyses were performed using R CRAN Software (Version 3.1.1).The VAS score was measured at these three follow-up examinations. OMEDD was recorded at baseline and after 1 month. Pre-and post-operative VAS and OMEDD were compared using the non-parametric Wilcoxon signed-rank test for paired data. Data are summarized in Table Treatment was technically successful in 17 cases and clinically successful in 16 cases according to VAS Fig , 3, 4. TOne patient received no morphine treatment and was not reported by OMEDD.Compared to the onset of treatment, all patients experienced a decrease in pain after 1 week and after 1 month. More than 40% of the cohort reported no pain at all after 1 month.p = 2.94.10− 4), and before the procedure and 1 month following the procedure- (p = 2.99.10− 4).The average evaluation of pain was 7.53/17 (SD: 1.33) before treatment, 2.29/17 (SD: 1.86) 1 week after treatment, and 1.88/17 (SD: 1.99) 1 month after treatment. Our results show a significant decrease of the pain felt by patients between before the procedure and 1 week following the procedure- .Mean OMEDD was respectively 270.6  at baseline and 113.75  at 1 month; no significant difference was observed  of patients. One patient who experienced pain progression was documented to have not been properly treated for pain. The other patient experiencing pain progression had a VAS score of zero but had a significantly higher OMEDD after 1 month.To our knowledge, there are only a few articles in the literature demonstrating the benefit of HIFU with MR guidance for the palliative treatment of bone metastases , 22, 23.p < 0,05) at 1 week and at 1 month post procedure. Ten elderly patients were significantly relieved of their pain following the procedure. These patients had several co-morbidities and had exhausted maximum radiotherapeutic and analgesic treatment options for their painful bone metastases. All suffered intense inflammatory pain, often associated with mechanical pain severely decreasing their quality of life. The procedure indication was evaluated very carefully for each patient, as management of symptomatic bone metastases by HIFU depends largely on clinical symptoms and the degree of pain felt by patients. All the patients suffered from a symptomatic bone lesion. The association of bone marrow edema and enhancement of the lesion on the MRI performed before treatment indicated the concordance between clinical symptoms and imaging.Our study shows a significant decrease in patient pain after treatment by HIFU with MRI guidance  at 3 months [Hurwitz et al. recently reported the first completed phase III randomized trial investigating MRgFUS in patients with painful bone metastases. They showed a response rate of 64.3% in the MRgFUS arm compared with 20.0% in the placebo arm P < .00 at 3 mon3 months . In the 3 months . MRgFUS These therapeutic techniques appear to be complementary for oncology patients suffering from metastatic disease and can be used in combination for optimal antalgic and therapeutic effectiveness. Further evidence from large randomized control studies is needed to establish MRgFUS as a possible palliative treatment of bone metastases alongside other available therapeutic options .HIFU seems to be a safe and effective treatment procedure as no immediate or delayed complications were observed in our study. To improve pain control during the intervention, patients were treated by direct approach with focused ablation of the periosteum as this is the most highly innervated component of mature bone tissue. In the literature, several possible ablation approaches have been described using HIFU: the “near-field approach” in patients with  intact cortical bone at the targeted lesion, in which treatment cells are initially positioned behind the cortical bone; and the “direct approach” in which treatment cells are positioned on the bone/soft-tissue interface. Although both ablation approaches can induce thermal ablation of the bone/soft-tissue interface, the direct approach requires lower sonication energies compared to the near-field approach, thus minimizing the risk of thermal damage beyond the targeted volume . HIFU trFor optimal effectiveness, the benefit of the HIFU procedure should be estimated in terms of patient pain. However, this can be difficult as pain can be multifactorial in oncology patients. Bone metastases are painful current lesions in oncology patients. HIFU treatment enables us to relieve the pain felt by patients but does not promote bone consolidation, which is often needed in such fragile patients. In these circumstances, the benefits provided by a therapeutic association between different modalities such as cementoplasty, radiotherapy and immunotherapy becomes paramount , 27–29.In MR-HIFU, image guidance is crucial for treatment planning and real-time temperature monitoring as lethal cell damage occurs when temperatures > 55 °C are maintained for longer than 1 s . The meaOur study has several limitations. First, we did not compare our results with a control group treated conservatively or with radiation therapy alone. In fact, it was difficult not to treat demanding patients suffering intense pain and to whom we could propose a safe and efficient treatment option. Second, our patient sample was small and the follow-up period was relatively short; long-term clinical outcomes still need to be evaluated. MR-HIFU also has its limitations as the procedure is time-consuming and required general anesthesia in our study. The cost of the technique and its availability are also limiting factors. Indications and benefits of MR-guided HIFU in the treatment of bone metastases should be clearly defined for routine use by interventional radiologists, while new indications for the technique are currently under investigation , 36.In conclusion, MR-guided HIFU seems to be a safe and efficient therapeutic option for patients suffering from bone metastases. The technique can be used alone or in combination with other treatments such as cementoplasty or radiotherapy for palliative treatment in metastatic disease. Patients should be carefully screened for optimal therapeutic effectiveness of the procedure. Future research should include a large well-designed cohort study with longer follow-up, in which patients with persistent metastatic bone pain are treated. The benefits versus risks ratio seems very positive, with a significant decrease in patient pain and the advantages of a non-invasive procedure. This non-invasive interventional radiology technique appears to be a promising additional tool for the management of patients in oncology.


To investigate the clinical efficacy of physical factors combined with early psychological intervention in treatment of patients with chronic limb pain.A total of 132 patients with chronic limb pain admitted to Affiliated Hospital of Hebei University, Baoding, China from June 2014 to June 2017 were enrolled. The patients were divided into control group (n=66) and observation group (n=66) according to the random number table method. Both groups of patients were treated with physical factors, and the patients in the observation group were also treated with early psychological intervention. PHQ-15 pain factor score, visual analog pain score (VAS score), Hamilton depression rating scale (HAMD) and clinical efficacy were compared between two groups.P=0.091, 0.161, 0.078). At the end of treatment and at 8 weeks of follow-up, PHQ-15 pain factor score, VAS score, and HAMD score of observation group were lower than those of control group, and the differences were statistically significant . Total clinical effective rates of observation group and control group were 92.43% and 86.37%, respectively, and the differences were statistically significant (P=0.019).Difference of PHQ-15 pain factor score, VAS score and HAMD score between two groups before treatment were not statistically significant (Compared with physical factors alone, combination of physical factors and early psychological intervention can significantly alleviate the pain and improve the depression of patients with chronic limb pain. It should be promoted in clinical practices. Chronic limb pain is caused by aseptic inflammation or chronic strain. Chronic limb pain patients often show neck and shoulder pain, limb joint pain, swelling of the affected side and limited function. In recent years, incidence of chronic limb pain has increased year by year, and has gradually become the most common occupational disease in the world .The occurrence of chronic limb pain is related to a variety of factors, including gender, age, height, dark gray economy status, weight, muscle strength, health status, smoking, posture deformity, occupation and so on . ChronicTherefore, we investigated the clinical efficacy of physical factors combined with early psychological intervention in treatment of patients with chronic limb pain.A total of 132 patients with chronic limb pain admitted to Affiliated Hospital of Hebei University, Baoding, China from June 2014 to June 2017 were enrolled. Patients were divided into control group (n=66) and observation group according to random number table (n= 66). Among 66 patients in the observation group, 41 were male and 25 were female, and age ranged from 19 to 88 yr old, with a mean age of (44.45 ± 5.66) years. Course of disease was 6 months to 5 yr, with a mean course of (20.43±5.23) months. In control group, there were 40 males and 26 females, and age ranged from 65 to 85 yr old, with a mean age of (73.78±5.78) years. Course of disease ranged from 6 months to 5 yr, with a mean course of (21.06 ± 5.31) months. No significant differences in general data were found between 2 groups.Inclusion criteria: 1) Patients with limb pain for more than 6 months; 2) Patients aged 18 years or older; 3) Patients who volunteered to participate in this study and have signed informed consent.Exclusion criteria: 1) Patients with a history of psychological intervention or antidepressant treatment; 2) Patients with mental or mental abnormalities; 3) Patients took analgesic drug or with a history of alcohol dependence; 4) Patients with physical illness or brain organic disease; 5) Pregnant or lactating patients.This research was reviewed and approved by the Ethics Committee of Affiliated Hospital of Hebei University. All patients enrolled were aware of this research and each one and/or their guardians signed an informed consent.Both groups of patients were treated with physical factors, and patients in the observation group were combined with early psychological intervention.Patients were treated with Chinese medicine fumigation and audio electric therapy.Chinese medicine fumigation: Traditional Chinese medicine fumigation multi-function treatment machine was used. In a special steamer, Chinese medicine such as safflower, angelica, scorpion, pepper, eucommia, aconite, dog ridge, etc. were mixed and 3 kg–4 kg water is added. Treatment temperature was set to 39 °C–45 °C, each treatment was performed for 30 min.Audio electric therapy: audio electric therapy machine was used for treatment. Two 4 mm thick 10 cm × 5 cm electrode plates were padded with cotton and soaked in 0.9% sodium chloride solution. Two electrodes were placed in the armpit and knee and fixed with an elastic band to control the current intensity at 30–50 mA. Each treatment was performed for 20–30 min.Psychological diagnosis: Patients are encouraged to express their understanding and worries about their own pain in the form of collective discussion and group discussion. Causes of misperceptions such as depression and anxiety are analyzed.Correcting false cognition: Multiple methods of exercise are used to help patients correct their original misconceptions and form reasonable cognition to eliminate or alleviate bad emotions. Specific methods: Patients who have been cured were invited to present their own opinions and debate with patients about their misconceptions, so that patients can realize that although pain cannot be completely eliminated, it will not produce terrible consequences, therefore negative emotions of anxiety and depression will be relieved.Strengthen the newly formed reasonable beliefs, such as: I should learn to adapt to the pain, coexist with it, and carry out mental function training such as imaginary relaxation training and abdominal breathing to help patients form correct beliefs and ways of thinking to cope with chronic pain. 1) Imagine relaxation training: beautiful and soothing music, beautiful scenery and guiding words are used to help patients recall the feelings of pleasure, 15 – 20 min for each time, twice per week, totally 20 times. 2) Abdominal breathing training: Semi-recumbent position was taken with one hand on the chest and the other on the abdomen. After exhaling breath, inhale with the nose, and slowly exhale the gas after 3 seconds of psychological silence. Gas enters the abdomen as it inhales, feeling that the hand on the abdomen is pushed up. At the same time, let the patient imagine that stress and trouble are slowly excluded from the body with exhalation, 15 min–20 min per training session, once a day.PHQ-15 pain factor score, VAS score, HAMD score and clinical efficacy were compared between two groups. PPHQ-15 pain factor, VAS and HAMD scoring were performed before treatment, at the end of treatment and at 8 weeks of follow-up. The results were compared. Clinical efficacy: HAMD score reduction rate was used to determine the efficacy, <25% is invalid, 25%–50% is effective, 50%–80% is markedly effective, ≥ 80% is cured.t test and χ2 test respectively. Differences at P<0.05 were statistically significant.SPSS 20.0 software  was used for statistical analysis. Measurement data and count data were compared by P=0.091). PHQ-15 pain factor scores of observation group were lower than those of control group at the end of treatment and 8 weeks of follow-up   .P=0.161). VAS scores of observation group were lower than those of control group at the end of treatment and 8 weeks of follow-up   .P<0.05)  .P<0.05)  .In recent years, with the continuous development of rehabilitation medicine, patients with chronic limb pain now have been treated with comprehensive rehabilitation therapy such as exercise therapy, intermediate frequency pulse electrotherapy, traction, etc., which has improved the rate of improvement . At the Eucommia, aconite and Rhizoma cibotii have the effect of warming the liver and kidney, and the sputum has the effect of reducing swelling and dampness  have been completely observed by the authors.


Background and purpose — It is unknown whether different trajectories of pain or function are associated with timing of total hip or knee arthroplasty (THA/TKA) in osteoarthritis (OA) patients. We investigated this association in early symptomatic OA patients.Patients and methods — Data from the prospective Dutch CHECK cohort (patients with early hip/knee OA complaints) covering 9 years of follow-up were used. Pain and function were measured annually using the WOMAC questionnaires. Changes in pain/function over time were estimated using a linear mixed model adjusted for baseline age, sex, BMI, maximal Kellgren and Lawrence score, number of painful joints, and comorbidities. The same covariates were included in a Cox regression model, with time to first arthroplasty as event. Both were combined in a joint model to assess the association between changes in pain/function and time to arthroplasty.Results — Of the 868 eligible patients, 84 received a TKA/THA during follow-up. Patients receiving arthroplasty were somewhat older, had a higher Kellgren and Lawrence score and worse WOMAC scores at baseline. Irrespective of receiving arthroplasty, about two-thirds of the patients showed at least 1 period of deterioration of pain/function . In approximately two fifths this deterioration was followed by another deterioration in the following year. Worse pain and function levels increased the hazard of receiving THA/TKA (1.08 [95% CI 1.06–1.10] for pain and 1.07 [CI 1.05–1.08] for function). Changes in pain or function over time were not associated with timing of THA/TKAInterpretation — Worse pain and function levels rather than long-term changes are associated with timing of THA/TKA. Although total knee arthroplasty (TKA) and total hip arthroplasty (THA) are effective interventions, their optimal timing is unknown. This is illustrated by the varying disease severity when surgery is performed across centres in Europe and Australia  are persistent rather than progressive  visited the research centre each year for collection of clinical, radiological, and biochemical data; patients with mild symptoms (n = 141) visited the research centre at years 0, 2, 5, 8, and 10. Patients could shift to the more serious symptoms group, and were then measured annually as well (n = 79 after 5 years) . Pain and function were assessed by the standardised WOMAC pain score  × (100/20)) and function score  × (100/68)). To investigate whether THA/TKA patients more often experienced episodes of deteriorating pain or function prior to THA/TKA, compared with patients not receiving arthroplasty, we defined deteriorating pain or function as the first ≥10 points increase on the standardised WOMAC pain/function subscales compared with the year before. Further deterioration in the year thereafter was defined as any increase in WOMAC pain/function. When patients received multiple arthroplasties during follow-up, the first arthroplasty was taken as event, and their follow-up was censored. Baseline maximal K&L was defined as the highest K&L in the hip/knee joints at baseline. Maximal K&L during follow-up was defined as the highest K&L in the hip/knee in all measurements.We included all measurements until 9 years of follow-up. Only patients with at least 2 measurements and no missing values for baseline characteristics were included  . The median follow-up was 9.0 (IQR 8.9–9.1) years. We used questionnaire data, data derived by a clinician from medical records, and radiographical data  or a chi-square test . To depict the timing of arthroplasties, a Kaplan–Meier curve was estimated.Descriptive statistics of the episodes of deterioration were reported, e.g., proportion of patients with deterioration of pain/function among those with and without arthroplasty. Differences between groups were evaluated with logistic regression adjusted for time to follow-up.In addition we fitted linear mixed-effects models with a random slope and random intercept per patient to the reported levels of pain and function. The random-effects part describes the time course of pain and function for each patient and takes into account the within-subject correlation of different measurements. Within these models we adjusted for age, sex, BMI, maximal K&L, number of painful joints, and comorbidities at baseline. As such we could estimate the adjusted course of pain and function for each patient separately. Pain and function are not assumed to be constant between successive measurements, so that direct inclusion in a time-dependent Cox model may produce biased results. Therefore, we included the estimated courses of pain from the linear mixed-effect model (each point in time can be estimated with this model) as a time-dependent covariate in the Cox model. The latter was done by joint modelling the longitudinal and survival data with the JM package (1.4-2) (R version 3.2.3) ). This foundation did not play a role in the study’s design, conduct, or reporting. The authors have no conflicts of interest to declare.Supplementary data). Of the 84 arthroplasties, 67 were implanted in the first 5 years . Mean WOMAC scores before arthroplasty were respectively 43.5 (SD 20.6) for function and 45.2 (19.2) for pain.Of the 868 included patients, 84 received TKA (n = 29) or THA (n = 55) during 9 years of follow-up. Patients receiving an arthroplasty were somewhat older at baseline, had higher K&L scores, and worse WOMAC scores compared with patients without arthroplasty . None ofThere was no difference in the percentage of patients that showed at least 1 period of deterioration of pain between patients who did or did not receive TKA/THA during follow-up: 56/85 patients versus 531/784. 13 of these 56 TKA/THA patients showed further deterioration of pain in the year thereafter against 88 of the 531 patients without arthroplasty.Similar results were found for function; at least 1 period of deterioration of function before arthroplasty was found in 56 of 84 TKA/THA patients and in 540 of 784 patients without arthroplasty. This deterioration was followed by further deterioration in the following year in 14 of these 56 the patients receiving arthroplasty during follow-up and in 118 of the 540 patients who did not.Hence, there are episodes of deterioration of pain/function in patients both with and without arthroplasty. However, patients without a prosthesis had more time to develop deterioration than patients who received an arthroplasty . When corrected for follow-up duration, arthroplasty patients had higher odds on a first deterioration in pain (odds ratio 3.2 [95%CI 1.4–7.2]) and function (odds ratio 2.3 [CI 1.1–5.0]) than patients without arthroplasty.Individual pain and function trajectories are depicted in The estimates from the joint model showed that higher levels on WOMAC score of pain and function significantly increased the hazard of receiving THA/TKA (1.08 [CI 1.06–1.10] for pain and 1.07 [CI 1.05–1.08] for function) .Supplementary data), nor did the slope itself increase the risk of receiving THA/TKA. The wide 95% CIs show that the model could not properly estimate the effect of the slope. Hence, long-term changes in pain or function over time did not affect the risk of receiving THA/TKA, when adjusted for other covariates and the level of pain/function.Adjusting for maximal K&L during follow-up did not change our results (data not shown). When investigating the effect of the long-term changes of pain and function over time by adding the slope of the initial mixed models, the effect estimates of pain and function levels on receiving THA/TKA did not change . However, this method would complicate our analysis and the interpretation of our results. Furthermore, adjusting for the maximal K&L most likely reflects the maximum effect of adjustment.In summary, pain and function levels rather than long-term pain and function changes over time (which can be seen as the progression rate) are associated with timing of THA/TKA in early OA patients.supplementary data in the online version of this article, http://dx.doi.org/Tables 2 and 5, and


Periodontal therapy usually requires local anesthesia. If effective, a non-invasive, liposomal anesthetic gel could increase the levels of acceptance of patients in relation to periodontal therapy.This study investigated the efficacy of liposomal anesthetic gel for pain control during periodontal therapy.®), or a liposomal lidocaine/prilocaine, which were applied to different sextants. Pain frequency was registered during treatment and the volunteers received a digital counter to register any painful or uncomfortable experiences. At the end of each session, the volunteers indicated their pain intensity using rating scales (NRS-101 and VRS-4). The volunteers had their hemodynamic parameters measured by a non-invasive digital monitor.Forty volunteers with moderate to severe chronic periodontitis were recruited, of which at least three sextants required periodontal therapy. At least one of the selected teeth had one site with a probing depth of ≥4 mm. The volunteers received the following three gels: a placebo, lidocaine/prilocaine (OraqixPain frequency/intensity did not show statistical difference between intervention groups. The tested gels did not interfere with the hemodynamic indices. Dental anxiety, suppuration and probing depth could influence pain during periodontal therapy.Our results suggest limited indications for the use of non-invasive anesthesia when used for scaling and root planing. Intra-pocket anesthetic gel could be a good option for anxious patients, or those who have a fear of needles. Severe periodontitis is the sixth most prevalent condition worldwide, affecting 11% of the global population (743 million people aged 15-99 worldwide). It has remained static on a global scale during the last two decades. The age-standardized incidence of the disease did not change from 1990-2010 . These prevalence and incidence rates were similar for males and females, and increased with age, with a steep increase among individuals aged from 30 to 40 years old, remaining stable thereafter.,,Periodontal therapy usually involves supra and/or subgingival scaling and root planing (SRP),–,,,,The usual technique to control pain and discomfort during SRP is applying local anesthetic injections (nerve block or infiltration anesthesia).,® (25 mg/g lidocaine and 25 mg/g prilocaine) was developed with the addition of a thermosetting agent.,,,,,––New anesthetic formulations have been developed to improve treatment conditions and ameliorate the patients' level of acceptance of dental procedures.® (positive control) gel, and a placebo gel (negative control). Our primary outcome was the frequency/intensity of pain, obtained by using a digital counter to register any painful experience; a numerical rating scale (NRS-101) and a verbal rating scale (VRS-4) were used. The secondary outcomes were hemodynamic parameters . The null hypothesis was that there would be no difference between intervention groups (placebo and anesthetic gels) in relation to pain control during scaling and root planing.The aim of this study was to compare the effects of a liposomal, lidocaine/prilocaine, thermosetting anesthetic gel for pain control during scaling and root planing  compared to OraqixA flowchart of the overall study design is shown in http://www.gpower.hhu.de).Sample size calculation was based on pain intensity (primary outcome) using visual analogue scale (VAS) data that was previously published in a study which reported the effects of intra-pocket lidocaine and prilocaine gel (2.5% each) in SRP.® and Liposomal), using a computer program . The random allocation sequence was printed and sealed in envelopes with the volunteer's number on the outside. This procedure was performed and monitored by one researcher (FAS).Block randomization was used to allocate three sextants of each volunteer in relation to the interventions  were required for them to be included in this study.The exclusion criteria were: individuals undergoing periodontal maintenance; any allergic reaction to amide anesthetic; consumption of any analgesic or anti-inflammatory drugs in the 12 hours prior to treatment; individuals with a history of alcoholism; smokers; pregnant or lactating women; individuals with any non-controlled systemic disorder such as cardiac, neurological, kidney, liver, hematological or psychological alterations; individuals with presence of ulcerative lesions, abscesses or acute infections; individuals with the need for dental extraction in the selected sextants; individuals with dentin hypersensitivity; and individuals with endodontic treatment or any other alteration that could compromise the measurement of data.®, Rio de Janeiro, RJ, Brazil). The volunteers were also asked to complete Corah's Dental Anxiety Scale (DAS) before the first treatment session.The data regarding probing depth, width of keratinized mucosa, bleeding on probing (presence or absence), dental plaque (presence or absence) and suppuration (presence or absence) were obtained at baseline. Measurements were performed using a standardized UNC periodontal probe , which served as positive control, a liposomal lidocaine/prilocaine thermosetting gel (granulated lecithin (6.6 g); isopropyl palmitate (7.6 mL); sorbic acid or benzoic acid (0.12 g); poloxamer 407 (6.78 g); poloxamer 188 (2.40 g); potassium sorbate or sodium benzoate (0.1 g); purified water (30 mL on the first day/10 mL on the second day); ethanol (2.5 mL); hydrochloric acid (0.1 mL); lidocaine (25 mg/g) and prilocaine (25 mg/g)). The large multilamellar liposomes were obtained by the thin film hydration method. Subsequently, lecithin and isopropyl palmitate were dissolved in chloroform. The lipid mixture was then deposited as a thin film into a round-bottomed flask using a rotary evaporator after full removal of the chloroform under vacuuming at 40°C in a temperature-controlled water bath for a period of 2 hours to ensure the absence of solvent residue. The films were suspended in 20 mmol/L HEPES buffer , and multilamellar vesicles were obtained after vortexing at room temperature . Large multilamellar vesicles were prepared by extruding (20 cycles) these vesicles within 400 nm-membrane filters at 25°C using an extruder device . The loaded liposomes containing lidocaine base (2.5%) and prilocaine base (2.5%) were prepared by adding these anesthetics directly to the previously obtained liposomes after extrusion at the final concentration of 5%. The loaded liposomes formed appear as concentric and non-concentric multilamellar vesicles by TEM with 327.5±17.5 nm and PDI of 0.21±0.08 by dynamic light scattering. The mean encapsulation efficiency was 54.9±15.2% by HPLC/DAD. The unloaded and loaded formulations were stable at 4°C for 3 months. The thermosetting gel was prepared using the poloxamer solutions (407 and 188). These polymers were dispersed in purified water via manual stirring. The solutions were then stored in a refrigerator at 4°C for at least 12 h to ensure complete solvation. Liposomal anesthetics were then added to the gel with manual stirring until a homogeneous dispersion was obtained. The placebo gel had the same composition as the liposomal gel, but without the anesthetic bases, and served as negative control. All the selected volunteers received the gels on different teeth, from different sextants, using a cross-over design and with one-week intervals between each appointment to avoid cross-over contamination (spill-over effect).®, Golgran, Rio de Janeiro, RJ, Brazil). The volunteers could ask for rescue anesthesia  if they were still feeling pain after two applications of gel.Three different gels were used in this study: a lidocaine/prilocaine thermosetting gel , and discomfort using a four-point verbal rating scale (VRS-4) . If rescue anesthesia was required, the pain and discomfort scores were obtained before it was administered. The volunteers were also asked to rate how unpleasant the taste of the anesthetic agent was .® Monitor Multiparamétrico, Instramed Indústria Médico Hospitalar Ltda, Porto Alegre, RS, Brazil).During the treatments, the volunteers had their hemodynamic parameters  measured by a non-invasive digital monitor . The mean number of teeth, dental plaque, bleeding on probing, suppuration, probing depth and width of keratinized mucosa were analyzed by the Kruskal-Wallis test .The clinical parameters, such as distribution of sextants, probing depth  and keratinized mucosa (≤2 mm or >2 mm), were compared using the chi-square test  and the various risk factorsThe hemodynamic parameters  were analyzed at baseline, during and after treatment by repeated measures ANOVA and the paired t-test.2 tests, according to the type and distribution of the variables.The data obtained via trans-operative and post-operative scaling and root planing in the three intervention groups, such as volume of anesthetic gel applied, number of applications, need for additional (rescue) anesthesia, time required for periodontal therapy (per sextant), difficulties during treatment, post-operative discomfort due to treatment and the volunteers' perceptions of the gel's flavor were analyzed by the ANOVA, Kruskal-Wallis and χ® SPSS® 21.0 Statistics, IBM Corp., Armonk, NY, USA).The tests were considered statistically significant when p<0.05  for liposomal gel. No statistically significant differences were found between intervention groups (p>0.05). The mean ±SD (95% CI) values for NRS-101 were 31.6±31.9 (21.1 – 42.1) for the placebo; 20.5±23.5 (12.8 – 28.2) for Oraqix®; and 25.0±29.6 (15.3 – 34.7) for liposomal gel. The number of volunteers reporting no pain  using the NRS-101 scale was two (5%) for the placebo; six (16%) for Oraqix®; and eight (21%) for liposomal gel. Using the VRS-4 scale, no pain was observed in 18 (47%), 26 (68%) and 25 (66%) volunteers for those who underwent SRP with the placebo, Oraqix®, and liposomal gel, respectively. No statistical differences were found between intervention groups (p<0.05).The sextants, number of teeth, and clinical parameters  are shown in The multilevel regression analysis  showed s2) was checked at baseline and after treatment. The results suggest that this type of intra-pocket anesthetic gel for periodontal SRP did not interfere with the hemodynamic indices.The results showed that the volume of gel applied, the number of applications, the need for additional (rescue) anesthesia, the time required to perform SRP during each session, the difficulties during periodontal treatment, and the discomfort caused by periodontal therapy were similar between the groups, as were the volunteers' perceptions of the gel's flavor, with no statistically significant differences between intervention groups .,,,,,,,,,The results of this study did not show statistically significant differences between intervention groups regarding pain and discomfort; therefore, the null hypothesis was accepted. Nevertheless, a recent systematic review concluded that topical anesthesia is superior to a placebo during probing and SRP because it reduces the risk and intensity of pain, as well as the need for rescue anesthesia.® group; in contrast, suppuration sites were present in 14% of the placebo group and 11% of the liposomal gel group. Suppuration was associated with higher pain frequency/intensity (NRS-101) during scaling and root planning . With regard to the issue of probing depth, it was associated with a higher level of pain intensity (NRS-101 and VRS-4); our results can be compared with those of other studies,,Our study had a cross-over design: all 38 volunteers were submitted to SRP using the three different gels (placebo and anesthetic) in different sextants. Sextant distribution and number of teeth per sextant were equivalent between intervention groups. The volunteers included in the study had similar periodontal parameters between sextants, including dental plaque, bleeding on probing, probing depth and width of the keratinized mucosa. Conversely, we found statistical differences regarding the percentage of suppuration. No suppuration sites were observed in the Oraqix–,The association of local anesthetics with liposomal formulations increases the duration of anesthesia, decreases central nervous and cardiac toxicity, and decreases circulating plasma levels.,® was below the threshold levels for toxic effect.This study is the first to evaluate hemodynamic parameters  and anxiety during SRP using non-invasive anesthesia. No statistically significant differences were found between groups, suggesting that lidocaine/prilocaine intra-pocket anesthetic gels do not interfere with these parameters. Anxiety and fear can have a pain-increasing effect, creating an intentional bias towards the painful stimuli or pain-related sensation. Anxiety-induced somatic changes may occur from the activation of the hypothalamus-pituitary-adrenal axis, the main result being increased secretion of cortisol. Endogenous or exogenous epinephrine may cause or contribute to hemodynamic and cardiac changes.,,–,,,Some authors have reported that the use of split-mouth and cross-over designs significantly increased efficiency in statistical testing;,,–,,,,,In our study, pain and discomfort were assessed during/after SRP using pain frequency and two pain-rating scales: a numerical rating scale (NRS-101) and a four-point verbal rating scale (VRS-4). Pain frequency provides similar results in comparison to the pain scale.In conclusion, we did not find differences between intervention groups in relation to pain frequency/intensity (primary outcome). The use of intra-pocket anesthetic gel for periodontal SRP did not interfere with the hemodynamic parameters (secondary outcome). Our results suggest limited indications for the use of non-invasive periodontal anesthesia: firstly, because periodontal procedures usually cause low or moderate pain, and secondly, because patients sometimes prefer not to receive local anesthesia. Nevertheless, some patients may experience severe pain during non-surgical periodontal therapy, and conventional local anesthesia is often necessary. The use of an intra-pocket anesthetic gel could be a good option for maintenance patients, anxious patients, or those who have a fear of needles. This is the first study to evaluate liposomal, thermosetting anesthetic gel during SRP. Consequently, further studies should be performed to verify its application in dental practice.


Intermaxillary fixation (IMF) is a classic method for immobilization of the mandible after mandibular fractures and corrective surgery. However, it has been suggested that IMF may be a risk for developing temporomandibular joint (TMJ)-related symptoms, especially when applied for longer periods.To evaluate the clinical function of TMJs and masticatory muscles 10-15 years after mandibular setback surgery and subsequent six weeks of IMF. The patients' self-reported TMJ and masticatory muscle symptoms were also addressed.Thirty-six patients (24 women and 12 men) treated with intraoral vertical ramus osteotomies and subsequent six weeks of IMF, underwent a clinical examination of TMJs and masticatory muscles 10-15 years after surgery and completed a five-item structured questionnaire reporting subjective TMJ-related symptoms. Mean age by the time of clinical examination was 34.1 years (range 27.2–59.8 years). The clinical outcome was registered according to the Helkimo clinical dysfunction index. Descriptive and bivariate statistics were performed and level of significance was set to 5%.Mean maximum unassisted mouth opening 10-15 years after surgery was 50.1 mm, , statistically significantly greater in men compared to women (p=0.004). Mean Helkimo dysfunction group was 1.5 . Eighty-one percent experienced pain on palpation in either the masseter muscle, temporal muscle or both, and 31% experienced pain when moving the mandible in one or more directions. Thirty-one percent reported pain from palpating the TMJs. In the questionnaire, none reported to have pain during chewing or mouth opening on a weekly or daily basis, but 22% reported difficulties with maximum opening of the mouth.Ten to fifteen years after mandibular setback surgery the patient's mandibular range of movement is good. Despite clinically recognizable symptoms, few patients reported having TMJ- or masticatory muscle-related symptoms in their daily life. Intermaxillary fixation (IMF) is a classic method for immobilization of the jaws and is widely used for fracture fixation, and also to some extent after orthognathic surgery. Advancement in osteosynthesis techniques has reduced the need for IMF, allowing for immediate function after treatment. On the other hand, osteosynthesis has the risk of complications such as infections and mental nerve injury.The aim of this study was to evaluate the clinical function of the temporomandibular joint and masticatory muscles 10-15 years after mandibular setback surgery and subsequent six weeks of IMF. The patients' self-reported symptoms from the TMJs and masticatory muscles were also addressed.The participants in this study were previous patients with genuine mandibular prognathism operated with intraoral vertical ramus osteotomy and subsequent IMF for six weeks from January 1998 to December 2002. Patients who had additional maxillary surgery or genioplasty were not included. The treatment was planned and coordinated by a regional orthognathic surgery team. The surgeries were performed at a university hospital. Pre- and post-surgical orthodontic treatment had been performed in all patients.The patients were contacted by mail and invited to attend a 10-15 years follow-up examination during the year 2012. Out of the 84 patients operated with the IVRO procedure from January 1998 to December 2002, thirty-seven patients (44%) agreed to participate in the study. Thirty-nine patients (46.6%) did not reply to the invitation, six patients (7.1%) were busy during the time the data collection took place, and two patients (2.4%) did not want to participate. One of the 37 participants was excluded due to a history of mandibular fracture during the follow-up period. The final study group consisted of thirty-six patients . Their mean age at the follow-up examination was 34.1 years (range 27.2–59.8 years) . The meaiI). Clinical dysfunction group 2 (dysfunction score 5-9 points) includes patients with moderate dysfunction which further represent the clinical dysfunction index 2 (DiII). Patients with severe dysfunction are those with a dysfunction score of 10-25 points, corresponding to the clinical dysfunction groups 3-5 and the clinical dysfunction index 3 (DiIII).The long-term follow-up consultation included examination of the masticatory muscles and TMJs according to the Helkimo clinical dysfunction index.Prior to the long-term follow-up examination, the patients completed a structured questionnaire. The questionnaire included five questions concerning pain and symptoms from the TMJs and masticatory muscles: pain during chewing/mouth opening, joint sounds such as crepitation and/or clicking, restricted mouth opening, and jaw fatigue. One of the participants did not return the questionnaire.t-test, and the Kruskal-Wallis test was used for the Helkimo dysfunction score. Fisher's exact tests were used to test for differences between genders for dichotomized variables. Level of significance was set to 5%. The statistics application software STATA/IC 14.1  was used for the analyses.Descriptive statistics were used to report age and gender distribution among the participants, as well as to report the clinical results and the responses to the questionnaires. Distribution of the continuous variables were tested with the Shapiro-Wilk test. Differences between genders for the measurements on jaw mobility were analyzed with the two-sample The results from the clinical examination 10-15 years after surgery are listed according to the Helkimo index (A-F):p=0.004). Mean maximum lateral movement to the right was 10.2 mm . Mean maximum lateral movement to the left was 10.1 mm . Female patients had significantly greater mean maximum lateral movement to the left compared to male patients (p=0.02). Mean maximum protrusion was 8.1 mm  , and statistically significantly wider in men compared to women ( SE 0.3) .Eighty-one percent of the patients had a straight opening and closing path, while the remaining 19% had lateral deviation during opening or closing of the mouth. Clicking in the joint, either uni- or bilaterally, was registered in 33% of the patients .All patients experienced pain on palpation of one or more masticatory muscles, either uni- or bilaterally. Seventy-two percent of the patients had 1-3 muscles that were painful upon palpation, while 28% of the patients felt pain on palpation in four or more palpated muscles . Only muThirty-one percent of the patients reported pain on palpation of the TMJ either uni- or bilaterally. Twenty-eight percent of patients experienced pain on palpation on the lateral aspect of the condyle, while one patient reported pain when the condylar head was palpated in the posterior area via the auditory canal .The majority of patients (69.4%) reported no pain on any movement of the mandible. Ten patients (27.8%) experienced pain on maximum opening of the mouth, and four patients (11.1%) reported pain during lateral movements or protrusion .The mean Helkimo dysfunction score was 4.0  .Mean clinical dysfunction group was 1.47 . Ninety-four percent of the patients were diagnosed as being in dysfunction group one or two. None of the patients had a clinical dysfunction score representing the two most severe dysfunction groups (group 4 or 5) .i0. Most of the patients were placed in the dysfunction index DiI (21 patients) or DiII (13 patients). Only 2 patients fulfilled the requirements of DiIII  have a multifactorial etiology, and limited knowledge exists on IMF-induced long term TMJ symptoms. Dervis, et al.The mean Helkimo dysfunction group in our study was 1.5, which is between mild and moderate dysfunction. A significant contributing factor to this result was muscle pain during direct palpation of the masticatory muscles. All of our patients reported pain upon palpation of the lateral pterygoid muscles. According to Türp, et al.iIII) according to the Helkimo index.A cross-sectional study on the prevalence of mandibular dysfunction in a randomly selected adult Swedish population in the year 2003 found that 4% had severe dysfunction (D,,Even though several studies have shown that maximum mouth opening is reduced after orthognathic surgery,Almost one third of the patients reported pain during movement of the mandible in one or more direction at the clinical examination. However, the 34.3% of the patients who reported on the questionnaire to have pain during chewing or mouth opening reported that the pain occurred rarely. None of the patients reported pain during chewing or mouth opening on a daily or weekly basis, hence pain during jaw movements does not seem to be a problem for patients 10-15 years after surgery.In conclusion, the results of this study show that 10-15 years after mandibular setback surgery and subsequent six weeks of IMF the patients' mandibular range of movement is good. Despite clinically recognizable symptoms, few patients reported to have TMJ- or masticatory muscle-related symptoms in their daily life.


This multicenter randomized clinical trial compares oral ketamine with placebo for treating neuropathic pain in patients with cancer. Patients had previously been treated with adjuvant analgesics for neuropathic pain, which had been ineffective or suboptimal. Preexisting analgesia was continued throughout the trial. Patients were centrally randomized using minimization, then ketamine or placebo was titrated across 2 weeks to an effective and tolerable dosage . The staThe primary end point was duration of analgesic benefit, defined as an improvement of 5 points or more in the index pain score (using the Sensory Component of the Short Form McGill Pain Questionnaire), compared with the baseline score during the 16 days of receiving a stable dosage of ketamine or placebo. Patients in whom titration failed were considered to have a duration of 0 days. Maintenance of analgesic benefit was considered to have failed in patients whose opioid dosage increased during this time. Secondary end points included mean and worst pain; mood ; mean change in global distress in the last 24 hours ; quality of life ; and serious adverse events .P values are 2-tailed, and P < .05 was statistically significant. Statistical analyses were performed using SPSS version 22.0 for Windows (IBM).An intention-to-treat approach was used, with a sample size of 107 patients per arm providing 80% or greater power to detect an improvement in the duration of analgesic benefit while receiving ketamine corresponding to a 20% increase in patients in whom analgesic benefit was maintained at 16 days . To compare duration of analgesic benefit, we used Cox proportional hazards regression with a confirmatory log-rank test. Secondary end points were analyzed using parametric and nonparametric methods. Quality of life data were analyzed by calculating the mean of the area under the curve over the time in the study after adjusting for the baseline value. All P = .75), supported by the log-rank test (P = .69). The median duration of analgesic benefit was 0 days  for ketamine and 0 days  for placebo. To illustrate, 34 of 107 patients (31.8%) receiving ketamine vs 39 of 107 (36.4%) receiving placebo maintained analgesic benefit at day 4 of the stable dosage . Corresponding figures at day 16 were 24 of 107 patients (22.4%) receiving ketamine and 27of 107 (25.2%) receiving placebo . There were no differences between arms among the secondary outcomes  were randomized, with comparable demographic features between arms . A varieoutcomes .There were 18 serious adverse events: 8 in patients receiving ketamine and 10 in patients receiving placebo. Common adverse events were cognitive disturbance, dizziness, fatigue, nausea, and somnolence.4 by examining ketamine in cancer-related neuropathic pain. There may be subgroups of patients for whom ketamine is helpful, such as those with central sensitization. A limitation of the present study was that we did not specifically select patients with clinical evidence of central sensitization, for whom it is reasonable to hypothesize a more specific analgesic target for ketamine. Future studies that examine ketamine in chronic neuropathic pain should focus on patients with central sensitization, which can be established by a bedside test. This approach would be congruent with preclinical knowledge and would address an important remaining unanswered question.5This trial reports that ketamine was equivalent to placebo for cancer-related neuropathic pain. Findings enhance previous work


Phacoemulsification under local anesthesia is regarded as the major surgery for cataract treatment. Recent research has compared the pain perception between the first eye and the second eye during phacoemulsification. However, these studies have also yielded controversial findings. Consequently, we performed a systematic review and a meta-analysis to investigate the difference in the pain perception between the first and second eyes during phacoemulsification.  We searched the PubMed, EMBASE, and Cochrane CENTRAL databases for the studies published up to October 5, 2018. Prospective observational studies were included. The meta-analysis was conducted by means of random-effects model and fixed-effects model according to the heterogeneity. Evaluation of the methodological quality of studies was based on Newcastle-Ottawa Scale (NOS). P < 0.00001). The average pain scores of the first eye shortly after surgery under the topical anesthesia were also lower than those of the second eye . Conversely, anxiety scores in the first eye surgery were significantly higher than those in the second eye surgery . However, the difference of the pain scores accessed on the first postoperative day between the first and second eye surgeries  as well as cooperation grades of patients between the first and second eye surgeries  was not statistically significant.  Overall, eight studies were included in the meta-analysis. The analysis of pooled data showed that the pain scores of the first eye shortly after surgery under local anesthesia were significantly lower as compared to the second eye (WMD: 0.69; 95% CI: 0.40, 0.98;  Patients experienced more pain in the surgery of the second eye than that of the first eye, which probably related to lower anxiety before the second surgery. It suggests that we should consider preoperative intervention to reduce the perceived pain during second eye cataract surgery. Phacoemulsification with implantation of a foldable intraocular lens is a common methodology applicable in the cataract surgery as a relatively safe procedure for patients. The method can be delivered in a comfortable surgical atmosphere and induce a relatively low stress level to patients under local anesthesia.However, phacoemulsification with local anesthesia, including topical anesthesia, intracameral anesthesia, and sub-Tenon's anesthesia, among others, is not a completely pain-free procedure. Pain level is possible and differs in various stages of phacoemulsification. Additionally, most of the pain experienced during an uneventful surgery was reported when the anterior chamber was extended by irrigation , 2. In tAs far as we know, there is no meta-analysis dealing with this topic. Therefore, we carried out a systematic review and a meta-analysis to examine whether the second eye was more painful during the uneventful phacoemulsification under local anesthesia, and to determine risk factors that influence pain perception. In a case where the result has a statistical difference, surgeons can pay more attention to the patients' perception before or during the second cataract surgery to lower the risk of the complication. Such an intervention can also help to improve clinical performances and reduce health costs.We searched the database of PubMed, EMBASE, and Cochrane to obtain eligible studies published up to October 5, 2018. Taking PubMed research as an example, following groups of keywords or medical terms were used: “Phacoemulsification” OR “Phacoemulsifications” OR “Cataract Surgery” OR “Phaco Surgery”) AND  AND  between the first and the second eyes. Last, the time of accessing the pain was the day of the surgery or the first postoperative day. In the meantime, the exclusion criteria were as follows: We excluded the trials that have not assessed pain scores or that the data were not available.The information provided herein was obtained from the selected studies, in which the following aspects were taken into consideration: every study's first author, publication year, study location, mean age of patients, measurement of outcome for pain and anxiety, scores of pain and anxiety, total numbers of surgery eyes, numbers of first and second eyes, and blind method, among others. In cases of disagreements on the items, a consensus was developed through the discussion among the research groups.κ) of 98%; the differences were alleviated by use of a third investigator. Evaluation of the methodological quality of eligible comparative studies was undertaken based on Newcastle-Ottawa Scale (NOS) [Two independent investigators carried out the reviews of study titles as well as abstracts, focused on retrieving studies that meet the inclusion criteria for the full-text evaluation. Subsequently, we conducted analyses of the trials for comprehensive analysis as well as data extraction with an agreement value (le (NOS) .I2 was regarded as the evaluation of heterogeneity among studies [I2 amounted to more than 50%, we utilized the random-effects model. Otherwise, we applied the use of the fixed-effects model. We estimated the mean deviation (MD) and standard deviation (SD) from the median, range, and the size of a sample which had been estimated by the ascertained calculation methodology [We used Review Manager 5.3  to carry out statistical analysis. For continuous measurements, we used the weighted mean difference (WMD) and standard mean difference (SMD) with 95% confidence interval (CI) as the effect estimate. Moreover,  studies , followehodology . We furtThe progress of the systematic studies search has been displayed in The selected eight studies were published between 2008 and 2018 –6, 11–14P < 0.00001; I2 = 80%). The pain value was lower in patients who underwent the first eye surgery. As demonstrated excluding one study at a time, the heterogeneity is still kept at high level and overall effect showed no obvious change. Therefore, we concluded that no single study markedly affected the overall pooled prevalence estimate. Sensitivity analysis showed the consistent result  by dropping the study with quality score less than 7, which suggested the robust outcome.The meta-analysis of seven studies of comparing the pain scores assessed shortly following the phacoemulsification under the local anesthesia showed that there were statistical differences in pain values between the first and the second eyes  compared with the high heterogeneity of the comparison under the local anesthesia, which may explain the source of heterogeneity. Because the rest of three studies used different anesthesia, they could not be included into one subgroup. Sensitivity analysis also showed the consistent result  by dropping the study with quality score less than 7.We also carried out an analysis of the pain scores only under the topical anesthesia as one of the subgroups. Four of seven studies were included, which also showed a difference . Three studies compared the anxiety values between the first and the second eye surgeries . The anxiety value was lower in patients who underwent the second eye surgery. Analyses of the cooperation values of the patients graded by surgeons were also carried out and showed no difference between the first and second eyes .In two studies, pooled data of pain scores on the first postoperative day did not show a significant difference  by the Egger test.Furthermore, an assessment of the publication bias was conducted for the outcome of pain score on the day of surgery under the local anesthesia and then presented as a funnel plot . No evidOur meta-analysis showed that there was a significant difference in pain perception assessed shortly after phacoemulsification between the first and the second eye surgery, which meant that the patients felt more pain during the second eye surgery. The meta-analysis of the two studies confirmed that there was a substantial decline in anxiety values in the second eye surgery. This was likely to relate more with pain in the second eye, even if the results of three studies showed no variations in cooperation of the patients. What's more, on the first postoperative day, the meta-analysis of two studies showed that pain perception had no statistical difference between the first and second eyes.Phacoemulsification is commonly accepted as one of the best surgeries for the treatment of cataract with the benefits of small incision, minimal induced astigmatism, as well as early visual rehabilitation . The topAs reported by the first study conducted by Sharma et al., no substantial difference was observed between the first and the second eyes . SubsequThe result of present meta-analysis shows that patients have more pain in the second surgery, which is explained by the assumption that patients who have successfully undergone the first eye surgery are likely to have less anxiety and expect lower pain perception for the second eye surgery. However, few studies support the fact that less anxiety is likely to induce the analgesia rather than hyperalgesia . As suchIn the recent past, one trial on patients undergoing laser-assisted in situ keratomi (LASIK) revealed that they experience more pain during the second eye surgery . ConsideThere were numbers of hypotheses considered to explain more pain in the second eye surgery. At first, the patients that had successfully undergone the first eye surgery were more probable to feel less anxiety while paying more attention to the pain perception during the second eye surgery , 14. SecIn consideration of the factors that had an association with pain during the surgery, Tan et al. showed that female patients tended to feel more pain during cataract surgery . As wellIn our meta-analysis, we encountered some limitations. Firstly, some studies did not use blind assessment in the methodology or bilateral eyes from an individual person were not available. Moreover, the interval time between two surgeries for some studies was not clearly stated. However, those problems did not strongly influence the overall effect of meta-analysis in pain because the results were quite consistent by sensitivity analysis of dropping the study with low quality. Secondly, the pain scores on the first postoperative day as well as the anxiety scores were only obtained from two studies that were likely to suggest the low reliability of the outcome. Therefore, further investigations are needed. Thirdly, the search strategy impacted on the number of included studies, since the search language was constrained only to English, possibly contributing to languages bias. However, we made use of specific analysis methodology to screen the studies and extract data with the consensus of discussion groups, in addition to assessing the maximum likely information in the studies. These approaches were effective in minimizing the likelihood of bias, thereby contributing to achieving reliable outcomes.Summarily, our findings have clearly shown that patients perceived more pain in the second eye surgery than in the first, which is likely to be associated with various anxiety values between the first and second eye surgeries. Still, there is need for further studies to figure out the reasons for second eye surgery during phacoemulsification being more painful, so that we can take the preoperative administration to reduce the perceived pain during second eye cataract surgery.


There is a paucity of research on the association between psychological factors and persistent shoulder pain. The aim of this study was to investigate whether emotional distress was associated with pain intensity and self-reported disability after physiotherapy treatment in patients with shoulder pain.Data from 145 patients treated at physiotherapy outpatient clinics aged ≥18 years with self-reported pain in the shoulder or arm, and movement activity problems related to the upper-extremity, were included. Outcome measures were pain intensity measured by Numeric Pain Rating Scale and disability measured by Patient Specific Functional Scale. Demographic and clinical characteristics, including emotional distress measured by Hopkins Symptom Checklist – 25, were obtained at study onset. Association between characteristics at study onset and pain and disability after physiotherapy treatment were analysed using multiple linear regression and a backward manual elimination method. The final models were adjusted for age and sex.P = 0.001). Emotional distress was not associated with self-reported disability after the physiotherapy treatment.Higher emotional distress at study onset  was associated with higher pain intensity after the physiotherapy treatment  contains supplementary material, which is available to authorized users. Shoulder pain is a common disorder in the general population, with a point prevalence ranging from 6.9 to 26%, and a lifetime prevalence from 6.7 to 66.7% . In manyA systematic review of prognostic factors in patients with acute and subacute non-traumatic shoulder pain found strong evidence that high scores on the Shoulder Pain and Disability Index (SPADI), more shoulder pain, and a longer duration of complaints were associated with persistent shoulder pain . ModeratA recent cohort study, which included a range of biopsychosocial factors, found that psychological factors were consistently associated with the outcome of physiotherapy for patients with shoulder pain . The psyThis study was a prospective cohort study of consecutive patients treated at two student clinics located at the Department of Physiotherapy at OsloMet – Oslo Metropolitan University in Norway between September 2013 and September 2016. Patients receiving physiotherapy at the two clinics answered questionnaires for the FysioPol database. The FysioPol database contains pre- and post-treatment information about the patients treated at the student clinics, and was established in order to measure the quality of treatment and facilitate research at the department . The datThe patients were treated by physiotherapy students in their second or third study year, under supervision of a teacher. The treatment period was intended to be up to nine weeks. The treatment consisted of individualised exercise therapy. In addition, some of the patients reported that they had received information, advice and manual techniques such as massage and stretching.Patients aged 18 years or older with self-reported pain in the shoulder or arm were included. We excluded patients who did not report any movement activity problems related to the upper-extremity in the Patient Specific Functional Scale (PSFS) . PatientThe study protocol was considered by the Regional Committee for Medical and Health Research Ethics in Norway (REC), which concluded that the study did not require ethical approval. The study was approved by the Norwegian Centre for Research Data (NSD). All patients had signed a written, informed consent form.The primary outcome in this study was the Numeric Pain Rating Scale (NPRS) . The NPRThe set of variables considered as potential prognostic factors was obtained by the FysioPol-questionnaire package at study onset, including clinical characteristics identified with prognostic value in previous research, and demographic factors. The Hopkins Symptom Checklist-25 (HSCL-25)  was usedDescriptive data are presented as number of patients and percentages, means and standard deviations or medians and interquartile range. Paired t-tests were used to identify changes from pre- to post- treatment measures of pain intensity and self-reported disability. Characteristics of the individuals who were lost to follow-up were compared to pre-treatment characteristics of the study sample. The groups were compared on pain intensity, disability, emotional distress and age using independent t-tests, and sex using a Chi-square test.P < 0.20) [P-value, one by one. The elimination was repeated until the remaining variables in the models were all statistically significant at the 5% level (P < 0.05). To prevent elimination of a variable at one step in the analysis process being crucial, the variables removed on backward elimination were all re-entered in the models one by one, and remained in the models if they were statistically significant at the 5% level. The multiple regression models were adjusted for age and sex.Simple linear regression analyses were performed to examine the relationship between each of the potential prognostic factors and the outcome (the NPRS and the PSFS). The variables with a statistically significant relationship with the outcome at the 20% level ( < 0.20)  were conAssumptions for the regression models were assessed. Correlation analyses were performed for all the independent variables and the correlation had to be less than 0.7 between the variables to be entered in the models . An extrSPSS version 24 was used for all of the statistical analyses.P > 0.05) . The patients had a statistically significant improvement in pain intensity from pre- to post-treatment (P < 0.001) of 2.0 (SD 1.9) points. The patients had also a statistically significant improvement in self-reported disability (P < 0.001) of 1.7 (SD 2.7) points. The average post-treatment pain intensity was 2.9 (SD 2.1) (n=140) and the post-treatment self-reported disability was 6.2 (SD 2.6) (n=133).The median length of the treatment period was 5 weeks (IQR 3 to 6)  are presented in Table This study showed that higher emotional distress at study onset, in combination with higher pre-treatment pain intensity and duration of pain for 4 to 12 months in comparison to 0 to 3 months, was associated with a poor outcome in terms of pain intensity after physiotherapy in patients with shoulder pain. Emotional distress was not associated with self-reported disability.In a recent systematic review of prognostic factors for shoulder pain, strong evidence was found that high scores on the SPADI questionnaire, more shoulder pain, and a longer duration of complaints, were associated with persistent shoulder pain . In contEmotional distress was investigated in two previous studies on shoulder pain, which found no association with outcome , 17. OneFurthermore, the present findings are not consistent with those in a previous study on patients presenting new episodes of shoulder- or low back pain to their general practitioner . InteresNevertheless, a recent cohort study from the UK reported that other psychological factors than distress, such as patient expectations of recovery and pain self-efficacy, were associated with the level of pain and disability after physiotherapy in patients with shoulder pain . AlthougOur data showed no association between emotional distress at study onset and self-reported disability after treatment. The factors associated with higher post-treatment disability were higher pre-treatment disability, duration of pain for more than 12 months in comparison to 0 to 3 months, concomitant neck pain and a lower level of education. The results indicate that patients with a history of chronic shoulder pain and disability may have a poor outcome in terms of disability regardless of emotional distress.Our findings that emotional distress was associated with pain, but not with disability, are difficult to explain. One explanation might be that mental functions are more directly associated with the experience of pain, than with disability. However, a cross-sectional study on people with chronic shoulder pain found that psychological distress was correlated with disability, but not with pain , which iThis study has some limitations that should be considered. Firstly, since the inclusion of patients was based on self-reported shoulder- or arm pain, we were not able to discriminate between localised shoulder pain and pain related to the shoulder, arm and hand. Secondly, a number of patients who met the inclusion criteria were excluded from the analyses due to loss to follow-up or missing values in some of the variables. However, the patients lost to follow-up did not differ from the study sample on characteristics such as sex, age, pain intensity, disability or emotional distress at study onset. A third concern involves the duration of treatment. There was a variety in duration of treatment, with a median of 5 weeks of physiotherapy (IQR 3 to 6). A period of 12 weeks of physiotherapy is often suggested for patients with shoulder pain . Future The results of this study showed that emotional distress at study onset was associated with the intensity of shoulder pain after physiotherapy. Psychological factors in general are little emphasised in the examination of shoulder pain, and it is rather the structural and biomechanical aspects of the condition that are usually considered in clinical decision-making. The findings of this study support, however, that emotional distress should be considered in the initial physiotherapy examination of shoulder pain.Emotional distress may be a cause or a consequence of shoulder pain, and whether the treatment should be directed towards reducing distress is not possible to tell based on the present findings. Nevertheless, findings of a meta-analysis on neck and back pain indicate that psychological distress mediates the relationship between pain and disability . Future This study found that higher emotional distress, in combination with higher pain intensity and duration of pain for 4 to 12 months in comparison to 0 to 3 months, was associated with a poor outcome in terms of shoulder pain intensity after physiotherapy, but not with disability. The present findings indicate that emotional distress should be included in the initial physiotherapy examination of shoulder pain.Additional file 1:Table S1. Characteristics of the group lost to follow-up compared to the study sample. (DOCX 15 kb)


The use of interdisciplinary patient-centered care (PCC) and empathetic behaviour seems to be a promising avenue to address chronic pain management, but their use in this context seems to be suboptimal. Several patient factors can influence the use of PCC and empathy, but little is known about the impact of pain visibility on these behaviours. The objective of this study was to investigate the influence of visible physical signs on caregiver's patient-centered and empathetic behaviours in chronic pain context.  A convenience sample of 21 nurses and 21 physicians participated in a descriptive study. PCC and empathy were evaluated from self-assessment and observer's assessment using a video of real patients with chronic pain. p < 0.001). Participants who show a greater difference in their patient-centered behaviour according to pain visibility have less clinical experience.  The results show that caregivers have demonstrated an intraindividual variability: PCC and empathetic behaviours of the participants were significantly higher for patients who have visible signs of pain  than for those who have no visible signs  ( The pain visibility in chronic pain patients is an important factor contributing to an increased use of PCC and empathy by nurses and physicians, and clinical experience can influence their behaviours. Thus, pain invisibility can be a barrier to quality of care, and these findings reinforce the relevance to educating caregivers to these unconscious biases on their behaviour toward chronic pain patients. Chronic pain is a common public global health problem, associated with significant disability and many social consequences . ChronicThere are many definitions of PCC in the context of nursing and medicine, but four dimensions are common to most cited definitions: patient-as-person, biopsychosocial perspective, sharing power and responsibility, and therapeutic alliance –10. The In addition, many researchers suggest that empathy is necessary for the use of PCC , 14, 15.Although many studies support the benefits of PCC, its use iPatient factors may also influence caregivers' empathy. Indeed, both behavioral and functional neuroimaging measures have demonstrated that some stigma or prejudice could modulate empathy . Since mVarious methods have been used for measuring the use of PCC and empathy, such as self-rating and observer rating , 23, 29.Thus, the main objective of this study was to investigate the influence of the presence of visible physical signs on patient-centered and empathetic behaviours of nurses and physicians using videos of real patients suffering from chronic pain. In view of the limited knowledge on the topic, we also sought to identify, in an exploratory fashion, the characteristics of the caregivers who respond differently to the presence or absence of visible signs of pain.This study is part of a larger study which investigated PCC and empathy in chronic pain management . A descrd = 0.5) between visible and invisible pain conditions with a power of 85% and a type-1 error of 5%. Participants did not know the detailed purpose of the study to avoid social desirability bias, but they were informed that pain management was investigated.All participants gave their written, informed consent, and a coding system was used to keep the data confidential. To take part in the study, the participants need to (i) be active members of the Quebec Board of Nurses or the Quebec College of Physicians, (ii) have chronic pain patients in their routine practice, and (iii) speak French. After signing the informed consent, a sample of 21 nurses and 21 physicians took part in the study. A minimum of 38 participants was needed to detect a moderate difference  . This ser = 0.40), internal consistency , test-retest reliability (test-retest reliability coefficient = 0.65), and construct validity [The self-rated empathy was measured with the French version of the Jefferson Scale of Physician Empathy (F-JSPE) . This self-administrated questionnaire comprises 20 items divided into 4 dimensions: (i) adopting the patient's perspective, (ii) understanding the patient's experiences, feelings, and signals, (iii) ignoring the patient's perspective, and (iv) adopting the patient's way of thinking. The F-JSPE also includes a single item measuring the value placed on empathy. Participants respond to items on a 7-Likert scale. The total score, ranging from not empathic (a score of 20) to empathic (score of 140), can be calculated with the addition of all the items. The original version of the JSPE has good criterion-related validity with the Empathic Concern Scale of the Interpersonal Reactivity Index  . This inAn adapted French version of Reynolds Empathy Scale (F-RES) has been used for the assessment of empathetic behaviour by a trained observer . The F-Rn=42 participants), three external observers watched the recorded interviews of each participant (4 interviews/participant). The group of observers consisted of a resident in psychiatry, a nurse, and a PhD student in the healthcare field. The observers were selected based on their experience in the healthcare field (more than five years) and their complementary expertise . To ensure the standardization in their assessment, they had previously been trained by the research team to complete the observation scale. They evaluated the PCC and empathetic behaviour demonstrated by participants for each video using the SOS-PCC and the F-RES. All study participants watched four videos of real patients with chronic pain and were subsequently interviewed individually. These 4-minute videos showed female patients aged between 16 and 45 years-old, with different pathologies in which chronic pain was experienced , Ehlers–Danlos syndrome, and fibromyalgia). A more detailed description of the development and content of these videos is available elsewhere . In thesn=42) according to the presence or absence of visible physical signs in the patients presented in the videos, paired T-tests were used on the mean score of the three observers.Statistical analyzes were performed using the software SPSS version 18.0. To describe continuous variables, mean (standard deviation) was used, whereas frequency (percentage) was used for nominal and categorical variables. To compare patient-centered and empathetic behaviour of the participants  and the majority was women (69%). Twenty-one (50%) of the participants were nurses, and 21 (50%) were physicians. Our sample was composed of nurses working in different settings, general practitioners, and medical specialists . The nurses and physicians had an average of 19.74 years of clinical experience. In this group, participants self-reported a mean overall orientation for PPC of 4.82. More specifically, the mean was 4.49 for the sharing subscale and 5.16 for the caring subscale. The participants self-reported a mean of 116.53 for empathy. These results suggest moderate levels of PCC and empathy when participants assess themselves. For the observer's assessment with observation scales, the results are presented for each video. For observed PCC, the mean for the 4 videos was 25.94, and for observed empathy, the mean was 20.70. The sample included 42 native French-speaking caregivers ranging from 27 to 67 years (p < 0.001) (p=0.03). For empathetic behaviour, the difference is not statistically significant (p=0.23)  interviews in response to the videos presenting patients with visible physical signs (rheumatoid arthritis and CRPS) and (ii) interviews in response to the videos presenting patients without visible physical signs . Regarding the observed patient-centered and empathetic behaviours, the mean for SOS-PCC and F-RES was calculated for both groups. The results support that patient-centered and empathetic behaviour was significantly higher for the group of patients with visible physical signs (< 0.001) . The gro(p=0.23) .The results suggest that our sample of caregivers have moderate levels of self-reported PCC and empathy. In comparison with other studies, nurses and physicians who have participated in our study used more PCC than other groups of nurses and physicians with similar sociodemographic characteristics , 39. ForThe main purpose of this descriptive study was to investigate the influence of the presence or absence of visible physical signs on caregiver behaviours and attitudes in chronic pain management. PCC and empathy were assessed from two perspectives, using a combination of self-administrated questionnaires and observation scales using innovative videos of real patients with chronic pain. Our results show that nurses and physicians show intraindividual variability. Indeed, we found that PCC and empathetic behaviour of nurses and physicians vary according to the presence or absence of visible physical signs in patients with chronic pain.Interestingly, another research team have demonstrated that residents in internal medicine have displayed more patient-centered behaviour when they consider that the patient has a more severe health condition and more visible physical symptoms . In the It has been shown that physicians tend to rely on their initial assessment of the pain of their patients with chronic pain even when this initial assessment underestimates the pain subsequently reported verbally by the patients . Thus, ip > 0.05). It is also possible that the most experienced caregivers are more aware of the impact of pain visibility, and they consider this potential bias in their interventions.Interestingly, we found that the clinical experience can influence the behaviours of nurses and physicians. Indeed, caregivers with more years of experience are less likely to change their behaviour were according to the presence or absence of physical visible signs. Many studies have investigated the influence of clinical experience on PCC and empathy , 45, butOne potential limitation of our study is the lack of a real interaction between participants and patients in the videos. As a result of its methodological advantages and low cost, we used standardized videos of real chronic pain patients. However, the observation scales used for the assessment of PCC and empathetic behaviours were adapted for this kind of situation. Another potential limitation is the reactivity bias. It is possible that participants have positively modified their answers regarding the treatment plan that they would provide in reality. However, many efforts have been made to mitigate this potential bias. First, the participants did not know the variables under study at the time of data collection. Secondly, the questionnaires were distributed at the end of the experimental session in order to avoid a modification in behaviour, conscious or not, from participants.In the last years, several studies have shown that practice orientation and empathy of professional caregivers could be influenced by many patients' factors , 45, 46,


The aim of the present study was to evaluate percutaneous tibial nerve stimulation (PTNS) for treatment resistant chronic anal fissure.Consecutive patients with chronic anal fissure were treated with neuromodulation via the posterior tibial nerve between October 2013 and January 2014. Patients had PTNS for 30 min on 10 consecutive days. All patients had failed conventional medical treatment. The visual analogue scale (VAS) score, St. Marks score, Wexner’s constipation score, Brief Pain Inventory (BPI-SF), bleeding and mucosal healing were evaluated before treatment, at termination, after 3 months, and then yearly for 3 years.p = 0.010) and pain relief improved from 50% at completion to 90% at 3 years. The patients’ Wexner constipation scores improved significantly (p = 0.007).Ten patients  were identified but only 9 were evaluated as one patient’s fissure healed before PTNS was started. At 3-year follow-up, fissures had remained completely healed in 5 out of 9 patients. All patients stopped bleeding and were almost completely pain-free at 3 years (VAS In this small series, PTNS enhanced healing of chronic anal fissure and reduced pain and bleeding with an associated improvement in bowel function. Chronic anal fissure (CAF) is a non-healing tear distal to the dentate line that has persisted for more than 6 weeks and characterised by pain and bleeding in and after defecation. The underlying pathophysiology is thought to be ischaemia exacerbated by spasm of the internal anal sphincter muscle (IAS) –3 and a Lateral internal sphincterotomy (LIS) has in most countries been the gold standard treatment for CAF for many years. So far no non-invasive treatment has been able to show healing rates equivalent to LIS, the major drawback of the latter being the risk of permanent incontinence , 2, 10. No prior studies present data regarding the long-term results and recurrence rate after PTNS for CAF. Thus, we aimed to investigate the reproducibility of CAF healing with PTNS (primary endpoint) and the effects on pain, bleeding and bowel function with a follow-up of 3 years (secondary endpoints).®  on an outpatient basis. A stimulator provides electrical current with a fixed pulse frequency of 20 Hz, pulse width 200 µs and current setting between 0.5 and 9 mA (amplitude). A surface electrode was placed at the medial arch of the midfoot and a needle electrode was inserted through the skin posterior to the medial malleolus and advanced towards the posterior tibial nerve. Stimulation was gradually increased until a tingling sensation was perceived in the foot, or a motor flexor response was observed at the hallux. All patients received the treatment for 30 min 5 days a week, for 2 consecutive weeks. The fissure was evaluated before and after the last treatment session, as well as at 3 months and 1 year . These evaluations were performed by one of two surgical specialists. The fissure was characterised as not healed, partially healed when the healing process was visible but not totally complete, and healed when no sign of the fissure was visible. At 2 and 3 years, all patients were contacted by phone, and those who had symptoms which made it impossible to rule out recurrence or persistence of CAF attended for a clinical examination.Patients presenting with CAF between October 2013 and January 2014 were treated with PTNS at our tertiary referral centre. The sample size was based on the number of units in a similar study , and thep value < 0.05 was considered statistically significant.The clinical outcome, i.e. none healed, partially or totally healed fissure, was analysed in relation to the VAS, mean St. Marks score and sum of the Wexner constipation scores. The Wilcoxon signed ranks test was used to analyse statistical significance. All analyses were performed with SPSS version 22 . A p = 0.010). Subjective pain relief improved after topical treatment and bowel regulation via stool softeners by 40% before PTNS treatment. After treatment, this increased to 50%. At 1 year, pain relief was significantly increased to 95% (p = 0.046) and 90% at 3 years (p = 0.046). The median St. Marks incontinence score was unchanged at 1 year. The median Wexner constipation score was significantly reduced  at 1-year follow-up . However, 1 patient’s CAF had healed with conservative treatment before PTNS was started and was excluded from the analysis. Complete healing of CAF was observed in 9 out of 9 patients (100%) at 3-year follow-up; however, only 5 of these patients (55.5%) had healed after the 10 PTNS sessions alone. Of the remaining 4, 1 needed a total of 20 sessions and 3 patients presented with recurrent symptoms. One was treated with botulinum toxin injection 6 months after PTNS, 1 got a top-up PTNS followed by SNS within 6 months, and 1 patient was found to have an underlying fistula which was laid open 2 years after treatment with PTNS. All these patients were completely healed at 3 years. Only 1 patient had recurrent bleeding symptoms and investigation showed the source to be other than fissure disease. All 9 patients were almost completely pain-free at 3-year follow-up .Moya et al. treated 6 patients with CAF that had failed all other treatments including LIS, with PTNS. Fissure healing was observed initially in all 6 patients but in 3 cases fissure recurred after 6 months . Ruiz-ToIn this study, subjective pain relief increased from 40% at start of PTNS (following conservative treatment) to 50% at the end of treatment with PTNS and to 95% at 1 year. Other studies using ES have also reported a decrease in wound-related pain , 26. TheAt the 3-month follow-up, 4 patients still had anal bleeding, emanating from partially healed but much less painful CAF. At 1- and 2-year follow-up, no patients reported any anal bleeding. At 3 years, 1 patient reported anal bleeding, but at examination with rigid sigmoidoscopy was found to be bleeding from haemorrhoids and not have a CAF.p = 0.007) at 1-year follow-up. This improvement in bowel function suggests that PTNS like SNS probably has an effect on colonic and anorectal motor function.Changes in bowel movements are most often associated with the onset of CAF, so before treatment all patients received stool softeners and or high-fibre intake to optimise stool consistency and frequency. The median value of the Wexner constipation score was significantly reduced from 7.5 to 3.0 (This study has limitations, primarily the small sample size and lack of a control group. Also it is difficult to draw more than association between treatment and relief of symptoms in such as small group using a technique with an unclear mechanism of action on CAF. We have not measured anal pressure or blood flow, which have been the two parameters most associated with CAF and healing. PTNS also requires specialist apparatus and skills, and so may not be generalisable as a treatment for CAF.PTNS may show early promise as a minimally invasive treatment for CAF, promoting long-term healing and a low rate of recurrence. The healing rate of approximately 56% 3 years following PTNS treatment alone indicates that PTNS may be used to reduce the number of patients needing surgery.