The aim of this study was to evaluate patient pain during and after MicroPulse Transscleral Laser Therapy (TLT) and vision-related quality of life using two different anesthesia protocols: “Topical Plus” anesthesia without standby anesthesia (study group), and analgosedation with standby anesthesia (control group).  A retrospective, comparative chart review was conducted to evaluate patient pain between the two groups based on an analog pain scale at baseline and postoperatively . Furthermore, vision-related quality of life at baseline was compared at 1 month postoperatively. p=0.003; mild pain); however, no difference was found at any later time point compared to baseline. The vision-related quality of life was similar in both groups and was not negatively impacted by the MicroPulse TLT at 1 month after the treatment. Discussion/Conclusion. The Topical Plus anesthesia protocol provides adequate pain control for the patient to remain comfortable during and post-MicroPulse TLT treatment, with no changes in vision-related quality of life. Although the sample size was small and, thus, the results cannot be generalized, this case series showed that it is possible to perform MicroPulse TLT under topical anesthesia. Four eyes underwent MicroPulse TLT under Topical Plus anesthesia and 4 eyes underwent analgosedation. The mean age at the time of the MicroPulse TLT was 78.3 ± 6.4 years. In the study group, the reported pain level increased significantly immediately after the treatment (from 0.5 to 2.8,  Glaucoma is one of the leading causes of irreversible blindness worldwide. Lowering intraocular pressure (IOP) is the only evidence-based treatment for glaucoma –4. TopicBesides penetrating, filtration surgery, and MIGS procedures, MicroPulse Transscleral Laser Therapy (MicroPulse TLT) is another option to treat glaucoma. It is a nonincisional laser procedure facilitated with an 810 nm infrared diode laser . The laser energy is applied transsclerally using the MicroPulse P3® Probe . The MicroPulse P3 is a handheld fiberoptic probe that the surgeon sweeps back and forth along the limbus in the superior and inferior hemisphere of the globe which enables laser energy delivery at a predetermined distance from the limbus. The area around the three- and nine-o'clock positions is spared to prevent damage to the long ciliary nerves. MicroPulse TLT can be used in various types and stages of glaucoma . The curPatients can expect effective anesthesia for sufficient pain control during the MicroPulse TLT procedure. In addition, sufficient pain control enables precise and correct execution of the sweeping motion by the surgeon. The following options for anesthesia for MicroPulse TLT have been discussed traditionally with patients: (1) subconjunctival anesthesia, (2) subtenon's anesthesia, or (3) a retrobulbar block. Conjunctival bleedings should be avoided due to possible laser energy absorption at the used wavelength, that is, 810 nm; otherwise, limited efficacy by minimizing laser transmission and absorption of the target tissue can result. Hence, the prior administration of a topical vasoconstrictor  should be considered. In addition, (4) analgosedation  can be offered for MicroPulse TLT. Analgosedation allows for excellent pain control and puts the patient to sleep for a few minutes, sufficient time for the MicroPulse TLT procedure. Furthermore, (5) general anesthesia is an option as well. Analgosedation eliminates the need for a retrobulbar block. For blocks, analgosedation, and general anesthesia, monitored anesthesia care is mandatory, while topical anesthesia including “Topical Plus” can be considered to be performed without monitored anesthesia care.We recently introduced the “Topical Plus” anesthesia protocol for MicroPulse TLT procedures. It combines topical anesthesia drops and Lidocaine 2%  nonalcoholic gel. “Topical Plus” anesthesia or analgosedation for MicroPulse TLT are routinely offered at the University Hospital Zurich.In our clinical experience using the “Topical Plus” regimen, we have observed that patients complain of minimal discomfort and pain during and after the MicroPulse TLT treatment and usually require minimal to no oral pain medication in the first 24 hours postoperatively. The pain level during the treatment did not increase to the point that the MicroPulse TLT treatment had to be discontinued due to pain. In fact, many patients were relieved having the option to choose “Topical Plus” anesthesia as an alternative to analgosedation, as medical conditions in some patients pose an increased risk for unexpected incidents during analgosedation.With the “Topical Plus” anesthesia protocol, MicroPulse TLT can be performed with or without standby anesthesia. It can be performed in the operating room, a minor procedure room, or in an ophthalmological examination room.Topical anesthesia with lidocaine gel is an established form of anesthesia for cataract surgery with proven pain control , 16. MosThe aim of this study was to evaluate pain during and after MicroPulse TLT and visual quality of life under the “Topical Plus” anesthesia protocol without standby anesthesia compared to analgosedation with standby anesthesia. We hypothesize that the “Topical Plus” protocol is sufficient to control pain during and after MicroPulse TLT.This is a retrospective, comparative chart review of patients with open-angle glaucoma treated with MicroPulse TLT at the University Hospital Zurich (USZ), Zurich, Switzerland, between September and October 2021. Data from previous months have not been included, as surgeons changed their treatment protocol for performing MicroPulse TLT; to achieve better success rates, sweep velocity was reduced from 10 seconds per hemisphere to 20 seconds per hemisphere –19. PrioPatients included in the study had open-angle glaucoma and underwent MicroPulse TLT between 09/01/2021 and 10/31/2021. Patients were excluded from the study if they did not provide their written study-specific consent.Topical unpreserved tetracaine 1%  eye drops were applied 1 to 3 times to provide more comfort during insertion of an eye speculum.An eye speculum was inserted.Lidocaine 2% gel was applied multiple times over 5 minutes on the eye surface to ensure full coverage of the surface by the gel during the entire 5 minutes. The speculum could be lifted slightly up to give better access for the Xylocaine gel to the fornices including the subtarsal conjunctiva.The speculum was removed.The MicroPulse TLT treatment was performed.All procedures were performed by one glaucoma specialist (MTH). Patients had either “Topical Plus” anesthesia (study group) or analgosedation (control group) as described below. The “Topical Plus” protocol was as follows:Analgosedation was performed by the in-house anesthesia team under monitored anesthesia. First, an intravenous bolus of 50 mg fentanyl was administered followed by a bolus of thiopental sodium 0.5 g/20 ml two to three minutes later, which was adjusted to the patient's weight and renal function. Both forms of anesthesia were explained and offered to all patients.MicroPulse TLT was delivered in a standardized fashion using 2′500 mW of power at a duty cycle of 31.3% with 60 seconds in the superior and 60 seconds in the inferior hemisphere, with each hemisphere receiving three 20-second sweeps. Two-percent Lidocaine gel (study group) or 2% methylcellulose  (control group) was used as a coupling agent. The footplate of the MicroPulse P3 probe was placed at the limbus with its “bunny ears” oriented toward the central cornea, which positioned the fiberoptic over the pars plana. Slight pressure of the revised MicroPulse P3 probe during the sweeping motion along the limbus ensured contact with the globe. Care was taken to avoid the three- and the nine-o'clock meridians as to not damage the long ciliary nerves, areas of scleral thinning, and sites of filtering blebs or glaucoma drainage devices. After the laser was applied, a fixed-combination ointment of tobramycin 3 mg/ml plus dexamethasone 1 mg/ml  was applied to the eye. The eye was left unpatched.The day after the procedure, patients were started on topical fixed-combination tobramycin 3 mg/ml plus dexamethasone 1 mg/ml  eye drops 5x/d for two weeks. The medical treatment was adapted from the standard of care treatment after cataract surgery. If cells or flare were still detected after two weeks, the drops were tapered over two additional weeks. Patients were directed to continue with their preoperative antiglaucoma medication regimen unless instructed otherwise. Medical hypotensive treatment was adjusted for each patient on every visit at the surgeon's discretion.Data were collected from the patients' medical records, including demographics, that is, age at surgery, diagnosis, gender, spherical equivalent, and mean defect on perimetry. Intraocular pressure (IOP), number of glaucoma medications, and best-corrected visual acuity (BCVA) were collected preoperatively and at 1 day, 1 week, and 1 month postoperatively. In addition, medical records were checked for adverse events at the postoperative time points. The pain level was recorded from medical records preoperatively, immediately after the treatment, and at 1 hour, 6 hours, 1 day, 1 week, and 1 month postoperatively. Pain was routinely recorded using a numeric rating pain scale from zero (no pain) to ten (unbearable pain) . The numt-test for equality of means (continuous variables) and chi-square test . A P value of <0.05 was considered to be statistically significant.Microsoft Excel for Macintosh Version 16.56 was used for data management, and IBM SPSS Statistics for Windows , Armonk, NY, USA) version 26 was used for statistical analysis. Descriptive statistics were reported as mean ± SD for continuous variables and as absolute values and percentage for categorical variables. Preoperative and postoperative data and differences between the study and control group were compared using Student's Eight eyes, four in the control group and four in the study group, were included in the study. The mean age at the time of the MicroPulse TLT was 78.3 ± 6.4 years. There was no difference between both study groups in regard to diagnosis, gender, eye, age at treatment, BCVA, IOP, number of meds, spherical equivalent, mean defect of static perimetry, pain level, or vision-related quality of life see . No adveP). Both groups reported mild or no pain, respectively. The reported pain level increased slightly but statistically significant in the study group immediately after the treatment . However, no difference was found at any later time point compared to baseline  and at one month 120.5 ± 8.5 and 124.5 ± 18.2, respectively. The change between baseline and one month was not statistically significant .The vision-related quality of life was similar in both groups and was not negatively impacted by MicroPulse TLT at 1 month after the treatment see . At baseThere was no statistically significant difference in regard to BCVA, IOP, or glaucoma medications between groups or within each group, not at baseline see  and not p=0.024). Thus, the results support sufficient pain control under the proposed “Topical Plus” anesthesia protocol. The pain levels at later time points  are very consistent with preoperative values. This is confirming the reliability of the used pain scale.The MicroPulse TLT procedures in the “Topical Plus” group in this study were performed as monitored anesthesia care. Historically, our Cyclo G6 Laser is located in the operating theater with standby anesthesia available for all glaucoma cases. This concept enables us even with MAC to provide all patients with immediate intravenous fentanyl for pain control, in case any form of topical anesthesia is not sufficiently controlling for pain. Although, there was a mild significant increase in the pain level of the study group compared to baseline, and compared to the analgosedation group, no patient in the study group requested fentanyl. The increase in pain level in the study group was only mild. A pain score equal to or smaller than 5 is considered to be mild . Furthermore, the increase in pain level in the study group was of short duration only; no increased pain level compared to baseline was reported at 1 hour or at any later time point in the “Topical Plus” group. The MicroPulse TLT treatment could be conducted sufficiently in all cases independently of the anesthesia protocol used. The pain level at baseline was statistically higher in the study group than the control group  and early to moderate glaucomatous visual defects in static perimetry. Although sample size was small and follow-up was only 1 month, MicroPulse TLT did not negatively impact VA and affirms the results from previous studies, which found no negative impact by MicroPulse TLT on VA in eyes with good central vision see  22, 23], 2322, 2No change in IOP or reduction in glaucoma medications was achieved, nor expected, due to the short follow-up period and because eyes were postoperatively treated with topical steroids for 2 to 4 weeks see . IOP decIn the literature, most often the use of subtenon's anesthesia, peribulbar, or retrobulbar blocks has been reported , 23–48. Prolonged or persistent mydriasis after MicroPulse TLT has been described . It is uThe limitation of this study is the retrospective design and the small sample size. The study was intended as a first proof-of-concept. However, the very similar results of pain control in both study groups, that is, “Topical Plus” vs. analgosedation, confirm our personal impression that the “Topical Plus” protocol enables adequate anesthesia for MicroPulse TLT. Another limitation is that one study arm is awake during the MicroPulse TLT while the other arm is not. Hence, there is potential confounding bias of the reported pain level immediately after the laser procedure by the experienced pain level during the laser procedure in the Topical Plus study arm. This bias is impossible to avoid. It is also not possible to record pain levels during the procedure in the analgosedation arm. Different coupling agents have been used in the two study arms, that is, lidocaine gel vs. methylcellulose. As anesthesia with 2% lidocaine gel was to be investigated in the study group and compared to analgosedation, 2% methylcellulose was not additionally applied to the eyes in the study group given that the surface of these eyes was already well covered with 2% lidocaine gel throughout the entire laser procedure. There is evidence for the importance of a coupling agent; however, there is no proof that the physical and chemical compound properties of different coupling agents  have a clinically significant divergent effect of laser conduction and efficacy . DiffereAs a next step, a study with a larger sample size, ideally prospective and randomized, comparing different forms of anesthesia  with the proposed “Topical Plus” protocol is desired. The analog pain scale at different time points  and the evaluation of patient comfort  should be incorporated in the randomized controlled trial. Because we found an increase in pain level immediately after the procedure in the study arm but not at 1 h or later, ideally pain levels should be monitored more closely in the immediate period after the procedure, for example additionally at 15, 30, and 45 minutes after the procedure. The study population consisted exclusively of Caucasians from Switzerland. Thus, it is unknown if the results are generalizable to a multiethnical population outside of Switzerland. A follow-up study should ideally include patients of various ethnicities and should include eyes with different levels of conjunctival pigmentation as the level of pigmentation could potentially influence pain sensation by transscleral laser treatment. Some authors reported higher odds of prolonged inflammation in heavily pigmented eyes by transscleral laser treatment . This coThe favorable pain control with the “Topical Plus” anesthesia protocol enables MicroPulse TLT to be delivered with sufficient pain control for the patient to remain comfortable during and post-treatment. The “Topical Plus” protocol does not require monitored anesthesia care; hence, no standby anesthesia team is necessary. Thus, MicroPulse TLT can be performed independently from an inpatient or outpatient surgical center. This was an initial proof-of-concept study only with a very limited number of patients. Thus, the results must be judged carefully, and it is unknown whether they can be generalized. However, a sufficient pain control with topical anesthesia only would enable glaucoma specialists to perform MicroPulse TLT safely in an office setting. The advantage for the patient would be a more comfortable treatment than a procedure in a surgical setting which often results in increased anxiety levels. The positive results of the proof-of-concept study encourage us to plan a prospective, randomized-controlled trial with a larger sample size. Ideally, the study should be conducted as a multicenter study to enroll patients of different ethnicities and ages.All study subjects gave written informed consent.


Additionally, a negative correlation between the TSK-11 and the educational background was shown. This study provided information about the relationship between foot function and pain with different levels of kinesiophobia in patients with RA. Additionally, the educational background of the patient was considered a predictor of whether or not a patient suffered from kinesiophobia.The main objective of the present study was to determine the relationship between kinesiophobia and pain , foot function, and disease activity in patients with rheumatoid arthritis (RA). A total of 124 interviews were carried out with participants with RA. Participants were recruited from the Hospital Universitario Virgen de las Nieves de Granada in Spain. Interviews took place in January 2021. Participants completed the following questionnaires during an appointment with their rheumatologist: Foot Function Index (FFI), Tampa Scale for Kinesiophobia (TSK-11), and the Visual Analogue Scale Pain foot (VAS Pain). Furthermore, the Simplified Disease Activity Index (SDAI) was used to measure disease activity. Of the 124 participants, 73% were women, and their mean age was 59.44 years (SD 11.26 years). In the statistical analysis, positive linear correlations ( Kinesiophobia is defined as the limitation of motor activity due to fear of movement. It was originally defined by Kori et al. in 1990, being considered as a weakening, destructive, and irrational fear of movement and activity based on the belief of being vulnerable and susceptible to injury .Patients with rheumatoid arthritis (RA) suffer from pain in their joints, especially the small joints of the hands and feet . RA causIn a high percentage of patients, even in the remission period of the disease, destruction of the joints has been observed. This leads to an alteration in joint alignment, instability, and a reduction in mobility . FurtherPrevious studies regarding kinesiophobia focus on the foot and ankle’s involvement, showing that people who present with ankle instability suffer from higher levels of kinesiophobia ,15. HoweThe main objective of the present study was to determine the relationship between kinesiophobia and pain , foot function, and disease activity.The study has been approved by the Investigacion Medica de la Universidad de Malaga ethical committee (CEUMA-91-2015-H) and the Portal de Etica de la Investigacion Biomedica de Andalucía (PEIBA) (ARC001) in accordance with the Declaration of Helsinki; all methods were performed in accordance with the relevant guidelines and regulations.This study was a cross-sectional study.Patients must have presented with foot pain and satisfy the 2010 RA classification criteria (approved by the American College of Rheumatology and the European League Against Rheumatism) . Participants were excluded if they presented with concomitant musculoskeletal disease, central or peripheral nervous system disease, endocrine disorders , or psychiatric disorders .Participants were recruited from the Hospital Universitario Virgen de las Nieves de Granada, Spain, from the rheumatology department. Participants were recruited from June 2021 to December 2021. They were provided with an information sheet and invited to participate in the study. The participants who agreed were interviewed and given further details about the study. All participants provided written informed consent to participate in the study.The following demographic information was collected: years of age, gender, educational background, treatment, and disease duration. The following scales were used to collect clinical information to assess the disease activity and influence of the disease: the Visual Analogue Scale (VAS)  for bothFinally, the Foot Function Index (FFI) was collected, which was developed to measure the impact of foot pathology on function in terms of pain, disability, and activity restriction. The FFI is a self-administered index consisting of 23 items divided into 3 sub-scales. Both total and sub-scale scores are produced. Higher FFI scores indicate poor foot health. Test–retest reliability of the FFI total and sub-scale scores ranged from 0.87 to 0.69. Internal consistency ranged from 0.96 to 0.73 .Two independent researchers interviewed the participants face to face. The interview took place in a hospital room, where the participants were also asked to complete the questionnaires described previously and some demographic questions. Additionally, the participants weight and height were assessed.The sample size was determined with EPIDAT 4.1, calculating an effect size of 0.61. This was calculated from a pilot study to evaluate the statistical power and used the TSK-11 as the primary variable. Finally, the pilot study involved a sample of 30 subjects. The study was designed to detect changes exceeding 0.8 (high effect size) for a variation in the sample according to the above classification, with a type I error of 0.05 and a type II error of 0.2. The result of sample size calculation was that at least 114 subjects were required, but 124 participants were included.p < 0.05. All the statistical analyses were assessed using SPSS software .The results obtained are reported as the mean and standard deviation (SD) due to the normal distribution of the sample. The normality of the distributions was examined by the Kolmogorov–Smirnov test. Pearson’s correlations were used for inter-item and item-total correlations in view of the normal distribution observed in most cases. Finally, a multivariable linear regression model was obtained to evaluate the predictors of kinesiophobia, according to the Spanish version of the TSK-11. In constructing the models, the regression assumptions of homoscedasticity, normality, and independence of the residuals and collinearity were tested. Homoscedasticity was evaluated by analyzing the distribution of predicted values and scatterplots of the residuals. Normality of the residuals was tested by analyzing histograms and by graphs of standardized residuals. Independence of the residuals was evaluated by the Durbin–Watson statistics. Finally, the presence of collinearity was tested by calculating the variance inflation factor, the tolerance, and partial correlations. The level of significance was established at In total, 147 participants were recruited, but five were not enrolled because they did not provide informed written consent. A total of 12 participants were excluded because they did not complete the questionnaires, and six participants declined to be enrolled in the study. Finally, 124 participants were included in the study and analyzed , and 91 patients (73.4%) were female. The mean age was 59.44 years (SD 11.26). The mean height and weight were 163.31 cm (SD 12.06) and 71.1 kg (SD 15.5), respectively, and the Body Mass Index (BMI) was 26.83 (SD 6.65) . The patThe results in pain (VAS-g) and disability (FFI) correlate with a higher level of kinesiophobia of 31.77 (7.77). Pain measured by the VAS-g was 5.88 (SD 3.18), and disability measured by the FFI was 40.56 (SD 29.23). However, an association was not shown between patients who are in remission of the disease and FFI. A total of 22.8% of the patients were in disease activity remission measured by the SDAI, 38.7% of them presented low levels of disease activity, 32.3% of them presented moderate levels of disease activity, and 6.5% of them presented high levels of disease activity .p < 0.001 and eta squared (η2) 0.197).The TSK-11 is highly correlated with pain levels, both general and foot pain (VAS-g 0.504 and VAS-f 0.421) . The resThere is a positive correlation except for the BMI, which means that high levels of kinesiophobia indicate high levels of foot pain and general pain: r of 0.421 ** and 0.504 **, respectively. However, there is no strong correlation between FFI and kinesiophobia, where high levels of kinesiophobia indicated low levels of FFI in all its domains. Finally, low BMI indicated high levels of kinesiophobia .According to the data for the TSK-11, the multivariable linear regression presented an R2 value of 34.1%. . Post-hoThe main objective of the present study was to determine the relationship between kinesiophobia and pain , foot function, and disease activity.Our findings show the relationship between foot function and pain with high levels of kinesiophobia in patients with RA. Patients showed a very high level of kinesiophobia (TSK-11 = 31.77) and both general pain and specific foot pain. Furthermore, patients presented low foot function (FFI = 39.72), meaning that there is an association between the included outcomes. Previous studies agree with the present results, such as Kinikli et al., where pain and function were considered as predictive factors to suffer from kinesiophobia . AdditioThe previous studies analyzed pain in the upper limbs, as opposed to the present study, which analyzes both general and specific foot-related pain, which is one of the most affected areas in patients with RA. It has been shown in previous studies focused on RA that patients suffer from pain due to the disease and to structural deformities ,8, provoHowever, in the presented results, kinesiophobia was not directly related with disease activity. Our results were supported by a previous study by Kinikli et al., where a statistically significant relationship was not found between RA disease activity, analyzed with the DAS28, and physical activity levels. Additionally, it was concluded that physical activity levels were not predictive of kinesiophobia . The present study shows a significant and inverse relationship between the educational background of patients with RA and the level of kinesiophobia. Highly educated patients presented with a low level of kinesiophobia. This fact could be explained because highly educated patients were able to understand the provided information , such asAdditionally, unlike patients with a low level of education, highly educated patients have access to tools to help in their pain management, such as databases of scientific papers such as PubMed, where they can read about the most recent recommendations for their disease, improving their lives and their pain levels. Furthermore, social activities may have an influence as well . In the Patients with high levels of kinesiophobia present greater functional problems in the foot and lower extremities ,40. In tFinally, it is important to emphasize that kinesiophobia has been related to other outcomes such as quality of life ,42, disaThis research presents some limitations. First, it is a cross-sectional study, which means that researchers were not able to detect developments or changes in the characteristics of the participants. Additionally, a convenience sampling was recruited, which made an impact on the homogeneity of the gender of the patients. Regarding the outcomes that measure foot pain, the results could be altered and increased because the sample was composed of mainly women. For example, one external factor typical in women may be footwear choice, and even though such data were not collected in the present manuscript, previous studies have highlighted this issue ,47. FootThe strengths of this study include: the analysis of the relationship between general pain, foot pain, and foot function with kinesiophobia in patients with RA, which is a disease that requires a lot of resources from the healthcare system, including expensive treatments; it is a study that does not show a relationship between the disease activity and kinesiophobia, which agrees with previous studies that have been mentioned in the present discussion section. There is a relationship between pain, function, and kinesiophobia and also between limitation of physical activity and kinesiophobia. It may be hypothesized that patients with RA who increase their physical activity may suffer from higher levels of pain, but due to their level of disease activity and not their level of movement. It has been demonstrated that patients who suffer from musculoskeletal pain in general or foot pain in particular present high levels of kinesiophobia ,48. TherThere are some recommendations to guide future research, such as increasing the sample size to ensure homogeneity in terms of the following: the patients’ gender, the educational background of the patients, the techniques used to manage the pain, and the use of conservative treatments prescribed by healthcare professionals with the purpose of improving pain perception and kinesiophobia. Future research should also include the psychosocial and emotional perception of the patients to study their quality of life in the long term. In addition, this study could have collected the selected questionnaires as part of the rheumatology appointment, making the sample size more representative; information about targeted therapies such as foot orthoses or similar podiatric interventions could have also been collected to examine if there is a significant statistical relationship between kinesiophobia and patients who wear podiatric treatments or not.Disease activity, general VAS, foot VAS, FFI physical activity, Body Mass Index, and age are all related to the level of kinesiophobia in patients with RA.This study provided information regarding the relationship between poor foot function and high levels of foot pain with high levels of kinesiophobia in patients with RA. Additionally, a lower level of education was considered a predictor of kinesiophobia.


Post-cholecystectomy Mirizzi syndrome (PCMS) is characterized by symptoms of recurrent abdominal pain, jaundice, and fever in patients who underwent cholecystectomy. Imaging is crucial in the diagnosis of PCMS and Mirizzi syndrome. Imaging modalities have evolved over the years with abdominal ultrasonography, computed tomography of the abdomen, and magnetic resonance cholangiopancreatography being used in the diagnosis of PCMS and Mirizzi syndrome. The imaging findings show obstruction of the common hepatic duct due to impingement by a stone in the cystic duct or gallbladder infundibulum. PCMS management has evolved over the years with the current first-line management being endoscopic intervention. This case describes a 61-year-old male presenting with recurrent right upper quadrant pain two years after undergoing cholecystectomy due to cholelithiasis. The patient was later diagnosed with PCMS, and endoscopic management was performed with complete resolution of the symptoms. Post-cholecystectomy Mirizzi syndrome (PCMS) is a clinical entity characterized by extrinsic obstruction of the common hepatic duct due to stone impaction at the level of the cystic duct or gallbladder infundibulum in patients who underwent cholecystectomy . MirizziA 61-year-old male presented to the emergency department with right upper quadrant abdominal pain of nine months duration. Past history was significant for symptomatic cholelithiasis requiring cholecystectomy two years prior to presentation. Right upper quadrant pain was non-radiating, sharp, intermittent, progressive, rated as 6/10, with no clear exacerbating or alleviating factors, and with unclear relation to oral intake. The pain was associated with nausea, jaundice, dark urine, light-colored stools, and subjective fever.On examination, vital signs were significant for tachycardia (110 bpm) and a fever of 38.8 degrees celsius. The patient had scleral icterus without conjunctival pallor. Abdominal examination was significant for right upper quadrant tenderness without rebound tenderness or guarding.Laboratory workup revealed: elevated alanine aminotransferase of 325 U/L , elevated aspartate aminotransferase of 104 U/L , elevated alkaline phosphatase of 165 IU/L , elevated total bilirubin of 140 micromol/L , elevated white blood cell count of 13,000, and a normal hemoglobin 12.8 g/L. Procalcitonin was mildly elevated at 0.94 mcg/L  and C-reactive protein was elevated at 58 mg/L. The panel for acute hepatitis was unremarkable.Compared with his prior imaging, abdominal ultrasound demonstrated an increase in the size of the convoluted cystic structure at the gallbladder bed, compatible with an increased size of gallbladder remnant, without sonographic evidence of biliary stones. To further evaluate the biliary tree, a magnetic resonance cholangiopancreatography (MRCP) was performed, which revealed a calculus in a dilated cystic duct stump with compression of the common bile duct (CBD) and upstream biliary dilatation Figure .The patient was started on intravenous piperacillin/tazobactam due to the suspicion of acute ascending cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and an intraprocedural cholangiogram revealed a filling defect in a distally inserted long cystic duct stump, consistent with a retained stone, resulting in partial biliary obstruction Figure .Following biliary sphincterotomy, the common bile duct was swept with a 9-12 mm occlusion balloon, with moderate resistance encountered at the site of cystic duct insertion. No filling defects were noted in the CBD afterward and no stones were retrieved. The cystic duct was then selectively cannulated using an Autotome™  and swept with the occlusion balloon, resulting in the extraction of a single large biliary stone Figure .Subsequent balloon sweeps of the CBD from the level of the bifurcation encountered no resistance. The final occlusion cholangiogram revealed no residual filling defects in the entire biliary tree, including the cystic duct stump. Excellent drainage of bile and contrast was observed. The overall cholangiographic findings were consistent with PCMS. The patient’s symptoms resolved promptly thereafter, with no subsequent recurrence.The patient was seen in the outpatient clinic after six weeks with no recurrence of his symptoms. Liver biochemical tests revealed normalization of aspartate aminotransferase (20 U/L), alanine aminotransferase (29 U/L), and alkaline phosphatase (78 IU/L). Indirect hyperbilirubinemia was present. Therefore, a workup for hemolysis was pursued after which he was diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency. He was referred to the hematology clinic for further management.PCMS and Mirizzi syndrome are complications of cholelithiasis that ensue when a gallbladder stone gets lodged in Hartmann's pouch or the cystic duct, leading to extrinsic compression of the biliary system. Mirizzi syndrome can be complicated by a cholecystobiliary or cholecystoenteric fistula, gallbladder empyema, and gallbladder perforation with subsequent sepsis . ClassifPCMS has been reported in more than 65 cases in the literature . It is eTypically, patients with PCMS present with right upper quadrant pain, jaundice, nausea, and vomiting. Fever can occur in patients with concomitant acute cholangitis .PCMS and Mirizzi syndrome are similar diseases, with the primary difference being the history of cholecystectomy. Therefore, clinical presentation, diagnosis, and lab values are similar between the two entities. Clinically, the primary difference between the two entities is that Mirizzi syndrome can present with acute cholecystitis (approximately one-third of patients), which does not occur in PCMS .Laboratory evaluation of PCMS reveals elevations in alkaline phosphatase (ALP), gamma-glutamyl transferase, and direct hyperbilirubinemia in the majority of patients. In a review of 25 cases of PCMS, approximately 45% had elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with non-specific patterns. Of those, approximately 55% had moderate elevations in AST and ALT while the remainder had severe elevations in AST and ALT . Leukocytosis can occur in patients with accompanying acute cholangitis .The diagnosis requires the presence of imaging findings and can be done through abdominal ultrasonography, CT of the abdomen with contrast, or MRCP. Ultrasonographic findings include intrahepatic biliary dilation, impacted stone at the gallbladder neck, and sudden normalization of the common bile duct below the stone level . AbdominPhysicians dealing with cases suspicious for Mirizzi syndrome should consider gallbladder cancer and cholangiocarcinoma in the differential diagnosis. A retrospective study was done by Redaelli CA et al., which evaluated the incidence of gallbladder carcinoma in patients with Mirizzi syndrome. The study found that 27.8% of patients with Mirizzi syndrome were diagnosed incidentally with gallbladder carcinoma. The study also evaluated the incidence of gallbladder carcinoma in patients with cholelithiasis, which was found to be approximately 2%. The difference between the incidence of gallbladder carcinoma in patients with Mirizzi syndrome and patients with cholelithiasis but without Mirizzi syndrome was found to be statistically significant  . MoreoveThe standard treatment for Mirizzi syndrome is surgical intervention, namely, cholecystectomy. ERCP can be utilized as a temporizing measure in patients with cholangitis while awaiting definitive surgical intervention . As patiTreatment of PCMS has evolved from surgical intervention to ERCP, where selective cannulation of the biliary duct is followed by directing the wire/biliary catheter to the cystic duct. Once access to the cystic duct is achieved, extraction of the stone is carried out using a balloon, basket, mechanical lithotripsy, or electrohydraulic lithotripsy . In casePCMS is a rare entity that can be easily overlooked. Therefore, medical providers should have a low threshold to consider the diagnosis in patients presenting with abdominal pain and jaundice post cholecystectomy. In our case, the patient presented with symptoms of biliary obstruction two years following his cholecystectomy. Further imaging and endoscopic workup revealed evidence of PCMS. Clinical awareness about the condition, coupled with appropriate imaging studies, helps in confirming the diagnosis. Abdominal ultrasonography and MRCP were utilized successfully in our report. Prompt treatment can prevent severe complications such as cholecystodochal fistula formation, acute cholangitis, and severe sepsis. Our patient underwent endoscopic intervention with complete symptom resolution. Endoscopic management of PCMS is feasible and is preferred over surgical treatment.


This study aimed to identify predictive factors for risky discrepancies in the emergency department (ED) by analyzing patient recalls associated with resident-to-attending radiology report discrepancies (RRDs).p < 0.001), CT examination , digestive diseases , and late finalized report . Digestive diseases  were identified as the only significant predictor of adverse outcomes.This retrospective study analyzed 759 RRDs in computed tomography (CT) and magnetic resonance imaging and their outcomes from 2013 to 2021. After excluding 73 patients lost to follow-up, we included 686 records in the final analysis. Risky discrepancies were defined as RRDs resulting in (1) inpatient management  and (2) adverse outcomes . Predictors of risky discrepancies were assessed using multivariable logistic regression analysis. The overall RRD rate was 0.4% . Of 686 eligible patients, 21.4% (147 of 686) received inpatient management, and 6.0% (41 of 686) experienced adverse outcomes. RRDs with neurological diseases were associated with the highest ED revisit rate  but not with risky RRDs. Predictive factors of inpatient management were critical finding (odds ratio [OR], 5.60; Risky RRDs were associated with several factors, including CT examination, digestive diseases, and late finalized reports, as well as critical image findings. This knowledge could aid in determining the priority of discrepancies for the appropriate management of RRDs.The online version contains supplementary material available at 10.1186/s13244-022-01233-4. Resident-to-attending radiology report discrepancies (RRDs) affected patients negatively despite their rarity.Neurological diseases contributed to not risky RRDs but the highest revisit.Risky RRDs were associated with CT, digestive diseases, and critical findings.Late finalized reports also significantly contributed to risky RRDs.Prediction of risky RRDs could provide efficient strategies for managing RRDs.In recent decades, emergency department (ED) radiology services around the world have moved toward in-house attending coverage for 24 h a day. Although there is growing agreement regarding the necessity of in-house attending radiologists, this service has not achieved universal implementation for a variety of reasons, including the associated costs and reluctance among radiology trainees and attending radiologists . As a reThere have been numerous studies on resident-to-attending radiology report discrepancies (RRDs). Most studies have focused on discrepancy rates between preliminary and finalized radiology reports and have underscored the diagnostic imaging modalities in which RRDs are frequently found –6. SeverThis study aimed to identify predictive factors for risky RRDs, leading to inpatient management  and major adverse outcomes  by analyzing patient recalls associated with RRDs on computed tomography (CT) and magnetic resonance imaging (MRI).This retrospective study was conducted at a tertiary academic hospital that manages > 150,000 ED cases per year. This study included a total of 759 adult patients (≥ 18 years old) who were recalled after discharge from index ED visits due to the discrepancies between the preliminary CT and MRI reports by radiology residents and the final reports by attending radiologists from January 2013 to January 2021. The RRD information was collected from our institution’s Radiology Critical Value Reporting System database, which contains the radiology medical records summarizing patient recalls associated with reading errors for critical or minor findings. Of 759 tests, 73 cases were excluded because of loss to follow-up. Finally, 686 eligible cases were included in this study. Patient recalls were defined as physicians' phone calls to request the patient return to the ED or explain the necessity of short-term follow-up in outpatient clinics due to RRD. However, some patients refused to return to the ED and visited outpatient clinics despite patient recalls. Patient revisits were defined as a patient’s return to the ED in response to patient recalls. Figure The variables collected were gender, age, radiology examination, preliminary radiology report, final radiology report, duty periods in radiology, time interval between preliminary and final radiology reports, disease categories of final diagnosis, disposition of patients, and adverse outcomes . The reading errors for RRDs were analyzed using a modified classification schema by referring to existing studies , 14 and The RRDs were categorized on a scale from 1‒4 according to the patients’ disposition and outcomes , 16. CatIn January 2011, our institution established a dedicated emergency radiology section. Dedicated radiology residents and dedicated in-house attending radiologists provided emergency radiology services during extended working hours (8:00 am to 10:00 pm on weekdays and 1:00 pm to 9:00 pm on weekends and holidays). Since March 2019, the in-house emergency radiology attending service has further extended the ED coverage hours (8:00 am to 10:00 pm on weekdays and 9:00 am to 9:00 pm on weekends and holidays). Outside of the working hours above, senior radiology residents provide preliminary reports to the referring clinicians at the ED with an available subspecialty faculty backup. Attending radiologists then review the preliminary reports and sign off the final reports the following day. To avoid delayed notifications or missed follow-ups, our patient recall system includes a streamlined reporting system. For critical discrepancies, attending radiologists refer discrepant cases to a discrepant liaison physician through a single phone line and then report the discrepant cases using the Critical Value Reporting System, which automatically sends a text message to notify on-call physicians. For minor discrepancies, attending radiologists only report discrepant cases using the Critical Value Reporting System. All discrepancies were notified to the affected patients by phone, with further explanations regarding the need for patients to return to the ED or attend outpatient clinics.t test and the Mann–Whitney U test for continuous variables. Univariable and multivariable logistic regression analyses were performed with the stepwise method using penalized maximum likelihood estimation to identify independent predictive factors for risky RRDs (inpatient management [discrepant category 3] or adverse outcomes [discrepant category 4]). All statistical analyses were performed using SPSS Statistics for Windows  and SAS ; p values < 0.05 were considered to indicate statistical significance.Comparisons between each of the discrepant category 3 or 4 groups and the control group were performed using the Chi-square test and Fisher's exact test for categorical variables and Student's Table Of the discrepant cases, 26.5% (182 of 686) were in category 1, 73.5% (504 of 686) were in category 2, 21.4% (147 of 686) were in category 3, and 6.0% (41 of 686) were in category 4. Figure p < 0.001); critical findings than minor findings ; CT than MRI ; off-duty periods than on-duty periods ; and late finalized reports than early finalized reports . The adverse outcome rate did not significantly differ according to the diagnostic error type, the presence or absence of critical findings, and the time interval between preliminary and finalized reports. However, the adverse outcome rate was significantly higher in the following conditions: CT than MRI  and off-duty periods than on-duty periods .Figure p < 0.001), CT , digestive diseases , and late finalized report . Table p = 0.006) were identified as the only significant predictive factor.Table Our study was the first to identify predictors of risky discrepancies necessitating inpatient management and closer monitoring of adverse outcome risk. To date, most previous studies have focused on low discrepancy rates with minor negative effects on patient safety. Although these results support the rationale of residents’ preliminary interpretations in academic hospitals, previous studies have been limited in terms of their ability to provide information on the characteristics of risky discrepancies or the severity of such discrepancies.n = 28) [Regarding the clinical impact of RRDs, our results were comparable to those in previous studies. In the present study, RRDs led to inpatient management (21.4%) and adverse outcomes (6.0%); however, there was no 30-day in-hospital mortality. Carney et al.  reportedOur data suggest that risky discrepancies have several distinct features from the overall discrepancy group. In the overall discordant population, results from our study were similar to those of previous studies. Our overall discrepancy rate (0.4%) was consistent with those found in previous studies of resident-to-attending discrepancies (ranging from 0.2 to 3.8%) , 21–25. Our study identified the predictors of risky RRDs as follows: critical findings, CT examination, digestive diseases, and late finalized reports. Our results are supported by those in previous studies of diagnostic errors. Carrara et al.  reportedThis study had several limitations. First, as a study conducted at a single tertiary hospital, there may be limitations in its generalizability. Second, the resident-to-attending report discrepancies were evaluated based on the final attending reports; however, the accuracy of final attending reports was not evaluated. Nevertheless, it reflects the real-world process because, in actual practice, patient recalls are decided based on the final radiology reports prepared by attending radiologists. Third, the discrepant cases could have been reviewed by available faculty backup during off-duty periods. However, the retrospective study design over a long period could have limited the evaluation of certain details in this regard. Fourth, outcomes measured in the present study heavily relied on unmeasurable variables ; however, the effects of these variables are difficult to define because of their complexity. Fifth, selection bias may have played a role in this study because the criteria for patient recalls may vary depending on the individual characteristics of radiologists or ED physicians. Particularly, minor discrepant cases could be overlooked in a busy emergency department, which would lead to an underestimated discrepancy rate. Finally, there is no consensus about risky discrepancies and the extent of their negative impact on patient care. The relevance of discrepancies to patient care and the negative impact has been measured variously in previous studies. To mitigate this bias, we investigated only inpatient management rates and adverse outcome rates for assessing effects on patient care; this, however, could have led to underestimates in our results.Our study identified predictors of risky discrepancies in radiology, leading to inpatient management and adverse outcomes. Although neoplasms and neurologic diseases accounted for a large proportion of our discrepant cases, they had little contribution to risky discrepancies. Our findings suggest that radiologists and ED physicians should pay attention to discrepancies in critical findings, particularly when CT is used, especially in the diagnosis and management of digestive diseases. Our results also revealed an association between late finalized reports and hospital admission. This finding highlights the importance of reducing the time from preliminary to finalized reporting. Although patient characteristics and conditions are most critical when making clinical decisions in light of RRDs, radiologists in the ED often have inadequate clinical information at the time of interpretation. Therefore, from the radiologist’s perspective, these predictive factors are important for assessing the level of risk associated with RRDs. The present study provides information on the priority of discrepancies and the necessity of patient recalls, which is vital for determining the appropriate management steps for RRDs and for facilitating communication among physicians to prevent delays in care and patient notification, as well as to prevent patients from being lost to follow-up.Additional file 1. The causes of diagnostic errors contributing to discrepancies and a list of actual pathologic diseases associated with discrepancies according to the patient disposition, management, and adverse outcomes.


In Poland, drotaverine is the most frequently purchased antispasmodic, yet there is a paucity of real-world data on its use. We evaluated the profiles of patients who used drotaverine, and we investigated prescription patterns among general practitioners (GPs). In this cross-sectional, questionnaire-based study, we asked patients who purchased drotaverine about their reasons for using it, its perceived efficacy, satisfaction with treatment, and physician consultation. We also asked GPs about the status of drotaverine in their practice. Among 650 recruited patients, 74% used drotaverine for pain, 67% for cramps, and 19% for abdominal discomfort. Approximately 83% of patients purchased drotaverine without a physician’s advice. Patients who used it after a physician’s advice were more frequently female, older, and less educated. For all symptoms, mean severity scores decreased by ~5 points  after the first dose. Ninety-eight percent of patients were satisfied with drotaverine. Among 210 GPs, the percentages prescribing drotaverine were: 42% for irritable bowel syndrome, 89% for cholelithiasis, 60% as supportive therapy for urinary infections, 89% for nephrolithiasis, and 75% for menstruation pain. The GPs perceived drotaverine as more useful, effective, and tolerable than other drugs for abdominal pain or cramps. Drotaverine significantly reduced the severity of all symptoms for which it was taken, and it was perceived as effective and tolerable. Abdominal symptoms, such as pain, cramps, or discomfort, occur in up to a half of the general population ,2. MoreoDrotaverine is among the most frequently used antispasmodics in Poland. The safety and efficacy of drotaverine have been validated in many controlled trials in patients with recurrent abdominal pain, gastritis, irritable bowel syndrome, menstrual pain, or renal colic ,5,6,7,8.This observational, retrospective, cross-sectional study using real-world data was carried out from September 2019 to February 2020 at pharmacies, among patients who purchased drotaverine and GPs who often prescribe the drug. We included patients who purchased drotaverine preparations  within the month before inclusion. We chose the No-Spa brand, the most commonly used drotaverine preparation in Poland.We recruited 97 pharmacists who worked in retail pharmacies in voivodship cities. Then, the pharmacists invited adult (18 years or older) patients who bought any No-Spa preparation. The No-Spa purchase had to be unsolicited by the pharmacist. Pregnant women were not included. Each pharmacist recruited 10 patients; those who signed informed consent to participate in the study were contacted by phone to complete a questionnaire. Patients answered questions about the reasons for using drotaverine , the perceived intensity of symptoms before and after the first dose , satisfaction with treatment , the perceived time of onset , and duration of symptom relief since the first dose . Moreover, we asked whether the patients purchased drotaverine after a physician’s advice. The recruitment of GPs was done with random quota sampling to obtain a representative sample for the type of residency across voivodeships. The eligible subjects were GPs with 3 or more years of experience in general medicine, who consulted 400 or more patients monthly and prescribed No-Spa preparations. All the physicians contacted during the recruitment satisfied the criteria of a minimum number of consulted patients and No-Spa prescription. The GPs filled out an online questionnaire on how they approached the patients with abdominal symptoms and on their views on different medications they prescribed for these symptoms. The study did not direct any additional diagnostic or therapeutic interventions, additional specialist consultations, or medical visits. Consequently, no formal ethical approval was required. The study was conducted in accordance with the principles of the International Code of Ethics for Market Research ESOMAR and the law in force in Poland  and in compliance with Sanofi’s procedures for monitoring and reporting safety information of No-Spa, No-Spa Max, No-Spa Comfort, and No-Spa Forte. These procedures were carried out by PEX Pharma Sequence on behalf of Sanofi. Informed consent was obtained from all subjects involved in the study.p < 0.05 (confidence level 0.95) was adopted when defining statistical significance. The analyses were carried out using SPSS 24 software.Data were presented with descriptive statistics. The Kruskal–Wallis test, the Wilcoxon test, or the Friedman test was used for continuous or ordinal variables to assess the statistical significance of subgroup differences or variable differences. Categorical variables were compared using the chi-square test. A significance level value of We included 650 patients  with a mean age of 43 ± 14 years . Most patients (58%) had normal weight , whereas 4% were underweight (<18.5), 29% were overweight (25–29.9), and 9% were obese (>30). Most patients had tertiary education (57%), followed by secondary education (28%), post-secondary education (9%), vocational education (5%), and lower secondary or primary education (2%) . Sixty-fNinety-one percent of all patients re-purchased drotaverine, whereas 9% purchased it for the first time. Among the patients purchasing the drug for the first time, drug information was commonly sourced from pharmacists (43%), friends or relatives (35%), and physicians (20%). The patients who re-purchased drotaverine received information primarily from family and friends (44%), pharmacists (30%), physicians (26%), and TV advertisements (28%). In the entire sample, 74% of patients used drotaverine for abdominal pain (±other symptoms), 67% for cramps (±other symptoms), and 19% for abdominal discomfort (±other symptoms). Most patients (54%) reported more than one symptom see . n = 107), taking No-Spa after a physician’s advice, 58% reported abdominal cramps, 38% reported abdominal pain unrelated to menstruation, and 24% of them reported abdominal discomfort (The majority of the patients (83%) purchased No-Spa without a physician’s advice. In these patients, the following symptoms were commonly observed: abdominal cramps (69%), menstrual pain (47%), and abdominal pain unrelated to menstruation 29%, a. In thescomfort b.p < 0.001), had tertiary education less frequently , and were older . As the starting dose, 58% of patients took 80 mg of drotaverine, 30% took 40 mg, and 11% took 160 mg. The dose of 80 mg was taken more frequently by patients without a physician’s advice , whereas 160 mg of drotaverine was often taken after a physician’s advice . Furthermore, 30% of the patients took a 40 mg dose, equally in both patient populations, with or without a physician’s advice.Patients purchasing drotaverine upon a physician’s advice, compared to those who purchased it without such advice, were more frequently male . Fifteen percent of patients regarded the onset of action as very fast, 78% as rather fast, 5% as rather slow, and 1% as slow. The duration of symptom relief was reported to be <4 h for 26% of patients, <8 h for 24%, <12 h for 16%, and <24 h for 9%. Notably, the symptoms never returned after the first dose of drotaverine in 25% of patients. Drotaverine was similarly effective for all symptoms: after the first dose, the mean severity scores had decreased by ~5 points for cramps, menstruation pain, abdominal pain unrelated to menstruation, and discomfort (in most cases caused by pain and/or cramps) . MoreoveThe overall pharmacological effect of drotaverine was excellent in 31% of patients, good in 55%, sufficient in 13%, followed by not good or poor (1% each). The effect was similar for individual symptoms (data not shown). Taken together, 42% of the patients were very satisfied with the treatment, 56% were satisfied, 1% were rather dissatisfied, and 1% were dissatisfied. The impact of drotaverine on daily activities was largely positive . The impact on physical activity was reported as follows: positive (50%), rather positive (8%), absent (42%), or negative or rather negative (<1%). The impact on emotional condition was positive in 29% of patients, 6% experienced a rather positive impact, whereas 64% and <1% of patients had either no impact or a negative/rather negative impact, respectively.We enrolled 210 GPs  with a mean experience in general medicine of 21 years. The GPs declared that 17% of patients in their practices had abdominal pain or cramps. Among these patients, GPs estimated that 39% had gastrointestinal diseases, 26% had urinary tract diseases, 23% had biliary tract diseases, and 12% had menstruation pain. When GPs were asked to name the five most frequent indications to prescribe drotaverine, the most common were as follows: cholelithiasis (83% of GPs), nephrolithiasis (80%), menstruation pain (54%), urolithiasis (49%), bladder inflammation (43%), and irritable bowel syndrome (39%). The proportions of GPs who prescribed antispasmodics were as follows: 96% for irritable bowel syndrome (42% of GPs prescribed drotaverine), 41% as supportive therapy for gastric and duodenal ulcers , 97% for cholelithiasis , 64% as supportive therapy for urinary infections , 98% for nephrolithiasis , and 83% for menstruation pain .For the 40 mg dose, the perceived onset of action was up to 15 min for 37% of GPs, 16–30 min for 41%, 31–60 min for 22%, and >60 min for <1%. GPs regarded the onset of action for this dose as very fast (50%) or moderate (50%). On the other hand, for the 80 mg dose, the perceived onset of action was up to 15 min for 47% of GPs, 16–30 min for 38%, and 31–60 min for 15%. Moreover, none of the GPs perceived the onset of action to be longer than 60 min; 62% of them regarded the onset as very fast and 38% as moderate. None of the GPs deemed the onset with any of the doses (40 and 80 mg) to be slow or very slow.In treating patients with abdominal pain or cramps, GPs perceived drotaverine to be more useful in daily practice. When compared with other antispasmodics , ketoprofen, and herbal preparations, drotaverine was more effective, more tolerable, and had a greater impact on quality of life .In this study, drotaverine was primarily employed to tackle abdominal pain or cramps that substantially impacted daily activities based on real-world data. The most common cause of the pain was menstruation. Over 80% of all patients in our sample purchased drotaverine without a physician’s advice. Drotaverine was the most prescribed antispasmodic for nearly all indications in general practices in Poland. Drotaverine significantly reduced the intensity of all symptoms and decreased the burden of symptoms on daily activities. The overall treatment satisfaction with drotaverine was high among patients. Similarly, GPs found drotaverine to be more effective and tolerable than other antispasmodics or ketoprofen in patients with abdominal pain or cramps. Drotaverine is available in Poland without prescription, and it is therefore not surprising that most patients purchased drotaverine without a physician’s advice. Self-medication is an increasing trend worldwide, and many people tend not to consult a physician when experiencing symptoms . InsteadWe observed that patients who purchased drotaverine without a physician’s advice took lower first doses. This observation can be associated with less serious symptoms that do not prompt a consultation with a physician. Moreover, patients who take drugs without a physician’s advice might not use higher doses because of the fear of adverse effects. Drotaverine reduced the severity of all surveyed symptoms, and the overall effect of drotaverine was assessed to be excellent or good by nearly 90% of patients. We observed that drotaverine was equally effective for all doses in patients irrespective of the drug being purchased with or without a physician’s advice. Nearly all patients were satisfied with the treatment, which lessened the burden of symptoms in daily activities. Over 90% of patients declared that the onset of action of drotaverine was fast or rather fast . The high treatment satisfaction with drotaverine suggests that it can improve quality of life. Therefore, further studies should assess the impact of drotaverine on quality of life in primary care and among patients using drotaverine without a physician’s advice . The GPs in our study estimated that about 20% of their patients reported abdominal symptoms. Similarly, in a prospective study encompassing ~3000 patients in general practice, 14% wished to consult because of abdominal complaints . HoweverThe limitations of our study need to be mentioned. First, we based our analyses on declarative data, which can lead to recollection bias. Future studies could be improved by a prospective collection of data or an analysis of medical charts in general practices. However, subjective measures need to be used while analyzing the effect of treatments on pain and everyday activities. Lastly, the data were not gathered with validated questionnaires. However, the questions were easy to understand, and similar basic questionnaires are often used without the need for validation ,25. We pIn conclusion, employing real-world data, our study showed that drotaverine was used primarily without a physician’s advice to restrain symptoms, e.g., abdominal pain, menstrual pain, or abdominal cramps. Drotaverine significantly reduced the severity of all symptoms for which it was taken. It was also the most commonly prescribed antispasmodic in general practice in Poland. The drug was perceived as effective and tolerable by patients and GPs. The overall treatment satisfaction was discerned to be high, with no new safety signals.


To evaluate the effects of a protocol treatment based on inelastic adhesive tape with cetylated fatty acids (CFAs) esters in breast cancer survivors with chronic neck pain.In this observational study, patients have been visited for chronic neck pain using numeric rating scale (NRS) for pain assessment, Neck Disability Index (NDI) for disability caused by neck pain, and range of movement (ROM) measures for cervical mobility. Scales have been performed at T0, after 15 days of treatment (T1) and successively after 15 days of stop treatment (T2). Patients have been treated with an inelastic adhesive tape with CFA esters  positioned, 8 h/day for 15 days, on specific anatomic sites .p < 0.05); a statistically significant improvement in the mobility of the cervical spine, as evidenced by ROMs, and in disability, as resulted by Neck Disability Index, have been reported from T0 to T1 and maintained at T2; moreover, ROM at T0 correlates inversely and statistically significantly with NRS and all NDI variables at T0, similarly at T1 and T2 (p < 0.001).Forty-five patients were included in the study. A statistically significant reduction in pain has been reported from T0 to T1 and maintained at T2 (CFA ester taping is a simple, effective, and side-effect-free treatment in order to reduce pain and improve cervical mobility in breast cancer survivors with chronic neck pain. World Health Organization), during 2020, about 7.8 million women have survived breast cancer diagnosed in the last 5 years, thus representing the form of cancer with the highest prevalence worldwide [Reduction in upper limb strength and mobilityUpper limb lymphedemaChronic pain FatigueOsteopenia and osteoporosisBreast cancer is the most prevalent and incident cancer in women, with 2.3 million of new cases reported in 2020 worldwide, and 685,000 deaths during the same year , 2. As rorldwide . Surgeryorldwide . The mororldwide :ReductioChronic musculoskeletal pain (CMP) is reported in 60% of breast cancer survivors: shoulder, neck, arm, and thorax are the most common sites of chronic pain, negatively affecting the quality of life –12. The As reported by Blanpied et al. , neck paCetylated fatty acid (CFA) esters are acids of vegetable origin esterified with cetyl alcohol that, after topical administration, are rapidly absorbed by a passive permeation, favored by the lipid nature of the cell membranes. CFA mechanism of action includes synovial membrane protection and cell membrane stabilization, promoting normal flexibility and mobility, obtaining a reduction in pain and an increase in joint fluidity and lubrication –29. CFAsThe aim of our study is to evaluate the effects of a protocol treatment in chronic neck pain with mobility deficits using inelastic adhesive tape with CFA esters in breast cancer survivors.Strengthening The Reporting Of Observational Studies In Epidemiology (Strobe) Guidelines.This observational quasi-experimental study has been performed at the Oncological Rehabilitation Clinic, Torre del Greco Hospital , between June and December 2021. The study has been performed in accordance with the The study recruited adult women with breast cancer and suffering from neck pain who came to our clinical rehabilitation unit and were evaluated by a team of physiatrists. Women with the following characteristic: neck pain for more than 90 days, breast cancer stadium I–IIIa, surgically treated with quadrantectomy or mastectomy associated to axillary lymph node dissection and/or sentinel lymph node biopsy, and patients who have finished chemo and/or radiotherapies were included. Patients with recent neck trauma, neck surgery, NSAIDs or muscle-relaxants drugs in the last 3 weeks, active radicular pain, and active arthritis with involvement of the cervical spine were excluded from the study.Numeric rating scale (NRS) for pain assessment Neck disability index (NDI) for disability caused by neck pain , 38Range of movement (ROM) measures , using a goniometry, for the mobility of the cervical spinePatients with breast cancer underwent a physical examination for chronic neck pain assessment, based on the following scales and measures:Scales have been performed at the first visit (T0), after 15 days of treatment (T1) and successively 15 days after the interruption of the treatment (T2). NRS requires the patients to rate their pain on a scale 0–10 where 0 is no pain and 10 is the worst pain imaginable . NDI is All patients are treated using a protocol treatment based on inelastic adhesive tape with CFA esters  positioned, 8 h/day for 15 days, on specific anatomic sites , depending on the pain, following the model attached see Fig. –c. One tAll patients gave their written informed consent to treatment, and all authors were instructed to protect the privacy and the study procedures according to Helsinki Declaration; the study was approved by our Local Institutional review board (ASL NA3SUD Ethics Committee).t test has been used to evaluate data pre and post treatment; Pearson’s correlation has been used for data correlation; p value < 0.05 has been considered statistically significant. This observational quasi-experimental study has not been registered on Clinical Trials Registry, because it is not an intervention trial, and reflects normal clinical practice.Analysis SPSS program has been used to analyze statistical data; Student A group of 62 patients with breast cancer and neck pain were visited in the period between June and December 2021: 11 patients had a stage disease > IIIa, so they were excluded from the study, while among the remaining 51 patients, 6 refused the treatment; therefore, 45 patients were finally included in the study . The pain reduction has been accompanied by a statistically significant improvement in the mobility of the cervical spine as evidenced by ROMs from T0 to T1 and maintained at T2: improvements have been reported in all directions, and more specifically in flexion , extension , rotation , and lateral flexion . Moreover, a statistically significant improvement of the Neck Disability Index has been reported from T0 to T1 (p < 0.05), as evidenced by the reduction in moderate disability from T0 to T1 (35/45 at T0 vs 5/45 at T1) and severe disability from T0 to T1 (6/45 vs 0/45), maintained at T2, and an increase in mild disability (4/45 vs 40/45) , indicating pain reduction improves cervical spine mobility; in addition, there is an inverse and statistically significant correlation between ROM and all NDI variables (p < 0.001), indicating mobility improvement is associated with disability reduction.Table Many breast cancer survivors will experience physical and psychological sequelae that affect their everyday lives. The side effects of treatment as well as inactivity secondary to treatment can impair activity and participation, decrease independence, and affect quality of life . ChronicIn this study, a group of patients suffering from a specific cancer-related disease showed a significant pain reduction and a significant improve in mobility. The reduction in moderate disability in favor of minimal disability after 15 days (T1) is the main goal of this study, to allow women to recover in a short time and their activities of daily living and improve their quality of life. Moreover, the data of the maintenance of this result after 15 days without treatment (T2), which shows that the benefit obtained is maintained over time, is equally important.In this specific historic period characterized by the Sars-CoV2 pandemic, access to rehabilitation and physiotherapy treatment (both in- and outpatient) has often been difficult for patients ; in factOur study certainly has some limitations: the absence of a control group, the short follow-up, the lack of association with a physiotherapy treatment. Further studies could be needed to confirm how long the treatment is effective, to evaluate if and when the pain recurs and its intensity, and how to repeat the treatment (for a shorter or the same period of 15 days).In conclusion, a protocol treatment based on inelastic adhesive tape with cetylated fatty acid (CFA) esters showed to be simple, effective, and easily manageable, especially when it is difficult access to rehabilitation treatment, as what happened during the pandemic in order to reduce pain and improve cervical mobility in breast cancer survivors with chronic neck pain. According to our results, this therapeutic strategy could be helpful in these patients, and also in patients with the same condition, for improvement in pain, mobility, and disability in activities of daily living.


Background and Objectives: Hysteroscopy is a reliable technique which is highly useful for the evaluation and management of intrauterine pathology. Recently, the widespread nature of in-office procedures without the need for anesthesia has been requesting validation of practical approach in order to reduce procedure-related pain. In this regard, we performed a comprehensive review of literature regarding pain management in office hysteroscopic procedures. Materials and Methods: MEDLINE, EMBASE, The Cochrane Library , Global Health, Health Technology Assessment Database and Web of Science, other research registers  were searched. We searched for all original articles regarding pain relief strategy during office hysteroscopy, without date restriction. Results have been collected and recommendations have been summarized according to the Appraisal of Guidelines for Research and Evaluation (AGREE) tool. Moreover, the strength of each recommendation was scored following the Grading of Recommendations Assessment (GRADE) system, in order to present the best available evidence. Results: Both pharmacological and non-pharmacological strategies for pain management are feasible and can be applied in office setting for hysteroscopic procedures. The selection of strategy should be modulated according to the characteristics of the patient and difficulty of the procedure. Conclusions: Accumulating evidence support the use of pharmacological and other pharmacological-free strategies for reducing pain during office hysteroscopy. Nevertheless, future research priorities should aim to identify the recommended approach (or combined approaches) according to the characteristics of the patient and difficulty of the procedure. Hysteroscopy is considered the gold standard procedure for the evaluation and management of intrauterine pathologies ,2. Over A thorough literature review was performed with a search on the following databases: MEDLINE, EMBASE, The Cochrane Library , Global Health, Health Technology Assessment Database and Web of Science, other research registers ; we used the medical subject heading (MeSH) term: “Hysteroscopy” (MeSH Unique ID: D015907) in combination with “Pain Management” (MeSH Unique ID: D059408) and “Outpatients” (MeSH Unique ID: D010045). We considered as suitable only papers written in English, published from databases inception until 31 January 2022.Titles and abstracts of the studies retrieved using the above-mentioned search strategy were screened by three review authors. They independently identified studies that could answer the objectives of this review. The full text manuscript of all the potentially eligible articles was retrieved and assessed for eligibility and inclusion in this review by another co-author. A third collaborator was inquired when disagreement occurred between reviewers regarding the possible eligibility of particular articles. Data from the articles were extracted by two authors regarding the study features, the included populations, the type of intervention and any outcomes. Similarly, a third co-author was inquired when some disagreement occurred. Due to the features of our results, we decided for a narrative description of the results from the selected articles. For each subsection, recommendations were provided according to the Appraisal of Guidelines for Research and Evaluation (AGREE) tool , and strOutpatient hysteroscopy is associated with pre-procedural and procedural anxiety. Anxiety, other than hampering the patient quality of life and procedure satisfaction, could be associated to pain perception . FrequenJawaid et al. performed a study to ascertain the preoperative anxiety level in patients admitted for an elective surgical procedure. The most common factors that are related to anxiety were fear of complications, postoperative pain, and results of operation . In addiIn 2014, Kokanali et al. designed an observational study including 148 patients aiming to define the correlation between anxiety levels screened before procedure and procedure-related pain in women undergoing office hysteroscopy. In this study, the STAI test was used for anxiety detection and the VAS score for pain measurement. Results showed positive correlations between pre-procedural waiting time, pre-procedural trait, or state anxiety scores, and reported pain level during the procedure .An interesting finding of the above-mentioned study was the correlation between in-hospital pre-procedural waiting time, which, other than the hysteroscopy itself, is correlated to anxiety and lack of pain relief. Based on this, in 2012, Carta et al. performed an observational study including 284 patients investigating the link between the waiting time between pre-procedure counseling with the healthcare specialist and the administration of office hysteroscopy, and the perception of pain. The STAI test was also used to detect anxiety, and the VAS score to detect pain. Interestingly, the waiting time was found slightly correlated with the procedural pain, but not with the anxiety state and trait . AccordiMoreover, Kokanali et al. provided evidence about the correlation between pain and the duration of the procedure . As expeStrategies aimed to reduce the anxiety level are useful to improve comfort and decrease pain during in office hysteroscopy (Level A).Waiting time before office hysteroscopy should be minimized as much as possible, since it is associated with increased pain levels (Level B).Procedural time should be reduced as much as possible, scheduling the patient for office hysteroscopy when the condition to be treated is suitable for the operator experience (Level A).Based on the available evidence, we promote the following recommendations:n = 37) and women with adenomyosis (n = 29). Their objective was to assess whether the endometrium and myometrium of women with painful uterine fibroids and adenomyosis present nerve fibers. For this reason, immunohistochemical markers were used such as polyclonal rabbit antiprotein gene product 9.5 (PGP9.5), which is a pan-neuronal biomarker, and antineurofilament protein (NF). Results from the study showed the statistically significative presence of PGP9.5-immunoactive nerve fibers located in the endometrium of women with pain. Differently, they were not present in women without pain, suggesting a role of PGP9.5-immunoreactive nerve fibers in pain generation [The importance of pain during a gynecological procedure needs to be fully understood in its anatomical background. In 2010, Zhang et al. performed a retrospective study with immunohistochemical staining on women who presented uterine fibroids (neration .p < 0.01) in endometrial samples from patients with VAS score > 5. Interestingly, confirming the findings of the previous study [This issue stimulated further research: in 2015, Di Spiezio Sardo et al. performed a prospective case-control study including 198 premenopausal women during fertility assessment to evaluate if nerve fibers were present in the endometrium of patients undergoing office hysteroscopy. Moreover, they aimed to assess their potential active role to the pathogenesis of pain in the intraoperative setting . They usus study , patientus study .In 2021, Yadav et al. designed a retrospective cohort study on 247 women with dysmenorrhea or chronic pelvic pain, aiming to determine the presence of nerve fibers in their endometrium and the correlation of them with VAS score and presence of endometriosis. Among them, in 190 patients who were recruited for undergoing hysterectomy or endometrial biopsy, endometriosis was confirmed, while 57 suffered from dysmenorrhea without endometriosis. For nerve fibers detection, the immunohistochemical staining for PGP9.5 was performed, and nerve fiber density was assessed in endometrial tissue biopsies. As consequence, nerve fibers were detected in slices of the endometrium and myometrium in 68% of patients with endometriosis who underwent hysterectomy or a deep endometrial biopsy. On the contrary, nerve fibers were not detected in the aspirated endometrium of women affected by endometriosis. Differently, 13.7% of women with adenomyosis and 3.3% of women presenting fibroids showed the presence of nerve fibers in their endometrial layer. More importantly, nerve fiber density was linked with pain, evaluated with validated scores, in women with endometriosis. Possibly, the presence of nerve fibers in the eutopic endometrial layer could be used as a diagnostic tool for detecting the presence of endometriosis with a specificity of 92.7%. However, it is important to note that the absence of nerve fibers is not correlated with the absence of the disease .Further interests have been directed into genetic polymorphisms investigations. Indeed, in order to find possible correlations among symptoms during the procedure and serotonin concentration, a genetic polymorphisms analysis have been proposed. In particular, polymorphisms of the serotonin receptors have been considered responsible for affecting the intensity of postoperative pain, and the evaluation of serotonin concentration have been found as a predictor for the use of opioid for pain relief .Regarding the possible clinical predictors, personal history of severe dysmenorrhea was identified as one of the main predictors for unacceptable pain during hysteroscopy . HoweverHysteroscopists should pay particular attention for pain management in women who experienced dysmenorrhea, since the level of pain could be significantly higher compared to women without dysmenorrhea (Level B).Women with known or suspected adenomyosis/endometriosis needs adequate pain management strategies before undergoing outpatient hysteroscopy, since the level of pain could be significantly higher compared to women without it (Level B).Considering on the available evidence, we provide the following recommendations:Although a pharmacological approach for pain management during office hysteroscopy seem the most efficient strategy , there an = 52) and the one which received conventional written information (n = 52). In this study, anxiety level measurement included the STAI, which was administered before the MMI, and the STAI-state (STAI-S) administered after MMI. A Likert scale was used to assess woman’s satisfaction, and the VAS score to assess pain during the procedure. Interestingly, the post-information STAI-S score was significantly decreased in the MMI group rather than that of the group who underwent only written information (p < 0.001). Moreover, the satisfaction rate of the MMI group was significantly higher rather than the control group (p < 0.001). However, the VAS score of intra-procedural pain was found to be similar for both groups [Interesting approaches in reducing patient’s anxiety before hysteroscopy have considered the use of multimedia. In 2020, Akca et al. tried to answer this insight performing a prospective randomized study on 104 patients investigating the efficacy of video-based multimedia information (MMI) on reducing the anxiety levels for women undergoing office hysteroscopy. Patients were allocated in two groups: the MMI group (h groups . Other ah groups .n = 176) and the non-listening to music during the procedure (control) group (n = 180), both of which were evaluated through the VAS score and the STAI scale. Interestingly, systolic blood pressure and heart rate were significantly decreased in the group which was administered music compared with the other group. More importantly, women listening to some music presented significantly lower anxiety and pain during and after the procedure [The use of music has also been considered an interesting non-pharmacological strategy for pain relief: in 2013, Angioli et al. investigated the impact of listening to music during office hysteroscopy on the woman’s perceived pain. They performed a prospective randomized trial including 356 patients to detect the effect of music on anxiety and pain perception during office hysteroscopy. Two groups were created: the listening to music during the procedure group (rocedure .n = 54) and group B, the non-listening to music group (n = 53). Intriguingly, women in the listening to music group presented a significantly decreased pain during office hysteroscopy recorded through the VAS score (p = 0.02) [Seven years later, Law et al. performed a prospective randomized trial on 107 patients to assess the effect of music administration in decreasing pain during office hysteroscopy. The patients were divided in two groups: group A, the music group ( = 0.02) . Moreove = 0.02) .The video-based multimedia information (MMI) administration before procedure is more efficient in anxiety reduction compared to traditional written information (Level B).Listening to music during the procedure provides pain and anxiety relief (Level B).Considering the available evidence, we provide the following recommendations:We found several studies investigating the use of misoprostol for cervical preparation/ripening.p < 0.001). However, pain scores evaluated 30 min after the procedure were not different in both groups. Moreover, women reported a greater satisfaction (p < 0.001) and the hysteroscope insertion through the cervical canal was easier (p = 0.003) and faster (p < 0.001) in group with a long-interval dinoprostone rather than the short-interval group. The prevalence of side effects was found similar in both groups [In 2021, Rund et al. aimed to determine the most efficient time for vaginal administration of dinoprostone in relation to performing office hysteroscopic procedures. For this reason, they performed a randomized double-blind controlled trial including 180 nulliparous patients. Participants were divided into two groups: in group A, defined as the long-interval group, 3 mg of dinoprostone was vaginally located 12 h before the office hysteroscopic procedure; in group B, defined as the short-interval group, the same dose of dinoprostone was administered 3 h before the procedure. For measuring pain, the VAS score was intra-procedural administered and after 30 min. Moreover, other outcome measures were the ease of entry of the hysteroscope into the uterine cavity, the women’s satisfaction score after the procedure, and drug side effects. Women included in the group A (dinoprostone administration 12 h before) presented decreased pain scores during the procedure (h groups .n = 100) were allocated to two groups: group A (n = 50) received 400 mcg vaginal misoprostol 4 h prior surgery; group B (n = 50) received intracervical normal saline infiltration immediately before cervical dilatation. This saline infiltration consisted of a total of 10 mL of normal saline administered along the cervical circumference divided into about 10 injections avoiding sites located at hours 3 and 9. The basal cervical dilatation was similar in the two groups, but the normal saline infiltration group presented a time to achieve the desired dilatation significantly shorter. Moreover, the women allocated to the misoprostol group had more complications and it was harder to dilate the cervix than in those allocated to the normal saline infiltration group [Hameed et al. performed a study comparing the efficacy of vaginally administered misoprostol to intracervical normal saline infiltration with the aim to act as a cervical ripening factor. The patients  was found significantly decreased in the misoprostol group compared with the other two groups. However, 15 min after the procedure there were no differences among the three groups regarding VAS score. Taking into account these results, misoprostol administration before procedure may be helpful in reducing pain in office hysteroscopy .n = 30) received placebo, group B (n = 30) received 200 mg rectal misoprostol 2 h before the procedure, group 3 (n = 30) received 20 mg rectal hyoscine-n-butyl bromide two hours pre-procedure. Interestingly, at 1 h after the procedure, analgesics need resulted lower in patients who received hyoscine-n-butyl bromide (13.3%) compared to placebo (43.3%) and misoprostol (36.7%). However, larger trials are necessary to further determine the role of hyoscine-n-butyl bromide in facilitating pre-procedural cervical dilation [In 2020, Gokmen et al. performed a prospective randomized study including 90 patients aiming to determine the effect of rectal misoprostol compared to rectal hyoscine-n-butyl bromide in women undergoing office hysteroscopy. In this trial, patients were divided in three groups: group A (dilation .n = 67) underwent a 900 mg of vaginal isoniazid administration (three pills) 8 h before hysteroscopic setting; the misoprostol group (n = 45) underwent 400 mcg of vaginal misoprostol administration 8 h before the hysteroscopic procedure. Results showed an easier hysteroscopic access to the uterine cavity (p = 0.001) in the INH group (95%) when compared with the misoprostol group (50%) without the need of any additional mechanical dilatation [In 2020, Haghighi et al. designed a randomized controlled trial with the aim to compare the ability of vaginal isoniazid (isonicotinic acid hydrazide: INH) and vaginally administrated misoprostol with the aim of cervical ripening before the hysteroscopic procedure. In this study, the authors included postmenopausal women or premenopausal who were nulliparous. The 183 patients were distributed in two arms: the INH group , increase the ease of procedure, and patient’s satisfaction (Level A).Misoprostol administration before office hysteroscopy is considered efficient in facilitating cervical priming (Level B) and reducing procedural pain (Level A).Vaginal isoniazid is more efficient than misoprostol in cervical priming (Level B).Considering all the available evidence, we support the following recommendations:Among the different strategies to relieve pain during office hysteroscopy, temperature, and pressure of the distension medium, as well as the use of forceps/morcellators, have a key role. Intuitively, the use of bigger scope diameter seems associated with pain severity. For instance, two previous systematic reviews and meta-analyses found an inverse correlation between scope diameter and office hysteroscopy pain reduction ,49. Simip = 0.001). Moreover, the post-procedural VAS pain score was significantly reduced among the warm saline group (p = 0.005). Interestingly, women found greater satisfaction with warm saline distension medium infusion rather than the room temperature group (p < 0.001) [An updated systematic review and meta-analysis, including five RCTs with 441 patients, found that warm saline infusion was correlated to an intraprocedural significant VAS pain score reduction compared to the control group (< 0.001) .n = 77), 70 mmHg (n = 78) or 100 mmHg (n = 79). Regarding the first outcome, adequate visibility was significantly decreased in the 40-mmHg group (87.0%) rather than the 70-mmHg group (94.9%), and in 100-mmHg group (97.5%). Interestingly, the pain score was not significantly different among all the groups [Other than temperature, one additional parameter can be modified by the gynecologist is the uterine cavity filling pressure. In 2014, Saridogan’s group performed a double-blind, randomized controlled trial on 234 patients with the aim to assess the relationship between uterine filling pressure and hysteroscopy visualization and pain. Specifically, they investigated whether adequate visualization could be achieved with a lower uterine infusion pressures and if patient discomfort, assessed through VAS score, could be reduced. The study included three groups using different uterine filling pressure during hysteroscopy: 40 mmHg  during office hysteroscopy with the purpose of decreasing pain level during the procedure is not effective (Level B).The distention media infusion pressure is correlated to the pain perceived during hysteroscopy and should be at the lowest possible for achieving an adequate visualization (Level B).The use of normal saline as distention media is better than carbon dioxide in reducing postprocedural pain, with lower side-effects, and increased patient satisfaction (Level B).The administration of analgesics could have an important role in reducing pain during hysteroscopic procedures.Cicinelli et al. reported that removing endometrial polyps larger than 2 cm and a duration of the procedure of more than 15 min are predictors associated with increased pain during hysteroscopic procedures. Women with previous caesarean section, a history of chronic pelvic pain, anxiety and post-menopausal were found to report higher levels of pain during hysteroscopic procedures .Regarding the analgesic administration, Souza et al. studied the difference between diclofenac and a combination of hyoscine and diclofenac to reduce pain during office hysteroscopy. They performed a randomized, double-blind placebo-controlled clinical trial including 217 patients assessing pain perception during and after outpatient diagnostic hysteroscopy without anesthesia. Three groups were created: group A received placebo; group B received diclofenac sodium 50 mg; and group C received diclofenac sodium 50 mg with Hyoscine-N-Butylbromide 10 mg, administered 1 h before the procedure. In this study, the main outcomes were VAS score after the procedure, the Likert acceptance scale, the post-procedural need for other analgesia, the need to remain in the post-operative room, and the presence of vaso-vagal symptoms. All the three groups had similar VAS scores after the procedure and reported similar procedure acceptance scores. Additionally, in a subgroup analysis of patients treated for chronic pelvic pain, prior medication with diclofenac sodium or hyoscine showed decreased pain levels compared to the placebo .n = 100) received 1000 mg paracetamol + 600 mg ibuprofen administered one hour before the procedure; group B (n = 100) received no medication. Although the group of patients who received analgesic had lower incidence of nausea, vomiting, and hypotension (p = 0.013), no differences in pain scores were observed [In 2014, Teran-Alonso et al. evaluated the administration of analgesic before office hysteroscopy. For this reason, a prospective randomized study on 200 patients was conducted. Two groups were created: group A (observed .p = 0.013), immediately after the procedure (p < 0.036), and 30 min after (p = 0.034). Only two women in the tramadol group reported nausea, but this did not require cancelation of the procedure [Hassan and Haggag in 2016 performed a prospective randomized double-bling placebo-controlled trial on 140 patients to assess the effectiveness of tramadol 50 mg in reducing pain associated with office hysteroscopy. Group A received 50 mg one hour before performing outpatient hysteroscopy, and group B received placebo. The median pain score evaluated through VAS score was significantly decreased in the tramadol group during the procedure . If used after the procedure, TENS administration has been found effective in reducing pain, compared to placebo . Other aA study by Keyhan and Munro  investigTo conclude, we believe that all the analgesic administration presented in the above studies can be offered to the patient during hysteroscopic procedure.Diclofenac sodium administration 1 h before office hysteroscopy is not effective in reducing pain during hysteroscopic procedures (Level B).Paracetamol and Ibuprofen administration 1 h before office hysteroscopy is not efficient in reducing pain during hysteroscopic procedures (Level B).Tramadol administration before hysteroscopy procedure is safe and efficient in reducing pain during and after diagnostic outpatient hysteroscopy (Level A).Considering all the available evidence, we provide the following recommendations:During office hysteroscopy, the gynecologist should consider these practical guidelines to minimize pain during hysteroscopic procedures. Pharmacological strategies are summarized in These recommendations were created based on expert opinion. The main aim was helping the gynecologist treat the average patient during office hysteroscopic procedures. We state that they should not be considered mandatory guidelines and were not built to substitute clinical judgment. Recommendations were decided upon the best available evidence, based on the scientific literature. Moreover, when disagreement was found, the expert panel consensus made a unanimous decision. These guidelines are likely to change as more knowledge of the procedural setting is gained.