Back pain is a common problem and a burden for the patient. MR-morphologically proven pain-causing changes of the spine is often successfully treated utilizing CT-guided pain therapy. The CT-guided execution enables a controlled and reproducible therapy. Nevertheless, treatment results can differ even with the same patient; the physician is a possible influencing factor of the outcome. Accordingly, the present study analyzes the different behaviors and forms of communication of the treating physicians during the course of the intervention as factors influencing the outcome of treatment.67 patients suffering from specific back pain were included in this study. 5 treating physicians  of different age (29–63 years), and experience and a total of 244 CT-guided treatments were included in this study. In every case a psychologist observed the treatment based on a standardized observation protocol. Observed were both the verbal and non-verbal interactions as well as the reaction of patient and physician. The success of the therapy was measured in the course of the treatment using the visual analogue pain scale. The technical comparability of the performed CT-guided periradicular therapy was ensured by the distribution of the drug mixture.p < 0.006) and feels understood . In addition, the outcome is better when the physician believes that the treatment brings a positive reduction of pain, underlining his belief with positive statements of affirmation before the intervention thus creating a positive atmosphere [correlation coefficient: 0.24 (p < 0.009)]. In contrast, the outcome is worse if the patient complains about pain during the intervention [average pain reduction M = 0.9 (pain group) vs. M = 2.0 (no-pain group)].The outcome is significantly better if the patient considers the treating physician to be competent (correlation coefficient: 0.24, Our study shows that with comparable implementation of CT-guided periradicular therapy, the outcome of the patient with specific back pain can be significantly improved by certain behavioral patterns of the performing physician and this without side effects and without significant additional time expenditure. Our findings indicate that there is a non-negligible psychological factor linking confidence in therapy to actual therapy success.Trial Registration: The study was designed as an observational study, therefore a trial registration was not necessary. Pain, especially lower back pain, is a common problem in the industrialized world with manifold reasons. The reported lifetime prevalence varies from 20 to 40% and causes annual costs in the US of $87.6 billion in 2013 . RecentlHence, there is a strong economic need to reevaluate the different forms of therapy in order to determine which therapy is most beneficial for the patient while considering the economic impact. This need is exacerbated by another major problem concerning the availability of the different therapy forms in the industrialized world. The limited availability of resources, combined with the cost of treatment leads to a restriction of offered therapy modalities . For exaIn the present study we focus only on specific back pain with proven morphological causes for the correlated back pain.It would be desirable to find a treatment or combination of treatment forms that show the best outcome at low risk and low cost. The different methods of treatment and the combination of them lead to a better therapy outcome, but the most relevant predictors of patient benefits remain unclear. In this regard, there is another important issue in research concerning the treatment of back pain, namely psychological effects on pain improvement originating from the doctor–patient relationship , 11. TheCT-guided pain intervention provides a high level of safety and accuracy in back pain treatment. Success rates span from 52 to 90%. Since CT-guided pain therapy should ensure comparable results as far as possible independently of the physician performing it, a physician-related success component may be assumed. –15.The purpose of the presented study is to examine which factors in doctor-patient interaction lead to an improved outcome in CT guided periradicular therapy under the assumption that the technical performance of CT guided periradicular therapy is comparable.The presented study was approved by the local ethics committee. From 11/2016 to 7/2018 we examined a total of 354 patients with specific back pain. A pain physician admitted all patients to the CT guided interventional therapy. To execute the interventional procedure, one physician was randomly selected from a group of five radiologists  whose experience levels ranged from 2 to 18 years  with a total of 244 examinations fulfilled the inclusion criteria and consented to participate in the study (Table expectation regarding (further) improvement of the pain.likelihood that the pain is successfully treated with the procedure(s) and will disappear.competency of the treating physician.the extent to which the patient feels understood by the radiologist regarding his/her condition.In addition, the radiologist also filled out a questionnaire querying his opinion on the chance of success for the individual patient.Immediately following the consultation with the radiologist, the psychologist again saw the patient, conducting another structured query concerning the patient’s expectations of the treatment and impressions about the radiologist, which included:After the initial examinations, the patients followed up on the CT-guided periradicular therapy. In 31% of the patients the intervention was performed on the cervical spine and in 69% of patients on the lumbar spine. In this type of procedure, a needle is positioned directly at the neuroforamen under CT control and, after verification of the needle position by means of contrast medium injection, the drug mixture of local anesthetic and glucocorticoid is administered. We used triamcinolone in a uniform dosage of 20 mg  in each patient. As a local anesthetic we applied 2% mepivacain  in an amount of 2 ml in each patient. For the documentation of drug distribution 1 ml of iodine-based contrast agent  was injected.The time frame after the initial examination varied from 1 to 14 days (average: 5 days). Prior to every treatment session, the patient was seen by the psychologist, receiving another structured query about his/her current well-being, and a re-evaluation of the current pain score. The psychologist, who observed the atmosphere and the interaction of the doctor and patient during the treatment, documented the CT-guided pain therapy treatment on a structured chart.current pain level on a 0–10 continuous pain scale,expectation of (further) improvement,competency of the treating physician and evaluation of the doctor–patient relationship.The names of the physicians were omitted from all patient questionnaires to prevent any impact on treatment behavior.Following each procedure, the patient was re-interviewed by the psychologist querying:In order to categorize the success of the treatment, we chose to monitor the decrease in pain levels of the patients. We classified pain reduction scores of less than 0.25 as unsuccessful, with scores of 0.25–3.0 as good success and all decreases bigger than 3.0 as excellent success.Four to 12 weeks after the end of the treatment we invited the patients to a final conversation or telephone interview to examine the long-term effects of the therapy.p ≤ 0.05 as significant. In assessing the strength of the effect of correlation, we followed a modified form of the Cohen’s classification, in which a classification into relatively small, typical, and relatively large is proposed [For statistical evaluation of the technical and non-technical data, a database was set up that was subject to computer-assisted evaluation using MatLab(R) R2017b. Depending on the evaluation criteria, subgroups were formed where all relevant data points were available. We defined all results with a proposed .In 209 cases (86%) an improvement after treatment was reported. Most patients showed a good reduction of pain (53%) whereas 33% exhibited an excellent pain reduction.p < 0.0084 on the general improvement (n = 209). Therefore, there is a dependency on how the physician behaves or how the physician interacts with the patient in respect to therapy outcome. No significant statistical correlation between age, gender and experience of the physician could be demonstrated.In 35 cases (14%) no improvement was documented. To evaluate if a potential dependency on an individual physician affects the general improvement of a patient, an exact Fisher test was performed; the null hypothesis was set to indicate that improvement does not depend on the treating physician. The null hypothesis was rejected with The results of the patient questionnaires as well as the patient-demographic dependencies were evaluated with standard statistic approaches. Using Spearman rank correlation, we could show that there exists a positive correlation between the following factors originating from the patient with respect to the outcome:p < 0.001). Also, if the patient considers the physician as competent the outcome is significantly better . However, the most significant observation noted by the psychologist is the atmosphere during the intervention. Using a Spearman rank correlation, the correlation between the pain-relief and the atmosphere was found to be 0.24 (p < 0.009) and is of a similar strength as the competency of the physician or if the patient felt understood .A positive affirmative statement from the treating physician prior to treatment leads to better outcome for the patient. We could show that if the physician states that the intervention will be successful, there is a greater pain reduction (mean reduction of pain score 1.9) than if such statements are omitted (mean reduction of pain score 1.3) Fig. . Hence pp < 0.05)  Figs. , 4.Fig. p = 0.018). In the former case the pain reduction is only M = 0.9 points on the pain scale in comparison to M = 2.0 points in the latter case  = 2.606, ase Fig. .Fig. 5IfApart from factors dependent upon the subjective impressions of the patient, we also found that the likelihood of success decreases with increasing patient age, though not significantly Fig. .Fig. 6SuMost of the patients showed a benefit from the interventional CT-guided therapy: 86% showed pain relief during and after therapy. The average improvement under therapy was 3.1; the pain score before therapy was 7.2 (3–10) and after therapy 4.1 (0–9). 45% of the patients were also questioned about their pain development in the follow-up; here a consolidation of the success is shown with an average pain score of 3.6 (0–8) and thus an overall improvement of 3.6. However, the follow-up was not always timely, the follow-up time ranged from 4 to 49 weeks.CT guided pain therapy in specific back pain is an established therapy reaching a significant pain reduction in 63–84% of the treated patients –20. Our The occurrence, recognition and processing of back pain involves sensory, cognitive, and affective factors. The impression and rating of pain varies across cultures and individuals . TherefoThe effects we observed in the current study complement these findings. We showed that interventional pain therapy depends upon the verbal and non-verbal communication of the treating physician with the patient. If the patient felt understood and the atmosphere was supportive, the treating physician was regarded as competent, resulting in a better outcome. If the treating physician expresses a warm welcome combined with a gentle touch and a short statement about the treatment and its expected effects, it has a positive (reducing) impact on pain experience. These actions do not take much time, but significantly improve the outcome.In the field of CT guided pain therapy these factors have not previously been considered in influencing the therapy outcome, though it is known that side effects from verbal and non-verbal communication exist and influence the variety of therapies and their outcomes , 25. In If in the treatment of specific low back pain only little elements of adequate patient treatment are included the outcome is better. Certainly, the treating radiologist does not have to behave as a psychologist, but when heeding the above-mentioned behaviors, the pain reduction will be better. If the physician gives the patient a conviction of assurance that the treatment will help, the outcome will be better. In psychology this type of therapy is known as framing , 26. It There is literary evidence that patient-therapist interaction influences the outcome in patients with low back pain . The stuThe field of empathy and its affection on the patient–physician relationship is of general interest and often hard to measure. Up to date there is evidence in different fields of medicine and in psychology that a trustful and well defined patient–physician relationship provides a better patient outcome . Also, mOur study shows in some respects that the effectiveness of the therapy depends on the treating physician. The most successful physician is the one with the most experience. However, when all five attending physicians are considered together, we could not prove that the physician's experience is positively correlated with the patient outcome. We also could not show a significant correlation for the age of the physician and gender. The purely technical factors can be excluded to a large extent by the study design we have chosen, as the CT controlled procedure ensures a comparable drug distribution in all cases included in the study. In addition to experience, a number of other factors are also discussed in the literature which are required to achieve an optimal result for the patient , 32.Our study has limitations. The number of included patients and observed examinations is comparable small, therefore our small sample size limits the presented study. Only 45% of the patients were willing to participate in the final survey a few weeks after the intervention. Even if the assumed trend towards improvement of pain symptoms was confirmed in these patients, the low number of response considerably limits the statement on long-term success. The number of participating physicians was too small to identify clear personal characteristics that could influence the success of the treatment. There is strong evidence to support that verbal and non-verbal interaction between physician and patient has a significant effect on patient outcome, but we could not trace which behavior and rituals are best to achieve a patient’s optimal outcome. The study was not video analyzed, so there could be details in the interaction between physician and patient that were not recognized and reported by the observing psychologist.Outcome of CT guided therapy is significantly correlated to the treating physician’s behavior. The pain reduction is significantly better if the atmosphere is friendly and patient centered, if the physician is competent in the view of the patient, and is understanding of the patients’ complaints. Additionally, framing before therapy leads to better results.


There have been no studies comparing patient-reported outcome measures including end-of-stem tip pain and patient satisfaction based on the use of cementing techniques in revision total knee arthroplasty (TKA). The purpose of this study was to compare end-of-stem tip pain and PROMs with hybrid and modified hybrid cementing techniques in revision TKAs.Sixty-two cases of revision TKA performed by a single surgeon were divided into two groups based on the cementing technique with a minimum follow-up of 2 years. Two types of cementing technique for femoral and tibial stems were used as follows: (1) a hybrid cementing technique (33 cases), in which cement was applied immediately distal to the modular junction of the stem and the component while the distal stem was press-fitted into the diaphysis without using cement; and (2) a modified hybrid cementing technique (29 cases), in which cement was applied to the tip of femoral and tibial stems. The thigh and shin were assessed for the end-of-stem tip pain. Patient satisfaction was evaluated based on the satisfaction items of New Knee Society Score.p = 0.029). Patients treated with the modified hybrid cementing technique showed a higher satisfaction rate (p = 0.003). Multivariate logistic regression analysis showed an increase in the odds of satisfaction 32.686-fold (p = 0.004) in patients without pain at the end-of-stem tip in the shin and 9.261-fold (p = 0.027) in patients treated with the modified hybrid cementing technique.Modified hybrid cementing significantly lowered the percentage of patients manifesting shin pain (3.4% vs. 24.2%, The modified hybrid cementing technique for fixation of long-stem in revision TKAs reduced the end-of-stem tip pain in the shin, leading to significantly higher satisfaction compared with the hybrid cementing technique after revision TKA.Level III Revision total knee arthroplasty (TKA) is more difficult than primary TKA due to severe bone defects and insufficient soft tissue , 2. StemTo the best of our knowledge, there have been no studies comparing PROMs (patient-reported outcome measures) including end-of-stem tip pain and patient satisfaction based on the use of cementing techniques in revision TKAs. The purpose of this study was to compare end-of-stem tip pain and PROMs with hybrid and modified hybrid cementing techniques in revision TKAs. Our hypothesis was that patients treated with the modified hybrid cementing exhibited a lower incidence of end-of-stem tip pain and higher satisfaction after revision TKA compared with patients treated with the hybrid cementing technique.Clinical and radiological data including patients’ charts and radiographs obtained between March 2012 and December 2016 were retrospectively reviewed. All patients who underwent revision TKA were included in this review. A total of 81 consecutive revision TKAs using the same Vanguard 360 revision knee system  with diaphyseal stem fixation were performed by the senior surgeon at a single institution. We used two types of cementing techniques for femoral and tibial stems. Between March 2012 and March 2015, 41 revision TKAs were performed using the hybrid cementing technique, in which cement was applied around the implant immediately distal to the modular junction of the stem and the component while the distal stem was pressed to fit into the diaphysis without cement , were exThe following valuables were compared between the two groups: age, gender, body mass index (BMI), the American Society of Anesthesiologists (ASA) grade, and comorbidities including hypertension, diabetes, cardiac disease , cerebrovascular event, thyroid, kidney, liver disease, and pulmonary disease (asthma and chronic obstructive pulmonary disease). The factors inducing revision TKAs were categorized except for septic cause: aseptic loosening, component malposition, stiffness, and instability. Polyethylene wear was included in aseptic loosening . ProsthePROMs were evaluated by an independent investigator based on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score  and patip value < 0.1). Odds ratios were reported for significant variables. All statistical analyses were performed using SPSS ver. 21.0 program . A p value < 0.05 was considered statistically significant.Data were compared between patient groups exposed to the hybrid and the modified hybrid cementing techniques. Linear variables were analyzed using Kolmogorov-Wilcoxon test for nonparametric date while dichotomous variables were analyzed using chi-square test or Fisher’s exact test where appropriate for two independent samples. Descriptive analyses were based on frequencies and percentages for dichotomous variables, and the mean and standard deviation for linear variables. Multivariable logistic regression analysis was used to assess the independent effects of predictors by adding backward substitution factors identified as significant in univariate analysis  than the group of patients exposed to hybrid cementing technique. The modified hybrid group also carried a lower proportion of patients with thigh pain without any statistical significance . The modified hybrid group showed significantly better subscores for pain and function and total WOMAC scores at 2 years postoperatively compared with the group treated with the hybrid cementing technique   of patients were satisfied with revision TKAs while 24.2% (n = 15) claimed that they were dissatisfied. No significant association was found between femur and tibia augmentation based on augments, and the thigh or shin pain . Patients treated with modified hybrid cementing showed higher rates of satisfaction compared with patients treated with hybrid cementing strategies . The modified hybrid approach resulted in significantly superior scores of total satisfaction   in patients without end-of-stem tip pain in the shin, and 9.261-fold (p = 0.027) in patients treated with the modified hybrid cementing technique (Table Multivariate logistic regression analysis showed that the odds of satisfaction after revision TKAs increased 32.686-fold p = 0.00 in patieThree cases of wound dehiscence were observed along with one case of superficial wound infection involving the surgical site. None of the cases showed deep periprosthetic infection during postoperative follow-up.The most important finding of this study was that the modified hybrid cementing technique significantly reduced the end-of-stem tip pain in the shin and enhanced patient satisfaction compared with the hybrid cementing technique.The use of intramedullary stem for fixation stability and proper alignment in revision TKA is widely accepted among orthopedic surgeons, although the stem fixation approach is still disputed , 7. AugmIn this study, the end-of-stem tip pain in the shin was a factor significantly related to patient dissatisfaction after revision TKAs. Although the cause of end-of-stem tip pain after revision TKA is not proven, the following factors have been implicated: micromotion at the bone-prosthesis interface, excessive stress transfer to the surrounding bone because of large differences in Young’s modulus of elasticity between the stem tip and the bone at the point of contact, and stress shielding leading to bone resorption of the tibial tray resulting in movement to the stem tip –24. BarrMihalko et al. [End-of-stem pain is commonly reported with press-fit stem revision TKAs. However, its incidence rate varies among clinical studies , 25. In o et al.  have repAlthough the overall satisfaction rate of our revision TKA patients was 75.8%, the satisfaction rate of hybrid cementing technique group was only 60.6%. Baker et al.  reportedOur study had several limitations. First, the demographic characteristics of the present study population such as the preponderance of female patients undergoing revision TKA should be considered when comparing with other populations comprising only Korean patients . NeverthOur novel technique of stem fixation in revision TKAs using a modified hybrid cementing technique reduced the end-of-stem tip pain in the shin and increased patients’ satisfaction postoperatively. Therefore, the modified hybrid cementing technique could be more effective option to reduce end-of-stem tip pain and enhance patient satisfaction following revision TKAs. Further research is needed to support our findings.


By multivariate analysis, female gender, BMI <25 kg/m2, puncture difficulty, the use of plastic needle and 6F sheath were identified as independent predictors of RAS. Procedural inhalation sedation by Kalinox is as safe as opioids analgesia during transradial coronary angiography.With respect to the transfemoral approach, transradial procedures enable a drastic reduction of bleeding events and are associated with a reduction of mortality. Radial artery spasm (RAS) is one of the most common complications and may lead to patient discomfort and procedural failure. Currently, there is no consensus on the optimal sedation protocol to avoid RAS. The aim of this study was to investigate the respective impact of opioids analgesia and inhalation sedation with a 50% nitrous oxide/oxygen premix  on pain and occurrence of RAS during transradial coronary procedures. Consecutive patients undergoing transradial coronary angiography were prospectively enrolled in one, single center observational study . Patients received opioids analgesia or inhalation sedation with Kalinox. The primary endpoints of the study were the incidence of a pain scale ≥5/10 and the occurrence of RAS. The secondary endpoints were the incidence of side effects. A total of 325 patients were enrolled . RAS and pain scale ≥5 rates were not significantly different in the opioids analgesia and Kalinox groups (respectively 13.5% vs. 10.0% and 16.2% vs. 11.4%). Headache was more frequently observed in the Kalinox group (6.4% vs. 0.0%;  With respect to the transfemoral approach, transradial procedures enable a drastic reduction of bleeding events and are associated with a reduction of mortality ,2. Radia12 inhibitors by opioids as a possible reduction of gut motility [Opioids are commonly used during PCI but they have numerous side effects including the depression of the respiratory system. Owing to their narrow therapeutic window, restriction of their use has been advocated by regulatory agencies and their administration is restricted to anesthesiologists or skilled, critical care physicians. Another important concern that could preclude the systematic use of opioids analgesia during PCI is the recent description of a limited absorption of P2Ymotility .2O/O2) to avoid hypoxemia. It is an effective analgesic/anxiolytic agent causing central nervous system depression and euphoria with little effect on the respiratory system. There are many attractive qualities of Kalinox due to its low solubility in the blood which allows a rapid onset of action in the brain as well as rapid clearance through the lungs shortly after administration. It provides a minor amnestic effect [Kalinox is an odorless gas used for procedural sedation and analgesia, typically administered as a 50-50% nitrous oxide-oxygen mixture  in comparison with opioid analgesia during transradial procedures. In addition, the secondary objective was to assess the predictors of RAS and pain after PCI.From September 2016 to February 2017, patients undergoing elective or urgent transradial coronary procedures were prospectively enrolled in a high volume (1560 PCI procedures in 2016) PCI center . Patients with contraindications , chronic kidney disease (CKD), medication and materials used during PCI.® Introducer II set, Terumo, Tokio, Japan) was used and patients in both groups received 3000 to 6000 units heparin according to body weight, 1 mg of isosorbide dinitrate and 1 mg of nicardipine through the radial sheath immediately after insertion. If required, another administration of nicardipine was added. A 0.038 inch guidewire was used . The procedure time was calculated as the time from local anesthesia to the removal of the sheath. Postprocedural hemostasis was achieved by placing of a wrist clamp device .For all patients, a puncture was made with a metallic or plastic 19-gauge needle after local anesthesia with 1–4 mL lidocaine 1%. Numbers of puncture were recorded. A 7 cm, 4–6F (hydrophilic coated sheath RadifocusAll participants gave their informed written consent for the recording of their data in an anonymized database before the procedure. The study was approved by the University of Strasbourg bioethics committee (reference number: CE-2020-49). The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki.Patients’ perceived discomfort was assessed in the evening after the procedure or the day after with a visual analogue scale (VAS) whereby the patient graded the discomfort on a scale of 0 to 10 (0 corresponding to “no discomfort” and 10 to “extreme pain and discomfort”). RAS severity was categorized as none, moderate and severe. Spasm was identified by appearance of marked resistance to the movement of the catheter or inability to further advance catheters with or without accompanying forearm pain.2 (1 point), height less than 170 cm (1 point), current smoking (2 points), hypertension (2 points) and PAD (3 points). A predefined score of 4 or more is related to a high risk of RAS [An RAS risk score was calculated for all patients as recently proposed by Giannopulos and coworkers . It consk of RAS .The primary endpoints of the study were the incidence of a pain scale greater than or equal to 5 and the occurrence of RAS. The secondary endpoint included the occurrence of the most frequent side effects of Kalinox such as nausea, vomiting, dizziness or faintness and headache.p < 0.05 in univariate analysis were entered into a stepwise ascending multivariate analysis. A p value < 0.05 was considered significant. Since Kalinox was never studied in PCI, the sample size could not be calculated. Based on previous studies on RAS, we estimated that a sample size of 300 patients would be adequate. Calculations were performed using SPSS 17.0 for Windows .Categorical variables were expressed as counts and percentages. Continuous variables were reported as the mean +/− standard deviation (SD) according to their distribution. Categorical variables were compared with Chi-square tests or Fisher’s exact tests. Continuous variables were compared with the use of parametric (ANOVA) or nonparametric Mann-Whitney test as appropriate. To determine predictors of radial spasm and pain, regression analysis was performed. Variables with p = 0.032). Conversely, patients in the K group were more frequently smokers  and had a higher rate of peripheral artery disease history (12.1% vs. 4.9% p = 0.017). Importantly, RAS risk score was equivalent between the two groups . Other characteristics  were equally balanced.A total of 325 patients were prospectively enrolled. Among these, 185 patients benefited from opioids analgesia by alfentanil/morphine (OA group) and 140 patients from inhalation sedation by Kalinox (K group). Baseline demographics, clinical, biological and angiographic characteristics of the two groups are described in p = 0.334) . Similar rates of RAS were observed in the Kalinox group and in the opioid analgesia group  . By univ= 0.334) . By mults of RAS .p = 0.220) . As observed on RAS, similar rates of pain scale ≥5 were observed in the Kalinox group and in the opioid analgesia group  . By univ= 0.220) . By mult= 0.220) .p = 0.44). Accordingly, comparable rates of dizziness or faintness could be observed between groups. Conversely, higher rate of headache could be evidenced in patients treated by Kalinox  in the OA group. Administration of Kalinox did not induce more nausea or vomiting  are nonrelevant. Not surprisingly, female gender was identified as an important risk factor of RAS. Important variations in the radial artery diameter between men and women have been described in the past (2.69 ± 0.40 mm in men and 2.43 ± 0.38 mm in women) [The transradial approach for left heart catheterization and PCI is increasingly used worldwide given its numerous advantages including lower bleeding rates, lower mortality, reduced mobilization time and shorter hospital stays . Increascatheter . To allocatheter . In the n women)  and radin women) . Of noten women) .Noxious connections between anxiety, pain, catecholamines release and RAS have been previously underlined. The possible impact of angina as a clinical presentation is more puzzling. Previous data have suggested that endothelial dysfunction, a key parameter during angina, and characterized by reduced production of nitric oxide (NO) and increased NO breakdown by reactive oxygen species may favor paradoxical vasoconstriction of the vessel and contribute to radial spasm. However, recent findings by van der Heiden failed to evidence any link between endothelial function as assessed by EndoPAT and RAS .Along with a technical approach that enables the reduction of spasm such as the downsizing of sheaths and catheters or the use of hydrophilic coated sheaths, the use of appropriate sedation together with vasodilation appears to be an intuitive approach to limit spasm and patient discomfort. In line with this view, data by Deftereos and coworkers have emphasized that routine administration of relatively low doses of an opioid (fentanyl) in combination with benzodiazepine is associated with a significant reduction of spasm, site crossover and patient discomfort . By contWith respect to opioid analgesia, inhalation sedation by 50% nitrous oxide/oxygen premix  presents several advantages: (i) its administration does not require the presence of an anesthesiologist and can be conducted under the supervision of a trained nurse with conditions and tools of monitoring already used for PCI; (ii) contraindications are limited and allow widespread use see ; (iii) i2O) have been described for more than 150 years and were first exploited in dental surgery, obstetrics and more recently pediatric settings [2O has been reported to decrease myocardial contractility in vitro, it also simultaneously stimulates catecholamine release by the sympathetic nervous system hereby leaving cardiac output, blood pressure and heart rate relatively unchanged in vivo [p = 0.04) at long-term follow-up but not at 30 days. However more recently, the ENIGMA-II, a powered study enrolling 7112 non-cardiac-surgery patients at risk of perioperative cardiovascular events, demonstrated the long-term safety of nitrous oxide administration without any elevation of death, myocardial infarction and stroke rates [The analgesic properties of nitrous oxide  and there is a weak relation between angiographic spasm and procedural outcomes . The radAn imbalance in diabetic or smoking status was evidenced between groups. Since current smoking is an important factor of RAS, we could not exclude that the higher rate of smoking in the Kalinox group may have blunted the protective effect of Kalinox on spasm.Patients evaluated their pain several hours after the procedure which may lead to a reduction in the intensity of the pain actually felt, especially when taken into account that Kalinox has an amnestic effect. Anxiety score was not assessed. Other possible impacts of nitrous oxide on hyperemia such as those induced during fractional flow reserve measurement should be investigated in appropriate trials.2O/O2 inhalation provides a safe and effective analgesia at a reasonable cost with a low rate of side effects. Further studies are needed to definitively recommend Kalinox for routine use during transradial PCI.Procedural inhalation sedation by Kalinox is as safe as opioids analgesia during transradial coronary angiography. Patient-administered N


The intensity of oral impacts and pain increased according to the increasing OLP clinical severity, except for the white striae lesions (Thongprasom sign score 1). The erosive/ulcerative OLP lesions (Thongprasom sign scores 4 and 5) were the most painful symptom and had the highest degree of oral impacts (p < 0.001). No significant associations were found between the number of affected lesion sides and OHRQoL (p = 0.316) and pain (p = 0.284). OHRQoL was associated with OLP type and clinical severity but not with the number of affected sides.Subjective patient’s symptoms and Oral Health-Related Quality of Life (OHRQoL) are recommended to be involved in oral lichen planus (OLP) studies. This study aims to assess the OHRQoL of OLP patients, and their associations with pain and OLP in Thai patients. Sixty-nine patients were interviewed using the Numeric Rating Scale (NRS) for pain perception and Oral Impacts on Daily Performance (OIDP) index. OLP signs examined included localization, types, number of affected sides and clinical severity using the Thongprasom sign scoring system. There were significant associations (r Oral lichen planus (OLP) is a chronic inflammatory disease that can lead to open sores in the mouth. Most patients are female and onset occurs most commonly in the fifth or sixth decade of life ,2,3. TheCommon OLP symptoms vary from a burning sensation to severe chronic pain . MeasureOLP is generally not life-threatening; however, the consequence of OLP could cause deterioration in OHRQoL both physical, psychological and social dimensions . The impThe concept of OHRQoL had been developed and introduced into all fields of dentistry, including oral medicine . For cliQuantitative assessment of OHRQoL consists of a variety of measurement tools, both General-Health and Oral-Health quality of life indices and a specific Chronic Oral Mucosal Disease Quality of Life Index (COMDQ) ,25. In oTherefore, the aim of this study was to assess OHRQoL of OLP patients using the OIDP index. Furthermore, the associations of OHRQoL and pain perception with OLP clinical characteristics in terms of localization, type, number and severity, according to Thongprasom sign scoring system were examined.This cross-sectional study was approved by the Ethics Committee of the Faculty of Dentistry Chulalongkorn University , and by the Thai Clinical Trials Registry (TCTR) . All recruited patients received study information. Patient approval was obtained through consent forms. The study was conducted by one well-trained and calibrated interviewer between July and November 2019. The inclusion criteria were patients aged 18 or more, clinically and histopathologically diagnosed as OLP or compatible with OLP as suggested by van der Meij and van der Waal (2003) . The exc2; “3”, white striae with atrophic area equal to or greater than 1 cm2; “4”, white striae with an erosive area less than 1 cm2; “5”, white striae with erosive area equal to or greater than 1 cm2 [Demographic characteristics were collected, included gender, age, patient types and the lesion duration since the first diagnosis of OLP, using dental records. For the clinical characteristics, OLP lesions were recorded for localization , types , and clinical severity classified by the Thongprasom sign scoring system, demonstrated as: “0”, no lesions; “1”, white striae only; “2”, white striae with atrophic area less than 1 cman 1 cm2 . In caseIn relation to pain, participants were asked for the Numeric Rating Scale (NRS) pain score by stating the number that best represented their current OLP-related pain intensity, ranging from 0 to 10: “0” for no pain at all, and “10” for the worst imaginable pain. Scores were grouped into three levels of “mild pain” (0–3), “moderate pain” (4–7) and “severe pain” (8–10) .OHRQoL was assessed through the Thai version of OIDP index, described elsewhere . In brieTo calculate the OIDP, the frequency score and the severity score were multiplied, resulting in a performance score which could range from 0–25. The sum of eight performance scores (ranging from 0–200), were divided by 2, resulting in a percentage score ranging from 0 to 100, and in which higher scores indicated poorer OHRQoL . In addip < 0.05).All statistical computations were performed by SPSS statistics for Windows, version 22.0 . The Kolomogonov Smirnov normality tests were applied to check for normal data distribution, however the distribution was found to be non-normal, and therefore, Mann-Whitney U tests were used. Spearman’s correlation was used to evaluate the association between the intensity of oral impacts and OLP clinical severity, pain perception (NRS) and the association between OLP pain perception and OHRQoL. The significance level was set at 5% . The study group consisted of 55 women (79.7%) and 14 men (20.3%). The mean age was 55.1 ± 13.9 years. Most participants were recall patients (82.6%). Forty-three of them (62.3%) had OLP lesions for 1–5 years; 20.3% for more than 5 years, and 17.4% less than 1 year. Almost all patients (95%) complained of having pain. However, mean pain intensities were mostly mild (59.4%), followed by moderate (34.8%) and severe (1.4%). The mean NRS pain scores were 2.56 ± 2.32.Regarding OLP clinical characteristics, the three most common sites were buccal mucosa (88.4%), followed by gingiva (60.9%), tongue and lip (14.5%), while floor of the mouth (4.3%) and soft palate (2.9%) were infrequently affected. All patients had the reticular type of OLP. The second most common form was atrophic (95.7%), followed by erosive/ulceration (26.1%) and bullous variant (2.9%). Regarding the number of OLP affected sides, about 40% had two affected sides followed by four, and three affected sides , respectively. The OLP clinical severity scores were 3 (39.1%), followed by 2 (31.9%), 4 (17.4%) and 5 (7.2%).The prevalence, intensity of oral impacts, percentage scores and performance scores among OLP patients are shown in s = 0.490, p < 0.001) (p < 0.001), that is, lesions scored 2 had significantly lower oral impacts than those scored 3 (p = 0.002), while lesions scored 3 had significantly lower impacts than those scored 4 (p = 0.030). However, there was no statistically significant difference in the intensity of oral impacts between lesions scored 4 and 5 (p = 0.604). Moreover, patients with score 1 reported the intensity of oral impacts with severe intensity level, higher than the impacts of patients with lesions of score 2 (p = 0.010). A correlation analysis showed a statistically positive association between clinical severity and the intensity of oral impacts (r< 0.001) . The ints = 0.298, p = 0.013). Similar to oral impacts, the NRS scores continuously increased accordingly to clinical severity. The mean NRS scores rose from 1.54 ± 2.04 for score 2, to 4.00 ± 1.00 for score 5 .In term of pain perception, OLP pain symptoms were significantly associated with clinical severity (r score 5 . Neverthp = 0.039), As regards the type of OLP, patients with the erosive/ulcerative OLP reported a severe to very severe intensity level, which was significantly worse than that of the other types (p < 0.001). Furthermore, patients with the erosive/ulcerative type of OLP had significantly higher pain, with mean NRS scores (3.88 ± 2.05), compared to the scores of the others . Additionally, neither OHRQoL nor pain perception depended on the number of affected lesion sides .The OLP localization, clinical type and number of lesion were related with OHRQoL . Our stuThe findings from this study have extended our understanding of OLP impacts on OHRQoL. Three predominantly relevant daily activities, corresponding to a deterioration in OHRQoL, were eating, cleaning the oral cavity and emotional stability. Some participants expressed their eating behavior had been changed, in that they frequently avoided or altered some types of food and beverages thought to be causes of chronic soreness or exacerbating symptoms. These included eating softer foods with a more liquid consistency, as well as the avoidance of highly seasoned, spiced, or acidic food. Our results are similar to those of Czerninski et al.’s study, which reported that patients with tongue lesions avoided acidic citrus fruits and tomatoes . In addiSubjective pain assessment is generally used as a patient-based outcome in OLP research. Our data exhibited a relationship between clinical severity of OLP and OHRQoL, similar to that with pain. Therefore, this finding supported the validity of the OIDP index to assess the effects of OLP on OHRQoL. The results from this study revealed, for the first time, an association between the clinical severity of OLP, according to the Thongprasom sign scoring system, and the OIDP. Greater clinical severity of OLP was associated with a poorer OHRQoL. Therefore, Thongprasom clinical scores 2 to 4 classify OLP patients according to the degree of daily life problems caused by OLP. For example, the transition from OLP clinical score 2 to score 3, reflects the enlarged atrophic area, diminished OHRQoL. Likewise, changing the clinical scores from 3 to 4 indicated that erosive/ulcerative OLP was associated with the worst OHRQoL. Contrary to expectations, the impacts of OLP with clinical severity scores of 4 and 5 on OHRQoL were unable to demonstrate a statistically significant difference, suggesting that patients might rate their ulcer’s effects to their daily activities, regardless of ulcer size. This finding agreed with that of Osipoff et al. . They peIn terms of OLP types, our findings revealed that erosive/ulcerative type of OLP was associated with more painful symptom and poorer OHRQoL. This was in line with abovementioned finding, indicating OHRQoL worsening for the transition of Thongprasom clinical score 3 to score 4, and was consistent with previous studies reporting more severe pain and problems in quality of life in patients with erosive/ulcerative OLP ,50. FurtThe current finding of reticular lesions, Thongprasom sign score 1 differ from current literature that reticular lesions might not cause any or much problem to patients’ quality of life. We found that patients having such lesions reported higher impacts on OHRQoL during the past 6 months, as well as higher current pain level, than those having OLP scored at 2. Previous studies reported that patients with symptomatic reticular type were more anxious and depressed than those with non-symptomatic reticular OLP ,31. HoweWith respect to OLP pain perception, our data exhibited the relationship between OLP clinical severity and pain perception which was similar to the other OLP clinical grading criteria ,52. ThisOur findings showed that the intensity of oral impacts and OLP pain perception did not depend upon the number of affected lesion sides, but rather on the most severe clinical lesion. As regards localization related to the OHRQoL, the OLP lesions most frequently involved were on the buccal mucosa followed by the gingiva, tongue and lip, while the involvement of the hard palate, floor of the mouth and soft palate were rarely affected. These results are in accordance with previously published studies ,3,53. OsTo the best of our knowledge, there has been scarcely published literature on the association between clinical severity of OLP and OHRQoL of patients, particularly OHRQoL in terms of the ability to perform daily life activities. This current study illustrates that OLP impacted patient’s daily life mostly through problems with eating, cleaning mouth and emotional state. Our findings on the associations between OLP and OHRQoL were slightly different from general expectation, that is, oral impacts were not associated with all aspects of OLP clinical characteristics. The number of lesions did not affect the degree of impacts, while the severity of each lesion did have an effect. The more clinically severe lesion, the higher impacts were perceived, with the exception of ulcerative OLP of which the impacts were highest regardless of the size of lesion. Localization of OLP also played an important role to the degree of impacts, that is, OLP at soft palate tended to cause higher impacts than those occurring at other areas. Therefore, our findings might help clinicians better understand their patients, provide treatment and instructions appropriate to their problem, as well as prioritize treatment needs according to OHRQoL.As discussed above, these preliminary results of association analyses from current investigation were subject to certain limitations. First, our cross-sectional data would not allow for evaluating the effects of OLP treatment on OHRQoL. The data were mostly derived from follow-up patients, while 17.4% of patients were newly diagnosed who never previously been treated. For recall patients, information on OLP treatment was not available. Treatment experience in terms of type and duration of treatment might affect patient’s quality of life. Two previous longitudinal studies following OLP patients after treatments reported significantly improved clinical signs, as well as OHRQoL ,34. TherThe current study demonstrated that nearly all patients had oral impacts affecting their daily activities. The impacts were frequently related to eating, cleaning the oral cavity and emotional stability. There were significant associations between OLP clinical signs and OHRQoL, as well as OLP pain perception among Thai OLP patients. However, some increasing clinical scores did not correspond with increasing OHRQoL. Therefore, using only an OLP sign scoring index or other clinical indicators might fail to acknowledge patient’s perceptions. The results supported the application of OHRQoL assessment to complement OLP clinical measures.


In this group, 56.7% (n = 42) had no or only mild p-OUD and 43.3% (n = 32) had current moderate or severe p-OUD. Patients with moderate or severe p-OUD were more likely to have a current antidepressant prescription, to have had psychotherapy, to currently use strong opioids and oxycodone, and to report taking more frequent doses than prescribed and feeling dependent. (4) Conclusions: We showed that the prevalence of current moderate/severe p-OUD concerned 43.3% of the patients with a CNCP seeking treatment in a pain centre. According to these results, several measures are relevant in managing p-OUD among patients with CNCP. (1) Background: Chronic non-cancer pain (CNCP) remains a public health challenge around the world. Opioids (PO) have been increasingly used in the treatment of CNCP in the last 20 years. This study aimed to assess the prevalence of opioid misuse and prescribed-opioid use disorder (p-OUD) among patients with CNCP in a pain centre in France, and to analyse risk factors for moderate or severe p-OUD. (2) Method: A cross-sectional study was conducted, including patients consulting for pain management in the pain centre of Brest University Hospital. A self-questionnaire was administered  criteria). Descriptive, univariate, and multivariate analyses were conducted, together with a principal component analysis, in order to identify factors associated with p-OUD. (3) Results: In total, 115 patients were included, the majority of whom were women, with a mean age of 52 years old [18–82]; 64.3% ( Chronic non-cancer pain (CNCP) includes any painful ailment that lasts for 3 months or more and is not related to a malignancy . CNCP isThere is poor evidence that the use of opioids for CNCP significantly reduces pain in the long term, and no conclusive evidence of improvement in the quality of life or functioning has been produced ,13,14. LDespite the high prevalence of CNCP and the frequent prescription of opioids, data on the prevalence, risk factors, clinical assessment and management of CNCP and opioid misuse and prescription OUD (p-OUD) is still sparse, particularly in France . A recenThis study aimed to assess the prevalence of current and lifetime opioid misuse and prescription-opioid use disorders (p-OUD) among patients with CNCP in a pain centre in France, and to analyse risk factors and risk indicators for moderate or severe p-OUD. A cross-sectional study was conducted, including patients consulting for pain management in the pain centre (CETD) of Brest University Hospital.Consecutive patients were recruited over a 3-month period from June to September 2016. Patients included were French speakers aged at least 18, which were referred for the first time to the pain centre for chronic non-cancer pain with a current or lifetime use of a PO (at least one month). All patients provided signed informed consent. Patients with pain caused by a current cancer or unable to provide informed consent were excluded. A self-administered questionnaire was developed by the study scientific committee, which included physicians specialised in pain and addictive disorders, general practitioners (GPs), and methodologists. The questionnaire was previously tested on a small sample of patients. All patients referred by their general practitioner to the pain centre in the inclusion period were sent the questionnaire to identify patients with opioid misuse and p-OUD. The patients completed questionnaires at home and returned them at the first visit. The following data were collected in the self-administered questionnaire. Socio-demographic data: Gender, date of birth, number and age of children, and marital and professional status. Medical data: Personal medical and surgical history, lifetime history of pain management . Opioid misuse variables according to the items in the Prescription Opioid Misuse index (POMI) were collected, but questions regarding medical nomadism were excluded, since patients completed the questionnaire before meeting physicians in the pain centre : The useOpioid use disorders (OUD): Current and lifetime prescribed opioid use disorders (p-OUDs) according to the DSM 5  criteria were collected by the questionnaire . This meData were gathered and anonymised in an Excel file. Statistical analyses were performed using R software version 3.5.3. Type 1 error was set at 5%.A descriptive analysis was performed to describe the socio-demographic data of the sample and relevant medical information, and in particular, to estimate the prevalence of p-OUD. Univariate and multivariate analyses were conducted to determine which variables were associated with having either moderate or severe p-OUD. Only variables that were significantly associated with moderate or severe p-OUD in the univariate analyses were included in the multivariate analysis. A stepwise backward elimination algorithm was used to eliminate variables that provided little information in the multivariate model. A principal component analysis was performed to identify whether there were highly correlated sets of variables among variables that were significant in the univariate analyses. The objective was to explore redundancy amongst the explanatory variables for p-OUD.n = 71) were women, 62.6% had a marital status (n = 72), 54.8% were currently working (n = 63), 24.3% (n = 28) were retired and 20.8% (n = 24) were unemployed. Additionally, 27.8% (n = 32) were on sick leave, among whom 10.4% were on occupational sick leave or had an occupational illness. During the 3-month study, 134 patients were referred to the pain centre, and 115 patients were included in the present study . The meaDescriptive characteristics of the population are presented in Characteristics of opioid misuse behaviours are presented in n = 74) had a current prescription for opioid analgesics (weak or strong). In this group, 56.7% (n = 42) had no or only mild p-OUD and 43.3% (n = 32) had current moderate or severe p-OUD. In the group of those meeting the DSM 5 criteria for p-OUD (n = 50), 36% (n = 18) had mild p-OUD, 34% (n = 17) had moderate p-OUD and 30% (n = 15) had severe p-OUD. In the sample, 64.3% (N = 46) of the sample were classified as having either moderate or severe lifetime p-OUD. For lifetime p-OUD, 40% (n = 43); recurrent PO use resulting in failure to fulfil major role obligations at work, school or home ; continuing use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by PO ; and continuing PO use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of PO . The frequencies of positive criteria among the 11 DSM 5 criteria for the diagnosis of OUD are presented in Patients with moderate or severe p-OUD were compared to patients with no or mild p-OUD (0 to 3 positive criteria). p-value is associated with a Fisher exact test. For quantitative variables, the p-value is associated with a Student t test (or a Mann–Whitney test for complex distributions).The results of the univariate analysis are presented in p = 0.986, χ2 = 1.807, df = 8). The multivariate analysis with a backward elimination algorithm retained four variables that were all significantly associated with moderate or severe OUD . The HosPatients with moderate or severe p-OUD were more likely to have a current antidepressant prescription, to have had psychotherapy, to currently use strong opioids and oxycodone, and to report taking more frequent doses than prescribed and feeling dependent. A principal component analysis was performed using variables that were significantly associated with p-OUD in the univariate analysis. The scree plot analysis and a parallel analysis retained four factors. The positions of patients and variables relative to the two main components are shown in Three factors were retained on the basis of the results from both the scree plot analysis and the parallel analysis. The most relevant factors are presented in In the present study, 43.3% of CNCP patients referred for the first time to a specialized pain center reported current moderate or severe p-OUD. Among those meeting the p-OUD criteria, 34% had moderate p-OUD and 30% had severe p-OUD. The proportion of severe patients is smaller in our study than in a recent French study led by Eiden et al. (52%) , but theRegarding the DSM 5 OUD criteria frequencies, the most frequent were the persistent desire to stop opioids (37.4%), the continuing use of opioids despite the psychological or physical damage induced or exacerbated by opioids 34.8%) and the failure to fulfil obligations due to opioid use (36.5%). This perceived damage in the daily life is coherent with the deterioration in quality of life described with long-term use of analgesic opioids [.8% and tThe patients also reported PO misuse: 16.5% of the sample did not always or never followed the medical prescriptions of PO, 15.6% reported that they used PO to obtain other effects than analgesia, 13.5% were using higher doses, and 10.4% reported a more frequent use than that provided for in the prescription. We also found that the use of more frequent doses of PO was significantly associated with moderate or severe p-OUD in the multivariate analysis (OR=5.36). Further to this, the feeling of being dependent on PO (OR = 3.7) was significantly associated with p-OUD in the multivariate analysis. This could reflect the need to implicate and inform patients before PO initiation on the risks of misuse and dependence . PreviouFactors significantly associated with p-OUD in the multivariate analysis were first related to pharmacological variables: current prescription of strong opioids (OR = 0.28), and current use of oxycodone (OR = 6.17) were both significantly associated with moderate or severe p-OUD. This could reflect the greater pharmacological addictive potential of strong POs, and more particularly oxycodone in this study . In the The second factor identified in the factorial analysis, was the factor termed “psychosocial vulnerability”. This factor combined three variables: the first was being on sick leave, which was associated with having received psychotherapy, and hypnosis. Sick leave could reflect difficulties regarding employment, and probably difficult financial conditions. It could contribute to greater environmental vulnerability towards p-OUD . One hypThe third factor, “psychiatric and addictive vulnerability” combines the current prescription of antidepressants, which was also significantly associated with p-OUD (OR=7.14) in the multivariate analysis, with the variables “history of addictive disorders” and “history of psychiatric disorders”. According to previous reviews, CNCP patients with a past or present history of substance use disorder and a psychiatric history, had a greater risk of PO misuse and dependence ,46,47,48This study has several limitations. It was a single-centre study, so that results cannot be generalized. The data was self-reported, while DSM-5 criteria assessed by a physician would have been preferable. The setting could influence patients, constituting a social desirability bias, but this method has already been applied in previous studies ,31. The Strengths of the present study include firstly the fact that studies on OUD among patients with CNCP in a specialized centre are sparse, particularly in Europe. Secondly, this study collected clinical data related to pain and also to addictive disorders and their risk factors. To our knowledge, it is the first in France to follow this method. Finally, the sample is large, compared to the existing literature, even if results need to be confirmed in a multi-centre study.In a therapeutic perspective, the high prevalence of moderate/severe OUD in this sample of patients with CNCP highlights the need to strengthen interdisciplinary communication, and to develop the multidisciplinary management of p-OUD, including pain physicians and physicians specialized in addictive disorders, as recently underlined by an international expert consensus . FurtherIn a preventive perspective, improving PO practices for pain management is necessary . EvidencIn this study, we have shown that the prevalence of current moderate/severe p-OUD concerned 43.3% of the patients with a CNCP seeking treatment in a pain centre. We evidenced that factors correlated with the risk of p-OUD in this population concerned individual and environmental vulnerabilities and also factors linked to therapeutic strategies. According to these results, several measures are relevant in managing p-OUD among patients with CNCP, combining specialized care including pain and addiction treatment, and prevention measures in primary care. Primary care-based interventions could be developed targeting psycho-education of patients with CNCP along with non-pharmacological interventions such as hypnosis or CBT, patient information on prescribed opioid side-effects, including dependence risks, and an evaluation of pain treatment management centred on patients’ feelings and quality-of-life. The implementation of these measures in specialized and primary care in collaboration with physicians specialized in addictive disorders and chronic pain management could help to reduce p-OUD among patients with CNCP.


Background and Objectives: Choosing a pain management strategy is essential for improving recovery after surgery. Effective pain management reduces the stress response, facilitates mobilization, and improves the quality of the postoperative period. The aim of the study was to assess the effectiveness of pain management in patients after surgery. Materials and Methods: The study included 216 patients operated on in the following surgical wards: the Department of Cardiosurgery and the Department of General and Endocrine Surgery. Patients were hospitalized on average for 6 ± 4.5 days. Patients were randomly selected for the study using a questionnaire technique with a numerical rating scale. Results: Immediately after surgery, pre-emptive analgesia, multimodal analgesia, and analgosedation were used significantly more frequently than other methods (p < 0.001). In the subsequent postoperative days, the method of administering drugs on demand was used most often. Patients with confirmed complications during postoperative wound healing required significantly more frequent use of drugs from Steps 2 and 3 of the World Health Organization (WHO) analgesic ladder compared with patients without complications. Conclusion: The mode of patient admission for surgery significantly affected the level of pain perception. Different pain management methods were used and not every method was effective. An important element of postoperative management is the reduction of pain caused by intraoperative tissue and/or organ damage. The intensity of pain is significantly affected by the extent of the surgical procedure, its location, and the postoperative day of monitoring, among others . ChoosinThis observational study included 216 consecutive patients who were operated on in the surgical wards of the University Clinical Hospital in Bialystok at the end of 2017 and the beginning of 2018. A group of 112 patients was selected from the Department of Cardiosurgery, where coronary artery bypass grafting (CABG), transcatheter aortic valve implantation (TAVI), ascending aortic aneurysm surgery, aortic arch aneurysm repair, minimally invasive direct coronary artery bypass (MIDCAB), and procedures performed due to congenital and acquired heart defects are performed. Patients were discharged from the department 15 ± 2.1 days after surgery, on average.A group of 104 patients was operated on at the First Clinical Department of General and Endocrine Surgery. Cholecystectomy, sleeve gastrectomy due to morbid obesity, esophageal hiatus hernia surgery, abdominal hernia repair, thyroid and parathyroid resection, and lower limb varicose vein removal were performed. All patients were operated on using the laparoscopic method. Patients were discharged from the department an average of 6 ± 4.5 days after surgery.The study analyzed the individual medical documentation of patients regarding the admission mode, the type of surgery performed, the state of the postoperative wound, the type of analgesics used, and the effectiveness of their action. The original questionnaire consisted of 10 closed-ended questions regarding place of residence, professional activity, and housing conditions. Additionally, in order to determine the intensity of pain and the effectiveness of analgesic treatment, a numerical rating scale (NRS) with 11 degrees of pain severity was used: from 0 to 10, where 0 meant a complete lack of pain and 10 the worst imaginable pain ,7,8. PaiThe study was performed from January to December 2017. The research conforms with Good Clinical Practice guidelines, and the followed procedures were in accordance with the Helsinki Declaration. All patients signed a consent form to participate in the study. The research was approved by the Bioethics Committee of the Medical University of Bialystok .p less than 0.05.Statistical analysis was done using the Statistica 7.0 software from StatSoft Polska. In the data analysis, we used significance tests for qualitative variables (categorized), the chi-square test, and Pearson’s correlation coefficient (Pearson’s r) . The condition for statistical significance was a level of n = 65, 58.4%). Postoperative pain was felt by 82.87% of patients. On the NRS scale, 9 points was indicated by 8.33% of patients, 8 points by 16.20%, 7 points by 21.76%, 5 points by 16.67%, 4 points by 12.04%, 3 points by 3.70%, and the maximum value on the NRS scale of 10 points was not indicated.The study included 109 women (50.46%) and 107 men (49.54%): 52 women (46.43%) and 60 men (53.57%) at the Department of Cardiosurgery and 57 women (54.81%) and 47 men (45.19%) at the First Clinical Department of General and Endocrine Surgery. The mean age of the respondents was 50 ± 11.4 years. The city was the most frequent place of residence for 62.95% of the patients. The occupational activity of the patients varied in both departments. Among the patients operated on at the Department of Cardiosurgery, there were more people on retirement and/or disability pensions (p = 0.017).In the admission to both departments, the scheduled mode was predominant . Patients who were admitted in the emergency mode had significantly higher pain severity according to the NRS scale than those hospitalized in the planned (scheduled) mode. We found that the admission mode significantly affected the level of pain perception by the patient , ketoprofen (67.13%), and metamizole (60.19%) were most commonly used, and in individual situations, ibuprofen (4.63%) was used.Pain of a severity of >4–6 was managed by means of a drug classified as Step 2 on the World Health Organization (WHO) analgesic ladder; in all patients it was tramadol. Administration of drugs from the first step was continued, combining tramadol with paracetamol.In the case of painful symptoms of significant intensity , which affected 46.30% of patients, drugs from the group of “strong” opioids were used. The most frequently administered were fentanyl and derivatives (84.00%), morphine (37.00%), pethidine (19.00%), buprenorphine (13.00%), or oxycodone (10.00%).Drugs from both Steps 2 and 3 of the WHO analgesic ladder were more often administered to patients in the management of pain at the Department of Cardiosurgery  rather tIn the analgesic treatment among the studied patients, drugs from Steps 2 and 3 of the WHO analgesic ladder were significantly more frequently administered to patients admitted in the emergency mode to both the Department of Cardiosurgery and the Department of General Surgery  rather tPatients with confirmed complications during postoperative wound healing required significantly more frequent use of drugs from Steps 2 and 3 of the WHO analgesic ladder  than patp < 0.001) than other methods. In the subsequent postoperative days, the method of administering drugs on demand was used most often  was adopted .2, r = 0.7488, p = 0.0001). All patients assessing the level of pain before treatment from 0 to 2 rated it at 0 on the NRS scale after treatment; among those assessing the pain level at 3, 57.69% indicated 0 and the remaining patients indicated 1 after treatment. In the group of people experiencing pain at 5 and 6 points before receiving medication, more than 90% indicated pain below 3 on the NRS after treatment. Patients evaluating pain at 9 points indicated a maximum of 4 (44.44%) after treatment  and patients undergoing extensive surgery. However, many studies indicate that the implemented procedures often remain inadequate for the pain intensity. This increases the risk of persistent postoperative pain and mood disorders, hinders rehabilitation, and extends the time it takes to return to full physical activity ,8,9,10.Pain occurs after intraoperative anesthesia subsidence, and its greatest intensity is observed on the first and second postoperative days. Systematic monitoring of pain at comparable time intervals is important, basic, and necessary. This allows the assessment of changes in the severity of pain over time. A study conducted in Denmark by Mathiesen et al.  among 12At the Department of Cardiosurgery, CABG (45.54%) procedures were the most frequently performed, as well as TAVI through the femoral artery (15.18%), ascending aortic aneurysm surgery (9.82%), and MIDCAB (7.14%). At the First Clinical Department of General and Endocrine Surgery, laparoscopic procedures were primarily performed: cholecystectomy (14.42%), gastric resection due to morbid obesity (14.42%), esophageal hiatus hernia surgery, and abdominal hernia repair (9.62%). The results of the study showed that on the second postoperative day about 90% of patients experienced pain between 2 and 4 points on the NRS. However, on the fourth day, a similar number of patients reported pain at a level of 1 to 3 points. The location of the pain depended on the surgical procedure performed.The results of our study confirmed higher pain intensity in the immediate postoperative day at the Department of General Surgery. The low pain score obtained at the Department of Cardiosurgery can be explained by the analgosedation method, i.e., pharmacological block, and the continuous infusion of analgesics from Step 3 of the WHO analgesic ladder. In the remaining patients, pre-emptive analgesia, administration of drugs in a single dose, or combination therapy dominated. Pain reduction was achieved in all patients, which was at least 50% compared with the baseline. This indicates effective pain management in accordance with the recommendations of the American Pain Society ,13. One In modern surgery, surgical site infections occur often. Among factors that have a significant impact on the occurrence of wound healing complications, Montewka M. et al.  indicateMinkowitz H. et al.  comparedIn a study conducted by Fassoulaki A. et al. , the anaIn our study, the choice of the pain management method was influenced by the surgical procedure. Jakubów P. et al.  analyzedAccording to generally accepted recommendations ,3,21, paAt the Department of General and Endocrine Surgery, the administration of drugs in single doses (at the patient’s request) was used more often than at the Department of Cardiosurgery. This is due to less invasive surgical methods being used. During treatment at the patient’s request, paracetamol (91.80%), ketoprofen (64.48%), metamizole (57.92%), tramadol (43.17%), and fentanyl (30.05%) were primarily used; in a few cases, morphine was used (9.29%). The presented results are in accordance with global recommendations for pain management after surgery.The mode of patient admission for surgery significantly affected the level of pain perception. Patients operated on in the emergency mode had significantly higher pain severity according to the NRS scale than those hospitalized in the planned mode. The state of the postoperative wound affected pain severity. The lowest pain intensity after the procedure was experienced by patients who did not have postoperative wound draining.Different pain management methods were used, and not every method was effective. The highest effectiveness in the treatment of postoperative pain was achieved using analgosedation, PCA, and pre-emptive analgesia.There is a need to introduce unified hospital procedures for postoperative pain management.


Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) carry significant morbidity and mortality. AECOPD treatment remains limited. High molecular weight hyaluronan (HMW-HA) is a glycosaminoglycan sugar, which is a physiological constituent of the lung extracellular matrix and has notable anti-inflammatory and hydrating properties.We hypothesized that inhaled HMW-HA will improve outcomes in AECOPD.We conducted a single center, randomized, placebo-controlled, double-blind study to investigate the effect of inhaled HMW-HA in patients with severe AECOPD necessitating non-invasive positive-pressure ventilation (NIPPV). Primary endpoint was time until liberation from NIPPV.Out of 44 screened patients, 41 were included in the study (21 for placebo and 20 for HMW-HA). Patients treated with HMW-HA had significantly shorter duration of NIPPV. HMW-HA treated patients also had lower measured peak airway pressures on the ventilator and lower systemic inflammation markers after liberation from NIPPV. In vitro testing showed that HMW-HA significantly improved mucociliary transport in air–liquid interface cultures of primary bronchial cells from COPD patients and healthy primary cells exposed to cigarette smoke extract.www.clinicaltrials.gov).Inhaled HMW-HA shortens the duration of respiratory failure and need for non-invasive ventilation in patients with AECOPD. Beneficial effects of HMW-HA on mucociliary clearance and inflammation may account for some of the effects (NCT02674880,  The morbidity and mortality associated with chronic obstructive pulmonary disease (COPD) is increasing worldwide. The World Health Organization predicts that COPD will become the third leading cause of death worldwide by 2030 . COPD reHigh molecular weight hyaluronan (HMW-HA) is a naturally occurring sugar, that is abundant in the extracellular matrix, including in the lung. HMW-HA has several properties that make it an attractive candidate as a therapeutic in AECOPD: HMW-HA is a very hydrophilic molecule , and has2 > 45 mm Hg in arterial blood gas analysis, new or increased compared to baseline, when a baseline value was available). Exclusion criteria were respiratory arrest or need for immediate intubation, overt pneumonia on chest X-ray, significant non-COPD contributing factors to respiratory failure (e.g. congestive heart failure), contraindications to NIPPV  or inability to consent or cooperate with NIPPV. After informed consent, patients were randomized 1:1 to receive study treatment, either HMW-HA or identical-looking placebo. The HMW-HA preparation was Yabro® . Yabro® and placebo were generous donations of the manufacturer, who had the key to the randomization schema. Patients were treated with NIPPV using a Hamilton C1 ventilator and medical therapy according to current guidelines  [® or placebo via a non-ultrasonic jet nebulizer  twice daily, until they were liberated from NIPPV or until NIPPV failure, defined as need for orotracheal intubation due to difficulty in managing airway secretions, worsening arterial blood gas parameters, or cardiorespiratory arrest. The decision to liberate from NIPPV was reached as follows: for patients not on home/chronic NIPPV, NIPPV was discontinued when an improvement of pH and/or a pCO2 < 55 was reached. For patients using home/chronic NIPPV (4/21 in the placebo group and 3/20 in the Yabro® group), NIPPV was reset to home settings when an improvement of pH and/or pCO2 was reached, and this was considered to be equivalent to “liberation from NIPPV” status. The study was co-sponsored by the National Institute of Environmental Health Sciences, National Institutes of Health, USA, and the Campus Bio-Medico, University of Rome, Italy. The manufacturer had no role in the conduct or analysis of this study. Serum was collected on admission and after liberation from NIPPV and stored at − 80 °C until analyzed.This was a parallel-arm, randomized, placebo-controlled, double-blinded, single-center pilot study of patients admitted to the Intermediate Care Section, Geriatric Unit, Campus Bio-Medico, University of Rome, between March 2016 and July 2019. Included were adult patients with known history of physician-diagnosed COPD and acute exacerbation requiring NIPPV, as evidenced by respiratory distress (new-onset moderate to severe dyspnea and use of accessory breathing muscles) and hypercapnic respiratory failure ; and (b) markers of systemic inflammation associated with AECOPD  [The primary outcome was duration until liberation from NIPPV or NIPPV failure. Secondary outcomes were: (a) respiratory physiology parameters  –24. AdveCumulative hours on NIPPV were plotted on GraphPad Prism, version 8, and analyzed using the log-rank Mantel-Cox test. NIPPV days and hospital length-of-stay values were analyzed for normality using GraphPad Prism software and comparisons were performed either using the Student’s t-test or Mann–Whitney test according to normality. Categorical variables were analyzed using Fisher’s exact test. For inflammation markers, values for the 4 analytes  were ln-transformed to more closely approximate normality. Data were cast in “long” format with 8 records per subject: 4 reactants × 2 times (pre- and post-treatment) and analyzed using SAS 9.4 Proc Mixed, regressing the ln on treatment group (HMW-HA vs. placebo), timing (pre vs. post), and reactant type, with timing and reactant type as repeated measures, and subject ID entered to capture the subject effect. In initial models we included the 3-way interaction of group × timing × reactant, plus all possible 2-way interactions and main effects. We tested this 3-way model with three different Kronecker product covariance structures , which aTo gain novel mechanistic insights into the effect of HMW-HA effects in COPD, we analyzed its effect on mucociliary clearance, since airway clearance is important for both chronic and acute COPD management . PrimaryCigarette smoke extract were generated using filtered cigarettes  and absorbed on Dimethyl Sulphoxide (DMSO), then sterile filtered before using in cell culture and stored at − 80 °C for further use , 30. DifTo assess the functional microanatomy in cell culture, µOCT imaging was performed before and 24 h after treatment conditions, as described –33. AirwThe physicians at Campus Biomedico have developed a home care monitoring system based on wearable sensors which allows detection of AECOPD in early stages . AccordiThe primary outcome for this study was cumulative duration on NIPPV. We found that patients treated with HMW-HA were liberated from NIPPV significantly faster than placebo-treated patients Fig. a. The ef2/FiO2 ratio improved significantly only in the HMW-HA treated group, comparing admission and day of liberation from NIPPV  and not in the placebo group   Fig. b. Notablups Fig. c, possibFor logistical reasons, we only evaluated serum markers of inflammation on admission and on the day of liberation from NIPPV. Unfortunately, some samples were destroyed inadvertently while in transit from Italy to the US lab for analysis, therefore only 13 samples per group could be analyzed. When we tested 3-way interaction of treatment effect with timing (pre-post) and inflammation marker, we did not observe a significant difference between HMW-HA and placebo. In both groups, acute phase inflammation marker values generally decreased over time, reflecting the general health improvement for patients. Interestingly however, HMW-HA-treated patients had a more pronounced response in inflammation markers than placebo-treated patients. When we ran separate models for each group, in placebo patients the timing-effect interaction lost significance (p = 0.162), while in HMW-HA-treated patients the timing-effect interaction remained significant (p = 0.039)  cells derived from patients with COPD. In other experiments we studied HBE cells from healthy non-smokers exposed to cigarette smoke extract (CSE). We evaluated functional microanatomy using µOCT before and after addition of HMW-HA in comparison to vehicle control Fig. . RepreseIn this work we demonstrate that treatment with inhaled HMW-HA shortens the duration of acute respiratory failure and is associated with improved lung function and systemic inflammation in patients with AECOPD. Mechanistically, we show that HMW-HA improves mucociliary transport in airway epithelia that exhibit COPD-like manifestations. Our study shows for the first time the therapeutic potential of an extracellular matrix molecule in acute exacerbation of human lung disease.HMW-HA had a clinically meaningful salutary effect in the primary outcome, duration of NIPPV. These results will need to be confirmed in larger studies but would suggest an important role of HMW-HA in the treatment of AECOPD, since they demonstrate added benefit in patients who were already receiving state-of-the-art AECOPD therapy. Duration of intensive care is independently associated with in-hospital mortality in AECOPD  and is aHMW-HA is found in high concentrations in the lung matrix under physiological conditions  and is d® inhalation. This is not unexpected; inhaled HMW-HA has been used routinely, together with hypertonic saline, in cystic fibrosis patients with no reported side effects; rather it improves tolerability and decrease the need for bronchodilators in these patients [HMW-HA possesses several beneficial properties which make it an attractive candidate as an exogenously administered treatment option in inflammatory lung disease. HMW-HA is a naturally occurring sugar , and thepatients , 52. In patients . This prpatients , HMW-HA patients  and coulpatients  and prompatients .x vivo, HMW-HA inhibited LPS-induced TNFα release by whole blood from COPD patients [HMW-HA also has potent anti-inflammatory and pro-homeostatic properties. In murine models, HMW-HA ameliorates acute allergic and non-allergic inflammation , 55, 56 patients . Thus, Hpatients –24. In aAnother mechanism of improved lung function by HMW-HA administration may be reduction of bronchial constriction. Several studies have shown that HMW-HA ameliorates inflammation-associated airway hyperresponsiveness in murine models –14 and i2 and NIPPV use, thus we would expect that there were no significant differences in lung function either. Also, as described in “2: these were not patients with hyperacute exacerbation, but rather progressively declining patients who failed to respond to outpatient management, and therefore had time to at least partially compensate their acid–base status. Finally, these patients represent cases of community- “acquired” COPD exacerbation, and therefore it is not clear if HMWHA benefits also apply to cases of deterioration in the inpatient setting, or in the case of patients that need invasive ventilation.There are several limitations to this pilot study. Due to the small number of patients and the single-center nature of the study, its results would certainly need to be validated and replicated in larger studies. This study stretched over 2–3 years, thus introducing a potential variability in treatment approaches. However, this was at least partially counteracted by the fact that only 2 dedicated physicians led the treatment of recruited patients throughout the study duration. We unfortunately did not have background information regarding lung function or baseline blood gas values in these patients, and therefore we cannot fully comment on the severity of pre-existing COPD. However, the two groups were well-matched with regard to clinical parameters, i.e. home OInhaled HMWHA may be beneficial in severe AECOPD, by improving inflammation and lung function, and reducing the need for ventilatory support. Our study supports the use of a novel class of treatment, i.e. matrix biologics, in acute and chronic lung disease. Additional studies should confirm our findings with higher number of patients in additional clinical sites and explore the use of HMWHA in chronic COPD, both to reduce COPD progression and to decrease exacerbations which are the major driver of morbidity, mortality and cost in this devastating disease.


The Fibromyalgia Survey Questionnaire (FSQ) was self-administered by a sample of 207 Italian individuals with obesity to screen for fibromyalgia (FM). We aimed to investigate the inter-rater reliability and the agreement in the detection of FM symptomatology between the self-administered FSQ and the clinical interview conducted by a rheumatologist. All the patients were divided randomly into two groups (group A and group B): a rheumatologist first interviewed patients of group A and after 48 h, the patients completed the self-report FSQ. Patients of group B first completed the FSQ and 48 h later were interviewed by a rheumatologist. The agreement between the measurements was good with the Bland-Altman analysis showing low bias scores for the two subscales of the FSQ. Results showed that 33% of the sample satisfied the criteria for a diagnosis of fibromyalgia. The FSQ is a self-reporting measure that showed substantial reliability providing fast screening for FM symptomatology. Fibromyalgia (FM) is a syndrome with unclear etiopathogenesis, characterized by chronic widespread pain, fatigue, sleep disturbances, and many other symptoms that significantly worsen quality of life  ≥ 7 and Symptom Severity Score (SSS) ≥5 or WPI 3–6 and SSS ≥9;Criterion 2: Symptoms have been present at a similar level for at least 3 months;Criterion 3: The patient does not have a disorder that would otherwise explain the pain.The WPI includes 19 non-articular pain sites; meanwhile, the SSS measures the severity of three major symptoms , and the severity of the somatic symptoms in general, rated by the physician. While for this classification, the SSS score required physician evaluation, a further change in 2011 removed the physician assessment of the extent of somatic symptoms and replaced it by a summary score of three self-reported symptoms, making it easier to use. This modification enabled researchers to use these criteria in epidemiological and clinical studies without the requirement for an examiner.Lastly, after the 2016 revision, fibromyalgia may be diagnosed when all of the following criteria are met: (1) WPI ≥ 7/19 pain sites and SSS ≥ 5/12 or WPI between > 3–6/19 and SSS > 9/12; (2) symptoms have been present at a similar level for at least 3 months; (3) the patient does not have another disorder that would otherwise sufficiently explain the pain; and (4) generalized pain, defined as pain in at least four of five regions, is present  has been proposed for this purpose to assess ACR conditions 1 and 2 on the two subscales: the WPI and the SSS , a clinic specializing in the rehabilitation of obesity and physical therapy. Consecutive patients were asked to take part in the study and give their informed written consent to the study, which had been approved by the Institutional Ethics Committee.Demographic data  were assessed using a self-report questionnaire. Two-hundred and twenty-five obese patients were recruited: 12 did not give their consent to the study and six patients were excluded from the analyses because of a high number of missing items; the final sample consisted of 207 subjects.The FSQ had been forward and back translated to ensure the semantic equivalence of the Italian and the English version by four rheumatologists, fluent in English, and experts in fibromyalgia. The clinical interview was conducted according to the 2010 ACR criteria  in which the patient indicates they experienced pain during the preceding week, i.e., it can range from 0 to 19. The SSS consists of two parts:Part 1: the patient grades the severity over the last week of three somatic symptoms  on a scale of 0–3, resulting in a maximum score of 9;Part 2: the patient grades the severity of the following three symptoms on a 4-point scale , occurring during the previous 6 months: headaches, pain, or cramps in the lower abdomen and depression .Furthermore, a poly-symptomatic distress (PSD) scale can be also calculated by the sum of the two component scores, WPI and SSS .Descriptive statistics were used to describe the socio-demographic and clinical data. Internal consistency of the total scales and relative subscales was assessed by Cronbach's α; values of 0.7 and higher were considered desirable  were used to measure agreement between the two different tools, using a two-way mixed-effect model based on single ratings, for criteria 1 and 2. Mean estimations along with 95% confidence intervals (CI) were reported for each ICC. Furthermore, to measure continuous variable agreement , we used Bland-Altman analysis . All participants had a diagnosis of obesity, with a level of BMI ≥ 30 (mean ± SD: 40.54 ± 6.45). More than half the patients (59%) had achieved a basic education and only 20 subjects (10%) had a tertiary education level.p < 0.0005, index of a substantial strength of agreement . Sixty-nine (33%) subjects were found positive by both the FSQ and interview vs. 103 patients that did not satisfy the criteria. There was good agreement between the two measurements, κ = 0.653 , with a  Altman, . A minorA high degree of reliability on criterion 1 was also underlined by the interclass correlation. For the PSD scale, the average ICC measure was 0.899 with a 95% CI from 0.867 to 0.923, indicating good reliability  was found with the Bland-Altman 95% limits of agreement of −0.97 and 0.11 (p = 0.472). Similar values were found for the SSS, with a bias of 0.030 (p = 0.062): mean scores found by the FSQ were 5.29 ± 3.22 vs. 5.59 ± 4.22 by the interview.A low bias score between the two assessments was found: regarding PSD, a bias of 0.43  results. Also, concerning the composition of our sample, we found that approximately a third of the patients satisfied the criteria for FM, in line with a previous study conducted on obese patients that reported a prevalence rate of 27.7% (Arreghini et al., Given the poor generalizability of our work, performed on a relatively small sample of patients with obesity, further validation studies in the Italian language and on a larger patient population are needed.In conclusion, a self-reporting measure like the FSQ could provide a time-efficient method for the initial identification of patients with high pain sensitivity. Early diagnosis allows for the initiation of non-pharmacological approaches, such as psychotherapy or physical treatment, and could also reduce national healthcare costs.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Istituto Auxologico Italiano-IRCCS. The patients/participants provided their written informed consent to participate in this study.GV and AG conceived and designed the study protocol with input from PC, MA, LC, and GC. GM carried out literature searches. AG designed and carried out the statistical analysis. GV, AG, MA, and EG interpreted the data and drafted the manuscript. EG and LC supervised the writing of the manuscript. All authors critically reviewed and contribute to the final version of the paper.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.