Trauma is a common aetiology of acute pain in the emergency setting, and traumatic injuries have been recognised as a global public health crisis leading to numerous deaths and disabilities. This study aimed to identify the prevalence of acute pain among high acuity trauma patients presenting to a public sector emergency medical service and to describe prehospital acute traumatic pain assessment and management practices amongst emergency care providers in the Western Cape Province, South Africa.A retrospective review of electronic patient care reports of trauma patients treated by the South African Western Cape Emergency Medical Services between January 1 and December 31, 2017 was conducted. Stratified random sampling was utilised to select 2401 trauma patients out of 24,575 that met the inclusion criteria.n = 194) of patients had pain or tenderness mentioned in the working diagnosis but no pain score noted. Eighty-one (18.6%) patients experienced mild pain, 175 (40.2%) moderate pain and 167 (38.2%) severe pain. No association was found between a pain score recorded and age group (≤ 14 versus > 14 years) (p = 0.649) or gender (p = 0.139). Only 7.6% of patients with moderate-to-severe pain and 2.8% of all trauma patients received any form of analgesic medication. No association was found between the administration of analgesia and age group (≤ 14 versus > 14 years) (p = 0.151) or gender (p = 0.054). Patients were more likely to receive analgesia if they had a pain score recorded (p < 0.001), were managed by advanced life support practitioners (p < 0.001) or had severe pain (p = 0.001).Of the 2401 patients reviewed, 435 (18.1%) had a pain score recorded, of which 423 (97.2%) were experiencing pain. An additional 8.1% (Acute trauma pain assessment and management practices in this prehospital cohort are less well established than reported elsewhere and whether this reflects emergency care training, institutional culture, scopes of practice or analgesic resources, requires further research. Emergency medical services need to monitor and promote quality pain care, enhance pain education and ensure that all levels of emergency care providers have access to analgesic medication approved for prehospital use. Clear and rational guidelines would enable better pain management by all cadres of providers, for all levels of pain. Traumatic injuries are a global public health crisis with more than 4.8 million deaths annually, and many more left disabled , 2. In SIn addition to relieving suffering and enabling diagnostic and treatment processes in the acute setting, pain control carries further benefits which include reducing the psychological (e.g. anxiety) and physiological effects of acute pain, infection risk, the risk for developing chronic pain and improving patient satisfaction, recovery time and outcomes –15. FailIn the African prehospital setting, little is known about acute pain, with no studies reporting on the epidemiological characteristics of acute traumatic pain, and limited studies describing pain management practices , 21. The2 and a population exceeding 6.3 million. WCEMS operates around 250 ambulances throughout the province, staffed at either basic life support (BLS), intermediate life support (ILS) or advanced life support (ALS) emergency care levels.A retrospective review of electronic patient care reports (ePCRs) of high acuity trauma patients treated by the Western Cape Emergency Medical Services (WCEMS) was conducted between January 1 and December 31, 2017. The WCEMS is a government-operated emergency medical service (EMS) which serves the communities of the Western Cape, one of the nine South African provinces, with an area of 190,370 kmPrehospital emergency care education in South Africa has occurred through short course (three-tiered) training, but increasingly through higher education and training , 24. MosBLS and ILS practitioners are restricted to the use of self-administered inhaled nitrous oxide (Entonox®) for the relief of pain arising from myocardial infarction, musculoskeletal trauma, burns, active labour and any other condition requiring pain relief where no contraindication is present. ALS practitioners, according to their specific qualifications, may administer intravenous (IV) morphine (some requiring permission from university degree ALS practitioners or a doctor), and IV or intranasal (IN) ketamine may be administered by ALS practitioners with a university degree.In 2016, WCEMS rolled out an ePCR system which replaced paper-based patient care reports with real-time digital capturing of patient care records of all prehospital patient encounters . The sysInclusion criteria were adult and paediatric patients with acute trauma (primary emergencies) and a South African Triage Scale (SATS) final priority colour of yellow, orange or red which denote urgent, very urgent or emergency patients, respectively , managedA total of 24,575 trauma patients met the inclusion criteria. Stratified random sampling was utilised to select a representative sample of the study population. A sample of 2401 was calculated using an online sample size calculator  with an M) and interquartile range (IQR)) were calculated for patient characteristics, incident types, injuries sustained, pain score, pain severity and non-pharmacological and pharmacological pain management and presented in graphs and tables. The Pearson chi-square test of independence  was used to determine relationships between the categorical variables, pain score recorded (yes/no) and age group (≤ 14 and > 14 years), gender, final triage colour  and analgesic medication administrated (yes/no) as well as between analgesic medication administrated (yes/no) and age group (≤ 14 and > 14 years), gender, crew highest qualification  and pain severity . If relationships between categorical variables were identified, the strength of association was assessed with Phi (ϕ) and Cramer’s V (ϕc) correlation coefficient.Data were extracted from the WCEMS ePCR system and analysed using the SPSS statistics software . Shapiro-Wilk tests were conducted to assess for normality. Descriptive statistics  while the remaining 2129 (88.7%) were > 14 years  of which 80.5% (n = 1713) were between 15–44 years of age. High acuity patients (SATS red or orange) accounted for 35.0% (n = 839) of all cases  patients were ≤ 14 years of age  of patients reportedly sustained fractures/dislocations/deformities (with 9 (4.8%) sustaining more than one fracture). The most common injury site was lower extremities  followed by upper extremities  while 5 (2.6%) of these patients injured both upper and lower limbs, and 15 (8%) patients were thought to have a pelvis/hip fracture.Almost 15% (Of the 59 (4.6%) patients who had burns documented, 25 (42.4%) had a percentage of burn area recorded (range 1–80%). The remaining patients either had no description of the burn or had the burn described in terms of location, type of burn and/or burn severity.IQR 4–8). Seventy-two (16.6%) of the patients with a pain score had at least one repeated pain score recorded. Figure A total of 435 (18.1%) patients had a pain score recorded. The median pain score was 6 (p = 0.649), gender (p = 0.139) or final triage colour (p = 0.076). The majority (78.6%) of those with a pain score reported moderate-to-severe pain  patients. Of note, the records of numerous other patients indicated injuries likely to be painful for which the presence of pain was not recorded.No association was found between a pain score being recorded and age group (≤ 14 versus > 14 years) , application of splints  and burn dressings .A range of physical non-pharmacological management approaches were recorded in the ePCR including haemorrhage control  patients received medication with analgesic properties of which 27 (39.7%) had a pain score recorded. IV morphine was administered to 66  patients while one received IV ketamine and one intramuscular (IM) diclofenac, firstly or only. Of all the patients (n = 66) who received IV morphine, 10 (15.2%) received an additional morphine dose  and 6 (9.1%) received ketamine [IV or IM] (one paediatric) in addition to the initial morphine. None of the patients received inhaled nitrous oxide.Only 68 (n = 26) received analgesic medication. Fifty-two (78.8%) of the 66 patients who received morphine were male, while 4 (6.1%) were ≤ 14 years. The patients who received ketamine and diclofenac were both > 14 years and male. No association was found between the administration of analgesic medications and gender (p = 0.054) or age group (≤ 14 versus > 14 years) (p = 0.151).Of the 342 patients with moderate-to-severe pain recorded, only 7.6%  or ILS  while for the remaining 62 (91.2%) patients it was documented as an ALS level qualification (Emergency Care Technician (ECT): n = 22, 32.3%, ALS: n = 32, 47.1% and Emergency Care Practitioner (ECP): n = 8, 11.8%). An association was found between the documented highest qualification  and the administration of analgesic medication (p < 0.001). Patients, where the highest qualification was documented as an ALS  level, were more likely to receive analgesia medication. The strength of the association was weak (ϕc = 0.242).For six (8.8%) of the patients who received analgesic medication, the highest qualification of the crew was documented as BLS (p < 0.001). Patients with a pain score were more likely to receive analgesic medication; however, the strength of association was weak (ϕ = -0.096). An association was also found between pain severity  and the administration of analgesic medication (p = 0.001). Patients with severe pain were more likely to receive analgesic medication; however, the strength of association was weak (ϕc = 0.188).Additionally, an association was found between a pain score being recorded and the administration of analgesic medication . International studies, likewise, report the prevalence of pain among trauma patients to be high (> 70%) , 31 with%. InternThe lack of pain assessment has been identified as a hindrance to adequate pain management , 32. TheThe use of age-appropriate pain scales as part of general patient care, and regarding all trauma patients with acute pain as candidates for analgesia with regular pain reassessment, is evidence-based recommendations made in a clinical practice guideline (CPG) published in the United States of America  and receWhile clear prehospital pain assessment guidelines are helpful, the most frequent reason proposed for the insufficient documentation of pain assessment is a lack of pain knowledge , 39, 40.Non-pharmacological pain management interventions are more commonly associated with the non-emergency setting. However, cognitive and psychological interventions like reassurance, distraction, and physical interventions like positioning, splinting fractures and burn dressings can all be utilised in the prehospital setting . PsycholMost prehospital studies examine acute pain retrospectively , 8, 31 aMorphine, ketamine and diclofenac This study revealed that inhaled nitrous oxide was not used. Similar observations were identified by Matthews et al.  in the sOur findings do not suggest disparity between adult and paediatric pain management. This is not consistent with other studies which suggest that adults are more likely to receive opioid analgesics , 34, 45.A finding which is difficult to explain was that six patients received medication with analgesic properties from crews not licensed to administer those medications. We attribute this to either documentation errors or in some high workload situations emergency care providers may be transporting patients after an analgesic medication had been administered by a higher qualified practitioner on scene.Findings of the study are concerning; however, consideration must be given to the possible reasons for the apparent poor pain assessment and management practices among emergency care providers in the Western Cape, South Africa.Studies conducted in HIC identified several constraints to prehospital pain assessment and management , 50–52. The prehospital setting is a challenging and dangerous work environment with emergency care providers in South Africa increasingly confronted by the threat of violence. In addition to the concerns for personal safety, high workload and demands on emergency care providers, analgesic agents are only available to a small proportion of prehospital practitioners in South Africa. Research to describe barriers and enablers to prehospital pain assessment and management in the South Africa setting may identify further issues. Epidemiological studies, further investigating inequalities in pain assessment and management, as well as the prevalence, assessment and management of pain in medical and obstetric cases, will add to the knowledge base.Like most other observational studies, retrospective reviews have various potential sources of bias including selection and information bias, uncertainty about generalisability and issues with missing data . ProbabiPain assessment and management were shown to be significantly lacking. Much can be done to improve pain care in the South African prehospital setting. For instance, better pain education during undergraduate studies, ongoing pain education, an EMS culture prioritising pain relief, monitoring pain care quality, optimising resources , scope of practice revision to consider other analgesic agents suitable for the setting and specifically for BLS and ILS practitioners, specific guideline recommendations for mild, moderate and severe pain and promoting pain assessment, reassessment and redosing to optimise pain care as well as the proper documentation thereof. This study provides clear directions for future research which could further improve pain assessment and management.Additional file 1: Types of emergency incidents.


We aimed to compare the effectivity of percutaneous disc coagulation therapy (PDCT) and navigable ablation decompression treatment (L-DISQ) in patients who were diagnosed with cervical disc herniation.  Visual analog scale (VAS) and Neck Pain Index (NPI) scores were recorded initially and at the 1st, 3rd, 6th, and 12th months after the procedures. Patient Satisfaction Scale (PSS) scores were recorded 12 months after the procedures. Mean VAS scores were 7.55 and 3.1 points in the PDCT group and 7.6 and 3.00 points in the L-DISQ group; mean NPI scores were 34.2 and 20.75 points in the PDCT group and and 34.1 and 20.4 points in the L-DISQ group initially and at the 12th month. When compared between months, there was a significant decrease in time-dependent VAS and NPI scores in both PDCT and L-DISQ groups (P = 0.001). Some complications included esophageal, vascular, and neural injuries; hoarseness; Horner syndrome; infections; dural puncture; and muscle spasm. The only difference between groups was the rate of cervical spasm within 1 month after the procedure: 75% in the PDCT group and 15% in the L-DISQ group. The diameter of the canal of the cervical vertebrae is narrower than of the lumbar and thoracic regions; therefore, the smaller part of the disc may be sufficient to create clinical signs. The response to decompression therapies is faster in the case of cervical percutaneous procedures that are performed correctly. Proper patient selection and practitioner’s experience are important in the treatment success.  The most common cause of cervical pain and/or radiculopathy is the mechanical compression of the roots due to such degenerative spinal pathologies as cervical disc herniation (CDH) and spondylosis (1). When compared to the lumbar region, the diameter of the spinal canal and neural foramens are narrower in the cervical spine. Accordingly, although smaller in size and less protrusive, a cervical disc herniation has a higher risk of developing radicular symptoms than a lumbar herniation (2). Functionally, cervical vertebrae are more mobile and have a wider range of motion than the lumbosacral ones. Therefore, pain and limitation of motion in the cervical region lead to considerable discomfort (3). The most common radiculopathic finding is at the C7 nerve root location, followed by C6, C8, and C5 in descending order of frequency (4).The choice of treatment for CDH is still controversial since the advantages of surgical treatment methods against nonsurgical ones have not yet been clearly defined (5). Interest in percutaneous procedures has increased due to the lesser threat of secondary tissue damage, operability with local anesthesia, avoidance of the risks associated with general anesthesia, and earlier discharge. As a result, interest in minimally invasive percutaneous methods for the treatment of CDH has increased, in which the nucleus pulposus is removed mechanically or through the application of energy .Some of the complications are esophageal, vascular, or neural injuries; hoarseness; Horner syndrome; infections; leakage of cerebrospinal fluid; neurological damage; increase in pain; muscle spasm; and retrosternal and retropharyngeal pain (8–10).There are some nonsurgical interventions for the treatment of CDH that usually aim to directly cauterize the discal parts, making use of various devices that approach anteriorly to the cervical disc . There is a need for comparative studies analyzing the results and long-term effects of these methods. There have been no publications investigating the performance of percutaneous disc coagulation therapy (PDCT) on the cervical region and only one study of cervical intradiscal navigable ablation decompression treatment (L-DISQ). To the best of our knowledge, this is the first study to evaluate the use of PDCT in the cervical region. The aim of this study is to compare the effectivity of percutaneous PDCT and L-DISQ ablation decompression treatments in patients diagnosed with CDH.Approval for the study was obtained from our institutional ethics committee. Data on patients who underwent treatment for pain in the posterior neck and in the superior extremities using L-DISQ and PDCT and/or with radiculopathy due to a CDH in the Pain Clinic between 2013 and 2017 was evaluated retrospectively.From a total number of 105 patients with neck pain who were diagnosed with CDH by MRI between 2013 and 2017, 48 were treated with percutaneous decompression. Forty patients who were able to comply with the 12-month follow-up period were included in the study.Inclusion criteria were as follows: Patients aged between 18 and 65 years old in the ASA I–II risk groups with with pain in the posterior neck and superior extremities and/or radiculopathy due to CDH were included in the study. All patients had cervical and upper extremity pain in most cases spreading to the scapular or occipital regions. None of the patients had only shoulder or neck pain. Exclusion criteria were as follows: Cervical myelopathy, cervical bone malformation leading to symptoms, upper motor neuron lesion findings with a history of cervical spinal surgery, extruded disc herniation, accompanying shoulder joint problems, symptom-related psychological discomfort, hematologic disorders, polyneuropathy, spinal cord stenosis, segmental instability or spondylolisthesis at the target level, infections, neoplastic diseases, and metabolic bone diseases.The patients’ demographic data, visual analog scale (VAS) scores, and Neck Pain Index (NPI) scores were recorded initially and in the 1st, 3rd, 6th, and 12th months following the procedures. The Patient Satisfaction Scale (PSS) scores and cervical spasm rates were recorded in the 12th month following the procedures.The PDCT system  and L-DISQ  were used.The same position and the same C-arm handling procedures were used in both patient groups. As two different devices were used, entry cannulas with different diameters, 1.2 mm and 0.8 mm, were used in the L-DISQ and PDCT procedures, respectively. In order to reduce the risk of infection and for sedation, 1 g of cefazolin and 2 mg of midazolam were injected intravenously (IV) prior the procedures. Intense sedation was avoided to allow full monitoring throughout the procedure. Patients were calm and able to speak to the practitioner when necessary. Blood pressure, heart rate, electrocardiogram, and oxygen saturation were monitored. While in a supine position, a thin roll was placed under the shoulders of the patient to allow a slight neck extension, and the shoulders were stabilized to allow better visualization of the lower cervical discs if needed. The neck was prepared and covered with sterile surgical cloths. First of all, all patients were injected with a local anesthetic of 2 mL of prilocaine into the skin and subcutaneous tissues. Deep injection was avoided during subcutaneous injection of the local anesthetic. This helped us to prevent development of side effects related to the local anesthetic agent such as Horner syndrome due to the proximity to the cervical sympathetic chain, bradycardia due to the effect on the carotid glomus, and bitonal sound or hoarseness due to the effect on inferior laryngeal nerve. An additional 0.5 µg/kg of fentanyl was administered intravenously in the case of pain until the disc was reached.The port cannula was placed through the midline into the right side via an anterolateral approach. Since the esophagus is located on the left of the midline, a right-sided approach seems relatively safer, especially at lower cervical levels. Tight pressure was applied to the space between the trachea and the medial border of the sternocleidomastoid muscle in order to remove the trachea from the midline in a controlled manner. Bleeding/coagulation tests and anticoagulant drug use were questioned in all patients before the procedure. The carotid artery was sensed by the middle and index fingers to determine the entry point while preventing possible major vascular injury and hematoma. As the diameter of the cannula is small, tampon pressure was planned in case of hematoma. A possible headache due to dural injury was planned to be treated by daily abundant fluid intake, additional caffeine-containing painkiller agent, IV hydration, and epidural blood patch in the event that the headache did not cease after 1 week of treatment.The cannula was moved obliquely into the intervertebral disc area 3–4 cm away from the midline at the index level. The C-arm was placed to obtain a lateral view of the surgical field, and then the cannula and trunk were advanced into the disc under fluoroscopic guidance. If both the anteroposterior and lateral views were located in the target area, we defined the needle position as “right”, and otherwise as “wrong”. The tip was retracted and retested in the event of such complaints as electric shock-like pain or muscle contractions. The pain resulting from a short test of electrical stimulation can prevent possible neural tissue damage. For both methods, the total duration of ablation after test stimulation was 100–150 s. All patients were prescribed antibiotics to use for 7–10 days and to take an antiinflammatory drug or paracetamol in the case of pain, along with a hard collar to be worn for 2 weeks during the day. Patients were informed not to drive for at least 72 h. No patient required additional invasive pain intervention after the procedure.The data analyses were carried out using SPSS 15 for Windows. Descriptive statistics were expressed as mean ± standard deviation for variables with normal distribution, median (min–max) for variables with abnormal distribution, and number of cases and percentage (%) for nominal variables. Within the groups, the significance of the difference in median values and in the median values between times was assessed with a Friedman test. If present, multiple intertime comparisons of differences were evaluated using appropriate post hoc tests. Between the groups, the significance of the difference in terms of average values was evaluated by two related sample tests, and in terms of median values by a Wilcoxon test.P < 0.05 was considered to be statistically significant, and a recovery rate of over 50% was considered successful.Forty patients were included in the study, of which 47.5% were female and 52.5% were male, with a mean age of 53 years. Lesions were predominantly at the C4–C5 and C5–C6 distances, as summarized in Table 1. The time-dependent VAS scores were found to be statistically significant for each treatment method (P = 0.001), as presented in Table 2. In a comparison of the PDCT and L-DISQ groups, the difference between the VAS scores in the 0th, 3rd, 6th, and 12th months was statistically insignificant, while the difference between the VAS scores in the 1st month was statistically significant (P = 0.033). In the PDCT group, the time-dependent VAS scores between the 1st and 3rd months were significant at P = 0.039 and between the 3rd and 12th months were significant at P = 0.012. In the L-DISQ group, the time-dependent VAS scores between the 0th and 1st, 0th and 3rd, 0th and 6th, and 0th and 12th months were P = 0.0019, and between the 3rd and 12th and 6th and 12th months were P = 0.008, and thus statistically significant (Table 2).The time-dependent NPI scores were found to be statistically significant for each treatment (P = 0.001). Time-dependent NPI scores are shown in Table 3. In a comparison of the PDCT and L-DISQ groups, the differences between the NPI scores in the 0th, 1st, 3rd, 6th, and 12th months were statistically insignificant. In the PDCT group, the differences in the time-dependent NPI scores between month 0 and the other months were statistically significant at P = 0.001. The differences between the 1st and 3rd, 1st and 6th, and 1st and 12th months were also statistically significant at P = 0.001, 0.011, and 0.006. In the L-DISQ group, the time-dependent NPI scores between month 0 and all the other months, and also between the 1st and 6th months, were statistically significant at P = 0.001, while the scores between the 1st and 3rd months were also statistically significant at P = 0.009 (Table 3).Among the PDCT patients, one patient rated the PSS as very good, while 14 patients and 5 patients rated it as good and moderate, respectively. Among the L-DISQ patients, 1, 16, and 3 rated the PSS as very good, good, and moderate. Of the 40 patients included, 2, 30, and 8 rated the PSS at the 12th month as very good, good, and moderate, respectively. Overall, 80% of the patients evaluated the procedure as very good or good according to the PSS (Table 1).In recent years, less invasive procedures have been developed for the treatment of patients with CDH, including those that use mechanical, chemical, and thermal methods to compress the discs . Although authors have previously addressed lumbar interventions in the literature, the present study discusses cervical interventions. During the follow-up year, a statistically significant reduction was noted in both VAS and NPI index scores in the PDCT and L-DISQ groups. The neck pain felt during the procedure and the risk of postoperative muscular spasm was reduced. Cervical spasm developed in 13 and did not develop in 7 of the PDCT patients, and among the L-DISQ patients, cervical spasm developed in 4 and did not develop in 16. The patients who experienced cervical spasms benefited from such short-term palliative treatments as supportive physical therapy, hot compress, and analgesics (Table 1).PDCT works by using a laser source called a plasma light, and produced plasma rays condense at the end of the dome-shaped probe and do not move forward. A fire sphere with a diameter of 4 mm is created around the coagulation area and all energy is concentrated at the end of the fiber. The PDCT system is a type of therapeutic system for disc coagulation, evaporation, and decompression with plasma. Most lasers use a power of 900 J in a pulsatile mode at cervical distances (15). The area within 4 mm around the tip on the fiber is lower than 40 °C for safety. This is why adjusting and healthy tissues are protected from thermal elevations. The diameter of the plasma fiber optic is 0.4 mm. The basic principle is to create 3 lesions in the intradiscal region. During the process, the evaporated disc is checked for output by opening a three-way valve (16). The total surgical procedure takes 15 min.Bellini et al. reported preliminary results of 19 patients with lumbar or cervical disc herniation treated with PDCT, defining the process according to quarterly evaluated VAS scores. No serious complications were reported, aside from mild muscular spasm and stomach complaints in 10 patients. Despite the fact that PDCT uses a modified plasma laser technology, we believe that the cervical muscular spasms were related directly to the high power effect of the applied energy .L-DISQ is a device that approaches the herniated disc sensitively along the intradiscal pathway and vaporizes the herniated nucleus using plasma particles and bipolar radiofrequency plasma for decompression. This device has been replaced with a valid form called L-DISQ-C to enter the cervical intervertebral space (17). The navigable electrode end of the L-DISQ is twisted by turning the control wheel and can penetrate completely into the discal hernia. This feature provides direct access to the herniated part of the disc to be ablated and reduces the amount of ablated discal tissue and fibrous damage to the outer ring (18). Since the distance between two electrodes at the end of L-DISQ is 0.2 mm, a nerve root farther from the electrode tip than 0.2 mm is theoretically protected from electrical damage. During the procedure, electrical current passes through the other electrode instead of the nerve root (17). Additionally, the thin outer membrane ring is a good barrier for electrical current and theoretically reduces nerve damage due to bipolar electrical coupling (13). During controllable ablation, the highest recorded temperature is between 40 and 60 °C and the temperature decreases rapidly with distance (19). This is why adjusting and healthy tissues are protected from thermal elevations. Temperatures do not rise inside or on the surface of the disc, but do rise significantly around the probe tip. As a result, nerves and surrounding tissues are protected from the risk of thermal damage as long as the probe tip is within the disc (20). The total surgical procedure takes 15 min.Lim et al., following interventions with L-DISQ in patients with extruded and protruded cervical disc herniation, came to conclusions that paralleled those of the present study (21). In the study by Kim (22), L-DISQ had technical properties that facilitated its use in extruded cervical disc hernias.Unlike in our study, previous studies using L-DISQ in the treatment of cervical disc herniation included extruded patients, but we only treated patients with protruded discs. We believe that it is more suitable to access to the target tissue in protruding disc hernias with higher rates of success. For the placement of the electrode by navigation within the herniated part, the experience of the practitioner and proper patient selection are important factors affecting success. Precise access to the target is crucial for success. In the present study, we observed no indications that the electrode had been falsely placed.In some of the patients in the present study, intradiscal treatment was applied at multiple levels, while all interventions in other studies were made at a single level. Although PDCT is used to reduce the problems associated with other laser applications, its probe cannot be seen in the disc through fluoroscopy, which can be considered a disadvantage . Since the entrance cannula of the PDCT is thinner than the L-DISQ cannula, intradiscal access is easier, despite the potential for bone surface problems. This feature provides significant benefit to the user. L-DISQ can be monitored under fluoroscopy, including its tip, which is an advantage for L-DISQ users. In our study, we did not perform MRI routinely for follow-up after the procedure. The pain and functional status was determined by clinical anamnesis and physical examination. Bonaldi et al. (8) reported that clinical improvement was not always accompanied by MRI findings. Schellhas et al. (7) reported that pain did not always correlate with radiological findings. Similarly, Arana et al. (18) did not observe a significant correlation between MRI findings and pain and various clinical signs.In conclusion, L-DISQ provided better pain control than PDCT in the early period while both methods were found to have similar effectivity in the long term. In the PDCT group, the higher VAS score values in the early period were thought to be associated with paracervical muscle spasms. The outcome of neither treatment method was superior to the other in terms of the outcomes of the two groups in treatment follow-up. The decreases in the VAS and NPI scores of the patients were statistically significantly. We believe that PDCT and L-DISQ can be considered safe and efficient procedures in patients with CDH.Although NPI evaluates the functional improvements of CDH patients and includes some questions judging parameters such as social life, daily functionality, and sleep quality, some additional indexes and questionnaires supporting these parameters can be evaluated in further studies including larger patient populations.


Pretherapeutic screening for dihydropyrimidine dehydrogenase (DPD) deficiency is recommended or required prior to the administration of fluoropyrimidine-based chemotherapy. However, the best strategy to identify DPD-deficient patients remains elusive.DPYD genotypes in a subgroup of 3680 patients who had completed the two tests. The extent to which defective allelic variants of DPYD predict DPD activity as estimated by the plasma concentrations of uracil [U] and its product dihydrouracil [UH2] was evaluated.Among a nationwide cohort of 5886 phenotyped patients with cancer who were screened for DPD deficiency over a 3 years period, we assessed the characteristics of both DPD phenotypes and 2]:[U] ratio identified 11.5% of the patients as having DPD deficiency (UH2]:[U] < 10). [U] classified two patients (0.05%) with complete DPD deficiency (> 150 ng/ml), and [UH2]:[U] < 1 identified three patients (0.08%) with a complete DPD deficiency. A defective DPYD variant was present in 4.5% of the patients, and two patients (0.05%) carrying 2 defective variants of DPYD were predicted to have low metabolism. The mutation status of DPYD displayed a very low positive predictive value in identifying individuals with DPD deficiency, although a higher predictive value was observed when [UH2]:[U] was used to measure DPD activity. Whole exon sequencing of the DPYD gene in 111 patients with DPD deficiency and a “wild-type” genotype (based on the four most common variants) identified seven heterozygous carriers of a defective allelic variant.When [U] was used to monitor DPD activity, 6.8% of the patients were classified as having DPD deficiency ([U] > 16 ng/ml), while the [UHDPYD variants have low performances in predicting partial DPD deficiency when evaluated by [U] alone, and [UH2]:[U] might better reflect the impact of genetic variants on DPD activity. A clinical trial comparing toxicity rates after dose adjustment according to the results of genotyping or phenotyping testing to detect DPD deficiency will provide critical information on the best strategy to identify DPD deficiency.Frequent genetic  The most well-known biochemical cause of intolerance to fluoropyrimidines is a deficiency in the catabolic enzyme dihydropyrimidine dehydrogenase (DPD).5 Patients with partial or complete DPD deficiency have a reduced capacity to degrade fluorouracil and are at risk of developing severe fluoropyrimidine-associated toxicity.Chemotherapy with fluoropyrimidine drugs, such as fluorouracil, capecitabine and tegafur, is the standard treatment for many types of advanced cancer and is used by millions of patients with cancer worldwide.DPYD, the gene encoding DPD, predict fluoropyrimidine-associated toxicity.9 Pre-treatment screening for the most clinically relevant defective variants, c.1679T>G, c.1905 + 1G>A, c.2846A>T, and Haplotype B3 (c.1236G>A or c.1129–5923C>G), and a dose adjustment according to the DPYD genotype improves the safety of chemotherapy regimens based on fluorouracil.11 International recommendations provide indications for drug-related genetic tests and DPYD genotype-guided dosing to improve their integration in routine clinical practice.12 The U.S. Food and Drug Administration and the Health Candida Santé Canada have added statements to the drug labels for fluorouracil and capecitabine that warn against use in patients with DPD deficiency, and genotype-guided prescribing recommendations for fluorouracil, capecitabine, and tegafur are also available from the Dutch Pharmacogenetics Working Group.12 The Clinical Pharmacogenetics Implementation Consortium (CPIC) has also proposed guidelines for the genotype-guided dosing of fluoropyrimidines.6Genetic polymorphisms in 2) to calculate the [UH2]:[U] ratio.1 [U] and the [UH2]:[U] ratios are highly correlated with DPD activity in peripheral blood mononuclear cells (PBMCs).1 Although debate exists regarding whether [U] or the [UH2]:[U] ratio correlates well with the clearance of fluorouracil,14 numerous studies have identified a relationship between fluoropyrimidine-induced toxicity and a DPD phenotype characterised by a high [U] or a low [UH2]:[U] ratio.15 Measuring the DPD phenotype has the potential to improve the performance of the prechemotherapy tests designed to identify patients at risk of fluoropyrimidine-associated toxicity.16 Additionally, dose individualisation in patients with DPD deficiency as evaluated by measuring [UH2] and [U] may improve the safety of these patients.19 A fast and reliable quantitative analysis of the DPD phenotype is performed with an accurate, precise, robust and sensitive liquid chromatography tandem mass spectrometry assay.21 Since December 2018 in France, prior to the initiation of treatment with fluorouracil or capecitabine, a search for DPD deficiency must be conducted by determining the pretherapeutic [U].22 Prescribers of fluoropyrimidines must mention on the prescription that the results of plasma [U] have been considered, and the pharmacist must ensure the presence of this statement before dispensation. The French guidelines do not include the [UH2]:[U] ratio as an indicator for the DPD metabolisation status. Thus, the mean and range of the pretherapeutic endogenous [UH2]:[U] ratio varies widely between studies, and the extent to which the [UH2]:[U] ratio correlates with fluorouracil plasma concentrations remains a subject of discussion.14 Indeed, [U] might be superior to the [UH2]:[U] ratio as a predictor of severe toxicity, and pre-treatment [U] concentrations > 16 ng/ml are strongly associated with global severe toxicity, with the risk of severe toxicity increasing proportionally with increasing [U] values.14Another approach to identify DPD-deficient patients is to assess DPD enzyme activity by determining the plasma concentrations of uracil ([U]), the endogenous substrate for DPD, or its product dihydrouracil ) was performed in 5513 patients and phenotyping by measuring [U] and [UH2]:[U] was performed in 5886 patients. The distribution of the [U] values of the 5886 patients is shown in Fig. DPYD gene was performed in 111 individuals with a wild-type genotype, and DPD deficiency was defined as [U] > 16 ng/ml14 and/or [UH2]:[U] < 10 14 (see the “Phenotyping” section). This cross-sectional study is reported according the STROBE statement.We retrospectively reviewed the laboratory database of the Hôpital Européen Georges Pompidou (Assistance Publique—Hôpitaux de Paris). All patients referred to the pharmacogenetics unit (2016–2019) for pre-treatment testing for DPD deficiency were considered Fig. . Screeni2] were measured using a Waters Acquity® TQD LC®/MS/MS System consisting of an Acquity® ultra high-performance liquid chromatography system  coupled with an Acquity® triple-quadrupole tandem mass spectrometer with an electrospray ionisation interface. Complete validation was performed according to the Food and Drug Administration guidelines on bioanalytical method validation. All data were acquired and processed using MassLynx™ 4.1 software with the QuanLynx™ program. The detailed technical protocol is described elsewhere.21 Based on the published data available to define a uracil threshold discriminating normal and deficient activity, a clinically relevant increase in the risk of severe toxicity occurs when [U] is >16 ng/ml.14 Therefore, the following cut-off values were used throughout the study: normal activity if [U] < 16 ng/ml and partially deficient activity if 16 ng/ml < [U] < 150 ng/mL.7 Completely deficient activity was defined as [U] > 150 ng/mL after a survey of 38,862 patients from the French laboratories performing DPD phenotyping (unpublished results). Thus, a [U] threshold value of 150 ng/ml was proposed as a consensus by experts to identify complete deficits. The cut-of value of [UH2]:[U] ratio to discriminate DPD deficiency may vary according to studies, mostly due to technical specificities of HPLC-UV23 or HPLC-MS24 to measure [U] and [UH2]. In the present study, a [UH2]:[U] ratio cut-off of < 10 has been chosen because it has been demonstrated that it was a good predictor of toxicity.14 Thus, partial DPD deficiency was defined when [UH2]:[U] < 10, and complete DPD deficiency was defined as [UH2]:[U] < 1.23[U] and  and [UH2]:[U] values were not normally distributed  was calculated to identify the optimal cut-off points for [U] and [UH2]:[U] values. Two-sided p-values < 0.05 were considered significant. Statistical analyses were performed using Prism® 5.0  and JMP (SAS) software.Data are described as the means ± standard deviations, or ted Fig. , nonpara2]:[U] (but not [U]) values, suggesting that DPD activity may decrease with age  values were slightly higher in men than in women , but the clinical relevance of this difference is questionable. Because pre-analytical conditions are critical for [U] or [UH2]:[U] measurements, and may vary according to centres that collect blood samples, we checked that there was not centre effect i.e. that there was no significant difference in [U] or [UH2]:[U] values from one health centre to another  (data not shown).Mean patients age was 64.5 ± 13 years, and the sex ratio (M/F) was 41%. A negative correlation was observed between patient age and [UHage Fig. . In addi2]:[U] ratio classified 423 patients (11.5%) with partial DPD deficiency, and 3 (0.08%) with complete DPD deficiency  of the patients  presented [UH2]:[U] > 10 and [U] < 16 ng/ml  with partial DPD deficiency and two patients (0.05%) with complete DPD deficiency. The  > 16 ng/ml and [UH2]:[U] < 10, the PPV of a DPYD mutation slightly increased to 37%. Reflecting the poor predictive capacities of DPYD mutations, considerable overlap was observed in the distribution of [U] and [UH2]:[U] values between each group of patients according to the DPYD mutation status  and 13.7 for [UH2]:[U] . Together, these results indicate that the presence of a defective DPYD allelic variant is a poor predictor of DPD deficiency and that the predictive value further decreases when [U] is used instead of [UH2]:[U].One hundred sixty-six (166) (4.5%) patients were carriers of one defective nt Table , and thecy Table , but ther when UH:[U] is uU] Table  generateDPYD common variants associated with impaired enzyme activity were homozygous carriers of these polymorphisms. Two patients (0.05%) carried compound heterozygous mutations, c.1905 + 1G>A plus c.2846A>T and c.1905 + 1G>A plus c.1129–5923C>G, and were predicted to have low metabolism according to an activity score of 0.5.6 However, only the patient carrying the c.1905 + 1G>A plus c.2846 A>T mutations displayed a complete loss of DPD activity ([U] = 320 ng/ml and [UH2]:[U] = 0.4), while the patient carrying the c.1905 + 1 G>A plus c.1129–5923 C>G variant alleles had normal [U] and [UH2]:[U] values , but the high level of [UH2] (479 ng/ml) suggested inadequate sample storage that may have resulted in increases in the U and UH2 concentrations, irrespective of DPD activity (16). Finally, two patients with [UH2]:[U] < 1  did not carry defective alleles, as assessed using genotyping or NGS. Based on these results, DPYD allelic variants may be poor predictors of complete DPD deficiency, and the absence of a mutation does not exclude the possibility of complete DPD deficiency.None of the 3680 patients who were tested for the 4 DPYD gene sequencing was performed in 111 individuals with discordant genotype-phenotype correlations ([U] > 16 ng/ml or [UH2/][U] < 10 and DPYD wild-type genotype). Eighteen genetic variants were identified; all were missense mutations ). Seven (7) patients (6%) were carriers of this variant and were predicted as having intermediate metabolism.6 Thus, in the subgroup of 111 patients with a genotype-phenotype discordance, whole-exome sequencing of the DPYD gene allowed us to correctly reclassify 6% (7/111) of the patients with DPD deficiency.ns Table  and the DPYD genotyping in non-selected patients with cancer. This timely resource is clinically relevant and consistent with the recent regulation in France related to the requirement for DPD phenotyping before the administration of fluoropyrimidines. The generalisation of a pre-treatment screen for DPD deficiency will exert a substantial effect on the volume of prescriptions of this test and will constitute a challenge in terms of health-care resources.20 Therefore, a comprehensive and accurate knowledge of the distribution of DPD activities and their relationships with DPYD mutations in a large and non-selected population is critical.We describe here the largest series of pre-treatment DPD phenotyping combined with 2]:[U] ratio are highly correlated with DPD activity in PBMC1 and DPYD variants show limitations to predict deficient DPD enzymatic activity as determined by measuring [U] and/or [UH2]:[U], we conclude that DPD phenotyping is a more appropriate approach to screen for DPD deficiency. However, our study provides information on the comparative performances of DPD phenotyping and DPYD genotyping in predicting fluoropyrimidine toxicity. Pre-treatment screening for the most frequently observed DPYD genetic variants and dose individualisation improve the safety of the patients,25 [U] and [UH2]:[U] might more comprehensively reflect DPD enzymatic activity than DPYD variants alone. A combined DPD phenotype-genotype testing to screen for DPD deficiency is a potentially clinically relevant approach,15 but it remains to be demonstrated that its yield a significantly higher predictive value.26 Hence, a majority of patients with DPD predicted to have intermediate or low metabolism according to activity scores based on the sum of alleles in fact have a normal DPD activity level based on [U] and [UH2]:[U] levels. This finding holds true for patients with partial DPD deficiency and complete DPD deficiency and may reflect a low penetrance of the mutations on the phenotype. However, a negative genetic test has a greater than 90% chance of an association with normal DPD activity.Since [U] and the  and [UH2]:[U], which, unlike the results of genotyping tests, have the disadvantage of being continuous, with the risk of severe toxicity increasing proportionally with increasing values. The current [U] and [UH2]:[U] cut-off values used to define DPD deficiency likely overestimate the prevalence of an actual DPD deficiency, which might increase the risk to patients under the current dosing regimen. Thus, trials comparing current cut-off values and more stringent thresholds for phenotype-guided dose individualisation of fluoropyrimidine therapy would ultimately help clinicians to better tailor the fluoropyrimidine doses administered to patients with cancer.Formal recommendations of DPD phenotype-guided dose individualisation of fluoropyrimidine therapy, similar to DPYD mutations are poor predictors of DPD activity, they are better predictors of partial DPD deficiency when it is estimated by measuring the [UH2]:[U] ratio compared with [U] alone. This assumption is supported by the fact that [UH2]:[U] is the ratio of the product to the substrate of DPD, and therefore more accurately reflects the enzymatic activity of DPD than [U] alone. Consistent with this finding, several studies have shown a significant correlation between the [UH2]:[U] ratio and systemic fluorouracil exposure and the degree of toxicity.27 However, some debate exists regarding whether [UH2]:[U] or [U] is the more reliable predictor of the pharmacological response. While most available studies have correlated the [UH2]:[U] ratio to fluoropyrimidine-associated toxicity,16 some studies have shown that [U] better correlates with fluorouracil plasma clearance than [UH2]:[U],14 and consequently [U] may be superior to the [UH2]:[U] ratio for predicting toxicity.7Although 2]:[U] ratio remains to be examined in specific settings. For example, the rapid or ultra-rapid DPD phenotype is poorly described, and its clinical impact is likely underestimated.28 However, it could be considered a potent predictor of critical end-points, such as the response to the chemotherapy or patient survival. In this case, DPD phenotyping becomes critically relevant based on the findings of pharmacokinetic studies aiming to balance therapeutic effectiveness with safety that have proposed target ranges using the area under the curve (AUC) and that have shown that in phase III trials, > 65% of the patients are below the target AUC, less than 20% are above the target range, and only 15% of the patients have an AUC for the drug within the target range.29 The implementation of more sensitive tests for DPD deficiency, which appears to be the case for DPD phenotyping instead of DPYD genotyping, would theoretically expose a greater proportion of patients to the risk of being undertreated with fluoropyrimidine and, consequently, of being less responsive to the chemotherapy. Dose escalation after the first cycle to achieve maximal safe exposure is probably the most reasonable therapeutic strategy in these cases.The complementary and additional information provided by the concomitant assessment of [U] and the  or [UH2]:[U] in a pre-treatment screening strategy. As such, our aim was not to compare the performances of two methods of DPD deficiency screening for fluoropyrimidines dose adjustment strategy, which would have required a prospective study to collect clinical outcomes. However, a clinical trial comparing toxicity rates after dose adjustment according to the results of genotyping or phenotyping testing to detect DPD deficiency will provide critical information on the best strategy.A limitation of this study is the lack of clinical outcomes, including the rate of grade 3/4 toxicities. The retrospective design of the study did not allow us to evaluate the impact of DPD deficiency screening on the occurrence of toxicities during fluoropyrimidine treatment. These patients were followed in numerous oncology departments throughout France and we could not generate a data collection gathering biological and clinical variables of the patients screened. The primary end point of our study was to examine the relationship between DPD phenotypes and DPYD variants alone are moderately predictive of DPD deficiency and DPD phenotyping is considered the most appropriate method to screen for DPD deficiency. An assessment of [UH2]:[U] ratio can easily be implemented for routine screening because it rapidly provides reliable results, while allowing a more exhaustive identification of patients at risk of severe toxicity due to DPD deficiency. Further prospective randomised clinical studies should be performed to compare safety and efficacy of fluoroprymidines-based chemotherapy after dose adjustment according to [UH2]:[U] or [U] pretherapeutic determination.In conclusion, common Supplementary material


Septorhinoplasty is a surgical procedure that provides functional improvements and esthetic adjustments to the appearance of the nose. Pain is a common postoperative complication, and pain management is known to decrease postoperative complications and total cost. Local anesthetics can cost-effectively decrease postoperative pain scores and reduce analgesic requirements.The primary objective of this study was to assess the effect of bilateral facial nerve blocks given with general anesthesia on pain scores and the use of postoperative analgesia. The secondary objective was to compare the vital signs stability between a group given bilateral facial nerve blocks with general anesthesia and a group given general anesthesia only.We conducted a retrospective observational study among 40 patients who were divided into two groups, each containing 20 patients. The patients in the nerve block (NB) group received general anesthesia and bilateral facial blocks of the infraorbital and infratrochlear nerves via 5 ml of 0.25% levobupivacaine with 5 ml of diluted adrenaline 1:100,000. Patients in the Control group received general anesthesia only. Both groups received the same local injection of a mixture of 5 ml of 1% lidocaine and 5 ml of 1:100,000 epinephrine at the surgical site, along with the standard general anesthesia. A numerical rating scale, the visual analog scale (VAS), was used to evaluate postoperative pain at 15, 30, and 45 minutes postoperatively, and the stability of the vital signs was also assessed.The results showed that using bilateral infraorbital and infratrochlear nerve block injection with 0.25% levobupivacaine for patients who underwent septorhinoplasty under general anesthesia provided greater stability of vital signs but had no effect on the pain score or analgesia need. Further assessment should be performed in a larger number of patients to either confirm or refute these results. Additional studies could be conducted in several hospitals within the Kingdom to determine how broadly applicable nerve blockade is in reducing pain sensation. Septorhinoplasty is a surgical procedure for aesthetically enhancing the appearance of the nose and repairing nasal deformities. The most common postoperative complications are pain, edema, and periorbital ecchymosis. Forty-five percent of patients have reported pain scores > 3 on a 0 to 10 numerical rating scale (NRS), and approximately 30% have reported pain scores of 6 . PostopeThe primary objective of this study was to assess the effect of bilateral facial nerve blocks given with general anesthesia on pain scores and the use of postoperative analgesia. The secondary objective was to compare the vital signs stability between a group given bilateral facial nerve blocks with general anesthesia and a group given general anesthesia only.We hypothesized that the use of bilateral extraoral infraorbital and infratrochlear nerve blocks with 0.25% levobupivacaine for patients who undergo septorhinoplasty under general anesthesia would reduce the needed dose of postoperative analgesia, reduce the pain score, and enhance the stability of the vital signs. The null hypothesis was that there would be no reduction in the need for postoperative analgesia, pain score, or vital stability after administration of 0.25% levobupivacaine as a nerve blocker.Study designThis was a single-center retrospective study conducted at King Abdullah Medical City (KAMC), Makkah, Saudi Arabia. The study was conducted between January 2017 and January 2018 and was approved by the ethical committee of KAMC. The population included all patients in the Otolaryngology Clinic at KAMC. Informed written consent was provided by all participants in this study. The inclusion criteria were all patients with an indication for septorhinoplasty. The exclusion criteria were age < 18 years old, patients with hypertension and ischemic heart disease, patients with BMI > 30, patients with preoperative chronic pain, and patients with an American Society of Anesthesiologists (ASA) classification III-IV. After applying the inclusion and exclusion criteria, only 40 adult patients were selected for the study. The patients were divided randomly into two groups of 20 patients each. The patients in the nerve block (NB) group received general anesthesia in addition to bilateral facial blocks via 5 ml of 0.25% levobupivacaine with 5 ml of diluted adrenaline 1:100,000. The patients in the Control group received general anesthesia only.Anesthetic, nerve block, and surgical techniquesBoth groups received the same standard general anesthesia. In the NB group only, following the tracheal intubation, the primary surgeon performed the bilateral facial block, consisting of infraorbital and infratrochlear blocks. The infraorbital nerve block was performed by using an extraoral approach by palpating the infraorbital ridge to locate the infraorbital foramen. Then, a 25-gauge needle was inserted laterally to the nostril and advanced forward 1-2 cm until it was felt beneath the finger locating the foramen. Next, with great caution not to enter the foramen itself and after negative aspiration of blood, 4 ml of 0.25% levobupivacaine with 4 ml of diluted adrenaline 1:100,000 were injected. The infratrochlear injection was made by inserting the needle 1 cm above the inner canthus and then injecting 1 ml of 0.25% levobupivacaine with 1 ml of diluted adrenaline 1:100,000. All of the patients (40) received 10 ml of local injection in the form of a mixture of 5 ml of 1% lidocaine and 5 ml of 1:100,000 adrenaline that was injected into the septum, the subcutaneous area at the dorsum, the tip of the nose, the site of the marginal incision and columellar incision, and the sites of the osteotomies. All patients underwent open septorhinoplasty by the same primary surgeon. The procedure involved lateral and medial osteotomies and cartilage grafts. Standard analgesia was given to both groups before the end of the surgery.Patient assessmentAfter extubation, all of the patients were moved to the recovery area for observation where they were evaluated for postoperative pain at 15, 30, and 45 min after the surgery by using the visual analog scale (VAS) varying from 0 (no pain) to 10 (maximum). For patients with a VAS score > 3, IV morphine was given. We assessed the vital sign stability of the patients postoperatively by measuring heart rate and mean arterial blood pressure (MAP) and comparing them with normal values, then categorizing them into two groups: vitally stable or vitally unstable. Every patient was assessed for vital sign stability once before discharge after recovery. The patients were moved to the daycare unit and evaluated for postoperative complications . After discharge, the patients were asked to return to the clinic 24 hours later for evaluation.Statistical analysisThe demographic data of the two groups were compared. A value of p < 0.05 was considered to be indicative of statistical significance. The statistical analysis was performed by using the Chi-squared test and binomial test in the IBM Statistical Package for Social Sciences (SPSS) software . The Chi-squared test was used to compare a group’s values to hypothetical values  and the binomial test was used to compare values  in two unpaired groups.Forty patients  were included from January 2017 to January 2018 for septorhinoplasty. The study flow chart is presented in Figure The morphometric characteristics were similar between groups Table . From thRegarding the type of operation, 85% of the participants in the NB group had a primary septorhinoplasty operation, 10% had septorhinoplasty as revision surgery, and 5% had septorhinoplasty with sixth and seventh rib grafts Table . In the The VAS scores for pain (mean (standard deviation)) were lower after 15 minutes in the Control group (0.7 (0.7)) than in the NB group (1.1 (1.7), P = 0.813) and after 30 minutes (0.5 (0.6)) than in the NB group (0.6 (0.7), P = 0.774). Moreover, at pre-discharge, the NRS score was lower in the Control group (0.3 (0.6)) than in the NB group (0.6 (0.6), P = 0.162)  after surgery. However, the NB group showed significantly more stable vital signs than those in the Control group (P = 0.018) .Finally, there was no significant difference in the need for postoperative analgesia administered, which was needed only for two patients in the NB group (P = 0.137). The first patient received 3 mg of morphine, whereas the other patient received 50 μg of fentanyl and 1 mg of midazolam. All results are presented in Table Effective treatment of postoperative pain should facilitate early mobilization, fluid and food intake, and the resumption of normal physical activities . HoweverThe surgical patient is often treated with a combination of non-opioid analgesics, referred to as “multimodal analgesia” . The aimA prospective clinical study compared postoperative pain in patients undergoing certain otorhinolaryngologic procedures under local anesthesia with sedation and found that pain was significantly higher in patients undergoing septorhinoplasty compared with septoplasty . These fThe use of bilateral nerve blocks during nasal surgery has been reported in the literature. A study done by Boselli et al. demonstrated that bilateral facial blocks using an extraoral approach and infra-trochlear blocks reduced the use of morphine significantly postoperatively . FurtherIn contrast to previous studies that found that 45% of patients reported pain scores > 3 on the 0 - 10 NRS , our stuIn this study, in addition to investigating the effectiveness of NBs on reducing postoperative pain and the need for analgesia, we also assessed their effect on the postoperative stability of the vital signs. We found that the use of 0.25% levobupivacaine as an NB significantly (P = 0.018) improved vital stability and reduced the incidence of vital instability. However, bilateral infraorbital and infratrochlear nerve blocks with 0.25% levobupivacaine require technical expertise from a variety of clinicians. Nurses also must be experienced in preoperative screening and assessment of this patient population during the intraoperative and postoperative phases. They must observe patients for potential side effects and complications to assess the levels of nerve blocks and the quality of analgesia that may not be suitable for some patients.There were some limitations to this study that should be considered. This was a single-center, retrospective, observational method with a small sample size (40 patients). Further studies conducted as multicentric randomized controlled trials would give greater confidence in the results.The use of bilateral extraoral infraorbital and infratrochlear nerve blocks with 0.25% levobupivacaine for patients undergoing septorhinoplasty under general anesthesia was found to enhance vital stability but did not reduce postoperative pain or the need for postoperative analgesia. Expert medical teams should be used for the injection of nerve blocks. Further studies should be conducted in a higher number of patients to obtain more representative and accurate results. We recommend that researchers conduct similar studies in hospitals within the Kingdom to help surgeons understand the effects of nerve blockade on postoperative pain, the need for analgesia, and vital sign stability.


Low back pain is highly prevalent and a major source of disability worldwide. Spa therapy is frequently used to treat low back pain, but the associated level of evidence for efficacy is insufficient. To fill this knowledge gap, this protocol proposes an appropriately powered, prospective, evaluator-blinded, multi-centre, two-parallel-arm, randomised (1:1), controlled trial that will compare spa therapy in addition to usual care including home exercise (UCHE) versus UCHE alone for the treatment of chronic low back pain.Eligible patients (anticipated sample size of 358) will have had low back pain for more than 3 months and scores for pain greater than 40 mm on a visual analogue scale (VAS). Following initial consent for UCHE and baseline evaluations, patients are randomised (1:1) to UCHE alone, or UCHE plus spa therapy . Patients in the latter arm will be requested to sign an additional consent form as per Zelen randomisation. Follow-up visits will occur at approximately months 1, 6 and 12 and  will cover changes over time in VAS pain scores, the impact of lower back pain on daily life (the Rolland and Morris Disability Questionnaire (RMDQ)), inappropriate fears and beliefs about lower back pain ), general quality of life ), Patient Acceptable Symptom State (PASS), consumption of analgesic drugs and nonsteroidal anti-inflammatory drugs (NSAIDs), and overall state of health. Health resource use and days of sick leave (and subsequently the associated costs) will also be recorded. The primary outcome is the presence/absence of a clinically relevant change (improvement of at least 30%) in the VAS score for pain at 6 months.Despite the fact that previous, rather dated recommendations encourage spa therapy for the treatment of low back pain, the current literary corpus is methodologically poor. This protocol has been designed to provide results spanning a thorough range of outcomes at the highest evidence level possible.NCT03910023. Registered on 10 April 2019.ClinicalTrials.gov:  Chronic low back pain is a common complaint. It is estimated that about 80% of people will experience lumbar pain at some point in their lives . EpidemiAs concerns treatments, the medications most often prescribed for chronic low back pain pose various problems. Analgesics, recommended as the first line of therapy in most clinical practice guidelines, have limited efficacy that was even considered negligible and insignificant in a recent review . NonsterGiven the variable inefficacy of pharmaceutic treatments, different types of physical therapy are an important part of the therapeutic arsenal for low back pain. There have been several trials of spa therapy as one such alternative, which is now recommended for the treatment of chronic low back pain , 8. The We propose to fill this methodological/knowledge gap by implementing a trial with the highest level of evidence possible. Our working hypothesis is that spa therapy in addition to usual care including home exercises (UCHE) will result in greater improvements in pain reduction, associated disability and quality of life in patients with chronic low back pain. It follows that health resource consumption and related costs should also be reduced. The primary objective of this study is therefore to compare the therapeutic effect of UCHE alone versus spa therapy in addition to UCHE for chronic low back pain Fig. . SecondaIn this prospective, evaluator-blinded, multi-centre, two-parallel-arm, Zelen randomised 1:1) controlled trial, we will compare UCHE alone with spa therapy in addition to UCHE for the treatment of chronic low back pain  usuThe UCHE intervention will correspond to current practice  as decided by the patient’s general practitioner. They will also be provided with a practical guide on how to manage back pain (the “back book”), including a recommended home exercise programme . The praThe composition of the spa therapy intervention is based on previous results in the domain. Massage –21, heatIf required, treatment-stopping for home-exercises will be decided via collaboration between the patient and his/her evaluating doctor. Treatment-stopping may occur for spa-therapy in case of an adverse event, is decided on a case-by-case basis by the on-site doctors overseeing spa-therapy, and does not result in study exclusion.Following initial consent covering the UCHE intervention and subsequent baseline assessments, patients will be randomly assigned to either control or experimental groups in a 1:1 allocation ratio Fig. . In lineAllocation is performed using a computer-generated randomisation schedule and stratified by the recruiting investigator/spa  and by whether or not the patient has a professional activity. Baseline evaluations and the subsequent randomisation are performed by the recruiting investigators through specific modules administered via a password-protected Internet-accessible electronic case report form (eCRF). The randomisation module will become accessible to investigators only after key elements of baseline data have been entered in the eCRF.To blind the study as much as possible, follow-up assessments are performed during specific follow-up visits  in the visual analogue scale (VAS) score for pain at 6 months after baseline assessments  and 38% (10/26). Our hypothesis is that the proportion of patients experiencing improvement at 6 months will be 40% in the experimental arm (UCHE plus spa treatment) versus 25% in the control arm (UCHE only). Considering a type 1 risk level set at 4%  and a type 2 risk level set at 20% , the minimum sample size required is 322 participants. To maintain power for analysis on observed data and expecting a drop-out rate of approximately 10%, this estimate is increased to a total of 358 paricipants (179 per study arm).Recruitment will be assisted by advertising (not mentioning spa therapy) in the local press and by posting information in local pharmacies, physicians’ offices or clinics. In the case of recruitment difficulties, local companies known to have high rates of workers on sick leave for low back pain may be contacted. Following the advertising campaign, telephone contact between responding, potential study participants and a clinical research technician (CRT) will result in referral to a recruiting investigator (depending on location), who is responsible for obtaining consent and for enrolment, baseline evaluations and randomisation. The enrolment visit will start with an initial presentation and provision of informed consent for the UCHE intervention Table . FollowiContinued contact between study CRTs and patients is encouraged. Patients are requested to contact the study CRT in the case of visit unavailability or other problems. Conversely, the study CRTs will be contacting patients during the week preceding follow-up visits to provide a visit reminder and/or rescheduling as required.Few prospective studies have sought to evaluate the adverse effects and complications that may occur during a spa treatment –45. Due Additional events that may be expected because they are associated with physical exercise in general are respiratory disorders and shortness of breath, cardiovascular disorders ).Harms reporting will be carried out in compliance with the French regulations in force  throughout the study (see Table https://osf.io/ahpwy/).Statistical analyses will be performed by the Department of Medical Information at the University Hospitals of Montpellier, Montpellier, France, using the R programming environment  or SAS  will be provided as means with standard deviations for quantitative variables with normal distributions according to the Shapiro-Wilks test, or as medians with interquartile variables for other quantitative variables. Numbers and percentages will be provided for categorical variables.2) test for independent groups, or alternatively Fisher’s exact test if the conditions for the χ2 test are not met. We expect to perform an interim analysis of the number of patients in both groups with clinically relevant improvement as soon as there are 100 patients suitable for analysis with 6 months of follow up. The purpose of the latter is to assess futility, and a difference between arms (intervention – control) < 0 will stop the trial.As indicated in Table t test) or non-parametric (Mann Whitney test) analysis for independent groups, as appropriate. For longitudinal data, the preferred method will employ mixed models with patients set as a random effect and study arm as a fixed effect; an appropriate interaction term (group × time) will be used to detect differences between study arms in the rate of change. In addition, a medico-economic analysis comparing the two patient management strategies will be conducted according to international [As concerns secondary analyses, comparisons of qualitative variables will be performed in the same manner as for the primary analysis. The centrality of quantitative variables will be compared between arms using parametric  may be used in sub-group analyses. Covariate-interaction tests are the preferred method for detecting sub-group differences . StatistThe general hypothesis of the study supposes more improvement in the experimental arm as compared to the control arm. A difference will be considered statistically significant when the type I error rate is less than or equal to 0.05. As concerns missing data, patients lost to follow up will not be considered as withdrawn from the study but will be analysed as failures for the primary endpoint. Any deviations from the statistical analysis plan must be authorized by the study methodologist and will be thoroughly documented and justified in the study analysis report.https://en.ennov.com) by participating investigators or their approved delegates. A paper version of the eCRF will be made available at https://osf.io/ahpwy/, and can be used to facilitate field requirements for speed or as back up in the case of electronic system unavailability. Data entry in the eCRF will be performed in real time as much as possible in order to take advantage of specifically designed data format, range and coherence rules. The Clinical Research and Epidemiology Unit at the University Hospitals of Montpellier  is responsible for randomisation lists, database maintenance and data management procedures. Data in the eCRF will be audited against resource documents by data-monitoring personnel throughout the study, and corrections made via a traceable system of queries and responses.Individual patient data will be entered in a password-protected, web-accessible eCRF  and subsequent study database, participants will be de-identified and only the following will be used for identification purposes during the study: two initials, year of birth and study number. Any publicly available deliverables will be completely de-identified .https://osf.io/ahpwy/), the French Public Health Code allows LOMBATHERM’ study data, including the data of patients who withdraw their consent or who are lost to follow up, to be used specifically for the purposes of this study, and only this study, unless the patient so opposes. Re-use of the data by other teams via data sharing is subject to approval by the Commission nationale de l’informatique et des libertés  (France), as stated in the data sharing plan (https://osf.io/ahpwy/).As explained in the patient information materials  via a subcontract with the University Hospitals of Montpellier. Monitoring will be performed by regular on-site or remote inspections at investigating centres . All monitoring visits will be the subject of a written report and will cover consent procedures and protocol adherence.https://osf.io/ahpwy/. The final study database will be available to all study investigators immediately after the database is locked. The final study report will be communicated to the study Sponsor and to French authorities within 12 months of database freezing. Aggregated trial results will be made available to the public on ClinicalTrials.gov and by publication in a peer-reviewed journal. At this time, the use of professional writers who are not recognized authors is not foreseen, and authorship will be attributed by general consensus and according to the criteria stipulated by the International Committee of Medical Journal Editors (http://www.icmje.org). In addition, results will be made available to any study participant upon request, as per French regulations in force. Finally, the study data sharing plan stipulates that requests to the AFRETh  for individual datasets can be made anytime following full publication of results.The LOMBATHERM’ steering committee  will (1) supervise study implementation and execution, (2) determine study continuation following interim analysis and (3) oversee communication activities in accordance with the data sharing plan. Key study documents  will be made available to the public on the study’s Open Science Framework website: The LOMBATHERM’ protocol aims to document a thorough range of endpoints highly relevant to the targeted population of patients with low back pain, including changes in pain and symptom acceptability, associated disability, fears and beliefs and quality of life. Should the expected positive effects of spa therapy in addition to usual care be confirmed, a safe, novel physical therapy regimen will be added to the treatment arsenal available for these patients who are difficult to treat.Care was taken to reduce sources of bias in as much as possible by selecting a clinically relevant primary endpoint and implementing a Zelen randomisation procedure . FurtheFurther limitations to the study include a lack of an independent data and safety monitoring board, which was deemed unnecessary due to the low-risk status of this trial. One must also consider the single-blind nature of the protocol, which is understandable given the impossibility of implementing full blinding of the patients receiving spa therapy. Furthermore, there is no way to guarantee the blinding of evaluators, which highly depends on patient collaboration. Nevertheless, the partial blinding of patients (control arm via the Zelen randomisation), the assessing physician, therapists and statisticians have all been addressed. The success of evaluator blinding will therefore be assessed by a guess-the-group question at the end of the final follow-up assessment.Chronic low back pain has a strong impact on patients’ daily lives and entails significant costs in terms of social protection/insurance . It freqAn additional interesting aspect is the follow-up period extended to 12 months. Classically, 90% of lumbar pain episodes are considered as resolved in the following month, but reality is more complex. An observational study of 490 patients consulting for a lumbar episode showed that 59% were satisfied with only one consultation and 32% had two consultations in 3 months. On the other hand, only 21% at 3 months and 25% at 1 year have complete recovery of their functional capacity and resolution of their pain . The repIn conclusion, the LOMBATHERM’ trial has been designed to provide results spanning a thorough range of outcomes at the highest evidence level possible. Low back pain is the most common symptom in patients undergoing spa therapy: 70% of the population aged 54 to 65 years who attend health examination centers have experienced low back pain and of these, 84% of the sub-population that went to spas . It shouProtocol version 2.1 (18 October 2019). The first patient was included on 15 June 2019. Recruitment is currently ongoing. The a priori end of recruitment is planned for 15 December 2021, but may be re-adjusted by protocol modification with ethics committee approval.


Chronic kidney disease (CKD) is a rising medical concern around the world. End-stage kidney disease (ESKD) is the last stage of CKD stages that necessitates renal replacement therapy (RRT), such as hemodialysis (HD), which seems to be the most commonly used type. However, patients on HD still suffer from high mortality and morbidity rates compared to those who receive a kidney transplant. Therefore, we aimed in this study to assess the prevalence of pain among ESKD patients on HD, as well as to explore the factors that were associated with this complaint.We conducted a multicenter cross-sectional study in the West Bank, Palestine, between August and November 2018. We used questionnaire-based direct interviews with subjects. After reviewing previous studies in the field, we developed our questionnaire and included items on patients’ social, demographic, and clinical characteristics, including dialysis-related data. It also contained the Brief Pain Inventory (BPI) to assess different aspects of pain symptoms. A convenience sampling technique was used to collect data.Of the 300 participants, 66.3 % reported having chronic pain. HD sessions themselves were the most commonly cited cause for pain (21.6 %). The most commonly cited site of pain was the upper and lower limbs (37.3 %). Paracetamol was the most frequently used pharmacotherapy for pain alleviation. Multiple regression analysis showed that BMI (p = 0.018), gender (p = 0.023), and the number of comorbidities (p < 0.001) were independently associated with pain severity score.Pain is a highly prevalent symptom among HD patients in Palestine. Subpopulations with higher pain severity include females, patients with higher BMI, and those with multiple comorbidities. Healthcare providers should routinely assess pain in HD patients as it is considered a significant concern. This would involve pain assessment and development of a treatment plan to improve clinical outcomes. The nephrology associations should also push for pain management in HD patients as a clinical and research priority to improve pain-related disability. End-stage kidney disease (ESKD) is associated with increased morbidity and mortality over the world. ESKD is considered the last stage of chronic kidney disease (CKD) that needs renal replacement therapy (RRT) in the form of renal transplantation, peritoneal dialysis, or hemodialysis (HD) , 2. ESKDHD is the most commonly used type of RRT, with over 90.0 % of patients receiving it . It is aThe International Association for the Study of Pain (IASP) describes pain as a physical or emotional unpleasant feeling associated with potential or actual harm and may cause weakened memory, inattention, problems with sleep, symptoms of depression, symptoms of anxiety, impotence, diminishing physical activity, and interrupted social relations and duties . Pain coIn ESKD patients, three broad categories of pain are usually described: poorly localized, throbbing, cramp-like, deep nociceptive pain; stabbing, aching, paroxysmal, and electric shock-like neuropathic; and mixed pain, which is the presence of both forms of pain at once .Approximately 55 % of HD patients reported extreme pain in the previous 24 h, and 75 % of HD patients reported poor pain control . The repNo previous studies have investigated the prevalence and factors that might be associated with chronic pain in HD patients. It is not obvious whether the situation is comparable to or different from that of other countries . In thisWe conducted a multicenter, cross-sectional study. Its setting was the HD centers at the Governmental Hospitals in Tulkarem, Qalqilya, Jenin, and Tubas, as well as that of An-Najah National University Hospital, from August to November 2018.The Palestinian Ministry of Health reported that eleven dialysis centers provided services to the West Bank population in Palestine, all of which were inside hospital buildings. Their size varied between 1 and 50 dialysis machines. We targeted five dialysis centers located in the Northern West Bank. There were approximately 570 patients served by these units at the time this study was carried out  and 16.5 [0.00–30], respectively. The internal consistency reliability indices of the two subscales through which these two scores were calculated, as calculated by Cronbach’s alpha test, were 0.947 and 0.963, respectively. Additionally, we found a significant positive association between pain interference and severity scores (r was 0.861 with a p = 0.001), gender (p = 0.001), BMI (p < 0.001), educational level (p = 0.003), employment (p = 0.004), income (p = 0.009), and number of comorbidities (p < 0.001) showed statistically significant association with pain severity score. The rest of the variables that we examined were not significantly associated with this score.Table p < 0.001), gender (p = 0.001), BMI (p < 0.001), residency (p = 0.027), level of education (p < 0.001), employment (p = 0.001), household income (p = 0.005), dialysis vintage (p = 0.012), and number of co-morbidities (p < 0.001) showed statistically significant association with pain interference score. The rest of the variables that we examined were not significantly associated with this score.Table p = 0.018), female patients (p = 0.023), and those who had a higher number of chronic diseases (p < 0.001) were independently associated with a higher pain severity score. Table We conducted a multiple linear regression analysis stratified by gender, age, BMI, level of education, employment, income, and the number of other comorbidities, with pain severity score as the dependent variable. Regression analysis revealed that subjects with higher BMI (p = 0.009), subjects with longer dialysis vintage (p = 0.008), those with less education (p = 0.010), and those who had a higher number of comorbidities (p < 0.001) were independently associated with higher pain interference score. Table Findings of the linear regression model, using pain interference score as the dependent variable and the covariates of gender, age, BMI, level of education, employment, income, number of other comorbidities, dialysis vintage, and residency as independent variables indicated that older subjects  . AdditioConcerning socio-demographic characteristics, we found a significant association between age and the two pain scores , which is consistent with the findings from the previous study . This reIn this study, social supports  were not significantly associated with pain. However, spiritual support and family relationships have the potential to improve clinical outcomes and quality of life through decreasing depression levels, increasing access to health care facilities, and improving patients’ compliance with prescribed therapies and nutrition .We also found that females suffer from higher severity and interference of pain. Some studies suggested that the higher the pain sensitivity, the lower pain threshold, higher nerve density, and different psychological experiences of pain and different responses to medications .BMI was another variable that was significantly associated with both pain scores in our study. Several previous studies have concluded that obesity may exacerbate chronic pain by reducing the pain threshold and increasing its sensitivity , 34. AddLower levels of education were also found to be significantly associated with more pain. The reason behind this finding might be that low education might lead to holding false beliefs about pain and performing maladaptive coping practices. It might also be associated with a lack of essential knowledge about the disease and proper access to pain relief options , 37. AddThe finding that longer dialysis vintage and having multiple comorbidities were significantly associated with higher pain interference might be due to the accompanying lifestyle changes , 40, 41.This research had several strengths, including its multicenter environment as well as its relatively large sample size. It is also the first study in West Bank, Palestine, to discuss chronic pain and pharmacotherapy used by ESKD patients undergoing HD. Additionally, data was collected through face-to-face interviews, which may have improved the reliability of data. However, the current study faced some limitations. For example, adopting the cross-sectional design in this study precluded making any statements on the causality between variables. Moreover, by adopting the convenience sampling technique, the generalizability of our findings to all HD patients in Palestine might have been somewhat jeopardized. Lastly, the absence of comparison between preexisting conditions  versus dialysis procedure-related pain limits the interpretation of the burden of disease and therapy options.Pain is a prevalent symptom among ESKD patients who are treated with HD in Palestine. Subpopulations that had higher pain severity include the elderly, females, patients with higher BMI, those who have less education, the unemployed, patients living in households with lower incomes, and people living with multiple comorbidities. Our findings provide educational institutions and health care providers who work with ESKD patients with crucial data on pain symptoms among HD patients that can help them achieve their goals of performing better pain documentation and management, achieving higher levels of pain relief, and establishing effective prevention programs. Health officials need to pay more attention to chronic pain in HD patients, develop a clinical and practical plan for managing chronic pain properly, and raise public awareness of ESKD causes and how to halt its progression to decrease healthcare costs and improve patients’ outcomes as much as possible.


Due to the exacerbation of the disease, the rehabilitation of patients with rheumatoid arthritis is often limited. The aim of the study was to analyze the impact of a comprehensive rehabilitation on a subjective perception of pain and quality of life in patients with rheumatoid arthritis depending on the level of disease activity. The study involved 58 women with rheumatoid arthritis aged 18–60, who underwent a 4-weeks comprehensive rehabilitation program. The assessment included the disease activity level on the DAS28 scale, pain intensity on the 10-point pain scale (VAS) and the value of the CRP protein. The HAQ-DI and KALU questionnaire were used to assess the quality of life. In both groups  the statistically significant effects in decreasing the level of pain and improvement of quality of life were observed. This indicates the need and effectiveness of rehabilitation regardless of the level of activity of rheumatoid arthritis according to the DAS28 scale. There were no significant changes in the CRP protein level. In conclusion, the rehabilitation of patients with moderate to high disease activity is effective and the success of comprehensive rehabilitation is demonstrated by the decrease of the DAS28 score and the pain level reported by patients, as well as improving self-assessment of health and quality of life. Rheumatoid arthritis (RA) is a systemic inflammatory disease that leads to functional limitations and premature death , 2. The The study involved patients of the Rehabilitation Department of the National Institute of Geriatrics, Rheumatology and Rehabilitation in Warsaw. The study group consisted of 58 women, age 18–60, with diagnosed rheumatoid arthritis according to ACR/EULAR , 15 critU tests were applied, respectively. The p value < 0.05 was considered statistically significant.Statistical analysis was performed using the STATISTICA 9.0 PL, statistical package software. The values are presented as the mean and standard deviation (SD), and range . The distribution of variables was non-normal, as stated by the Shapiro–Wilk test. Therefore, to assess the significance of the differences between variables before and after rehabilitation and between A and B groups, the Wilcoxon and Mann–Whitney p = 0.006). Statistically significant reduction of pain level on the VAS scale was observed, falling from 4.2 ± 2.2 to 2.5 ± 1.8 (p < 0.001). In group B the disease activity also decreased statistically significantly from 5.0 ± 0.6 to 4.2 ± 0.8 (p < 0.001) as well as the pain level reduced from 5.4 ± 1.6 to 3.7 ± 1.7 (p < 0.001). Both groups differed statistically significantly before and after rehabilitation due to these parameters. However, the CRP levels did not change significantly in both groups after the rehabilitation  and unbearable pain (8–10 VAS) was reported by 7 patients which is 25% of the study group. Whereas, after the rehabilitation program only 1 patient has reported such intensive pain. Only 3 patients (11%) reported mild pain level (0–2 VAS) before the rehabilitation program, while as many as 12 patients (43%) have reduced the discomfort to no pain or mild pain (0–2 VAS) after the treatment. In group B before rehabilitation, 14 (47%) patients reported high or unbearable pain, whereas after 4 weeks physiotherapy none of the patient-reported unbearable pain (8–10 VAS), high level (6–8 VAS) pain was reported only by 4 patients which is 13%. Before the rehabilitation, there were no patients with mild pain or no pain at all, while after rehabilitation there were 6 such patients (20%).Based on the results of questionnaires used in this study a significant statistical improvement of the patients’ quality of life and health was observed Table .Table 2Rp < 0.001). In group B, the mean values decreased from 1.45 ± 1.02 to 0.93 ± 0.57, the change was statistically significant (p < 0.001). The results obtained in the HAQ-DI questionnaire, which assess disability also showed improvement in the patients’ condition. In group A, the average score decreased from 0.74 ± 0.67 to 0.47 ± 0.48, the change was statistically significant (p = 0.001). Also in group B, patients’ outcome was better. The mean values were statistically significantly lower (p < 0.001). The score diminished from 1.03 ± 0.52 to 0.71 ± 0.53. Both examined groups differed statistically significantly before and after rehabilitation considering those parameters.The KALU questionnaire was used to assess individual functionality. Both groups of patients achieved significantly lower average results after rehabilitation and following a better quality of life. In group A, the average points obtained in the questionnaire decreased from 0.85 ± 0.47 to 0.57 ± 0.47 points, which was statistically significant (. Analysis of the level of CRP after 4 weeks rehabilitation indicated no statistically significant decrease, what is confirmed in a study done by Sadura-Sieklucka [Rehabilitation of patients with RA and the pharmacological treatment are the key elements of successful therapy. Rehabilitation is reducing pain, that is demonstrated in a systematic review done by Park et al. , whereinieklucka . Howeverieklucka  researchieklucka . In reseieklucka , the meaieklucka –31. Reseieklucka  revealedieklucka , it was ieklucka , 25, 27.ieklucka . To sum Rehabilitation in rheumatoid arthritis is a part of treatment that must be carried out from the moment of diagnosis and during periods of exacerbation and remission of the disease. Rehabilitation of patients with moderate to high disease activity remains essential. The effectiveness of a comprehensive rehabilitation is noticable based on the lowering level of DAS28 and lowering pain reported by patients, as well as the improving self-assessment of health and quality of life.