Materials and methods. The study group consisted of 72 patients who reported to the prosthetic treatment because of temporomandibular joint dysfunction. The study group included 36 patients with pain form of dysfunction, and the control group included 36 patients with painless form of disorder. Each patient underwent specialized examination of functional disorders in order to diagnose the type of dysfunction and was commissioned to carry out a study of the blood test concerned with evaluation of the C-reactive protein (CRP) level in the same analytical laboratory. The results of the investigation were subjected to statistical analysis. The research obtained approval from the Ethics Committee of the Jagiellonian University (KBET/125/L/2013). Level of Evidence for primary research was established as type V. Results. The mean values of C-reactive protein levels in both groups were in the normal range and did not differ statistically significantly, which indicates the fact that the pain form of the temporomandibular joint disorders is not associated with inflammation of the soft tissues of the joint. Conclusion. Painful form of the temporomandibular joint dysfunctions is not connected with the inflammation of joints.Temporomandibular joint dysfunction is a functional disorder concerned with the abnormal functioning of the muscles of the stomatognathic system and temporomandibular joints involved in the dynamic movements of the jaw and surrounding structures. The aim of the study was to compare the level of C-reactive protein in patients with pain and painless forms of temporomandibular joint dysfunction.  Temporomandibular joint dysfunction includes dysfunction of the masticatory muscles of the stomatognathic system and temporomandibular joints and the surrounding structures. They are often associated with abnormal conditions of occlusion. Functional disorders do not include all disorders associated with musculoskeletal organs including inflammatory, degenerative arthritis, and cancer lesions of the muscles . They are often the result of muscles undergoing prolonged and excessive work and nonphysiological loads occurring in the stomatognathic system –4.The pain form of the disease is manifested by spontaneous pain in the preaural region, accompanied by pain or tenderness of the masseter muscle. Pain that appears during palpation examination of temporomandibular joints is frequently not related to inflammation of the soft tissue around the temporomandibular joints, as it is claimed by several authors , 3, 5–9.C-reactive protein (CPR) was first isolated in the blood serum in 1930 by Tillet and Francis in a bacteriological laboratory in the Rockefeller Institute in New York. Long years of research on the protein allowed for its assessment in a clinical setting. CRP is synthesized primarily by hepatocytes and the Kupffer and Browicz cells and is a cyclic pentamer with a molecular mass of 120 kDa. Its expression was also found in monocytes and lymphocytes. Each of the subunits of the protein is composed of 206 amino acids noncovalently linked together –12. EachMarking of C-reactive protein concentration is based on the immune reaction of monovalent antibodies against CRP using the methods of radial immunodiffusion, immunoelectrophoresis, immunonephelometry, radioimmunoassay, and enzyme immunoassay. In recent years, the methods are immunoblotting, ELISA assays, and techniques of modern molecular biology , 14.The aim of the study was to evaluate the level of C-reactive protein in patients treated for the pain form of temporomandibular joint dysfunction.The study enrolled a group of 72 patients, aged 21 to 48 years, of both sexes, who reported to the prosthodontic treatment in the Consulting Room of Temporomandibular Joint Dysfunction at the Dental Institute at the Jagiellonian University in Cracow, between January 2015 and February 2017, due to the pain and painless forms of the temporomandibular joint dysfunction, and acoustic symptoms, accompanied by excessive tension of the masticatory muscles. Symptoms persisted from 3 to 12 months prior to the beginning of the treatment. All patients were subjected to a specialist functional examination of the masticatory organ using typical procedures: information of spontaneous and provoked ailments, muscles and temporomandibular jaw palpation, functional manipulation, assessment of ranges of mandibular movements, joints' sounds, and dental rating. Patients were consecutively and alternately assigned to the study and control groups, 36 patients in each. The study group consisted of pain form of temporomandibular joint dysfunction and the control group included painless form of this dysfunction.During the study, we analyzed information concerned with general health and present complaints, and a functional examination of the stomatognathic system was conducted, with particular regard to the nature and intensity of the perceived pain and discomfort of temporomandibular joints and masticatory muscles, which occurred prior to treatment and radiation of pain, the type of sound symptoms (clicks), volume, and the phase of the movement of lowering and lifting the jaw, during which there were tension-type headache and back pain . ExaminaFunctional assessment of the masticatory apparatus and muscles consists of a medical interview and a physical examination. Another important element of a medical interview was to evaluate the patient's posture, facial expression, and the general well-being after the patient enters the surgery. Through a medical interview, detailed information about the current general health condition was revealed (including information about chronic and hereditary diseases); the examining physician obtained information about the patient's surgical treatment and head trauma history within the last 6–8 months and the current medications being taken on daily basis. In this context, particular attention was given to muscle and joint conditions, with a focus on multiple sclerosis, osteoporosis, fibromyalgia, trigeminal neuralgia, hormonal disorders, and autoimmune diseases.Physical examination started with a facial symmetry test; the oral cavity was examined for the dental and periodontal status and the condition of oral mucosa. If the patient had any missing teeth, the number and location of existing natural teeth in the occlusion support zones were investigated. Dental classification  was recorded in the patient's medical file. Dental prosthetic restorations, if present, were examined in terms of their clinical value.A clinical examination of temporomandibular joint consists of palpation and auscultation; palpation was performed simultaneously on both sides of the face by exerting a force of around 400 g per square centimeter. Auscultation was performed with the aid of a double-tube stethoscope. The individual palpation force was measured using an electronic kitchen scale , 17, 18.Factors of inclusion in the study were pain form of temporomandibular joint dysfunction, the required age range, and a good general state of health (particularly with regard to cardiac and metabolic disorders). Good general state of the patients' health means that patients did not suffer from the medical conditions that could have an influence on the level of CRP.Factors for exclusion from the research included the will (consent) of the patient, the presence of general diseases, traumas, or local inflammations.All respondents were directed to one external medical analysis laboratory to determine the level of C-reactive protein in the blood serum. For this purpose, the immunoturbidimetric assay was performed for the in vitro quantitative determination of CRP in human serum and plasma using Roche/Hitachi cobas c systems. It was also assumed that the correct level of this marker in patients who show no evidence of inflammation taking account of the above method is 0 to 5 mg/l , 14. AllIn case of the measure giving the constant results, statistical analysis was based on the traditional methods of calculation: mean values, standard deviation, minimal values, maximal values, standard error of the mean, variance analysis for dependent variables, and post hoc Tukey test for dependent variables being the statistical significance measure.p value less than 0.05 was accepted as statistically significant. The research obtained approval from the Ethics Committee of the Jagiellonian University (KBET/125/L/2013). Clinical Trial Gov. Identifier was registered as well: NCT03065608.To compare the dependencies between the results obtained in consecutive clinical tests, the nonparametric Friedman test, Kendall's W, and Wilcoxon signed-rank test (comparing two related samples) were used. For statistical studies, special computer software STATISTICA 2010 was used. A Level of Evidence for primary research was established as type V.The study involved 72 patients, ranging from 21 to 48 years, divided into two groups of 36 people. Group I included 24 women and 12 men (mean age 29), and group II control included 27 women and 8 men (mean age 31). Analysis of the results of clinical examinations conducted in both groups show a homogeneous clinical material  with the exception of pain, which is a factor differentiating patients between group I and II. The results of the clinical examination  are summarized in p > 0.05. The results of the statistical calculations are graphically depicted in Figures In group I, the mean level of CRP was 2.54, the extreme values were 5.9–0.14, median was 2.15, and the standard deviation was 1.54. In group II, the average value of C-reactive protein was 2.69 (peak of 5.2–0.7), median was 2.4, and the standard deviation was 1.87. Average values of amounts of CRP did not significantly differ statistically, since None of the examined patients had signs of inflammation in the temporomandibular joints in ultrasound examination .The authors of many publications –16, 19 eIn the dental treatment specificity, the elevated level of CRP has been found in many diseases, such as periodontal disease, gangrenous pulp, fungal diseases of prosthetic base, or posttraumatic conditions—fractures of the jaws , 15. WhiCRP levels in our own study of both groups are in the normal range, and therefore this indicates that the pain form of temporomandibular joint dysfunction of subjects is not associated with the occurrence of the state of the inflammation in the soft tissues and bones of the temporomandibular joints. The presence of pain in the palpable test is often interpreted as an evidence of inflammation of tissues, but it is not confirmed in the clinical and laboratory tests.Pain in any joint structure is called arthralgia. It would seem that pain is originated from the articular surfaces when the joints are overloaded by the work of muscles. It is impossible because of lack of the innervation of the articular surfaces, so arthralgia can originate only from nociceptors located in the soft tissue of the temporomandibular joints, like disc and capsular ligaments, and retrodiscal tissue , 21, 22.In general, diseases such as arthritis and temporomandibular joint dysfunction can occur with elevated CRP because of general disease, as indicated by Lin et al. . NordahlAnalyzing the available literature, it can be assumed that the use of studies evaluating CRP levels can be very helpful in diagnosing or excluding the inflammatory component of the temporomandibular joints. Kostrzewa-Janicka et al. indicate that more information could be obtained from synovial fluid of joints, like cytokines and their receptors, which are involved in the pathogenesis of temporomandibular joints. However, it is very difficult to aspirate the proper amount of synovial fluid from such a small joint, although recent advances in arthroscopic surgery allowed the direct examination of these joints . These aThe above test results show the importance of information on the general principles of the treatment of pain form of temporomandibular joint dysfunction that the administration of antibiotics in case of pain on the palpation test of the temporomandibular joints may be wrong. Such a clinical situation requires careful verification and use of additional tests to plan an appropriate treatment , 2.This provides valuable information for proper diagnosis and correct treatment in temporomandibular joint dysfunction with the use of occlusal splints and occlusal correction of the teeth contacts and supporting numerous treatments in physiotherapy, such as laser biostimulation, sonophoresis, physiotherapy, and manual therapy. Intraoral splints are commonly used in dental treatment for a variety of conditions. Such splints alter the condyle-disc-fossa relationship, probably by changing the loading status of joints and discs. The antibiotics are not necessary for such a kind of treatment .Despite the etiological factor associated with the psychosocial sphere, this provides valuable information for proper diagnosis, and correct treatment of temporomandibular joint dysfunction is primarily occlusal splint, correction of occlusal contact, and numerous supporting physiotherapy treatments, such as biostimulation laser, sonophoresis, and manual techniques , 25–28.Pain form of the temporomandibular joint dysfunctions is not connected with inflammation of the temporomandibular joints.


Acute postoperative pain delays recovery and increases morbidity and mortality. Traditional administration of postoperative analgesics by nurses is often inefficient. The present study evaluated the safety, efficacy, and usability of a novel, patient-controlled analgesic dispenser, the PCoA Acute.n = 43), opioids dispensed by nurses, and a test group (n = 27), opioids dispensed via the PCoA Acute. Pill intake data were recorded. Pain ratings at rest and during movement were surveyed. A controlled pilot study was conducted at three medical centers. Patients scheduled for elective surgery were enrolled into two groups, both taking oral analgesics: a control group . The test group took 67% more pills than the control group, indicating enhanced compliance. Pain scores were significantly lower for patients in the test group . Over 90% of PCoA Acute users were satisfied with its use. No severe adverse events were recorded. Average pill intake time was reduced from 8 : 58 minutes in the control group to 1 : 17 minutes in the test group ( The study confirmed that PCoA Acute is safe and effective. It is well accepted by patients and medical staff. Its use can optimize pain medication administration. The management of acute pain in the hospital setting is a continuing challenge for healthcare professionals. More than 80% of patients who undergo surgical procedures experience acute postoperative pain. Most of them report inadequate pain relief, leading to increased morbidity, mortality, and costs . PreventIn most hospitals nurses play a key role in the assessment and management of patients' pain. However, it has been shown that nurses tend to underestimate patients' pain and undermedicate patients for their pain . Other fPatient-controlled analgesia (PCA) is a delivery system in which patients self-administer predetermined doses of analgesic medication to relieve their pain. PCA has become a standard of care in pain management. However, most common routes of PCA administration are intravenous (IV) and epidural (PCEA) . AdvantaIt uses pain medication in the original packaging. The device is therefore easily integrated into clinical routine.It safely delivers and tracks each pill right to the patient's mouth. The device verifies consumption of pills by the patient, enables stringent control of pill consumption, and monitors drug dispensing by caregivers in real time.It provides a locked safe for high risk narcotic drugs.It dispenses to the prescribed patient only, using personalized identification.It allows remote monitoring and management including alerts and reminders.It enables data collection and management related to the patient's clinical status.PCoA Acute is an innovative personalized oral PCA device, which provides a comprehensive solution for the provision of pain medication at the bedside. The system has the following capabilities and benefits:A feasibility, pilot clinical study was conducted to initially evaluate the PCoA Acute in the clinical setting for pain medication provision to postoperative patients. To our knowledge, this is the first clinical study evaluating pain medication provision where a standard solid pill is sucked by the patient and the pill is monitored right to the patient's mouth.The study aimed to evaluate safety, efficacy, and usability of PCoA Acute, along with the acceptance of the novel pill sucking approach by patients and medical staff. The study also aimed to demonstrate optimization of the administration process by the device, compared to the conventional method of nurse administration of pain medication.PCoA Acute safety: no pill overdose or pill malformation occurs upon dispensing and no pill inhalation occurs during pill sucking via the PillBox.PCoA Acute efficacy: 90% of pill intake attempts are successful and no device critical malfunction occurs.PCoA Acute usability: 90% of patients and medical staff can easily operate the device and are satisfied with its use.PCoA Acute advantage over conventional method of nurse-provided medications: the time from pill request to pill intake is reduced by at least 50%.The study specific objectives were as follows:NCT03134001). Centralized Institutional Review Board (IRB) approval of the study was given by the Ethics Committee, North Rhine-Westphalia . Subsequently, patients 18 years and older, scheduled to undergo elective surgery, provided written informed consent and were enrolled to the study. The study included a control group of 43 patients requiring postoperative pain therapy from nursing staff by conventional means. The test group comprised 27 patients who used PCoA Acute to receive their pain medication. The follow-up time was 48 hr (2 postoperative (PO) days). The time duration from pill request to pill intake by the patient was recorded as well as the number of pills obtained by each patient. Pain scores (pain at rest and during movement) were recorded by the PCoA Acute on each occasion of a pill intake. Safety and efficacy parameters of the PCoA Acute were evaluated using questionnaires filled in by patients and medical staff.An open-label, multicenter, controlled, feasibility pilot clinical study was conducted. The study was registered on ClinicalTrials.gov , Gynecology, Orthopedics, and Thoracic, and required postoperative pain therapy for at least 48 hr. All patients enrolled signed an informed consent form prior to surgery. Pain medications were identical for patients in both groups, undergoing similar surgery type in the same medical center, but varied between medical centers and surgery types . Inclusion CriteriaOperative procedure with at least 3 days' hospital stayPlanned postoperative pain therapy with oral medication using a strong opioidNo contraindication for opioid therapyNo contraindication for oral pain therapyPatient being able to understand and complete the questionnairePatient signing an informed consent form Exclusion CriteriaOpioid or drug addictionOpioid intolerancePain therapy using anesthesia, IV PCA, or infusionPatient's refusal of an opioid therapyInability to swallow medicineDepartment of Anesthetics, Interdisciplinary Intensive Care, CURA Hospital, Bad Honnef—Center for Pain Medicine.Clinic of Anesthetics and Intensive Care, Bethanien Hospital, Moers.Clinic of Anesthesiology, Intensive Care and Pain Therapy, Teaching Hospital of the University of Cologne, Oberberg Hospital, Gummersbach.The study was conducted at three medical centers in Germany:μ-opioid receptor agonists. Oxycodone reveals binding properties at the opioid κ(2b) receptor. The efficacy and safety of morphine and oxycodone for postoperative pain therapy has been reported previously [In all 3 medical centers, there existed a standardized postoperative pain procedure involving different step 1 and step 3 analgesics. In both patient groups, basic pain medication consisting of oral nonopioid analgesics was given. Dipyrone—which is widely used in Germany—was prescribed in combination with Etoricoxib, Ibuprofen, or Diclofenac. The centers differed in the prescription of either Etoricoxib, Ibuprofen, or Diclofenac. Contraindications for the use of these step 1 analgesics were allergy, blood count abnormalities, cardiovascular diseases, renal impairment, pulmonary diseases, and any kind of gastrointestinal disorder. The daily doses for these analgesics were standardized as follows: Dipyrone: 4 × 1 g, Etoricoxib: 1 × 60 or 90 mg, Ibuprofen: 3 × 500 mg, and Diclofenac: 2 × 75 mg. With regard to the opioids, the centers used 2 different step 3 opioids: oxycodone and morphine. In addition to the “basic” treatment with step 1 analgesics, controlled-release formulation of oxycodone/naloxone is used at daily doses of 2 × 5/2,5 mg or 10/5 mg and the controlled-release formulation of morphine is used at daily doses of 2 × 10 mg. Morphine and oxycodone are eviously , 14.The PCoA Acute is an oral PCA device which provides patient-controlled analgesics at the bedside. A standard drug package is inserted into the device, which is operated by a touch screen. The medication used in this study consisted of short-lasting formulation of oxycodone (5 or 10 mg) or morphine (10 mg). Medication is dispensed only after the patient's identity has been confirmed by the RFID wristband. The system connects to the hospital database. Medication history, therapies, and pain scores are saved and easily displayed on the touch screen.Setup included device programming by a trained nurse, with the appropriate therapy regimen for each patient and loading the blister pack of the relevant pills. Patient training was then conducted by the nurse. The setup time and patient's training time were measured, for each patient, by a third person. During the study, patients used the PCoA Acute to obtain their pain medication by pressing the device's button followed by wristband registration. If the pill request was made during the safe time interval , the patient received a pill. However, if a pill was requested during the lockout time interval (time period in which the device is locked to prevent drug overdose) no pill was released. The device screen indicated the time left to the next pill intake. Before each pill intake, the patient was requested by the device's screen to score his pain at rest and during movement. All data were recorded and saved in the device's log files. The patient could also ask for an extra pill from the nurse, if needed. Using a security code, the nurse was able to release an extra pill during the lockout interval, subject to physician's approval. At the study's termination questionnaires were filled out by patients and nurses and the data recorded by the device were analyzed.Nurse administration of pain medication, upon patient's request and according to patient's therapy regimen, is a routine procedure in hospitals. This procedure includes the following steps, conducted near the patient's bedside and also in the nurses station: a patient who feels acute pain calls the nurse and waits for her attendance. The nurse reviews the patient's prescription and time of previous drug intake. Once a new pain medication intake is approved, the nurse retrieves the key for the drug safe, dispenses the medication, and documents drug withdrawal. The nurse then returns to the patient's bedside, provides the medication, and documents the fact in the patient's record file.The patients of the control group were advised to report pain to the nurses early and to order the acute pain medication. In the control group, nurses were instructed to dispense the short-lasting formulation of oxycodone (5 or 10 mg pill) or morphine (10 mg pill) to patients who reported a NRS (pain) > 3. In both groups, the acute pain medication was restricted to the short-lasting formulations of oxycodone or morphine. Nurses were informed that the time of analgesic pills administration was being recorded. During the study, a third person measured the time from a patient requesting a pill from a nurse until pill intake by the patient. Endpoint of this was the number of pills obtained by each patient which was counted by a third person and by the nurse. The study outcomes are as follows: PCoA Acute SafetyNo pill overdose in dispensing No pills malformation upon dispensingNo pill inhalation during pill suckingNo severe adverse events related to pill intake by the PCoA Acute The safety outcomes were measured using questionnaires filled by patients and medical staff participating in the study and data recorded by PCoA Acute devices. PCoA Acute EfficacySuccess rate of 90% for pill intake upon patient's request. This outcome was measured by analysis of data recorded by the device for each patient as well as by questionnaires filled out by patients.No critical device malfunctions. This outcome was measured by the questionnaires filled out by patients and medical staff.Time of pill intake reduced by at least 50% in the test group compared to the control group. PCoA Acute UsabilityAt least 80% of patients and medical staff are satisfied with device use and will recommend its use for their colleagues. This outcome was measured using questionnaires filled out by patients and medical staff participating in the study.t-test with a 0.05 two-sided significance level [The calculation of the sample size was based on demonstrating an effect size of at least 1.0 with 80% power and 5% statistical significance. Effect size is calculated as the difference in outcome between the study groups divided by the common standard deviation. A sample size of minimum 20 subjects in each group will have 80% power to detect an effect size of 1.0 using a two-group ce level .The study had a sequential design; the control group study was conducted before initiation of the test group study. The rationale for this design is that the same nurses had a role in both groups. This design minimized nurses burden and bias towards one group. This patients' allocation approach provides random enrollment of patients to groups, by their operation date, without any selection bias. Subjects eligible for the study were assigned as follows: Bad Honnef enrollment dates: control group 16/05/2015–22/06/2015 and test group 18/08/15–24/08/15; Moers enrollment dates: control group 16/05/15–22/06/15 and test group 18/08/2015–22/06/15; Gummersbach enrollment dates: control group 03/09/2015–14/09/15 and test group 15/09/15–28/10/15.The two-sample nonparametric Wilcoxon-Mann–Whitney Rank sum test for independent samples was used to analyze the difference in outcomes between the study groups.Analysis of variance (ANOVA) was applied for analyzing the difference in the study outcomes between study medical centers within study groups .The study was conducted at three German medical centers. The first patient was enrolled in May 2015 and the last patient was enrolled in October 2015. The whole study duration was 6 months. The patients disposition flow diagram is illustrated in Safety of the PCoA Acute was evaluated by questionnaires filled in by patients and medical staff and confirmed by data recorded by the device. No incidence of pill overdose dispensed occurred and no pill malformation was reported either by patients or by medical staff. Furthermore, no severe adverse events, such as pill inhalation, were reported by medical staff . Based oEfficacy of PCoA Acute was measured by the success rate of pill intake upon patient's request. Other functions documented were attempts of pill request during the lockout interval and extra pill obtained from the nurse. The performed actions are summarized in The study aimed to compare two processes of pain medication provision, use of PCoA Acute and nurse-provided medication. The duration from a patient requesting pain medication to actually receiving the pill was compared.P value was calculated separately to distinguish differences between groups for all medical centers and within each center. All differences between groups were statistically significant. Differences observed between control groups within medical centers were not statistically significant. Differences observed between study groups of all centers were statistically significant.Data analysis revealed that the mean time of the control group was 8.58 minutes and the maximal time was 1 hour . In contrast, the mean time to receive a pill by PCoA Acute was 1.17 minutes, including setup and training time. The maximal time was 3.77 minutes. These results indicate 86% reduction in time required to obtain a pill upon patient's request when using PCoA Acute.P value was calculated separately to distinguish between groups for all medical centers and within each center. Differences observed between control and test groups of all centers were found to be statistically significant. Differences in medical centers A and B were found to be statistically significant, whereas differences in medical center C were not found to be statistically significant.P value = 0.0058). The mean rating of movement pain was 6.38 on the first PO day and reduced to 4.25 on the second . Both pain scores' reduction was statistically significant.The PCoA Acute collects patient clinical data using simple surveys. During the study, patients in the test group were asked to score their pain before each pill intake. Usability and ease of care (EOC) of PCoA Acute were evaluated by questionnaires completed by patients and medical staff. PCoA Acute is safe and effective as an oral PCA for hospitalized patients who require pain therapy.PCoA Acute is easy to use and well accepted by patients and medical staff.Use of PCoA Acute is valuable for patients and medical staff: nurse time is significantly saved compared to conventional procedure. Pill intake occasions are increased, indicating enhanced patient's adherence to their therapy regimen. Patient's pain is reduced towards the 2nd PO day indicating positive clinical outcome.The major findings of this pilot study were as follows: The mean time of pain medication provision by nurse upon patient's request (the control group) was found to be 8.58 minutes. Nurses were informed that the time of pill provision is being measured. This awareness certainly contributed to their motivation to shorten the measured time. These results are in agreement with a previous study indicating 10.9 minutes as average nursing time required to provide oral opioids in a postoperative orthopedic nursing unit . By contInterestingly, and unexpectedly, the study results further showed that patients using PCoA Acute obtained more pain medications, according to their therapy regimen, relative to patients of the control group. The mean pill number obtained by a patient in the test group was 5, compared to 1.67 pills in the control group. Although the parameter of pill number per patient was not part of the study outcomes, results suggest that the rapid and simple provision of pain medication by PCoA Acute can increase pill intake events (by 67%) and lead to increased patient's compliance with their therapy regimen.Notably, differences between the control group and the test group were statistically significant for both duration of pill administration and number of pills taken by patients. Despite the small size of groups enrolled for this pilot study, statistical significance was achieved for all medical centers and also within each medical center. The only exception was number of pills intake at MC-C, in which the control group took more pills compared to the test group . A possible explanation is that patients at MC-C underwent orthopedic operations. This procedure is highly painful and specific instructions are given for extra pain medication. Moreover, the department was relatively highly staffed with nurses, located centrally. Nevertheless, the time required for pill administration by nurse in MC-C was significantly longer relative to the use of PCoA Acute (8.64 min for nurse administration versus 1.55 min for PCoA Acute), as was found for all centers.Nurse-administered pain medication is a burdensome process and requires direct interaction between patient and nurse as well as nurse availability for the patient at the right time. Moreover, the nurse is responsible for assessment and management of the patient's pain. Interruption to this process may occur for different reasons; for example, patient feels uncomfortable to distract a busy nurse; nurse is not available or delays medication provision. By contrast, use of PCoA Acute enables the patient to control his pain medication consumption. This results in increased number of pills intake by the patient during his hospitalization period. Studies conducted in various clinical settings have consistently shown that nurses tend to underestimate patients' pain and undermedicate patients for their pain . They usRosati et al. conducted a pilot clinical study to evaluate the functionality and usability of an oral PCA device for oncology patients. Patients reported that use of the device provided better pain control, since it allowed them to receive medication directly without delay. Moreover, all patients preferred using the device to calling a nurse for each dose of as-needed medication. In addition, most nurses reported that the device saved their time and that patients' pain appeared to be better controlled when the device was used . These rThe 2016 guideline, for the management of postoperative pain, from the American Pain Society and the American Society of Regional Anesthesia and Pain Medicine, strongly recommends oral over IV administration of opioids for postoperative analgesia, in patients who can use the oral route. IV PCA is only necessary in hospitalized patients with an ileus, aspiration risk, or after surgical procedures that affect the ability to take medications orally .Comparable oral PCA devices have been introduced to hospitalized patients with postoperative pain medication; Sufentanil Sublingual Tablet System  uses Sufentanil tablets for sublingual transmucosal drug uptake . SSTS waMOD® (Medication on Demand) is another oral PCA device (Avancen MOD Corporation). A clinical study evaluated pain management in patients after total knee arthroplasty, compared between MOD and usual care of nurse-provided pain medications. It was found that device patients had significantly better pain scores than the usual care group. Moreover, all measured functional parameters, including general activity, mood, sleep, and appetite, were significantly better in the device group than in the usual care group .The fast administration of pain medications, the high number of consumed pills, and the pain scores reduction for patients using the PCoA Acute suggest that pain control is improved by using PCoA Acute and that the device can be successfully used for real time pain evaluation of postoperative hospitalized patients.Limitations of the study included the heterogeneous small groups size, different surgical procedures, and differing use of step 1 and 3 analgesics applied at each medical center . Statistical analysis confirmed significant difference between groups in all centers and also within the study group in each medical center. However, differences observed between control groups within medical centers were not statistically significant. More young patients aged < 65 were enrolled to the control group. The number of pills consumed by patients in the test group at MC-C was lower compared to the control group. This may be due to a different patient population, the availability of medical staff, and organization and logistics on the wards. For the control group, more patients aged below 65 years were enrolled. The study had a sequential design; the test group study was initiated only after the control study was completed in each medical center; hence, randomization, as defined, was not conducted. With regard to opioid-induced symptoms or other adverse effects of drugs, symptoms as nausea, vomiting, dizziness, fatigue, or others were not assessed because of the study's specific objectives and according the ethical approval which only allows the evaluation of a medical device but not pharmacological endpoint. Ethical approval limited us to the assessment of adverse effects only in relation to the device.Evaluation of clinical outcome requires different study design, larger sample size, and homogeneous patient population. This therefore was not part of the study goals and will be tested in a pivotal clinical study specifically designed to meet this goal.All study endpoints were achieved. 1) Safety Endpoint. The PCoA Acute system is safe under the study conditions: no severe adverse events, no pill provision during the lockout interval, no overdose, and no pill malformation.(2) Efficacy Endpoint. 82% of patients in the test group completed the study and successfully used PCoA Acute to obtain their pain medication. Only rare device malfunctions were reported. The average time for pill intake was reduced by 86%, from 8.58 minutes under current practice of nurse-provided medication to 1.17 minutes with the PCoA Acute. Moreover, patients in the test group took 67% more pills (average of 5 pills/patient in the test group compared to 1.67 pills/patient in the control group). This data indicated better therapy compliance. Pain scores of patients using PCoA Acute were significantly reduced on the 2nd PO day, indicating desired clinical outcome. Almost all differences between study groups were statistically significant. (3) Usability Endpoint. The PCoA Acute was well accepted by medical staff and patients. Over 90% of study participants described it as easy to use and were satisfied with its use.(


This pilot study was designed to compare the efficacy of ultramicronized palmitoylethanolamide (um-PEA) as add-on therapy to tapentadol (TP) with TP therapy only in patients suffering from chronic low back pain (LBP).This pilot observational study consists in two arms: the prospective arm and the retrospective one. In the prospective arm patients consecutively selected received um-PEA as add-on therapy to TP for 6 months; in the retrospective arm patients were treated with TP only for 6 months. Pain intensity and neuropathic component were evaluated at baseline, during and after 6 months. The degree of disability and TP dosage assumption were evaluated at baseline and after 6 months.Statistical analysis performed with generalized linear mixed model on 55 patients (30 in the prospective group and 25 in the retrospective group) demonstrated that um-PEA as add-on treatment to TP in patients with chronic LBP, in comparison to TP alone, led to a significantly higher reduction in pain intensity, in the neuropathic component, the degree of disability and TP dosage assumption. No serious side effects were observed.Overall, the present findings suggest that um-PEA may be an innovative therapeutic intervention as add-on therapy to TP for the management of chronic LBP with a neuropathic component, as well as to improve patient quality of life. Additionally, this combination treatment allowed a reduction in TP dose over time and did not show any serious side effects. Low back pain (LBP) is one of the most common chronic pain conditions encountered in clinical practice worldwide, with a lifetime prevalence estimated to be >70% in industrialized countries . LBP is while opioids target both nociceptive and (to a lesser degree) neuropathic pain, and antidepressants target only the neuropathic component, although data concerning their efficacy is conflicting  twice daily as adjuvant to TP. Retrospective group patients were treated with TP only for 6 months between January 2013 and June 2014. The dose of TP could vary between 100 mg and 500 mg depending on patient needs, as established by normal clinical practice. Paracetamol (1000 mg) was habitually used as rescue drug in case of exacerbations of pain.In all patients, the main outcomes were: i) pain intensity evaluated by the VAS. The VAS is a continuous scale comprised of a horizontal line, 10 cm (100 mm) in length, anchored by 2 verbal descriptors, one for each symptom (0 = no pain and 10 = the worst pain imaginable). ii) Neuropathic pain component detected by DN4 (Douleur Neuropathique 4). DN4 questionnaire included four questions consisting of both sensory descriptors and signs related to bedside sensory examination . iii) Pep-value of less than 0.05 was considered significant for both GLMM and responder analysis. All patients for both groups were evaluated at each time point.The above parameters are evaluated as part of normal clinical practice in the pain therapy outpatient clinic at the University of Campania “Luigi Vanvitelli”, for afferent patients affected by chronic low back pain. Statistical analysis was performed using the generalized linear mixed model (GLMM). Variables such as gender and age were included in the model as covariates. All scores are given as mean ± standard error (S.E.) unless otherwise specified. Responder analysis was also performed. For this propose, minimal important difference (MID) was established as fixed effects, since percentage reductions depend on baseline values. In particular, a patient was considered a responder in case of: i) pain intensity reduction of at least 2, 3, or 4 points or by achieving a VAS score ≤ 3 (gold standard) . ii) neuFifty-five patients affected by chronic LBP were considered for this study; 30 patients  were enrolled in the prospective group treated with um-PEA as add-on to TP (um-PEA-TP group); 25 patients  were included in the retrospective group treated with TP only (TP group) . VAS values in the um-PEA–TP group decreased from 7.4 ± 0.08 (T0) to 4.5 ± 0.09 (T3), and in the control TP group from 7.7 ± 0.10 (T0) to 5.9 ± 0.09 (T3). The reduction in VAS mean score was statistically significant in the um-PEA–TP group compared to the TP group (p < 0.0001)  Fig. .Fig. 2Pap < 0.0001), with a significantly higher reduction in favor of the prospective group (p < 0.0001)  .DN4 questionnaire scores showed that the neuropathic component significantly decreased over time in both groups (01) Fig. . Patientp < 0.0001), with a greater reduction in favor of the um-PEA-TP group (p < 0.0001). In fact, patients in the um-PEA-TP group received a mean dose of 203.3 ± 6.75 mg at study start (T0) which decreased to 121.7 ± 6.20 mg after 6 months (T3). In contrast, patients in the TP group initially took a mean dose of 196.0 ± 10.38 mg (T0), which decreased to 158.0 ± 8.50 mg (T3)  was used as rescue medication in 10% of patients in um-PEA-TP group vs 12% of patients in the TP-only group. This study did not present missing data. No serious side effects were reported/observed, although episodes of diarrhea occurred in 15% of patients in the um-PEA-TP group. Percentages of responder patients for each established MID and gold standard are given in Table p < 0.0001) showing a further significant reduction in favor of the um-PEA-TP group (p < 0.0001)  Figs. . These r. By modulating the activation of non-neuronal cells that normally controls neuronal cell sensitization, PEA can effect TP action on neurons, thus promoting a major remission of chronic pain also with a neuropathic component.The improved effectiveness of this combination therapy in the management of chronic LBP may be attributed to different mechanisms of action for um-PEA and TP in pain processes. PEA acts on immune-derived non-neuronal cells, in particular microglia and mast cells, which are involved in pain signalling but not directly in the transmission of pain perception , 15. Thep < 0.0001). Importantly, the reduction of TP mean intake was significantly higher in the um-PEA-TP group (p < 0.0001)  Fig. . These rThe association of um-PEA and TP led to a significant reduction compared to TP alone in the degree of disability measured by the ODQ low back pain questionnaire Fig. . RespondIt is important to point out also that none of the patients showed serious adverse effects. In the um-PEA-TP group only 15% of patients presented some episodes of diarrhea which did not necessitate discontinuation of therapy. Several clinical studies already support the tolerability both of um-PEA .p = 0.0510). As far as were are aware of, no study until now has evaluated this interaction in clinical practice. There was, however, a modest but significant association between chronic venous insufficiency and um-PEA-TP (p = 0.0429) (Table There was no statistically significant group difference in the incidence of dylipidemia p = 0.050. As farFuture studies are needed to evaluate a possible direct effect of PEA on chronic venous insufficiency.Caveats of the present observational study include lack of blindness and small patient sizes, which increases the difficulty in estimating the size effect of combination treatment. Furthermore, a treatment period longer than 6 months would allow one to better appreciate effectiveness and tolerability of the drug combination. In spite of these limitations, this exploratory study provides encouraging findings on the potential benefits of PEA addition to TP in patients affected by chronic LBP, and should stimulate confirmatory trials with larger patient cohorts.Overall, our findings suggest that um-PEA may be an innovative therapeutic intervention as add-on therapy to TP for the management of chronic LBP with a neuropathic component, also to improve patient quality of life – at least for a treatment period of 6 months. Additionally, this combination treatment allowed a reduction in TP dose over time and did not show any serious side effects. Um-PEA could thus allow for the maintenance of low dosages of TP, thereby delaying the occurrence of serious side effects of this drug over longer periods. Further prospective studies with a double-blind design and larger patient numbers are needed to confirm our findings.


Background. Patients with SCD now usually live well into adulthood. Whereas transitions into adulthood are now often studied, little is published about aging beyond the transition period. We therefore studied age-associated SCD differences in utilization, pain, and psychosocial variables. Methods. Subjects were 232 adults in the Pain in Sickle Cell Epidemiology Study (PiSCES). Data included demographics, comorbidity, and psychosocial measures. SCD-related pain and health care utilization were recorded in diaries. We compared 3 age groups: 16–25 (transition), 26–36 (younger adults), and 37–64 (older adults) years. Results. Compared to the 2 adult groups, the transition group reported fewer physical challenges via comorbidities, somatic complaints, and pain frequency, though pain intensity did not differ on crisis or noncrisis pain days. The transition group utilized opioids less often, made fewer ambulatory visits, and had better quality of life, but these differences disappeared after adjusting for pain and comorbidities. However, the transition group reported more use of behavioral coping strategies. Conclusion. We found fewer biological challenges, visits, and better quality of life, in transition-aged versus older adults with SCD, but more behavioral coping. Further study is required to determine whether age-appropriate health care, behavioral, or other interventions could improve age-specific life challenges of patients with SCD.  Sickle cell disease (SCD) is an autosomal recessive genetic disorder of hemoglobin structure whose classic symptomatic manifestations are acute episodes of ischemic pain, termed vasoocclusive crises (VOC), from deformed red blood cells. VOC may begin within the first year of life and generally continue throughout life. VOC worsen with age –3 even aFortunately, newborn screening , prophylNot surprisingly, the adolescent transition period to adulthood has become an intense focus of health services and implementation research in SCD, because it is fraught with difficulty. Many have described the challenges of transition to adulthood from pediatric care –28. LikeHowever, in contrast, few have studied age-specific life challenges, including biological challenges and psychosocial challenges, beyond the transition period, that is, among the oldest SCD patients. Most previous studies of utilization and their predictors among adult SCD patients were done with adults with an average age of 30 years . It is cWe are therefore interested in several age-associated differences among adults with SCD. We theorized three age groups by stage of life: transition-aged, younger adults, and older adults. Building off of ours  and othePiSCES (the Pain in Sickle Cell Epidemiology Study) was a longitudinal study of pain in SCD but also a methodologic study of the relationship among measures of pain, crises, and utilization in sickle cell disease. The methods of PiSCES have been described in detail elsewhere , 41. BriWe recruited patients 16 years of age or older from across Virginia, mostly from the Richmond  and Tidewater  areas. Both the study and our recruitment methods were approved by the Institutional Review Board of Virginia Commonwealth University, Richmond, Virginia, and we obtained informed consent.Patients received routine care for their sickle cell disease from either community-based physicians or sickle cell specialist physicians associated with academic medical centers . Emergent care for the cohort was provided in Emergency Departments regardless of the patients' usual source of ambulatory care. No day hospitals for sickle cell disease are located in the region.Coping was assessed using the Coping Strategy Questionnaire-SCD (CSQ-SCD), originally developed to measure cognitive and behavioral coping styles in chronic ow back pain . This scThe Smith-Bovbjerg Sickle Cell Stress scale (STRESS) is a 10-item scale that assesses stress using our internally developed measure . More specifically, items are measured on a Likert scale from 0 (strongly disagree) to 4 (strongly agree) and assess issues as worry about access to pain medication or whether pain medication will control pain, being hospitalized, limited work activities, sexual performance, insurance, and so on. Higher scores indicate more perceived stress.Health related quality of life was assessed at baseline using the Medical Outcome Study 36-item short form (MOS SF-36), one of the earliest well-known and accepted generic measures of HRQOL . There aSocial Support was measured using the Multidimensional Scale of Perceived Social Support , 49. PatDepression, anxiety, alcohol abuse, and somatic symptoms were each measured using the Patient Health Questionnaire (PHQ). The PHQ is a widely utilized screening instrument based on subjects' self-reported symptoms that was designed to facilitate the recognition and diagnosis of the most common mental disorders in primary care subjects . For theSomatic symptom burden was assessed with the portion of the PHQ referred to as the PHQ-15 , which iDaily pain assessment utilized daily diaries completed by patients for up to 6 months. Patients were encouraged at the initial baseline visit and with reminder calls by study staff to return diaries daily by mail using provided stamped envelopes. They received payment for each returned diary, with a higher payment in the latter 2 months of the study to encourage study completion. We modeled the diary after that of the Multicenter Study of Hydroxyurea (MSH) . PatientFor purposes of analysis, we defined home days as days without ED or hospital utilization marked on the diary and pain days as days when pain intensity was rated 1 or higher on the 0–9 scale. We defined opioid use as the report of use of any of the known opioids then on the market, inclusive of Tramadol.Mean scores of pain intensity as well as rates of pain occurrence, health care utilization, and home opioid use were calculated for each patient using daily diary information. Since the number of diaries completed by each subject varied, the numbers of pain days, opioid use days, crisis days, and utilization days were converted to percentages by dividing by the total number of diary days completed by each subject. The exception was the percentage of home pain days on opiates, which used home pain days as the denominator. The denominator for mean pain was pain days. For mean pain on crisis days we used number of diary days reporting crisis in the denominator, while for mean pain on noncrisis days the denominator was number of pain days without crisis.A measure called ED reliance  was calculated as the proportion of ambulatory visits (ED + outpatient visits) that are ED visits . This meGuided by our cited hypotheses, as well as by Sanders et al. , who comAnalyses were conducted by using SAS, version 9.4 for Windows .The National Heart, Lung, and Blood Institute provided an unrestricted grant for this project. The funding source did not have any influence on the planning, conduct, analysis, or publication of this study or its results.https://doi.org/10.1155/2017/4070547). Subjects in the transition group were less likely to be depressed/anxious than either of the adult groups, but this difference did not persist when controlling for frequency of pain and comorbidities.Subjects in both the transition group and the younger adult group recalled significantly fewer comorbidities and less often reported ischemic ulcers, hypertension, or rheumatic diseases over their lifetime compared to the older group. Subjects in the transition group also less often recalled avascular necrosis and gout than did those in the adult groups . There were no significant differences for ED visits, hospital days, or total health care utilization. Notably, ED reliance for health care was twice as high for either the transition group or younger adult group  as compared to the older adult group. With values greater than 33 percent, the two younger age groups had EDR which would be considered excessive [p = 0.0237). There was also a trend for the younger adult group to use the ED/hospital for a crisis more than the older adult group.Regarding health care and opioid utilization, xcessive . The ED p = 0.1123). The transition group also reported using significantly less passive-adherence coping than the younger adults. This difference persisted when controlling for pain days and comorbidities.The transition group reported significantly better physical health , which persisted when controlling for pain days and comorbidities. All individual SF-36 subscales were significantly better for the transition group than for the two older groups, except for mental functioning, where there were no significant differences across age groups. When controlled for pain frequency and comorbidities, vitality, physical functioning, and physical role function subscales were still significantly better for the transition group . There were no differences between age groups in reports of social support or SCD stress.Although our results are not the first to compare age groups of patients with SCD with regard to disease or psychosocial outcomes, our results are some of the first to compare simultaneously age differences in measures of physical outcomes, utilization, pain outcomes, and psychosocial outcomes of SCD adults. Our goal was to further test hypotheses about important theoretical subthemes and potential predictors of utilization of care and pain in SCD that we raised in 1997 .For this study, we hypothesized age-related changes in these predictors and outcomes. Regarding outcomes, we hypothesized that pain, utilization , and psychosocial outcomes of older SCD adults were sometimes even worse than those for transition-aged adults. Regarding predictors, we hypothesized worse organ failure (worse laboratory measures) and comorbidities for older adults. We were aware that transition-aged adults were already well-documented as having worse utilization of health care, life disruption , 30, andRegarding physical outcomes, consistent with our hypotheses, the transition group did report fewer physical challenges via comorbidities and non-SCD somatic complaints. But contrary to our hypotheses, we found few differences in hemoglobin or white cell count, other than higher HbS. This is somewhat different than McKerrell et al.  who, comAlso contrary to our hypotheses, the transition group reported less frequent pain, pain in fewer locations, and utilized opioids less often when in pain than either adult groups. Interestingly, pain intensity did not differ significantly between age groups on either crisis or noncrisis pain days. This agreed with the results of Ahmed et al. .Considering utilization, consistent with our disruption hypotheses, the transition group made fewer ambulatory visits unadjusted for pain days and number of comorbidities. In addition, after adjustment, those in the transition group were more likely to use ED/hospital resources to manage a crisis than the older groups. An additional explanation for this finding involves access to insurance. Minors with SCD are likely to be on Medicaid  but loseWhen considering psychosocial and behavioral outcomes, despite more unplanned visits, the transition group reported less depression/anxiety, less behavioral coping, and better HRQOL than older patients. This was consistent with our hypotheses. In the case of behavioral coping strategies, the differences were strong and remained after adjustment. We have previously reported that catastrophizing did not differ by age .We also tested our hypotheses comparing younger (but posttransition age) adults to older adults. Contrary to our hypotheses, younger adults did not have less pain or better psychosocial function that older adults. Surprisingly, there appeared to be a (nonsignificant) tendency for younger adults to have more ED visits and hospitalizations than either the transition group or older adults, who looked similar to each other. Further, contrary to our hypotheses, based on other differences in HRQOL, such as gender differences in PiSCES  and chilOur findings can also be compared to those of Sanders et al.  who studAhmed et al. used similar age categories when comparing SF-36 quality of life measures for a sample of people with sickle cell disease in Saudi Arabia . ContrarBlinder et al.  found thWe did not find differences between age groups on specialty care, with about 50% in specialty care across all age groups. Thus even our youngest group, while transitioning to adult care, still received specialty care at the same rate as the others. This may have mitigated some of the findings that others found for utilization, where specialty care may not have been as common.Ours was not a longitudinal study. As such, age differences we found could be due to cohort effects, rather than specific age effects. Survival of only the “fittest” SCD patients to an older age could explain some of the characteristics of the older patient group. Also, pain and utilization summary estimates were based on as few as 30 days and as many as 188 days of diaries. Since pain may be episodic in SCD, some important pain episodes could have been missed by our diary methods. If this differed by age group it would bias comparisons. We have no reason to believe, though, that this missing data would differ by age. In fact, the distribution of number of diary days was similar in the 3 age groups . Further, our study did not include children, so we could make no comparisons of children versus adults, which would have been useful to further explore our adolescent disruption hypothesisMany of our hypothesized age-associated differences in biological, psychosocial, quality of life, and utilization outcomes in adults with SCD were confirmed. In general, older age patients have worse biological, psychological, and HRQOL outcomes than transition-age patients. In some instances, the oldest patients are not the worst with regard to these outcomes. In contrast, while transition-aged SCD patients do not have worse biology than older patients, they do have more utilization for the amount of pain and biological abnormalities seen, compared to older adults. This sheds some light and adds some validity to current interventions focused on transition-aged patients. But further study is required to determine whether analogous, age-appropriate health care or other interventions could somehow improve the quantity and quality of life for older, posttransition patients with SCD.Supplementary tables provide additional information on comorbidities and health related quality of life. Specifically, Supplemental Table 1 has detailed SCD comorbidity information (frequencies and percentages) by age group, along with a comparison across age groups. Supplemental Table 2 has means and standard deviations of the eight SF-36 subscales, along with a comparison across age groups.


Using alpha blockers such as intravenous (IV) lidocaine has been deemed effective in controlling acute pain. Therefore, the current study was designed with the aim of evaluating the efficiency of IV lidocaine in comparison to IV fentanyl in pain management of patients with renal colic in emergency department (ED).In this double blind clinical trial, 18-65 year old patients that presented to ED with colicky flank pain and met the inclusion criteria of the study were allocated to either lidocaine or fentanyl group using block randomization and compared regarding pain severity 5, 10, 15, and 30 minutes after drug administration.th minute and 4.4 (95% CI: 13.3-22.2) 30 minutes after injection. Number needed to harm (NNH) in treatment with lidocaine 15 and 30 minutes after injection were 4 (95% CI: 2.2-12.0) and 23, respectively. 90 patients with the mean age of 35.75±8.87 years were divided into 2 groups of 45 . The 2 groups were not significantly different regarding the studied baseline variables. Pain severity was not significantly different between the 2 groups at various times after injection. Treatment failure rate 15 minutes after injection was 44.4% (20 cases) in IV lidocaine and 17.8% (8 cases) in IV fentanyl group (p = 0.006). These rates were 26.6% (12 patients) versus 22.2% 30 minutes after injection (p = 0.624). Absolute risk increase of treatment failure in case of using lidocaine was 26.7 (95% CI: 8.3-44.9) in the 15Although mean pain severity was not significantly different between IV fentanyl and lidocaine at various times after injection, treatment failure rate was significantly higher in the IV lidocaine group 15 minutes after injection. Renal colic is one of the most common clinical manifestations of a stone being present in the urinary system, which presents as sudden and severe flank pain . In the One of the major duties of emergency department (ED) is reducing patients’ pain and suffering before taking any treatment or surgical measures. Recently, using alpha blockers such as intravenous (IV) lidocaine, nifedipine and nerve blockers in the intercostal area has been deemed effective in reducing renal colic pain -6. When narcotic drugs lack the required effectiveness and lead to undesirable side effects, lidocaine can be a good choice. IV lidocaine has been deemed effective in controlling neuropathic pains such as diabetic neuropathy, post-surgery pains, bone fracture pain, headache and nervous system malignancies -10. ContUsing opioids has some dangers due to reasons such as inhibition of respiratory center in medulla region and activation of vomiting center . These dFinding an effective analgesic with minimal side effects has been continuously desired by the physicians involved with these patients. Therefore, the current study was designed with the aim of evaluating the efficiency of IV lidocaine in comparison to IV fentanyl in pain management of patients with renal colic.Study design and settingIn this double blind clinical trial, the effectiveness of IV lidocaine and IV fentanyl was evaluated and compared in pain management of patients with renal colic admitted to ED of Golestan Hospital, Ahwaz, Iran, in 2015. The study was approved by the ethics committee of Ahwaz University of Medical Sciences under the number “ajums.REC.1392.324” and the researchers adhered to all the principles stated in the declaration of Helsinki regarding ethical practice and confidentiality of patient data. Informed consent was obtained from all the participants for taking part in the study. All the expenses of patients’ treatment were covered by the project executive and no additional fees were inflicted upon the patients. This study was registered on the Iranian registry of clinical trials under the number IRCT2017081415446N12.ParticipantsPatients in the 18-65 years age range that had presented to the ED with colicky flank pain and lacked histories such as: cardiac dysrhythmia and ischemia, parenchymal tissue problems in liver and kidney, and history of using mono amino oxidase (MAO) inhibitor drugs in the last 2 weeks, were included in the study. In addition, patients with a history of allergy to morphine or other opiates, definite or possible pregnancy, lactating women, addiction to opiates, and receiving analgesics in the last 6 hours were excluded from the study. To confirm absence of dysrhythmia or underlying ischemic disease, electrocardiogram was used on admission. All the clinical examinations were done by 2 physicians, one senior resident of emergency medicine and one senior resident of urology.Clinical diagnoses were confirmed by performing ultrasonography or spiral computed tomography (CT) scan, or presence of hematuria in urinalysis after management of the patient’s pain and those who did not have definitive evidence of stone in evaluations were excluded from the study.InterventionPatients were allocated to a group receiving either lidocaine (1.5 mg/kg) or fentanyl (1.5 µg/kg) via block randomization. Drug prescriptions were as IV infusion during 2 minutes while patients were under cardiac monitoring. For patients who still had moderate to severe pain 30 minutes after injection, morphine sulfate with the standard dose of 0.1 mg/kg was prescribed as additional analgesic. The physician prescribing the drug and the patient were blind to the prescribed drug. Drugs were prepared by a nurse in syringes with the same volume and color in the absence of the physician and were then given to the physician.OutcomeThe primary outcome of this study was evaluating the pain score of patients based on visual analog pain scale (VAS) 5, 10, 15, and 30 minutes after injection. 3 points pain reduction based on VAS was considered as clinically significant pain reduction. Therefore, lack of 3 points pain reduction 15 and 30 minutes after injection were considered as treatment failure.Data gatheringDemographic data  and data regarding pain severity on admission to ED and 5, 10, 15, and 30 minutes after injection were gathered using a checklist. The senior emergency medicine resident was responsible for data gathering and was blind to the drug received by the patient.Statistical analysisSample size was estimated to be 40 for each group considering 95% confidence interval and type 2 error of 0.2% (Baseline characteristics90 patients with the mean age of 35.75±8.87 years (20-55) were randomly divided into 2 groups of IV lidocaine (45 patients) and IV fentanyl (45 patients) . Pain managementTreatment failure rate 15 minutes after injection was 44.4% (20 cases) in IV lidocaine and 17.8% (8 cases) in IV fentanyl group (p = 0.006). These rates were 26.6% (12 cases) versus 22.2% (10 cases), 30 minutes after injection (p = 0.624). th minute and 4.4 (95% CI: 13.3-22.2) 30 minutes after injection. Therefore, the absolute risk increase of treatment failure in case of using lidocaine was 26.7 (95% CI: 8.3-44.9) in the 15Number needed to harm (NNH) in treatment with lidocaine 15 and 30 minutes after injection were 4 (95% CI: 2.2-12.0) and 23, respectively.Based on the findings of the present study, although mean pain severity was not significantly different between IV fentanyl and IV lidocaine groups at various times after injection, treatment failure rate was significantly higher in the lidocaine group 15 minutes after injection.In addition, the absolute risk increase of treatment failure in case of using lidocaine 15 and 30 minutes after injection were 26.7 and 4.4 percent, respectively.Renal colic is caused due to increased pressure in the upper urinary tract or dilatation of kidney capsule following urinary retention. In a study by Khaniha et al. on evaluating the effect of various drugs in relieving renal colic, the results showed that pethidine 10 to 45 minutes after injection, methadone 30-60 minutes and morphine 1.5 to 30 minutes after injection showed their analgesic effects . Using intranasal fentanyl led to an effective sedation in patients 30 minutes after administration . In anotBased on the results of this study, it seems that IV lidocaine has proper ability in controlling renal colic during 30 minutes. However, if the speed of analgesia induction is of higher priority for the physician and patient compared to probable side effects, considering the high rate of treatment failure of IV lidocaine in 15 minutes (44.4% vs 17.8% for fentanyl), it cannot be a good choice for this purpose.The absolute risk increase of renal colic management failure with IV lidocaine 15 and 30 minutes after injection were 26.7 and 4.4, respectively. It seems that IV lidocaine cannot be a good choice when quick pain control is of higher priority for the physician.


Patients with back and neck pain are often seen in primary care and it is important to provide them with tailored interventions based on risk stratification/triage. The STarT Back Screening Tool (SBT) is a widely used screening questionnaire which has not yet been validated for a population with back and/or neck pain with short duration. Our aim was to compare the concurrent validity of the SBT and the short form of the ÖMPSQ including psychometric properties and clinical utility in a primary care setting.n = 329). We used the Spearman’s rank correlations to study correlations, cross tabulation and Cohen’s kappa to analyze agreement of patient classification. Clinical utility was described as clinician scoring miscalculations and misclassifications of total and/or subscale scores.Patients who applied for physiotherapy by direct access (January 2013 to January 2014) at 35 primary care centers in south Sweden, with acute or subacute back and/or neck pain, aged 18–67 years, who were not currently on sick leave or had been on sick leave less than 60 days were asked to complete the SBT and ÖMPSQ-short questionnaire (p < 0.01). In subgroup analyses, the correlations were 0.69 (p < 0.01) for males and 0.57 (p < 0.01) for females. The correlations were lower among older age groups, especially females over 50 years . Classification to high or low risk for long-term pain and disability had moderate agreement (κ = 0.42). Observed classification agreement was 70.2%. The SBT had fewer miscalculations (13/315) than the ÖMPSQ-short (54/315).Completed SBT (9-items) and ÖMPSQ-short (10-items) data were available for 315/329 patients respectively. The statistical correlation for SBT and ÖMPSQ-short total scores was moderately strong (0.62, The correlation between the SBT and the ÖMPSQ-short scores were moderately strong for individuals with acute or subacute back and/or neck pain. SBT seemed to be clinically feasible to use in clinical practice. We therefore suggest that SBT can be used for individuals with both BP and/or NP in primary care settings but it is important to be aware of that SBT’s agreement with the ÖMPSQ-short was poor among females aged over 50 years.NCT02609750 Registered: November 18, 2015.ClinicalTrials.gov ID:  Musculoskeletal disorders are very common in the general population worldwide –3 causinAbout 85% of all low back pain and NP is classified as nonspecific, where the specific underlying disease or pathology remains unknown . Most inBack pain (BP) is multi-factorial in both etiology and management . Treatmen = 62) [Psychological risk factors have a key role in the transition from acute to chronic pain and the development of long-term disability –27. The n = 62) .The Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) aims to identify patients at risk for developing work disability due to BP and NP . ÖMPSQ iWe conducted a cross-sectional study, nested within an ongoing clinical trial including patients with acute or subacute BP and/or NP .Patients were consecutively recruited between January 2013 and January 2014 from 35 primary care centers in the southern parts of Sweden. We asked patients that applied for physiotherapy due to an episode of acute or subacute nonspecific BP and/or NP, to participate in the study. Patients that were between 18 and 67 years, who were not currently on sick leave or had been on sick leave less than 60 days, completed SBT and ÖMPSQ-short at the first visit to the physiotherapist. Patients that were pregnant, had severe pathology (“red flags”)  or were All participants completed the SBT and ÖMPSQ-short at the same time at their first physiotherapy session. The questionnaires were scored by the physiotherapist according to the methods specified by the instrument developers , 37. DatThe SBT is a 9-item questionnaire including questions on known modifiable physical (item 1–4) and psychosocial (item 5–9) risk factors for long-term disabling BP, designed to support clinicians in directing individuals to different levels of care . Item 1–The ÖMPSQ-short is a 10-item questionnaire with questions about psychosocial risk factors for work disability due to the pain . The ÖMPSPSS 22.0 was used for all analyses. We used a non-parametric approach which was chosen based on the distribution of the data. We used the Spearman’s rank correlation coefficient to study the correlations between the SBT total scores with the ÖMPSQ-short total scores. We also conducted subgroup analyses, based on pain sites reported by the patients, gender and age. For pain sites, we divided the population in two groups based on the answer on question number two in SBT, which is about neck or shoulder pain. All patients who reported neck or shoulder pain were allocated to the NP + BP group (a mixed group of patients with neck or shoulder pain with or without BP). Patients who didn’t report neck or shoulder pain were allocated to the BP group and were regarded as having BP only. The reason for not analyzing patients with neck pain only was that we had no possibilities to identify them as we didn’t have access to the diagnoses of the patients. For gender, we divided the study population into females and males and for age, we divided the population in three age groups . We found these age groups clinically relevant to study as the age 40–49 years is a period of life often associated with higher demands both at home and at work and might therefore result in a higher sick leave. A correlation coefficient less than 0.3 was considered as poor, 0.3–0.5 as fair, 0.6–0.8 moderately strong and greater than 0.8 was considered very strong .We used cross-tabulation to describe the observed agreement, regarding classification into risk groups, between the ÖMPSQ-short (low and high risk) and the SBT . To allow an agreement analysis of the SBT and the ÖMPSQ-short risk classifications, we did two analyses. First we merged the low and medium risk group for the SBT in the first analysis and then we merged the medium and high risk group for the SBT in a second analysis. We chose to present the results of the second analysis, in line with Fuhro et al.  as this We described the clinical utility of the two instruments as screening tools from a clinician’s perspective. Clinical utility was described as clinician scoring miscalculations and misclassifications of total and/or subscale scores of the two instruments. First, we calculated the number of physiotherapist scoring miscalculations of ÖMPSQ-short total scores and SBT total and subscale scores. Then, we calculated the miscalculations that had led to a misclassification. To analyze if a miscalculation of a total score had led to a misclassification to a higher or lower risk group, we used the cut-off scores specified by the instrument developers , 48 withThe flow chart of inclusion and exclusion of patients through the study and reasons for exclusion is presented in Fig. n = 121) 51.2% were females and 48.8% were males. In the NP + BP population (n = 194) 69.6% were females and 30.4% were males. Among females (n = 197) 68.5% reported neck pain. Median age was 45 (range 20–66) for both females and males. The median scores (range) for SBT and ÖMPSQ-short were 4 (0–9) and 46 (9–81) respectively (Table Baseline characteristics of the study population are summarized in Table p < 0.01) which was considered as moderately strong  and for patients with NP + BP  was also moderately strong.The Spearman’s rank correlation coefficient for the SBT total scores and the ÖMPSQ-short scores was 0.62 (p < 0.01) and for males it was moderately strong . For participants aged ≤39 years, the correlation was moderately strong  and for the group between 40–49 years  and ≥50 years , the correlation was fair. In further subgroup analyses, when we combined gender and age, we found the correlation for males ≥50 years moderately strong  and for females ≥50 years poor .A summary of the statistical correlations for subgroup analyses, based on gender and age, is presented in Table p < 0.01). We found differences regarding classification into low and high risk subgroups . The disagreement observed (29.8%) was significantly skewed towards the high risk group with a higher proportion of patients allocated to the SBT high risk group (53.7%) than to the ÖMPSQ-short high risk group (36.5%).The purpose of the SBT and ÖMPSQ-short was to identify patients that are at risk for long-term disability and in need for extended treatment. The observed agreement between the two questionnaires subgroup classification is shown in Table We studied the clinical utility from a clinician’s perspective. Physiotherapists had done more miscalculations on total scores in the ÖMPSQ-short (54/315) than in the SBT (13/315). In the SBT questionnaires we found 22 miscalculations of the SBT subscale scores. Among the miscalculations of total scores, seven of the ÖMPSQ-short questionnaires and five of the SBT questionnaires, led to misclassifications to a higher or lower risk group. In four respectively 21 SBT questionnaires, total scores and subscale score calculations were missing. First author (MF) calculated these scores. There were no missing calculations of total scores in the ÖMPSQ-short.This is the first time that the SBT has been compared with the ÖMPSQ-short for a large group of patients with acute or subacute BP and/or NP in primary care in Sweden. This study demonstrated moderately strong correlations between the SBT and ÖMPSQ-short total scores for individuals with back and/or neck pain with short duration. The observed classification agreement was 70.2%. In subgroup analyses, we found the correlation was lower among females than for males and also lower among older age groups, especially females aged over 50 years. Clinicians made less miscalculations with the SBT compared to the ÖMPSQ-short.The moderately strong correlation between SBT and ÖMPSQ-short total scores (0.62) in this study is similar to the results in a previous Swedish study (0.61)  and a BrIn the subgroup analyses, we found the correlation was lower in females than for males and was further reduced among increasing age groups. We have also used other age groups in the analyses but regardless of which type of age group we used, we found the same results. We unexpectedly found the correlation for females ≥50 years as poor while the correlation for males ≥50 years were still moderately strong. We can’t rule out that this difference between males and females ≥50 years might be random but there may also be biological differences. There is a gender gap concerning low back pain, where females are having more prevalent comorbidity of neck and shoulder pain and psychosocial distress than males . In thisParticipant classification to low or high risk for long-term pain and disability by the SBT and the ÖMPSQ-short questionnaires had moderate agreement (κ = 0.42). Similar results were also found in the Brazilian study κ = 0.49)  and in a  and in When choosing a classification instrument, clinicians and organizations need to be aware of, that patients at medium and especially patients at high risk need a more extensive treatment compared to those at low risk who can be reassured and offered less intensive treatment . PatientHowever, patients with medium and high risk are those who will benefit most from physiotherapy  and to in = 11) while the ÖMPSQ-short had none. One contributing factor might be the order in which the questionnaires were completed. Patients completed the ÖMPSQ-short first, as the ÖMPSQ-short was used as an inclusion criteria to the clinical trial . The physiotherapists might have checked all questions and calculated the ÖMPSQ-short scores more carefully. Physiotherapists in Sweden are also more used to score the ÖMPSQ-short than the SBT. The rates of missing calculations of total and subscale scores in the SBT might be due to the instructions to the physiotherapists. They were not explicitly told to do these calculations. The fact that it was the treating physiotherapist that administered and scored the SBT and that they had different experiences of using the two questionnaires may have influenced the rates of miscalculations of scores. But, at the same time, this might have had minimal impact of the results as there were so many primary care centers (35) in different regions included. The higher rate of miscalculations of total scores in ÖMPSQ-short (54/315) compared to SBT (13/315) indicates that the SBT is easier to score for clinicians. A potential benefit of using the SBT instead of the ÖMPSQ-short might be that the SBT seems to be more clinical feasible to use in routine clinical practice. More miscalculations in the ÖMPSQ-short might be due to the more complex scoring with 0–10 points for each item and also the reversed scoring in three items . However, even though there were more miscalculations of total scores in the ÖMPSQ-short than in the SBT, there were no difference in misclassification to either a higher or lower risk group between the ÖMPSQ-short (n = 7) and the SBT (n = 5) questionnaires. Consequently, miscalculations of the SBT and the ÖMPSQ-short total scores do not seem to substantially influence the risk classification. Clearly introducing electronic questionnaires with automatic summations have the potential to eliminate errors even further.To the best of our knowledge, this is the first time that clinical utility has been focused when comparing the two instruments. It was a difference regarding completion rates from patients with SBT having some incomplete questionnaires (n = 315) at a great number (35) of different real world primary care settings. The same individuals completed both the SBT and ÖMPSQ-short at the same time. We have thoroughly checked and validated all questionnaires and also studied psychometric properties and clinical utility in a primary care setting. The population studied was relatively homogenous including only patients with short duration of pain, not participants with chronic pain. This means that we can identify patients at risk of poor prognosis at an early stage where it is still possible to do brief interventions and influence outcome by treating modifiable prognostic factors and stratify care.The main strength of the present study is the size of the study population (To our knowledge, this is the first time SBT is validated in a population with both NP and BP. A limitation in this study is that we have no diagnoses registered for the study population and therefore we were not able to distinguish patients diagnosed with only NP. On the other hand, having NP with or without comorbid BP is common , 50 and This study showed that the correlation between the SBT and the ÖMPSQ-short scores were moderately strong for individuals with acute or subacute BP and/or NP. SBT seemed to be clinically feasible to use in clinical practice.We therefore suggest that SBT can be used for individuals with both BP and/or NP in primary care settings but it is important to be aware of that SBT’s agreement with the ÖMPSQ-short was poor among females aged over 50 years.