Low back pain is the highest reported musculoskeletal problem worldwide. Up to 90 % of patients with low back pain have no clear explanation for the source and origin of their pain. These individuals commonly receive a diagnosis of non-specific low back pain.Patient education is a way to provide information and advice aimed at changing patients’ cognition and knowledge about their chronic state through the reduction of fear of anticipatory outcomes and the resumption of normal activities. Information technology and the expedited communication processes associated with this technology can be used to deliver health care information to patients. Hence, this technology and its ability to deliver life-changing information has grown as a powerful and alternative health promotion tool.Several studies have demonstrated that websites can change and improve chronic patients’ knowledge and have a positive impact on patients’ attitudes and behaviors. The aim of this project is to identify chronic low back pain patients’ beliefs about the origin and meaning of pain to develop a web-based educational tool using different educational formats and gamification techniques.This study has a mixed-method sequential exploratory design. The participants are chronic low back pain patients between 18–65 years of age who are attending a primary care setting. For the qualitative phase, subjects will be contacted by their family physician and invited to participate in a personal semi-structured interview. The quantitative phase will be a randomized controlled trial. Subjects will be randomly allocated using a simple random sample technique. The intervention group will be provided access to the web site where they will find information related to their chronic low back pain. This information will be provided in different formats. All of this material will be based on the information obtained in the qualitative phase. The control group will follow conventional treatment provided by their family physician.The main outcome of this project is to identify chronic low back pain patients’ beliefs about the origin and meaning of pain to develop a web-based educational tool using different educational formats and gamification techniques.NCT02369120 Date: 02/20/2015.ClinicalTrials.gov The online version of this article (doi:10.1186/s12911-015-0220-0) contains supplementary material, which is available to authorized users. Low back pain (LBP) is the most commonly reported musculoskeletal problem in the world –7. Up toPain is a multifactorial experience associated with psychological and emotional factors that play important roles in the transition from the acute to chronic states –12. AddiCompared with patients with acute LBP whose levels of fear-avoidance beliefs (FAB) decrease over time through the healing process, CLBP patients exhibit persistent elevated levels of FABs that remain unchanged , 17, 18.Patient education could be a way to provide information and advice aimed at changing patients’ cognition and knowledge about their chronic state to reduce fear of serious outcomes and allow the resumption of normal activities –21. The The use of information and communication technology in health care to deliver information to patients is becoming a powerful tool. The internet is an example of a new technology that is part of our everyday lives. Thanks to the wide spectrum of possibilities that the internet offers, different authors have proposed using it as an important platform to display high-quality interactive evidence-based information –30. OtheNine studies –49 examiTherefore, the main outcome of this project is to identify chronic low back pain patients’ beliefs concerning the origin and meaning of their pain to develop a web-based educational tool using different educational formats and gamification techniques.Persistent chronic low back pain and its consequences are maintained by the lack of understanding of the origin and meaning of pain.Pain neurophysiology as an educational internet-based intervention for chronic low back pain will change cognition about the origin and meaning of pain, with the outcome of pain reduction, disability reduction, and better quality of life compared to normal care.The hypotheses being tested by our project are:There are specific objectives for each phase of the study.To identify chronic low back pain patients’ beliefs concerning the origin and meaning of pain.Phase 1 (QUAL):To construct and develop a biopsychosocial web-based educational intervention using the QUAL results.Phase 2 (Connecting procedure):Primary outcome. To evaluate the effect of a biopsychosocial web-based educational intervention for chronic low back pain based on pain intensity compared to normal care.oFear avoidance beliefs.oKinesiophobia.oPain catastrophizing.oDisability.oQuality of life.Secondary outcomes. To assess the effect of a biopsychosocial web-based educational intervention for chronic low back pain compared to normal care on:Phase 2 (QUAN):One of the utilities of QUAL is to better understand the beliefs of chronic low back pain patients concerning their pain, including the origin and meaning of their pain. This information is paramount not only to aid in the construction of the web site but also for health professionals involved in the diagnosis and treatment of these patients.If the web-based intervention is found to be successful in modifying CLBP patients’ pain cognition, this will open the possibility of including this web site-based approach in future chronic pain management programs in primary care. Moreover, the web site will be developed with the future aim of including and adding new technologies to help patients and professionals involved in chronic pain.The study follows the Declaration of Helsinki and the “Guidelines for Good Clinical Practice” (CPMP/ICH/135/95) and has been approved by the Ethical Committee of Clinical Research in Primary Care IDIAP in Catalonia, Spain (P14/138).Because our intervention does not involve any physical activity/intervention, we do not expect to have any physical side effects. Patients in the experimental group will be advised to contact their family physician if they experience any physical problems or worsening of their condition. Additionally, all subjects in the experimental group will be able to contact the researchers through the web site.Qualitative data collection through semi-structured personal interviews followed by thematic analysis.Construction of the educational tool with the results obtained in the previous step (topics or emerging categories).Analysis of the effectiveness of the educational tool using a randomized controlled trial.To answer the research question, the authors will use a mixed-method sequential exploratory design. The purpose of mixed methodology is not to replace qualitative or quantitative methodologies, but to use the strengths of both while reducing their weaknesses . SpecifiThe use of a mixed-method design is fully justified in this protocol because the integration of both methodologies (QUAL-QUAN) occurs when the data from the qualitative phase contribute to the construction of the educational tool .The recruitment process will be performed independently in each phase of the study, although in both phases this recruitment process will take place in the same primary care centers in the city of Lleida through family physicians. The inclusion and exclusion criteria are also common to both phases. Prior to the beginning of the first phase, the first author of this study will perform a presentation of the project to the medical and nursing staff in each of the primary care centers involved in the study to ask for their cooperation.QUAL: In this phase, patients will be recruited by their respective family physicians. Once the physician makes the diagnosis of CLBP and ensures that the individual meets the inclusion and exclusion criteria, the physician informs the patient about the existence of this project and invites him to contact the first author by telephone. If the person agrees to participate in the study, the interview will be scheduled to take place in the Faculty of Nursing and Physiotherapy of the University of Lleida.QUAN: The recruitment process will start after the end of QUAL and the development of the educational tool. This phase will consist of an educational intervention using a randomized controlled trial design. The recruitment process will be the same as in QUAL. Prior to the beginning of the intervention, the first author will meet the study subjects individually to inform them of the study conditions and provide them with the informed consent form.History of CLBP longer than 6 months.Patients between 18–65 years of age.Able to read, speak and understand Spanish and Catalan.Access to the Internet, a computer or laptop and e-mail address.Accept and sign the informed consent form.Onset age < 20 or > 55 years.Non-mechanical pain (unrelated to time or activity).Thoracic pain.Previous history of carcinoma, steroid use, or HIV infection.Feeling unwell.Weight loss.Widespread neurological symptoms.Structural spinal deformity.Any red flag condition :Onset agQUAL: In this phase, a purposive convenience sample will be used to achieve a representative number of patients with CLBP . To ensuQUAN: The sample size calculation is based on the study of Ryan et al.  and the Accepting an alpha risk of 0.05 and a beta risk of 0.2 , using a two-sided test, and assuming a 20 % withdrawal rate, it will be necessary to include 29 subjects in each group to detect a difference greater than or equal to 15 units (assuming a baseline distribution of 50 ± 18). We assume that there will be a 20 % withdrawal rate.The researchers will use a simple randomization technique. An external researcher from the Higher Polytechnic School of the University of Lleida will generate the randomization assignment using the STATS® program  and keep-Visual Analog Scale (VAS): This scale was developed by Huskinson in 1976 [ in 1976  as a met in 1976 –62.Cognition:- Fear Avoidance Beliefs Questionnaire (FABQ): The FABQ is a self-reported questionnaire that consists of 16 items about the beliefs of LBP patients on the influence that physical activity and work have on their pain. Each item can be scored from 0  to 6  [isagree) , 64. Theisagree) .- Tampa Scale for Kinesiophobia (TSK): This scale is widely used in pain medicine to assess pain-related fear. The Spanish format has 11 items, with each score ranging from 1  to 4 . The Spanish version of the TSK is easy to use, reliable and valid [nd valid .- Pain Catastrophizing Scale (PCS): The PCS was developed in 1995 by Sullivan and colleagues [lleagues  to facillleagues . This sclleagues –69.Pain intensity:- Roland-Morris Questionnaire (RMQ): This is a self-reported questionnaire assessing function and disability. It is an easy instrument for patients with scores ranging from 0 to 24; a change of 4 or more points is considered clinically important [mportant , 70. Themportant , 70, 71,Disability:- Health Survey SF-36: This questionnaire was developed in 1992 by Ware and Sherbourne [erbourne  to asseserbourne , includierbourne , and haserbourne .Quality of life:- Other variables will also be measured, including acceptability, patient satisfaction, and the number of times that the information provided in the web site is watched/used by subjects in the experimental group.Other variables:Staff of the Higher Polytechnic School of the University of Lleida will assist in the development of the web site and the educational material. Once the results of QUAL have been obtained, the authors will generate a variety of topics related to patients’ misbeliefs about their CLBP. The outcome of the educational material is to answer wrong pain conceptions using the neurophysiology of pain as a starting point. This educational material will be evidence-based and elaborated using understandable language and different formats, including video and 2-3D animation. Therefore, the platform will provide patients with customized tasks that allow them to use the metaphor of the journey (the narrative as a dynamic of the game) to feel that they manage their own path, which will change negative perceptions into positive perceptions about certain actions. At all times, the patients will be able to choose among different information sources, such as videos about the origin of chronic pain, 3D representations of different neurophysiological processes, and FAQs. Additionally, the patients will be able to contact a specialist in the neurophysiology of pain by email or videoconference. Furthermore, to reinforce patients’ motivation and participation, gamification techniques (defined as elements forming part of the design of video games but used in a different context) will be implemented –78.The web site will be developed using Drupal as a content management system. Some modules of the management system, including those related to questionnaires and video tutorials, will be modified and adapted to the needs of the project. This will increase the versatility of the platform, resulting in better utilization of the majority of the systems .Data collection will be conducted in two phases (QUAL and QUAN).QUAL: To meet the qualitative objective of this study, the authors will use semi-structured personal interviews because they are very useful for obtaining a better and wider understanding of the issues related to the chronic problem from the patient's perspective –81. The QUAN: The intervention will last for two weeks, and variables will be measured pre- and post-test. The researchers based the duration of the intervention on the study of Keulers et al. , which ht-test or Chi-square test or a non-parametric test if a normal distribution cannot be assumed. Pain is the main numeric variable, with a range between 0–100. The differences between groups will be contrasted using the Student’s t-test or the Mann–Whitney test when assuming a non-normal distribution. The statistical analysis will be performed with an alpha of 0.05 using the SPSS and R software.QUAN: Quantitative variables will be described using the mean, standard deviation, median and interquartile range. The bivariate analysis will be contrasted using the Student’s One limitation in QUAL is that a single interviewer will perform all interviews and one analyst will perform the initial thematic analysis. Although both the interview and analytic processes will be validated by an external researcher, this may be a source of potential bias. Another limitation may come from the author’s interpretation of the data provided by the subjects of the study; this potential bias will be overcome using triangulation of researchers. The researcher’s perspective can be accepted as rigorous if appropriate tools for appraising quality are used , 87. MorOne of the possible limitations in QUAN is that participants will know which group they are allocated into, making the study blinded only to the researchers. The sample size may represent another limitation. A smaller than expected final sample size increases the likelihood of a type II error and limits the internal validity of the study, leading to inconclusive results.Regardless, our results will be limited to CLBP patients and will need to be replicated in randomized control trials with a larger sample size.Finally, there is another possible limitation derived from the use of new technologies. In our project, the web-based intervention will contain educational materials in different formats, such as video, audio, and 3D images. However, as noted by Camerini et al. , other aThis study will use mixed methods to identify chronic low back pain patients´ beliefs about the origin and meaning of pain to develop a web-based educational tool using different educational formats and gamification techniques. Stage one of the study will identify chronic low back pain patients´ beliefs concerning the origin and meaning of pain using qualitative data collection through semi-structured personal interviews. Stage two of the study will allow the construction of the educational tool with the results obtained in the previous stage (topics or emerging categories). Stage three of the study will analyze the effectiveness of the educational tool using a randomized controlled trial.Our investigation will open the possibility of including this web site-based approach in future chronic pain management programs in primary care. Moreover, the web site will be developed with the future aim of including and adding new technologies to help patients and professionals involved in chronic pain.


Guidelines to aid in managing settings may fail to adapt general goals to the individual patient physiology. The Beacon Caresystem  is a commercial version of a physiological-model based system for advising on mechanical ventilation (1). Mathematical models are tuned to patient measurements allowing advice to be patient specific. Beacon 5 provides advice for control and support modes of ventilation, with advice on: inspiratory oxygen , not meeting inclusion criteria at study start (1) and technical issues with the system (3). Average and spread are reported as mean ± SD or median [252 and PS/PC were reduced from 50 [40-50] to 43 [31-49] % and 12 ± 4 to 9 ± 6 cm H2O, respectively (P < 0.05). Vt was reduced from 497 ± 121 to 452 ± 120 ml (7.9 ± 1.9 to 7.2 ± 1.8 ml/kg IBW) (P < 0.05). Rf was increased from 16 [13-21] to 19 [15-24] min-1 (P < 0.05). PEEP was not changed significantly with values of 8 [6-9] and 8 [7-10] cm H2O at baseline and study end, respectively. Plateau pressure was reduced from 19 ± 5 to 17 ± 7 cm H2O (P < 0.05). Pulse oximetry oxygen saturation and end-tidal CO2 did not change significantly with baseline to end values of 97 ± 3 to 96 ± 3 % and 5.0 ± 1.1 to 5.1 ± 1.1 %, respectively.Seven and 18 patients were in control and support mode, respectively. Eleven patients (44%) were diagnosed with ARDS. SOFA score and age at day of study were 7.0 ± 2.8 and 67 ± 13 yrs, respectively. Sixteen (64%) of patients were male. Advice was provided 5 ± 2 times. FiOThese initial results indicate that Beacon Caresystem provides rational advice, lowering ventilator support whilst maintaining adequate ventilation and oxygenation.DSK and SER are minor shareholders and perform consultancy for Mermaid Care.


There are few comparisons of Modic changes (MCs) in the lumbar and cervical spine.Compare the prevalence of MCs in the lumbar and cervical spine, and determine how MC prevalence depends on spinal pain, age, disc degeneration, spinal level, and the presence or absence of kyphosis.Retrospective clinical survey.Magnetic resonance images (MRIs) were compared from five patient groups: 1. 1223 patients with low-back pain/radiculopathy only; 2. 1023 patients with neck pain/radiculopathy only; 3. 497 patients with concurrent low-back and neck symptoms; 4. 304 asymptomatic subjects with lumbar MRIs; and 5. 120 asymptomatic subjects with cervical MRIs.The prevalence of MCs was higher in those with spinal pain than in those without, both in the lumbar spine (21.0% vs 10.5%) and cervical spine (8.8% vs 3.3%). Type II MCs were most common and Type III were least common in all groups. The prevalence of lumbar MCs in people with back pain was little affected by the presence of concurrent neck pain, and the same was true for the prevalence of cervical MCs in people with neck pain with or without concurrent back pain. When symptomatic patients were reclassified into two groups , the prevalence of lumbar MCs in people with back pain was greater than that of cervical MCs in people with neck pain. The prevalence of lumbar and cervical MCs increased with age, disc degeneration, (descending) spinal level, and increased kyphosis.There is a significantly higher prevalence of MCs in patients with back and neck pain. The reported association with increased kyphosis (flat back) is novel. Degenerative changes of the vertebral endplate or “Modic changes” (MCs), have been considered important in low back pain since Modic first described them in magnetic resonance images (MRI) from patients with spinal degeneration If Modic changes represent a progressive response to injury then it is possible that some types of Modic change may be more highly correlated with pain than others, especially if they are linked with inflammatory changes. Modic changes have been studied most extensively in the lumbar spine where they are most common The medical records of patients attending the Sir Run Run Shaw Hospital over a 12 month period (Jan–Dec 2011) were reviewed to identify all patients who had back and/or neck pain. The MRI scans of these patients were then assessed to evaluate disc degeneration, sagittal spinal curvature and the presence and type of Modic changes in the lumbar and/or cervical spine. In order to investigate whether pain is associated with a higher prevalence of MCs, we also collected MRI scans from 424 asymptomatic patients who underwent physical examination in the authors’ hospital between January and December 2011. Patients with any pathological lesions, such as tumor, infection, fracture or congenital abnormality, were excluded. The study was approved by the Medical Ethics Committee of Sir Run Run Shaw hospital, and all patients gave written informed consent for their information to be stored in the hospital database and used for research.Patients were subdivided into five groups: 1. a “back pain” group comprising 1223 patients  with a mean age of 45.3±12.7 yrs (range 22–85 yrs) who had low-back pain or sciatica only; 2. a “neck pain” group comprising 1023 patients  with a mean age of 44.9±11.1 yrs (range 19–86 yrs) who had neck pain or radiculopathy only; 3. a “back and neck pain” group comprising 497 patients  with a mean age of 44±9.3 yrs (range 22–73 yrs) who had both low-back pain and neck pain concurrently; 4. asymptomatic lumbar group comprising 304 patients  with a mean age of 44.8±9.5 yrs (range 24–64 yrs) and 5. asymptomatic cervical group comprising 120 patients  with a mean age of 43.3±10.2 yrs (range 24–64 yrs).MRI scans of all patients in the three symptomatic groups were reviewed to determine the prevalence and types of MCs and investigate their associations with disc degeneration, disc level, age, and spinal kyphosis. Subsequently, symptomatic patients were reclassified into two groups. Group 6 comprised all patients with back pain, and Group 7 comprised all patients with neck pain. The prevalence of MCs in Groups 6 and 7 were investigated to determine whether the prevalence of MCs in the lumbar spine of low back pain patients is different from the prevalence of MCs in the cervical spine of neck pain patients. Groups 6 and 7 were also compared with the corresponding asymptomatic groups (4 and 5 respectively) to determine whether MCs are more prevalent in people with back and neck pain.All lumbar MR scans were performed on a GE Sigma CV/I (1.5 T) using a surface coil. Sagittal T1- and T2-weighted imaging sequences (T1WI and T2WI) were used to examine the lumbar spine. T1-weighted images were obtained using repetition/echo times of 420/13 msec and a bandwidth of 140 Hz/Px, while T2-weighted images used 2300/105 msec and 160 Hz/Px. The matrix size was 320×224 for both T1 and T2 images, with a field of view of 28×28 mm. Slice thickness and inter-slice gap were 4 mm and 1 mm respectively for both T1 and T2 images. For each imaged lumbar spine, nine sagittal slices were obtained for both T1WIs and T2WIs. For the cervical spine, T1- and T2-weighted sequences were obtained on the same machine using the same parameters as those used for the lumbar images, except that the slice thickness was set at 3.0 mm.All MRIs were evaluated by two independent observers, an experienced radiologist and an orthopaedic surgeon, in order to determine the intra-observer and inter-observer reliability of these measurements.According to the classification criteria of MCs Intervertebral disc degeneration was classified into five grades based on the T2-weighted MRI, according to the criteria of Pfirrmann Lumbar lordosis was assessed using the Seze method . In the Borden’s method was used to measure cervical lordosis . In the The kappa statistic was used to evaluate the inter-observer and intra-observer reliability of the grading of MCs and disc degeneration from MRI. A kappa value of 0.5 was considered to indicate moderate agreement, with a value of 0.8 or higher indicating substantial agreement.In symptomatic Groups 1 to 3, the prevalence of the three types of MCs at lumbar and cervical levels were compared using the Chi-squared test. Correlations between the prevalence of MCs and disc degeneration, spinal level, and age were assessed using the Spearman rank correlation test, and comparisons of MCs between individuals with kyphotic and non-kyphotic spinal curves were assessed using the Chi-squared test. The Chi-squared test was also used to compare the prevalence of MCs in patients with any back pain (Group 6) or neck pain (Group 7) with the corresponding asymptomatic groups . Statistical software (SPSS 15.0) was used for analysis.Kappa values for the intra- and inter-observer analysis of the grading of MCs and disc degeneration were all between 0.74 and 0.89, indicating good to excellent reliability.The prevalence of the different types of MCs in all patient groups is shown in The prevalence of MCs in the lumbar spine was slightly higher in the back pain group compared to the back and neck pain group. Similarly, the prevalence of MCs in the cervical spine was slightly higher in the neck pain group compared to the back and neck pain group . Based oThe effects of age, degeneration, and spinal level on the prevalence of cervical and lumbar MCs are shown in As shown in In this study, we compared the prevalence of MCs in the lumbar and cervical spines of patients with and without spinal pain, and estimated their association with pain, age, disc degeneration, spinal level and spinal curvature. Type II MCs were most common and Type III were least common in all three patient groups. The prevalence of lumbar MCs in people with back pain was little affected by the presence of concurrent neck pain, and the same was true for cervical MCs in people with neck pain with or without concurrent back pain. The prevalence of lumbar MCs in all patents with back pain was greater than that of cervical MCs in those with neck pain. Both lumbar and cervical MCs increased with disc degeneration and decreasing spinal level, and in both regions, kyphotic spinal curvature was associated with a greater prevalence of MCs . AccordiAs far as the authors are aware, this is the first large scale study comparing lumbar and cervical Modic changes in people with and without spinal pain. The MRIs were evaluated by an experienced radiologist and orthopaedic surgeon which led to good levels of reliability in evaluating the presence and types of MC, and the grading of disc degeneration. The main limitation of this cross-sectional study is that it can assess associations only, rather than cause and effect. Cervical MRI scans are not included in routine checkups in China, so our sample size of asymptomatic cervical MRI scans was relatively small.Eugen et al Two aspects are important in the origins of MCs: biomechanics and biochemistry. The spine is a nonlinear viscoelastic structure, and the vertebral endplates comprise its ‘weak link’. Axial (compressive) loading deforms the bone and cartilage endplates, and excessive or repetitive loading may result in irreversible injury. MCs may arise from this mechanism. Compared to superincumbent body weight, the cervical spine is relatively weak in bending, but relatively strong in compression Endplates play an important role in disc nutrient transport higher prevalence of MCs in patients with degenerative scoliosis The association between MCs and increased kyphosis can be explained by reduced vertical shock absorption in a flattened spine. This would increase the risk of endplate damage during incidents such as a fall on the buttocks. Wu et al. have shown a vice versa. The influence of spinal level on the occurrence of MCs could be due to increased disc degeneration at lower levels, but other explanations are possible. Associations between MCs and age may also be related to disc degeneration The results of our study suggest that disc degeneration is associated with MCs, both in the lumbar and cervical spine. However, the exact relationship between MCs and disc degeneration was not clarified and we cannot conclude that disc degeneration results in MCs or Although it is one of the most common disorders of middle and old age, low back/neck pain is often difficult to explain in terms of pathological anatomy. Most  is classified as non-specific pain, which can be unsatisfying for both patients and surgeons. Therefore, a causal relationship was not proven but there is a significantly higher prevalence of MCs in patients with back and neck pain.Normal spine curvature is a manifestation of biomechanical balance, and increased kyphosis can be an early indication of degenerative disease in both the lumbar and cervical spine. Postural education could possibly help to maintain normal lordosis, and reduce the risk of endplate damage, MCs, and pain.Our sample size of asymptomatic cervical patients is relatively small and we will expand our data base to investigate more accurately the prevalence of cervical MCs in asymptomatic patients in the future.In patients with back or neck pain, MCs of the lumbar endplate mainly occurred at L5/S1, and then at L4/5, while those affecting the cervical endplate mostly occurred at C5/6, then at C4/5 and C6/7. The prevalence of MCs in the lumbar spine was much higher than in the cervical spine, probably because the latter is less vulnerable to compressive overload. Type II MCs were the most common and Type III the least, both in the lumbar and cervical spine. MCs increased with age, spinal pain, increasing disc degeneration, increased kyphosis, and at lower spinal levels, although the causal mechanisms are not clear.


To investigate mid- to long-term efficacy of MRgFUS in the treatment of symptomatic osteoid osteomas.This prospective, IRB approved study involved 29 consecutive patients with clinical and imaging diagnosis of Osteoid Osteoma; all patients underwent MRgFUS ablation . Lesions located in vertebral body were excluded; prior RFA or surgery was not considered an exclusion criteria. Patients received therapy using MRgFUS, delivered toward the nidus, identified on MRI and/or CT. Primary endpoints were adverse events (serious and otherwise) and pain relief assessed using questionnaires on Visual Analog Pain Score (VAS) and daily intake of Non-steroidal drugs (NSAIDs). Patient’s follow-up, including clinical and imaging examinations, was established at 1, 12 and 24 months. As secondary endpoint, imaging examinations  were used to evaluate inflammatory status after treatment and bone remodeling.29 patients  were recruited for MRgFUS treatment; all safely completed the procedure. The treatment was well tolerated by all patients and no adverse events were recorded after and during 12-24 months follow-up period. A mean number of 4 ± 1.8 sonications with mean energy of 894 ± 209 J was necessary to complete the treatment. Three patients underwent staged treatment . Complete clinical response was found in 27/29 (93% CI 6–18) patients in term of pain absence and no intake of NSAIDs. There was a statistically significant difference  between baseline  and follow-up values  for pain severity, according to VAS. Two patients (0.6%) reported pain recurrence requiring both RFA. Imaging evaluation with CE-MRI demonstrated edema and hyperemia decrease in every lesion associated with complete response. At CT, bone remodeling was evident in all complete responders (27/29); in 15/27 (55%) patients, nidus fading was demonstrated. MRgFUS can be safely and effectively adopted for the treatment of Osteoid Osteoma. This application is totally non-invasive, carried out in a single session and with pain relief attainable since the following day after treatment. Our results also indicated a positive trend to bone restoration.


ClinicalTrials.gov (NCT02179437).Patients receiving total intravenous anesthesia (TIVA) with propofol have been shown to experience less postoperative pain. We evaluated the post-operative analgesic effects of propofol compared with sevoflurane maintenance of anesthesia in liver surgery. This study was registered at In this retrospective study, records of patients who underwent liver surgery between 2010 and 2013 were reviewed. Ninety-five patients anesthetized with propofol TIVA were matched with 95 patients anesthetized with sevoflurane. Numeric pain rating scale (NRS) pain scores, postoperative morphine consumption, side effects and patients’ satisfaction with pain relief were evaluated.The TIVA group reported lower NRS pain scores during coughing on postoperative days 1 and 2 but not 3 . They also consumed significantly less daily , accumulative  and total morphine (p = 0.03) when compared with the sevoflurane group. There were no differences in total duration of intravenous patient controlled analgesia (PCA) morphine use and patient satisfaction. No difference was found in reported side effects.Patients anesthetized with propofol TIVA reported less pain during coughing and consumed less daily, accumulative and total morphine after liver surgery. Postoperative pain can be severe after liver surgery due to the upper abdominal incision and pain management can be difficult for this group of patients . EpiduraPropofol  is an intravenous anesthetic. Its pharmacokinetic profile makes it very suitable for total intravenous anesthesia (TIVA) and this is a widely used technique in many centers , 6. Its The aim of this retrospective study is to evaluate the analgesic effects  of intraoperative use of propofol TIVA in liver surgery. The data from patients receiving TIVA with propofol were matched with those receiving the inhalational anesthetic sevoflurane. Tolerability (side effects) and patients’ satisfaction with pain relief were also assessed.ClinicalTrials.gov (NCT02179437). As this was a retrospective study, there was no requirement to obtain written informed consent from patients. The data was delinked from patient identifiers and anonymized prior to analysis so that none of the researchers were aware of patient identification. Records of patients after liver surgery and under the care of the acute pain service (APS) between 1 January 2010 and 31 December 2013 in our tertiary university hospital were reviewed and analyzed. Data collected included demographic data  physical status); types of liver surgery performed ; types of general anesthesia techniques ; with or without intraoperative use of ketamine; pain intensity as verbal numerical rating scale  at rest and during coughing from postoperative days 1 to 3; daily, accumulative and total postoperative morphine consumption and duration of PCA use; incidence of adverse events and patients’ satisfaction with pain relief. Exclusion criteria were missing essential data, difficulty in assessment of postoperative pain , early termination of PCA due to deterioration of patients’ condition, patients requiring a second operation and patients participating in other research projects.The study was approved by the Institutional Review Board of Queen Mary Hospital and the University of Hong Kong and registered at None of the patients in this study received premedication. Patients in the TIVA group had anesthesia induced and maintained with propofol. For patients in the SEVO group, general anesthesia was induced with propofol 1–2 mg/kg and then maintained with sevoflurane in air and oxygen, titrated according to heart rate and blood pressure by the attending anesthesiologist. Cis-atracurium 0.15 mg/kg or rocuronium 0.6 mg/kg was administered to facilitate tracheal intubation. All patients were given a bolus of remifentanil 1mcg/kg before intubation and then an infusion titrated to hemodynamic response and maintained up to 0.2 mcg/kg/min during surgery. Morphine 0.1 mg/kg was given intravenously before incision. Additional morphine 0.1 mg/kg was given in divided doses at the discretion of the attending anesthesiologist if surgery continued for more than 2 hours. Ketamine 0.5–1 mg/kg was given at the discretion of the attending anesthesiologist. Wound infiltration with 0.5% levobupivacaine (up to 2 mg/kg) was performed by the surgeon during wound closure. After completion of surgical procedures, reversal of neuromuscular blockade was achieved with atropine 0.02 mg/kg and neostigmine 0.05 mg/kg, followed by tracheal extubation.2) and heart rate were monitored. A 2 mg bolus of morphine was given intravenously every five minutes until the patient’s verbal numerical rating scale (NRS) was three or below. A PCA device , configured to give morphine at 1 mg per bolus with a five-minute lockout duration and a maximum dose limit of 0.1 to 0.15 mg/kg/hour, with the continuous basal infusion mechanism disabled, was connected for use. Subcutaneous or intramuscular morphine injection (0.05 mg/kg) was prescribed as rescue pain medication. Anti-emetics were not routinely administered for prophylaxis of postoperative nausea and vomiting (PONV), although intravenous ondansetron 4 mg 6 hourly was prescribed routinely, to be given if required.In the post anesthesia care unit (PACU), vital signs including blood pressure, oxygen saturation  if they reported an ‘unsatisfactory’ pain service.A retrospective power calculation was performed for this study. Using NRS during coughing on day 1 as the primary outcome, the mean (SD) of the TIVA group was found to be 4.301 (1.986), while the mean of the SEVO group was 5.08, at 80% power and an alpha of 0.05, 52 subjects would be required in each group.Each patient who received TIVA was matched 1:1 to patients who had received sevoflurane according to age, gender, ASA physical status, types of liver surgery performed (hepatectomy vs radio-frequency ablation) and with or without intraoperative use of ketamine . This onOne thousand two hundred and eighty two records of patients who underwent liver surgery under the management of the APS team were screened. It was found that 95 patients had received TIVA with propofol as maintenance of general anaesthesia during the specified period, while 720 patients received sevoflurane. Patient demographics are shown in Pain scores as NRS at rest and during coughing for the first three postoperative days are presented in Daily morphine consumption is shown in No difference was seen between the number of patients suffering from nausea, dizziness and pruritus in either group, and only the incidence of pruritus was lower in the TIVA group (p = 0.029). Since side effects were a rare occurrence in both treatment groups, and though statistical analyses and comparisons were performed, the low rate of events renders the power to detect differences in side effects to be very low . SeventyOur study showed that patients receiving propofol for maintenance of general anaesthesia in liver surgery reported significantly less pain as reflected by lower mean NRS pain scores during coughing and less daily, accumulative and total postoperative morphine consumption. With a large upper abdominal wound, high doses of strong opioids may be required for pain control but its side effects may become apparent as morphine metabolism is impaired after liver resection, especially for those with liver cirrhosis and impaired liver function . There aIn contrast to previously mentioned studies which measured pain scores at rest , our stuAs well as improving patient comfort, adequate relief of pain on movement and during coughing is important in reducing risks of cardiopulmonary and thromboembolic complications after surgery . In addiA receptors that propofol exerts its anesthetic as well as its analgesic effects [A receptors, propofol antinociception is also mediated by a spinal delta opioid receptor [Propofol’s exact mechanism of action remains unknown, though both cell culture and animal studies suggest that it is through interaction with GABA effects , 32, 33.receptor  is throureceptor  and antireceptor .With regard to side effect profiles, our results showed no difference in the incidence of nausea, vomiting, dizziness, or post-operative delirium between the SEVO and the TIVA groups, although pruritus was significantly lower in the TIVA group. It is to be noted here that this study was not powered to detect side effects with a low incidence and, essentially, raw data does show that 15.8% of the SEVO group had nausea, versus 11.6% in the TIVA group, while 5.3% in the SEVO group reported dizziness, versus 1.1% in the TIVA group.There are several limitations to this study. Firstly, this was retrospective with data retrieved from a registry. We did not utilize a standardized target for maintenance of depth of general anesthesia such as processed EEG. Another limitation is the interplay between drugs and hepatic function. There is uncertainty about the remaining liver function after hepatectomy compared with radiofrequency ablation, although studies have shown that patients who received radiofrequency ablation exhibited less derangement in albumin and bilirubin levels on postoperative day 7 . In addiIn conclusion, patients who underwent liver surgery using propofol for induction and maintenance of anesthesia had less pain during coughing on postoperative days 1 and 2 and reduced daily, accumulative and total postoperative morphine consumption when compared to the use of sevoflurane. No difference was found in pain at rest on post-operative day 1 to 3, total duration of PCA use and patients’ satisfaction with pain relief. The incidence of post-operative nausea, dizziness and pruritus was lower in the TIVA group.


Patellofemoral pain syndrome (PFPS), also known as Anterior Knee Pain, is a common cause of recurrent or chronic knee pain. The etiology is considered to be multifactorial but is not completely understood. At the current time the leading theory is that pathomechanics in the patellofemoral joint leads to PFPS. Traditionally, conservative treatment has focused on improving strength and timing in the quadriceps muscles. In recent years, evidence has been accumulating to support the importance of hip control and strengthening in PFPS. Two recent studies have shown promising results for hip strengthening as an isolated treatment for PFPS. The aim of this randomised contolled trial (RCT) is to compare isolated hip strengthening to traditional quadriceps-based training and a control group with free physical activity.An observer-blinded RCT will be performed. We intend to include 150 patients aged 16–40 years, referred from primary care practitioners to the department of Physical Medicine and Rehabilitation in Kristiansand, Norway for PFPS with more than three months duration. Patients meeting the inclusion criteria will be randomised using opaque sequentially numbered sealed envelopes to one of three groups: isolated hip strengthening, quadriceps based training, or a control group . All groups will receive standardized information about PFPS formulated with the intention to minimize fear avoidance and encourage self-mastery of symptoms. Standardized exercises will be performed under supervision of a study physiotherapist once per week in addition to home training two times per week for a total of six weeks. The primary outcome measure will be the Anterior Knee Pain Score (AKPS) at three and 12 months. Secondary outcome measures will include Visual analogue scale (VAS) for pain, hip abductor and quadriceps strength, the generic EuroQol (EQ-5D), Hopkins Symptom Checklist (HSCL), Knee self-efficacy score and Tampa score for Kinesiophobia.This trial will help to elucidate the role of hip and quadriceps strengthening in the treatment of PFPS. Information as to the role of anxiety and depression, kinesiophobia and self-efficacy will be collected, also as regards prognosis and response to exercise therapy.NCT02114294.ClinicalTrials.gov reference:  Patellofemoral pain syndrome (PFPS), also known as Anterior Knee Pain, can be defined as pain behind or around the knee cap (patella), provoked during loading of the knee in flexion or extension, in the absence of other specific pathology of the knee joint . It is oThe etiology of PFPS is not completely understood, and is considered to be multifactorial ,9. The pSeveral studies have underlined the importance of the quadriceps muscle function including timing and/or activity of the vastus medialis obliquus (VMO) -21 althoIn recent years there has become an increased focus on the importance of hip strength and control in PFPS. Several studies indicate that women with PFPS have altered hip kinematics during more demanding loading such as running, jumping and landing -28. StudMore recent studies have reported promising results when strengthening hip abduction and external rotation on women with PFPS are used prior to , or in aThe aim of this study is to compare the effect of isolated hip strengthening exercises, traditional quadriceps based exercises and free physical activity in patients with patellofemoral pain syndrome. The primary outcome is the Anterior Knee Pain Score (AKPS) at three months and one year. Our null-hypothesis is that there is no difference between the three groups for primary or secondary outcomes, measured at three months and one year.This is an observer-blinded randomised controlled trial (RCT) with first primary endpoint at three months, and second primary endpoint at one year Figure : diagramEthics approval for this study has been received from the Ethics Committee Health Region Southeast, Norway.Participants will be recruited from general practitioners, chiropractors, manual therapists and from departments of orthopedic surgery, rheumatology and physical medicine and rehabilitation. To increase awareness of the trial, potential sources of referral will receive regular written information on the ongoing trial, and general practitioners will be invited to attend lectures on knee complaints with a focus on the current study.All potential participants will be screened to determine their eligibility according to the following inclusion and exclusion criteria. For inclusion, patients should be 16–40 years of age and have at least three months history of peri- or retropatellar pain with worst pain intensity during previous week of VAS 3 or more. The pain should be provoked by at least two of the following activities: Stair ascent or descent, hopping, running, prolonged sitting, squatting or kneeling. On clinical exam, pain should be present during one of the following: Compression of the patella, palpation of the patellar facets. In patients with bilateral pain the worst knee will be included, and presence of bilateral pain will be documented. One specialist in Physical Medicine and Rehabilitation (PM&R) will perform clinical examinations of all patients. Possible candidates will have a plain x-ray and MRI of the knee joint performed, if this has not already been performed within the previous six months.Exclusion criteria include clinical, x-ray and MRI findings indicative of meniscal or other intra-articular injury, injury to or increased laxity of cruciate or collateral ligaments, or other pathology including: osteoarthritis, Osgood-Schlatter or Sinding-Larsen-Johanssen syndrome, jumpers knee, or of significant knee joint effusion, significant pain from hip or lumbar spine on clinical evaluation, with potential for causing referred pain to the knee, or hindering the patient’s ability to perform the prescribed exercises, recurrent patellar subluxation or dislocation, previous surgery to the knee joint, NSAID or cortisone use over an extended period of time, having suffered trauma to the knee joint judged during clinical evaluation to have a significant effect on the presenting clinical condition. Patients having received physiotherapy or other similar treatment for patellofemoral pain syndrome within the previous three months will also be excluded.Patients who fulfill the inclusion criteria and consent to take part in the trial after they have received the standardized oral and written information, will be randomized to receive hip strengthening (H), quadriceps-based training (Q), or control group (C). Sealed opaque randomization envelopes with a study-specific patient number will be supplied by an external statistician. The randomization sequence is computer-generated with randomization blocks of a variable size which is unknown to any of the research team. A nurse not otherwise involved in the research study will take the sealed opaque numbered envelopes in order, by number, and deliver the correct envelope to the treating physiotherapist. The envelope contains a piece of paper which is labeled with the same patient specific number, plus the group assignment . The group assignments will be communicated for the purpose of data analysis in coded form. The code will only be revealed when the data analysis is complete.All groups receive standardized oral and written information from the Physical Medicine and Rehabilitation (PM&R) specialist at the time of inclusion to the study focusing on understanding of the etiology of PFPS, and especially reassurance as to the benign nature of the condition. The information is formulated with the intention to minimize fear avoidance and encourage self-mastery of symptoms. Advice will be given to stay physically active without excessively provoking knee pain, and types of potential activities will be explored with the patient. Participants will be asked to refrain from seeking other forms of treatment  during the study. The same written and oral information will be repeated by the study physiotherapists at randomization. Standardization of information will be achieved by regular meetings for the research staff before initiation of the study and throughout the study period.The hip strengthening exercises consist of side-lying hip abduction, hip external rotation (clam-shell) and prone hip extension. The exercise positions are based on previous studies of hip strengthening ,39,40, aThe quadriceps exercise regime is based on previous studies ,44, and The control group will receive the same standardized information and advice from the specialist as the exercise groups at study inclusion. At randomization, the control group will meet with the study physiotherapist and will again receive standardized information about PFSS and advice about choice and dosage of activities. They will receive no prescribed exercise regime but are encouraged to be physically active according to their own wishes. The purpose of the control group is to assess whether specific hip strengthening or quadriceps-based training is better than free physical activity. This is important if there is no difference in effectiveness between hip strengthening and quadriceps-based training and also for assessing whether any of the specific training regimens are better than free physical activity.Baseline data will include gender, age, height, weight, body-mass index, level of physical activity, unilateral vs. bilateral symptoms, duration of symptoms, work status, whether on sick leave or disability, highest level of education achieved, use of pain or anti-inflammatory medication, a plain film x-ray including skyline view, and MRI examination of the knee joint . We will also record the Beighton score with regard to joint mobility .Blinded observers will assess all participants at baseline, three months and one year after inclusion. Pain and function, health related quality of life, activity level, strength, self-efficacy, anxiety and depression, number of pain regions, and kinesiophobia will be assessed by standardised, validated questionnaires at each time point. At six weeks, a mid-term assessment will be performed including pain and function (AKPS and VAS) and strength measurements. The treating physiotherapists will be blinded to all baseline data. Due to the nature of the study, blinding of the patients and physiotherapists to the intervention is not possible, but patients’ expectations about the effectiveness of each intervention will be assessed at baseline.The main hypothesis in the present study will be examined at three and 12 months using the Anterior Knee Pain Scale (AKPS) as the primary outcome measure. This is a self-report questionnaire consisting of 13 questions to assess severity of pain and disability . It has Include a range of standardised, generic self-report measures including VAS for pain, global score of change, step-down test, strength and endurance testing, quality of life, kinesiophobia, anxiety and depression, self-efficacy, number of pain regions, and activity level.A 10-cm Visual Analog Scale (VAS) will be used to measure pain, where 0 corresponds to no pain and 10 corresponds to worst imaginable pain. The scale is validated for use with patellofemoral pain . We willAn 18-point Likert scale for measuring patients’ global assessment of change compared with baseline will be carried out at three and 12 months. The scale ranges from −9 (maximum deterioration) to +9 (maximum improvement) .According to Loudon et al.  the stepIsometric strength will be measured for hip abduction, hip external rotation and knee extension. Strength will be measured with a force gauge (MuscleLab Force Gauge 300 kg) using stabilizing straps to ensure correct positioning of the patient, according to the current standard for studies of this type. Standardized positions and procedures are based on techniques proposed by Caldwell et al.  and ThorA novel test for hip abduction endurance has been developed for use in this study. A parallel article will be published quantifying normal values for this test, values for PFPS patients (men and women), its inter- and intra-rater reliability, validity compared to strength testing with force measurer, and its predictive value for clinical response to hip strengthening in PFPS patients. Testing is carried out in side-lying position with a 5 kg weight around the ankle of the upper leg, which is in 0-10° hip extension and abducted to 30° above the horizontal plane. Time successfully held in target area is measured in seconds. All participants in the study will be tested at baseline, six weeks, three and 12 months. Parallel with the RCT, normative data will be collected in a group of 75 healthy controls of both sexes from 16–40 years old.Euro-Qol – 5 Dimensions (EQ-5D) is a questionnaire used to measure health related problems and quality of life . The queThe Tampa scale for kinesophobia (TSK) is a 13 –item questionnaire aimed at the assessment of fear of movement/re-injury. Each item is scored on a 4-point Likert scale with alternatives ranging from strongly disagree (0) to strongly agree (4). This gives a possible total score range from 0 to 52. The TSK is translated to Norwegian and a cross-cultural adaptation and validation study showed satisfactory validity and reliability in a Norwegian population with sciatica .The Hopkins Symptom Checklist (HSCL) is a symptom inventory which measures symptoms of anxiety, depression and somatisation, originally consisting of 58 items . CompariSelf-efficacy will be measured using the Knee Self-Efficacy Score (K-SES). This score is originally developed in both Swedish and English for measuring self-efficacy in patients with anterior cruciate injury  and willAn adaptation of the Standardized Nordic Questionnaire  will be 2 Armband) using the techniques validated in a study by Berntsen et al. [Activity level will be monitored using a multi-sensor which includes an accelerometer .The power and sample size calculations are based on a one-way Analysis of Variance (ANOVA) model at follow-up that does not take into account adjustment for the baseline values. Based on previous studies, standard deviation of AKPS and VAS is assumed to be 13.5 and 2.25, respectively. MCID for AKPS or VAS is set at 10 and 2, respectively . With thAll eligible patients, regardless of their compliance with the protocol  will be included in the main analysis.To assess the primary endpoints of the study after three months and one year the differences between the three treatment groups will be analysed with an Analysis of Covariance model using the baseline value as one of the covariates. Assumptions of the model will be checked. To analyse the time course repeated measures will be analysed using linear mixed models. The influence of factors including compliance, muscle strength, psychological factors, joint hypermobility and baseline pain levels will also be examined with regard to treatment response.A blinded statistical analysis and review of the outcome data is planned . Only afPFPS is a common cause of knee pain in which there are significant levels of recurring or chronic problems. The etiology is not completely understood, and heterogeneity and existence of subgroups has been proposed by many as an explanation for varying results of treatment ,63. Trad


Pain is a major public health issue throughout the world and represents a major clinical, social, and economic problem . The inaVarious pharmacologic factors may increase the probability of excessive/prolonged effects in ICU patients including altered pharmacokinetic and pharmacodynamic characteristics with prolonged administration, altered protein binding, altered volume status, and end-organ dysfunction .Special complications of inappropriate pain management in ICU are as follows: under-treatment leading to prolonged mechanical ventilation, increased ICU stay, hypoxemia, thromboembolic and pulmonary complications, self-removal of tubes and catheters, violence toward caregivers, patient-ventilator asynchrony, pain-related immune suppression, and readmission for further pain management, agitation, myocardial ischemia, delirium, and chronic pain. The complications of over-treatment for pain include prolonged mechanical ventilation and associated problems such as ventilator-associated pneumonia, post-traumatic stress disorder, prolonged cognitive impairment, unnecessary testing for altered mental status, prolonged ICU stay, skin breakdown, nerve compression, delirium, respiratory depression, brain or other neurologic injury, sedation, circulatory depression, urinary retention, impairment of bowel function, and sleep disruption -8.It is strongly recommended that in patients with impaired cognition or concurrent diseases and in critically ill patients, additional interventions are needed for optimal pain management. A therapeutic trial of an analgesic should be considered in patients with increased blood pressure and heart rate or agitated behavior . The inclusion of pain management in the ICU checklist, as a part of daily rounds, can be a valuable tool for reducing the patient’s discomfort . AnestheDo patients undergoing different type of surgery have different need for analgesia?A systematic pain assessment method for mechanically ventilated ICU patients could function as a criterion for good practice in the ICU .The efficacy and outcomes of analgesic protocols for acute pain management have been studied extensively and are widely adopted. The latest practice guidelines were updated as the “Practice Guidelines for Acute Pain Management in the Perioperative Setting” in February 2012 and have been adopted by the ASA . These gTechniques for pain management include the following modalities:Intermittent or continuous systemic opioids;Multimodal techniques ;Central regional  opioid analgesia; andPeripheral regional analgesic techniques, including intercostal blocks, plexus blocks, and local anesthetic infiltration . Techniques that reduce drug dosage (opioid-sparing effect) may be suitable for ICU patients. Behavioral modalities and techniques such as PCA that depend upon self-administration of analgesics are generally less suitable for the cognitively impaired.Most patients on mechanical ventilation receive sedatives and analgesics without further evaluation . A prospSeveral scales and tools such as the visual analog scale, behavioral pain scale, and critical care pain observations are used for the assessment of analgesia and sedation in ICU. These scales and checklists for pain emphasize the complex nature of the problem.The structured approaches and use of protocols to prevent the accumulation of drugs and metabolites that could lead to a slower recovery are supported by rapidly expanding evidence .Awissi and coworkers concluded that establishing protocols for the management of sedation, analgesia, and delirium is a cost-effective practice and allows savings of nearly $1000 per hospitalization . Thus, w


The accurate diagnosis of pediatric acute abdominal pain is one of the most challenging tasks in the emergency department (ED) due to its unclear clinical presentation and non-specific findings in physical examinations, laboratory data, and plain radiographs. The objective of this study was to evaluate the impact of abdominal multidetector computed tomography (MDCT) performed in the ED on pediatric patients presenting with acute abdominal pain. A retrospective chart review of children aged <18 years with acute abdominal pain who visited the emergency department and underwent MDCT between September 2004 and June 2007 was conducted. Patients with a history of trauma were excluded. A total of 156 patients with acute abdominal pain  who underwent abdominal MDCT in the pediatric ED during this 3-year period were enrolled in the study. One hundred and eighteen patients with suspected appendicitis underwent abdominal MDCT. Sixty four (54.2%) of them had appendicitis, which was proven by histopathology. The sensitivity of abdominal MDCT for appendicitis was found to be 98.5% and the specificity was 84.9%. In this study, the other two common causes of nontraumatic abdominal emergencies were gastrointestinal tract (GI) infections and ovarian cysts. The most common etiology of abdominal pain in children that requires imaging with abdominal MDCT is appendicitis. MDCT has become a preferred and invaluable imaging modality in evaluating uncertain cases of pediatric acute abdominal pain in ED, in particular for suspected appendicitis, neoplasms, and gastrointestinal abnormalities. Acute abdominal pain is a common cause of pediatric visits to the emergency department (ED). Most cases are attributed to nonsurgical illnesses, and only a small fraction actually have an organic cause necessitating surgical intervention; the most common condition requiring surgery is acute appendicitis , 2. AlthThe application of multidetector computed tomography (MDCT) has practical advantages for children in the ED because of its faster scanning time, better imaging quality (multiplanar reformation), lower sedation rate, and decreased radiation exposure.The purpose of this study was to describe and evaluate the role of MDCT in pediatric acute abdominal pain in the ED.This was a retrospective registry-based cohort study of abdominal MDCT ordered in the ED by pediatric emergency physicians. From the ED CT log, consecutive patients aged <18 years old who had acute abdominal pain from September 2004 to June 2007 were identified. Trauma patients and patients who were discharged against medical advice were excluded.Clinical information of age, sex, clinical presentation, sonography, CT results, and final diagnoses were obtained from charts. Sonographies were performed by a pediatric gastroenterologist. The decision to perform abdominal CTs was made by a pediatric emergency physician or a pediatric surgeon. The final diagnoses were recorded by reviewing the chart entries made by the attending pediatric emergency physicians after considering clinical history, laboratory data, and radiologic findings.All CT scans were obtained with intravenous contrast enhanced using a 16- MDCT scanner . All images were interpreted and recorded with a consensus between two radiologists. The CT criteria for acute appendicitis used by the reviewing radiologist included the following: a distended appendix greater than 7 mm in maximal diameter, appendiceal wall thickening and enhancement, an appendicolith, circumferential or focal apical cecal thickening, pericecal fat stranding, adjacent bowel wall thickening, focal or free peritoneal fluid, mesenteric lymphadenopathy, and intraperitoneal phlegmon, or an abscess [All the excised appendices were sent for a pathology examination, and the final diagnosis of acute appendicitis was based on a histological examination. Negative appendectomy was defined as patients who underwent non-incidental appendectomy and the appendix was not found to be inflamed on pathologic examination.The hospital’s institutional review board concurred that this retrospective study was a continuous quality improvement initiative for patient care and did not require informed consent.There were 156 ED computed tomography studies performed for acute abdominal pain in the pediatric emergency department during the 3-year period of this study. There were 85 males and 71 females, with an age range of 1-17 years .via MDCT prior to surgery, but only one case of appendiceal perforation without abscess was detected via MDCT before the operation.Among 118 children with suspected appendicitis, 72 were initially diagnosed as having appendicitis by CT, and 64 had the diagnosis of appendicitis confirmed later by pathologic results. Among the eight patients with false positive findings with MDCT, five of them did not have surgery because the family were reluctant, and their abdominal pain subsided after six to eight hours of observation. The remaining 3 patients had an operation: of these three patients, one’s pathology results revealed diverticulitis, and the other two had no inflammation in their excised appendices. All eight patients with false positive findings had an out-patient department follow-up and recovered completely. Forty-six patients who underwent MDCT revealed findings negative for appendicitis; however, one of them had persistent abdominal pain, and was later diagnosed with appendicitis that was proven by postoperative pathology. The rate of negative appendectomy was 9.7% (7/72). The sensitivity and specificity for diagnosing appendicitis by MDCT were found to be 98.5% and 84.9%, respectively. Moreover, ten patients with appendicitis had appendiceal perforation, and six of them had abscess formations. All abscess formations were detected via MDCT. One of these patients underwent an appendectomy because of persistent right lower quadrant pain, and was diagnosed as having appendicitis from pathology after surgery. Another patient underwent exploratory laparotomy because of persistent rebounding pain, and was diagnosed as having gastric perforation. Among the 57 patients with GI infection, 12 of them were admitted to the ward for further treatment.The MDCT findings of 59 patients with acute abdominal pain showed thickening of the bowel walls, and five of them had ascites noted via MDCT.Of the 12 children with gynecological diseases, eight had ovarian cysts, 3 had pelvic inflammatory disease, and 1 had ovarian torsion. Eight of these patients received sonographies initially, in which three were found to have fluid accumulation in the cul-de-sac and the other five had uncertain diagnoses. Subsequently, one ovarian torsion, one ruptured hemorrhagic ovarian, 4 ovarian cysts, and 2 pelvic inflammatory disease were detected The patient with ovarian torsion and another with a ruptured hemorrhagic ovarian cyst both received surgeries. The remaining 10 patients were discharged after observation and medical treatment.via MDCT. One patient who was diagnosed with inflammation of the bowel via MDCT pre-operatively actually had gastric perforation diagnosed after surgery. For this patient, two locations of extraluminal air bubbles were detected around the liver and stomach, and the perforations were associated with peptic ulcers diagnosed after a surgery. Another 4 locations of extraluminal air bubbles were found on the small bowel wall in 2 patients, the rectal wall in one patient, and the sigmoid wall in one patient. The perforation sites found via MDCT were compatible with the operative findings.A total of 7 patients had bowel perforations, and 6 of them were diagnosed There were five patients with intraabdominal masses detected initially via sonography, and MDCT was then performed for detailed evaluation. Their diagnoses were as follows: 2 teratomas, 1 lymphangioma, 1 hepatoblastoma, and 1 pheochromocytoma. All of them underwent operations, and their post-operative pathologies confirmed the pre-operative MDCT findings.A cystic mass was noted over the right lower quadrant of the abdomen in one patient via sonography, and a duplication cyst or an omental cyst was suspected after an abdominal MDCT. An exploratory laparotomy was performed and cystic duplication was proven by pathology. Abdominal MDCT of another patient revealed encapsulated small bowel loops on the right side of the abdomen and left-sided displacement of the ascending colon Figures  & 2. A dvia MDCT in one patient, and hydronephrosis with urethral stones was detected via MDCT in another patient. Both of these patients did not receiv a sonography before MDCT.The MDCT scan demonstrated colon wall thickening, a diverticulum and mild stranding of the pericolic fat in one patient, and a diagnosis of colonic diverticulitis was made. A huge renal cyst was found There were 5 patients with a final clinical diagnosis of abdominal pain of unknown origin. All of them had negative MDCT results and all were treated with intravenous hydration and several hours of observation in the ED. They were all later discharged after the symptoms of abdominal pain improved or abated.The results of the final diagnoses are summarized in Table The purpose of this study was to evaluate the role of MDCT in diagnosing acute abdominal pain in children visiting the ED. In 156 children with acute abdominal pain who underwent MDCT in the ED, the three most frequent diagnoses were appendicitis (41%), inflammatory bowel disease (36%), and ovarian cyst (5%). A previous study observed that the three most frequent diagnoses in 775 children with abdominal pain were gastrointestinal infection (65%), appendicitis (14%), and non-specific abdominal pain (13%) . TherefoImaging studies are not always needed in children with acute abdominal pain, and sonography should be used as the initial imaging modality for the evaluation of pediatric acute abdominal pain suspicious of appendicitis -13. HoweCT scans are always performed particularly when children have atypical presentations of appendicitis, abscess formations, or appendiceal perforation is suspected . In a reIn our study, when children were suspected of having appendicitis by a physician in the ED, they were evaluated by the pediatric surgeon or, if a pediatric gastroenterologist was available, they underwent sonography first. In other words, a CT scan was performed when patients presented with atypical clinical findings, had equivocal sonographic results, or when the pediatric surgeon required a CT scan in order to make a decision. During our study period, appendicitis was diagnosed in an additional 243 patients; including 81 who underwent surgery without sonography and MDCT imaging studies, and another 162 patients who underwent sonography without MDCT scan. In our study, twelve patients with suspected appendicitis underwent sonography first and then MDCT. These patients underwent MDCT because of equivocal sonographic results. Subsequently, MDCT proved appendicitis in 8 patients, gastroenteritis in 3, and an ovarian cyst in 1.Reviewing the detailed records of the false positive findings of MDCT, one of 5 patients had a distended appendix greater than 7 mm in diameter according to MDCT, and the other 4 had undirected signs such as cecal thickening, focal peritoneal fluid, mesenteric lymphadenopathy, or pericecal fat stranding. The sensitivity and specificity for diagnosing appendicitis by MDCT in the present study were 98.5% and 84.9%, respectively, whereas in the literature the average sensitivity and specificity of CT have been reported as 90.8% (range: 87%-100%) and 94.2% (89%-98%) respectively .Other than appendicitis, GI infection is also a very common cause of acute abdominal pain of children who go to the ED, and it can easily be misdiagnosed as appendicitis. At the same time, GI infection is the most common diagnosis in cases of missed appendicitis -16. In tSonography is the initial imaging study done to young females with acute abdominal pain. When sonography findings are too equivocal for a diagnosis, further evaluation with a CT scan is advocated . Many gyBowel perforation is also a common cause of pediatric acute abdominal pain. There were 7 patients who had bowel perforations in this study, and six of them were diagnosed preoperatively through MDCT, which has already been established as the most valuable imaging technique for identifying the presence, site, and cause of a bowel perforation -22. HoweAbdominal neoplasms and gastrointestinal abnormalities are relatively uncommon causes of pediatric acute abdominal pain. In this study, there were five cases of neoplasms and two cases of GI anomalies. Most of the abdominal neoplasms or abnormalities had nonspecific findings on sonography, and they were identified more clearly by second-line examination of MDCT after contrast material injection, particularly in both the axial plane and the coronal plane images of the abdomen after reconstruction. In other words, it may be possible to make a precise pre-operative diagnosis of neoplasms and GI abnormalities through MDCT, and this is of great importance because it provides excellent anatomic details for correct diagnosis .The main disadvantage of CT is the relatively high dose of radiation the patient receives. Furthermore, increased use of CT in children can raise their risk of cancer due to radiation exposure. The projected lifetime attributable risks of solid cancer are found to be higher for younger patients and females than for older patients and males; and they are also higher in patients who undergo CT scans of the abdomen/pelvis or spine than in patients who undergo other types of CT scans . BesidesThis study has some limitations. The patients with abdominal pain without undergoing MDCT were not enrolled in our study because we focused on evaluating the impact of MDCT. The most important limitation, however, is that this is a retrospective review of medical records. The decision to use MDCT was not made by some pediatric emergency physicians, and their overuse of CT maybe criticized. The overuse of CT in ED is an important issue, and it may well be due to the clinician being afraid of malpractice suits or lacking experience, or else patient demand .The small sample size of the study might have affected the sensitivity and specificity of MDCT to diagnose appendicitis. The follow-up information was insufficient except for those patients who were admitted to the wards or those who came back to the out-patient department. Lastly, this study only covered the experience of one hospital. A prospective study in multiple medical centers is required for a more thorough evaluation of using MDCT to diagnose abdominal pain in children.Acute abdominal pain is a common complaint in children who are brought to the pediatric ED. Considering the risk of radiation from CT scans, MDCT is recommended in cases of pediatric abdominal pain with confusing presentation in the ED that cannot be diagnosed correctly after clinical data and sonography. The use of MDCT scans can offer greater accuracy as well as an ability to identify alternative diagnoses such as appendicitis, neoplasms and gastrointestinal abnormalities.


The sore throat pain model has been conducted by different clinical investigators to demonstrate the efficacy of acute analgesic drugs in single-dose randomized clinical trials. The model used here was designed to study the multiple-dose safety and efficacy of lozenges containing flurbiprofen at 8.75 mg.Adults (n = 198) with moderate or severe acute sore throat and findings of pharyngitis on a Tonsillo-Pharyngitis Assessment (TPA) were randomly assigned to use either flurbiprofen 8.75 mg lozenges (n = 101) or matching placebo lozenges (n = 97) under double-blind conditions. Patients sucked one lozenge every three to six hours as needed, up to five lozenges per day, and rated symptoms on 100-mm scales: the Sore Throat Pain Intensity Scale (STPIS), the Difficulty Swallowing Scale (DSS), and the Swollen Throat Scale (SwoTS).P <0.05 compared with placebo). After using multiple doses over 24 hours, flurbiprofen-treated patients experienced a 59% greater reduction in throat pain, 45% less difficulty swallowing, and 44% less throat swelling than placebo-treated patients . There were no serious adverse events.Reductions in pain (lasting for three hours) and in difficulty swallowing and throat swelling (for four hours) were observed after a single dose of the flurbiprofen 8.75 mg lozenge  and overall patient satisfaction from the flurbiprofen lozenges were also demonstrated in this multiple-dose implementation of the sore throat pain model.NCT01048866, registration date: January 13, 2010.This trial was registered with ClinicalTrials.gov, registration number:  As foe throat -9, earace throat , and othe throat ,12 makesRecognizing this investigational challenge in examining multiple-dose efficacy in patients with an acute, self-limited infectious disease, we employed four specific principles of research architecture in order to tighten the design of this multiple-dose trial. First, to avoid confusion with other expressions of URTI that can also cause a sore throat (such as laryngitis) and might respond differently to treatment, we enrolled only patients with sore throat due to pharyngitis. Homogeneity of diagnosis was confirmed on the Tonsillo-Pharyngitis Assessment (TPA), an index of distinct clinical features of pharyngitis ,13,14. Mdis-ease which the patients described, we sought to evaluate other dimensions of throat pain in addition to the evaluative quality of ‘sore’ throat (pain intensity). We asked the patients to evaluate two other prominent throat-related symptoms which they also complained of, the sensation of a ‘swollen throat’, a sensory quality commonly reported by patients with sore throat, as well as ‘difficulty swallowing’, a throat function  [Second, to fully characterize the many expressions of throat ophagia) ,5,15-18.Third, because patients with acute sore throat require treatment mostly during the early course of disease, we sought to enroll patients within three days of their first throat symptom . Thus, we would be more likely to observe patients who provided assessments of sore throat throughout the first 24 hours of the clinical trial. Also, to help assure that symptom severity would be more likely to persist for at least 24 hours and efficacy could be assessed over this treatment period, patients were eligible only if they reported at least a moderate severity of sore throat pain, swollen throat, and difficulty swallowing at baseline.Previous studies have demonstrated the efficacy and safety of a single dose of a lozenge containing the nonsteroidal anti-inflammatory drug flurbiprofen in patients with sore throat -9,19,20,This was a randomized (ratio 1:1), double-blind, placebo-controlled, multiple-dose, parallel-group study. The first subject was enrolled in November 2009 and the last subject completed in March 2011. The study was conducted in accordance with the International Conference on Harmonization Good Clinical Practice and the ethical principles contained within the Declaration of Helsinki . The study also complied with the Code of Federal Regulations (CFR) of the United States Food and Drug Administration (FDA) and the United States Good Clinical Practice Regulations. The study protocol was reviewed and approved by The New York University School of Medicine’s Institutional Review Board, Compass Institutional Review Board and IntegReview Ethical Review Board. The study was registered with the ClinicalTrials.gov registry, registration number: NCT01048866.Patients were screened by the study investigators at research sites in the United States after seeking medical care for sore throat, being referred to the trial site, or responding to advertisements about this study. All participants provided written informed consent prior to participation in the study. Adults ≥18 years) were included if they had a sore throat of recent onset (≤3 days), moderate or severe pain on the Throat Pain Scale , at least one symptom of URTI on the URTI Questionnaire ,14, obje8 years wPatients were ineligible if they displayed confounding features of URTI: mouth breathing which causes throat drying, coughing which causes throat discomfort, or any disease that could compromise respiratory function. Patients were also ineligible if they had a history of allergic reaction or hypersensitivity to aspirin or other nonsteroidal anti-inflammatory drugs, or any gastrointestinal, hepatic, or renal dysfunction. Patients were excluded if they had used any throat lozenge, throat spray, cough drop, or menthol-containing product within one hour prior to study screening, used any ‘cold medication’ or immediate-release analgesic within the previous four hours, used any sustained-release analgesic within the previous 12 hours, taken an antibiotic for an acute disease within 24 hours, or any quinolone antibiotic or inhaled therapy in the previous week.Under double-blind conditions, patients were randomly allocated to receive sugar-based, flavored flurbiprofen 8.75 mg lozenges or sugar-based, identically flavored placebo lozenges (containing the same vehicle ingredients as the flurbiprofen lozenge). Randomization was achieved using a computer-generated randomization schedule provided by a statistician who was not involved in the analysis of the study. The patients, study investigators, and all other study personnel remained blinded to the treatment allocation after randomization.Patients were instructed to suck one lozenge (flurbiprofen 8.75 mg or placebo) and were then not permitted to have anything by mouth for the next two hours. Patients were assessed onsite for the first two hours, then discharged with a supply of the same trial lozenges  and acetaminophen 650 mg tablets . No other medications were permitted during this 24-hour period. Over 24 hours (while awake), patients used a diary to record hourly assessments of sore throat pain, swollen throat, and difficulty swallowing, their medication consumption, and any adverse events (AEs). A follow-up visit was conducted for the 24-hour assessments. Over the following six days patients assessed secondary outcomes before and after each self-dosing. At the end of the seven-day observation period patients returned to the site for final assessments and review of AEs and were discharged from the study.At baseline, all patients were examined for physical findings of tonsillo-pharyngitis, as measured on the TPA Table , and forPreviously validated 100-mm visual analog scales , a six-category scale ranging from ‘no relief’ to ‘complete relief’ ,23.At the 24-hour visit patients were asked to rate their satisfaction or dissatisfaction with the study medication by completing the Patient Satisfaction Scale, a seven-category scale ranging from ‘extremely dissatisfied’ to ‘extremely satisfied’ [The primary endpoint of this study was the time-weighted summed difference in pain intensity on the STPIS over 24 hours after the first dose of study medication (SPID24). Based on a previous study utilizing this endpoint , and assEfficacy was calculated using least square (LS) means, and analysis of variance (ANOVA) was used to compare flurbiprofen 8.75 mg and placebo groups, with treatment and site included as a fixed effect and the relevant baseline  included as a covariate. The time-weighted summed differences in DSS and SwoTS over 24 hours were similarly evaluated. The time-weighted summed differences for all three outcomes were assessed over two hours after each dosing over days two to seven. If a patient used rescue medication for pain, all subsequent STPIS, DSS, and SwoTS scores in the 24-hour interval were assigned the baseline value . Missing scores for time-weighted summed differences from baseline were imputed using linear interpolation, assuming the time of the missing assessment to be the nominal time since the first dose, in order to give a more reliable approximation of the AUC from the non-missing data. Two-sided statistical tests were performed with significance determined by reference to the 5% significance level.Wilcoxon rank sum tests were performed to analyze the data obtained for the pharyngeal inflammation category (on the PrAoI), duration of sore throat, size of tonsils (on the TPA), sore throat relief, and patient satisfaction. The chi-square test was performed to analyze the sex and AE data, and two-sided statistical t-tests were used to analyze the other parameters assessed at baseline.To determine the efficacy of a single dose of study medication as measured on the STPIS, DSS, and SwoTS ,5,22,23,P >0.1 for differences between groups). Only 4.1% of the patients had group A beta-hemolytic streptococcal pharyngitis, with no difference between the treatment groups , and most patients had evidence of moderate or severe pharyngeal inflammation (Table P >0.1). Most patients had moderate pain at baseline   or placebo (n = 97) lozenges Figure . One patP <0.01; Figure P <0.01; Figure P <0.01; Figure P <0.05).On average, patients used 4.7 lozenges (standard deviation (SD) 0.96, range 2 to 8) over the initial 24-hour treatment period. For the study’s primary endpoint (SPID24), patients in the flurbiprofen 8.75 mg group reported a 59% greater reduction in pain than patients taking placebo  –321.0 to -72.2; P <0.01). Reductions in absolute DSS and SwoTS levels were also observed at each hourly assessment up to and including four hours post-dose for patients in the flurbiprofen 8.75 mg treatment group compared with placebo  , in difficulty swallowing , and in swollen throat . Using a cumulative responder analysis of patients achieving at least 20% reduction in sore throat pain intensity  and two hours (mean (SD) scores 2.0 (1.23) and 1.3 (1.24); P <0.0001), the two time points relief was directly measured (on the STRRS).Sore throat relief was significantly greater for patients who used the flurbiprofen 8.75 mg lozenge than placebo at one hour (mean (SD) scores 1.8 (1.22) and 1.2 (1.15), respectively; P = 0.07), a 36.9% greater improvement in difficulty swallowing , and a 45.0% greater relief of swollen throat compared with patients taking placebo lozenges .Patients taking flurbiprofen 8.75 mg lozenges over days two to seven experienced a 38.0% greater relief of sore throat pain . Most AEs were related to URTI symptoms (headache and throat irritation). Severe AEs were reported by 1.0% of patients in both treatment groups (P >0.1); the incidence of gastrointestinal AEs related to study treatment was also similar between groups . Over seven days, the proportion of patients reporting any AE remained similar between the treatment groups , as was the incidence of treatment-related gastrointestinal AEs .The percentage of patients who reported any AE in the first 24 hours of the study (when most lozenges were consumed) was similar for both treatment groups , eliminating confounding clinical features, using validated rating scales for different throat symptoms (not only pain intensity), and measuring these symptoms over the first 24-hour period when throat symptoms are most prominent and require repeated treatment, this multiple-dose trial was sufficiently sensitive to differentiate an active analgesic drug from placebo. The patients were able to detect distinct differences between the sugar-based, flavored flurbiprofen 8.75 mg lozenges and the sugar-based, identically flavored placebo lozenges for the five patient-reported outcomes .The study was also sensitive to single-dose effects, confirming results of previous studies on a single flurbiprofen lozenge compared with placebo -9. NotewWhile this study did achieve its objective of demonstrating pharmacologic activity after multiple doses of study medication, there was one major limitation. Approximately 40% of the patients reported the onset of throat symptoms in the previous three days (and five patients were inadvertently admitted with onset in the previous four to five days). Therefore, the first 24 hours of the study was actually the fourth, fifth, or sixth day of these patients’ symptoms. Acute sore throat is an illness of short duration, with 85% improving within seven days . This naIn this study, using specific design and methods, the sore throat (pharyngitis) pain model demonstrated that multiple doses of flurbiprofen 8.75 mg lozenges are an effective, well-tolerated treatment for patients with sore throat. Efficacy was evident for the patient-reported outcomes of pain intensity, pain relief, and swollen throat as well as throat function  and overall patient satisfaction. We therefore conclude that this pain model is a practical and efficient multiple-dose assay for the safety and efficacy of analgesic agents.AE: Adverse event; ANOVA: Analysis of variance; AUC: Area under the curve; BOCF: Baseline observation carried forward; CFR: Code of Federal Regulations; CI: Confidence interval; DSS: Difficulty Swallowing Scale; FDA: Food and Drug Administration; h: Hour; LS: Least square; PrAoI: Practitioner’s Assessment of Inflammation; SD: Standard deviation; SPID24: Summed pain intensity difference over 24 hours; STPIS: Sore Throat Pain Intensity Scale; STRRS: Sore Throat Relief Rating Scale; SwoTS: Swollen Throat Scale; TPA: Tonsillo-Pharyngitis Assessment; URTI: Upper respiratory tract infection.This study was funded by a research grant from Reckitt Benckiser Healthcare International Ltd., UK. SA, AS, TS, and GS are employees of Reckitt Benckiser Healthcare International Ltd. BS and ES received an investigational grant from Reckitt Benckiser Healthcare International Ltd., UK, to design and conduct this study.All of the authors have contributed substantially to the study reported in this manuscript and the development of this manuscript: BS, SA, AS, and ES contributed to the study concept and design. GS performed the statistical analyses. BS, TS, and ES were involved in the conduct of the study and acquisition of data. BS, SA, AS, TS, GS, and ES contributed to the interpretation of results. All authors have reviewed and approved this manuscript.