Can the application of local anesthetics  alone durably improve pain symptoms in referred patients with chronic and refractory pain?If the application of local anesthetics does lead to an improvement that far exceeds the duration of action of local anesthetics, we will postulate that a vicious circle of pain in the reflex arcs has been disrupted (hypothesis).Case series design. We exclusively used procaine or lidocaine. The inclusion criteria were severe pain and chronic duration of more than three months, pain unresponsive to conventional medical measures, written referral from physicians or doctors of chiropractic explicitly to NT. Patients with improvement of pain who started on additional therapy during the study period for a reason other than pain were excluded in order to avoid a potential bias. Treatment success was measured after one year follow-up using the outcome measures of pain and analgesics intake.280 chronic pain patients were included; the most common reason for referral was back pain. The average number of consultations per patient was 9.2 in the first year (median 8.0). After one year, in 60 patients pain was unchanged, 52 patients reported a slight improvement, 126 were considerably better, and 41 pain-free. At the same time, 74.1 % of the patients who took analgesics before starting NT needed less or no more analgesics at all. No adverse effects or complications were observed.The good long-term results of the targeted therapeutic local anesthesia (NT) in the most problematic group of chronic pain patients  indicate that a vicious circle has been broken. The specific contribution of the intervention to these results cannot be determined. The low costs of local anesthetics, the small number of consultations needed, the reduced intake of analgesics, and the lack of adverse effects also suggest the practicality and cost-effectiveness of this kind of treatment. Controlled trials to evaluate the true effect of NT are needed. The number of chronic pain syndromes is rapidly increasing , 2. MoreThe present case series was undertaken to answer the question if the application of NT alone  can produce long-term improvement of the pain symptoms in referred patients with chronic and so far refractory pain. A case series design was used to investigate the level of pain relief, the consumption of pain medication as well as safety issues.At the same time, we tested the following hypothesis, postulated on the basis of the interpretation of findings from modern neurophysiology of pain: A vicious circle in the pain process can be disrupted by injecting local anesthetics into suitable sites of the body, which is reflected by the fact that the effect lasted much longer than could be expected from the duration of action of the local anesthetic. At the same time, we accept that specific and non-specific effects of treatment cannot be clearly discriminated.NT is a treatment modality using injections with local anesthetics for diagnosis and therapy . The real purpose, though, is not to achieve local anesthesia (except for diagnosis). The generation of targeted stimuli (through the needle) and the selective extinction of other stimuli  affect both the organization of the nervous system and tissue perfusion, thereby disrupting positive feedback actions (vicious circle) in the pain cycle. This treatment modality utilizes the regulatory mechanisms and plastic properties of the nervous system, mainly on two levels: first, via segmental reflectory processes –11, and A case series design was used including patients from a University practice specializing in NT . All patients that met the inclusion criteria and had been referred explicitly to NT between January 1, 2000 and December 31, 2007, were included in the retrospective analysis. Each patient was followed over a period of 12 months. The local ethics committee concluded that no special approval was needed for the following reasons, and therefore, granted permission for us to access patients’ data for the purposes of our study: Not only the referral explicitly to NT, but the treatment, too, was completely independent from the retrospective analysis; written informed consent was obtained from all patients; and the application of an accepted treatment was by definition in full compliance with the statements in the Helsinki Declaration. Therefore, the study passed the review process at the University of Bern to be accepted as doctoral thesis.Patients with pain and written referral explicitly to NT from physicians or doctors of chiropracticChronic condition lasting more than 3 monthsTreatment-resistant pain, i.e., pain persisting after all other evidence-based  measures compatible with the diagnosis  have failed.Only patients were included whose pain was at least severe,Conventional medical treatment options (in accordance with the diagnosis) have not been fully exhausted at the beginning of NT.To avoid a potential bias, patients with improvement of pain who started on another therapy during the one-year treatment period for a reason other than pain but with the potential to influence the pain level in a positive way  were excluded from the analysis.Discontinuation of NT due to accident, new onset of a serious disease, moving house, etc.Exclusive diagnostic and therapeutic application of the local anesthetics procaine or lidocaine in terms of NT (see definition).first consultation data were collected on age, sex, duration of pain problem, diagnosis, severity of pain, secondary diagnoses, and both the outcomes of previous therapies and the medication documented. For each individual consultation, interventions with local anesthetics, change in pain, medication use, adverse effects and complications were recorded over a 12-month study period. At the final visit (12 months after starting NT) the patients were asked to indicate their current level of pain, and both the number of consultations during the past 12 months and the current medication was documented.During the In order to grade the severity of pain (see inclusion criteria) and examine the change in pain a deliberate choice was made to forego the use of a visual analog scale in favor of MacNab’s criteria, which for the purpose of the present case series seemed to be more appropriate (modified according to Schmid ). RegardPatients with a fluctuating course who reported improvements with NT, but rated their level of pain after one year as being no different from the pain intensity before the beginning of NT, were assigned to the “no improvement” category. In the case of patients with multiple pain problems only the primary diagnosis  was evaluated.For purposes of documenting the medication use after treatment with NT (after one year) the following categories were used: 1. more medication than before starting treatment, 2. less medication, 3. no change in medication intake, 4. no medication taken before and after treatment. Only pain-relieving and pain-modulating drugs were considered.The case series did not include patients who had not fully exhausted either conventional medical treatments previously or had not been resistant to treatment before beginning NT. Patients were not excluded, though, if NT was prematurely discontinued due to lack of success, but were assigned to the “no improvement” category (two patients).The diagnoses were recorded according to the ICD-10 Code and then subdivided into four large pain-related diagnostic groups: 1. disorders of the spine and back, 2. disorders of other parts of the motor system, 3. headaches, 4. other pains.The outcome of NT interventions were summarized in a report and communicated to the referring physician.p value of <0.05 was used to denote statistical significance.Fisher’s exact test was used to statistically identify differences in the frequency between groups. With continuous and discrete data , the Wilcoxon or the Kruskal-Wallis test was used to determine the magnitude of difference between groups. Monotonic associations between some of the variables were identified using Spearman’s rank correlation coefficient. A In the above-mentioned period a total of 361 chronic pain patients had a written referral for NT. 59 patients were not included since their pain levels did not exceed categories 1–3 (see inclusion criteria). Seven patients could not be enrolled in the case series because they had started another treatment simultaneously with the beginning of NT. To avoid another potential bias, eleven patients with improvement of pain were later excluded because they began another treatment for a reason other than pain during the one-year study period, potentially influencing the pain level in a positive way . Another four patients were excluded because of external factors .Finally, 280 patients were included in the case series. All patients suffered from chronic pain which had so far been treated with no success and may thus be regarded as unresponsive to treatment. All conventional treatment options had been fully exhausted in accordance with the respective diagnosis. All patients had previously received medical treatment; in 31 % of the patients the pharmacologic treatment approach of pain had been stopped before starting NT, one reason being a lack of effect, another the occurrence of adverse effects. More than two thirds of the patients had previously undergone physical therapy, physiotherapy, osteopathy or chirotherapy, and 25 % of the patients had also tried acupuncture. All pain conditions were resistant to these procedures as well.176 women and 104 men were included; the average age of the females was 50.1 years  and of the males 50.9 years   suffered from treatment-resistant pain disorders of the spine and of other parts of the motor system. Every eighth patient (12.2 %) complained of headache Table .Table 3Dp = 0.04), in that patients afflicted with headache and facial pain showed a longer duration of illness before their referral than the other three groups (Table p = 0.14). Also, there was no difference between female and male patients (p = 0.41).The mean duration of illness in all patients before starting NT was 64 months, i.e., more than five years. The distribution of duration of illness was skewed, meaning that 50 % of all patients had been ill for less than 36 months and 4 patients for more than 360 months. Table p = 0.01). In the first year, patients suffering from painful musculoskeletal disorders affecting the spine and back needed more consultations than the other three groups (Table p = 0.11), but female patients required significantly more  consultations (p < 0.01) than male patients (7.6 consultations).The number of treatment sessions utilized by patients in the first year varied between one and 40, the average number being 9.16 SD: 5.69), and the median number 8.0. There was a statistically confirmed difference in the number of treatments between diagnostic groups .Treatment success from the patients’ perspective is shown in Table p value Fisher test = 0.28). Due to the small number of patients, interference field therapy alone was not included in the statistical calculations (Table 157 patients (56 %) underwent local/segmental therapy, 5 patients (2 %) received interference field therapy, and 118 patients (42 %) a combined  treatment  pain medication consumption was unchanged, and 143 patients (74.1 %) used less or no more pain medication at all after the period under study.No adverse effects or complications occurred except minor, spontaneously resolving hematoma and mild dizziness lasting up to 15 min following treatment, which in patients with normal blood pressure was assessed as the known systemic procaine effect and simultaneous, mild vasovagal reaction. There was no case where an adverse effect would have required drug treatment or any other intervention.Nociceptive processes cause a reflex response evoked by cutivisceral, viscero-cutaneous, viscero-somatic motor, etc. reflex pathways. This reflex response, which is largely mediated by sympathetic nerves, involves changes in blood flow, increased skin turgor, hyperalgesia in localized areas of skin, dysregulation of the organ at the corresponding metameric level, as well as increased muscle tone –20. NociAnalogous to mathematical chaos theory these connections create a vicious circle  of pain . This viThe sympathetic nervous system can induce a neurogenic inflammation via vasodilation and plasma extravasation and the release of pro-inflammatory neuropeptides from its own nerve fibers –31. ThisTracey  describeAs early as 1924 Ricker  was ableUsing local anesthetics (NT) these different levels can be accessed directly and logically: by applying an impulse (needle prick) and by disrupting a vicious circle . Repeated application can lead to the “extinction” of the engrammatically stored pathological irritability of the sympathetic nervous system and to the restoration of normal tissue perfusion , 20, 34.Moreover, Cassuto  was ableIn addition, needle prick and local anesthetic can produce a favorable effect on the control of synaptic input to the neurons in the dorsal horn of the spinal cord .Reflecting the real-life setting of our University NT practice, our case series included the most difficult category of patients with chronic pain, i.e. chronic pain unresponsive to all evidence-based, conventional medical measures and various complementary treatments over a long period, who had been referred explicitly to NT. For these reasons randomization of a part of these patients in a control group without NT was not possible. Upon closer consideration, the fact that all previous therapies had failed can serve as a kind of comparison  between conventional (incl. complementary) medical treatments and NT, but cannot, of course, replace a real control group. However, there is a probability of a spontaneous effect of pain regression to the mean because the pain level of our patients was severe. Therefore, it would be expected that some patients by chance would find their pain reduced over the study period. Without a control group it is therefore difficult to assess what amount of pain reduction is due to the treatment and what amount due to the potential regression to the mean. Nevertheless, it is fair to say that the mean duration of pain illness without regression before NT was more than five years. After this long period, a significant improvement without therapy seems improbable.Despite the severity of the pain disorder and the long duration of illness prior to NT, patients only needed an average of 9.2 consultations within a period of one year.In the long term only one fifth of our patients remained resistant to NT . Another fifth experienced a slight improvement, and three fifths a marked improvement of pain or even freedom of pain. These results are supported by a Health Technology Assessment report  and otheCombined injections of local anesthetics (NT) primarily affect the efferent and afferent fibers of the peripheral spinal reflex arc, largely via the sympathetic nervous system involved in the pain processes. Due to the connection of the central reflex arcs in the brain stem and in the cortex with neurons within the spinal cord it seems likely that they are indirectly affected by NT. On the other hand, these central reflex arcs are also subject to other influences, such as emotions , especially in the presence of the respective neuroplastic changes. For this very reason we cannot determine the exact size of the specific effect of NT with our present results. However, the majority of our patients had received interventions within a similar doctor-patient setting  prior to their enrollment in this case series, and still had been unresponsive to treatment. This is why we suppose that a part of the effect of NT may be specific.The second outcome measure was the consumption of pain-relieving drugs: out of the 193 patients under pain medication three quarters took less pain medication or none at all after one year. These findings are noteworthy for their cost-effectiveness implications. In our cross-sectional studies , 43 commAlthough the present case series was conducted under circumstances similar to those found in daily practice and its results can be transferred into the clinical and practice setting, there are still limitations. As it was – in this real-life setting with patients referred explicitly to NT – not possible to opt for a controlled study design, the exact size of the specific effect of NT cannot be determined in this case series. Although the chance of a significant spontaneous improvement without therapy in our patients with refractory chronic pain over a long period was little, this possibility cannot be ignored. Being designed as a case series and not a multicenter trial makes it difficult to generalize the findings. Moreover, general quality of life and activities of daily living as well as secondary diagnosis were recorded in the course of history taking, but not included in the analysis of data.Chronic pain, especially back pain, is extremely common. Treatment-resistant pain syndromes or adverse effects of medical treatment demand other treatment options. Both the present results for the outcome measures pain and medication use are in line with the results of other studies and demonstrate that therapeutic local anesthesia (NT) is a good treatment option. This is also reflected in the fact that many of the referring physicians were pain specialists or specialists in musculoskeletal disorders, and that every eighth referral was made by university hospitals or their outpatient departments. The good long-term outcomes achieved in just a few visits – such as medication reduction and virtually no side effects – are interesting from an economic perspective as well. As discussed above and mentioned under limitations, we cannot determine the exact size of the specific effect of NT in this uncontrolled case series. It would be, therefore, worthwhile to carry out a controlled trial to evaluate the true effect of NT.Nevertheless, the results of our study can be logically explained by mechanisms of action that are based on modern neurophysiological concepts of pain. In addition, the fact that in most patients the effect persisted much longer than was to be expected from the duration of action of the local anesthetic also supports our initial hypothesis that the injection of local anesthetics at suitable sites can disrupt the vicious circle of pain (multiple reflex arcs maintaining each other through positive feedback) and thus initiate a reorganization (self-organization) of the pain-processing systems. The results of further research into the mechanisms of action on the one hand and the outcome of future randomized controlled trials on the other will be eagerly awaited.


Temporomandibular joint dysfunction are often accompanied by symptoms of headache such as tension-type headache which is the most frequent spontaneous primary headache. Masseter muscle pain is commonly reported in this group. The purpose of the study was to assess the efficiency of intramuscular botulinum toxin type A injections for treating masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache.p ≤ 0,005).This prospective outcome study consisted of 42 subjects of both genders aged 19–48 years diagnosed with masseter muscle pain related to temporomandibular joint dysfunction and tension-type headache. The subjects were treated by the intramuscular injection of 21 U (mice units) of botulinum toxin type A  in the area of the greatest cross-section surface of both masseter bellies. Pain intensity was evaluated using visual analogue scale (VAS) and verbal numerical rating scale (VNRS) 1 week before the treatment and 24 weeks after the treatment. The obtained data were analyzed using the Wilcoxon matched pairs test .The results of this study showed a decrease in the number of referred pain episodes including a decrease in pain in the temporal region bilaterally, a reduction of analgesic drugs intake as well as a decrease in reported values of VAS and VNRS after injections (The intramuscular botulinum toxin type A injections have been an efficient method of treatment for masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache. Symptoms characteristic for temporomandibular joint dysfunction (TMJD) such as masticatory muscles pain, temporomandibular joint pain, derangements of the condyle-disc complex and deviations of mandible movements are often accompanied by symptoms that are not directly related to the functioning of the temporomandibular joint –8. Such Diagnostics of TTHs is based on the data collected in a screening history consisted short questions which let to analyze the background of the pain and the factors responsible for pain origin. Specialized neuroimaging modalities  are used less frequently. The results of additional tests provide to exclude other causes of the TTH, especially migraine headache, aseptic meningitis, neuroborreliosis or pseudotumor cerebri , 17–18. Bilateral, constant, dull ache of mild to moderate intensity without preexisting aura, vomiting, nausea is characteristic of TTH. Although TTH are not as widely recognized as migraine headaches, they constitute an important and frequent clinical problem, as they exert negative impact on the patients’ quality of life. Tension-type headache is affecting the temporal and occipital region. The patient may also report the feeling of squeezing within the head. In the beginning the headache is not intensive. Later it could intensify and gain the same level of pain as the migraine headache. Moreover, the frequency at which TTH occurs is important for diagnosis: it lasts at least 30 min daily, occurs on 15 days in a month, affects the patient for more than 3 months, and is detected in all age groups, but it affects middle-aged people most frequently. TTH are frequently accompanied by sleep disorders, chronic fatigue syndrome, noise hypersensitivity and appetite loss , 15, 22.The aim of this prospective outcome study was to assess the efficiency of intramuscular botulinum toxin type A (BTXA) injections in a case of masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache.This is a prospective outcome study which consisted of 42 subjects of both genders, aged 19–48 years (mean age was 30) with masseter muscle pain related to temporomandibular joint dysfunction and tension-type headache. Patients were recruited from the Department of Dental Prosthetics at the Jagiellonian University in Krakow during the years 2009–2014 and were included in the study if they met the following criteria: (1) presence of TMJD which include unilateral or bilateral disc displacement with or without reduction, arthralgia, degenerative joint disease, subluxation, (2) masseter muscle pain, (3) increased masticatory muscles tension, (4) TTH, (5) absence of previous neurological treatment due to headache and a head injury within 6 years and (6) patient consent to be involved in the study. The rest of patients were excluded because of general  and/or local (infection at the proposed site of injection) contraindications for intramuscular botulinum toxin type A injections as well as absence of consent to be involved in the study.Clinical assessment of temporomandibular joints and masticatory muscles was performed by one experienced and self-trained examiner according to the RDC/TMD recommendations , 28. FurThe data collected during the survey have been important for the purpose of the study: localization of the headache, pain duration, and factors responsible for pain origin. The patients were also asked whether the pain was constant, episodic, recurrent, referred, and whether it was felt as dull, sharp, burning or stinging. It was important whether the patient reported that the pain was squeezing the head as well as previous treatment due to the headache. Authors paid close attention to symptoms that accompanied pain, such as: sleep disorders, chronic fatigue, noise hypersensitivity, and pain referral within the face or other areas of the head. An important aspect was the necessity for analgesic drug administration.After patient enrollment the treatment of masseter muscle pain consisted of intramuscular injection of 21 U (mice units) of type A botulinum toxin , in the area of the greatest cross-section surface of both masseter bellies.Clinical algesimetry, e.g. the evaluation of pain intensity with the use of various scales is not devoid of subjective influence. However, it is the currently indicated method of measuring pain intensity at following appointments. For the purpose of the study two scales were applied by the authors: VAS  and VNRS . VAS is a psychometric response scale which can be used in questionnaires . It is ap ≤ 0,005. The software used in the statistical analysis was STATISTICA version 8 .The results were analyzed using the Wilcoxon matched pairs test, with statistical significance at The most frequently reported complaints included: spontaneous masseter muscle pain and/or temporomandibular joint pain, clicking in the temporomandibular joint during mandible movements, impaired mastication and tension-type headaches in the anterior temporal region, medial temporal region and/or occipital region. The pain was dull, squeezing, or crushing, rarely encircling the head, and it lasted for minimum four hours daily and had been present for at least 4 months. It was unpleasant for the patients but it did not interfere with their everyday quality of life. Medication- and injury-induced migraine headache was excluded.p = 0,00000).Table p = 0,000. The comparison of the examination I and II data have shown a positive changes in tension–type headache intensity. The differences mostly included: a decrease in the number of subjects with bilateral pain in the temporal region and lower number of referred pain episodes, as well as a reduction in the amount of analgesic drugs intake.It is important that mean value of headache intensity during examination I was 4,86 points , while the result of examination II was only 1,21 . The difference between them was statistically significant because Independently from the results of various studies, the relationship between tension-type headaches and temporomandibular joint dysfunction can be confirmed by the decrease in headache intensity observed after the management of temporomandibular joint dysfunction. It is apparent particularly in cases in which no significant improvement in the patient’s well-being is observed after conventional neurological treatment or in which a quick recurrence of the symptoms occurs if temporomandibular joint dysfunction treatment is not initiated , 13, 17.The aim of the population-based cross-sectional study conducted by Goncalves et al. was to determine the coexistence of TTH and TMJD in adult patients . The resThe decrease in reported the headache following pharmacotherapy of temporomandibular joint dysfunction suggests that tension-type headaches are in many cases related to excessive and long-lasting tension within the muscles of the temporomandibular joint, which remains closely interrelated within the head and neck. After the injections, the character of tension-type headache changed and its intensity decreased. Moreover, a decrease in the daily number of hours and monthly number of days during which tension-type headache affected the patient, was observed , 37–40.Numerous authors in contemporary literature underline the role played by stress in the development of TTH. At the same time, for several years authors of various studies concerning etiological factors of TMJD have been underlining that stress is an increasingly important etiological factor in its development . Also, tJackson et al. have shown in the meta-analysis concerning the use of BTXA in the prophylaxis of migraine and tension-type headaches that the discussed drug had a positive effect in both disorders . AccordiThe results of in vivo and in vitro research performed by Ashkenazi and Blumenfeld have shown that botulinum toxin type A is effective in reducing tension-type headache intensity . The stuTaking into account a positive results of the BTXA injections applied in the study, it should be noted that the dose of 21 U and used operative technique are sufficient to decrease the masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache. However we don’t know what happens after 6 months observations. We can assume that with the passage of time the effect of the neurotoxin goes away and the patient will begin to feel the pain again. We are able to repeat whole procedure in a case of recurrence. We have to know that current studies proofed that BTXA injections cause mandible bone loss and uncontrolled structural changes in affected and unaffected muscles , 50. TheThe intramuscular botulinum toxin type A injections have been an efficient method of treatment in a case of masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache. The authors recommend this therapy as a method of choice in a masseter muscle pain management.


Background. Patients with rheumatoid arthritis may experience increased negative outcomes if they exhibit specific patterns of dispositional affect. Objective. To identify subgroups of patients with rheumatoid arthritis based on dispositional affect. The secondary objective was to compare mood, pain catastrophizing, fear of pain, disability, and quality of life between subgroups. Methods. Outpatients from a rheumatology clinic were categorized into subgroups by a cluster analysis based on dispositional affect. Differences in outcomes were compared between clusters through multivariate analysis of covariance. Results. 227 patients were divided into two subgroups. Cluster 1 (n = 85) included patients reporting significantly higher scores on all dispositional variables  compared to patients in Cluster 2 (n = 142). Patients in Cluster 1 also reported significantly greater mood impairment, pain anxiety sensitivity, and pain catastrophizing . Clusters did not differ on quality of life or disability. Conclusions. The present study identifies a subgroup of rheumatoid arthritis patients who score significantly higher on dispositional affect and report increased mood impairment, pain anxiety sensitivity, and pain catastrophizing. Considering dispositional affect within subgroups of patients with RA may help health professionals tailor interventions for the specific stressors that these patients experience. Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint swelling and tenderness at multiple sites in the body. These symptoms have a disabling effect on an individuals' mental and physical health . An inteIndividuals with RA experience significant levels of chronic pain that negatively impacts multiple quality of life domains . The relHowever, aspects of personality are also increasingly being viewed as important by pain researchers, clinicians, and patients with chronic pain. Newth and Delongis (2004) found that personality was a strong moderator of coping after chronic pain in RA individuals . SpecifiThese dispositional variables have also been discussed in a qualitative study that included eight overactive chronic pain patients . All patThe present study represents a preliminary step in identifying subgroups among persons with RA based on dispositional affect. The aims of the study were to use a cluster analysis to identify homogenous pain behavior subgroups among persons with RA through a number of dispositional personality variables that have been previously linked to maladaptive coping styles . The secParticipants included patients with RA diagnosed by a rheumatologist (using the American College of Rheumatology Criteria) that scheduled a regular outpatient clinic appointment and were recruited over a 20-month period from an academic rheumatology clinic in London, Ontario . Patients at least 18 years who had a diagnosis of RA and self-reported pain secondary to RA for greater than three months were eligible for inclusion. Given that this study involved the completion of questionnaire booklets, exclusion criteria included the inability to read and write in English. Ethics was reviewed and approved by the Office of Research Ethics at the University of Western Ontario in London, Ontario, Canada. All eligible participants signed informed consent prior to completing any questionnaires for the study.Patients who met the inclusion criteria and agreed to participate were referred to the research coordinator by their primary physician. The research coordinator provided potential participants with the letter of information and consent form. Patients were made aware that their decision to participate in the study would in no way interfere with their standard care at the hospital. All patients received individualized pharmacotherapy and psychotherapy or referrals as seen fit by the multidisciplinary team. Eligible participants were mailed a package introducing the study two weeks prior to their scheduled clinic appointment with their rheumatologist. The package contained the study information letter, a consent form, and the first of two questionnaire booklets. Research assistants followed up with phone calls to all eligible patients to explain the procedures of the study, answer any study related questions, and confirm that the patient was still experiencing pain secondary to RA. Consenting participants completed the first booklet of questionnaires regarding demographics , time since RA diagnosis, and average pain intensity prior to their clinic appointment. Participants were asked to arrive half an hour early to their clinic appointment to provide research assistants with their first questionnaire booklet and complete the second booklet questionnaires that included measures of dispositional affect, pain catastrophizing, fear of pain, quality of life, and disability. One researcher independently entered questionnaire responses into a SPSS database which was then validated by a second researcher.Demographic variables including age, sex, years of education, marital status, and years since RA diagnosis were assessed with single straightforward patient-report items.Pain ratings for current, least, average, and worst pain were summed to yield an aggregate pain intensity score.The AAQ  is a 9-iThe ASI  is a 16-The FMPS  containsThe PSWQ is a 16-item measure of the frequency and intensity of worry that yields a single score . The PSWThe RRAQ is a nine-item factor analytically derived measure of fear of relaxation . ParticiThe DASS-SF  is a 21-This questionnaire is an assessment for patients with RA where patients report the amount of difficulty they have performing specific activities . Each question is scored from 0 to 3 based on whether the patient has no difficulty with the activity (0) or the activity cannot be done at all (3). The construct, convergent, and predictive validity and sensitivity to change have also been established in numerous observational studies and clinical trials . The HAQThe PASS-20 is designed to measure fear of pain. This measure includes 4 subscales: avoidance, cognitive anxiety, fearful thinking, and physiological anxiety. PASS-20 has demonstrated good psychometric properties and is highly correlated with its longer version .The PCS contains 13 items assessing the tendency to misinterpret and exaggerate the threat value of pain sensations. It has good psychometric properties and includes 3 main factors: rumination, magnification, and helplessness .The SF-36 is a 36-item self-report measure that assesses eight domains of health related quality of life. These domains include the following: (1) limitations in physical functioning; (2) social limitations due to emotional or physical troubles; (3) role limitations due to physical health problems; (4) role limitations due to emotional health problems; (5) general mental health; (6) bodily pain; (7) vitality; (8) general health perceptions . The SF-t-tests and χ2 tests for categorical variables in order to characterize differences between the resulting clusters. A multivariate analysis of covariance (MANCOVA) was conducted on outcome measures including mood (DASS-SF), pain catastrophizing (PCS), fear of pain (PASS), quality of life (SF-36), and disability (HAQ-DI) according to cluster membership. Any significant difference on demographic characteristics between clusters was entered as covariates in the MANCOVA. Pairwise comparisons were conducted with Bonferroni adjustment. SPSS version 23.0  was used for all tests performed, with the significance level set at alpha 0.05 and all tests were two-tailed.A two-step cluster analysis was performed using SPSS 23 to identify and classify observations into two or more mutually exclusive groups, where members of the groups share properties in common. Five dispositional trait-like variables were used to cluster the observations: experiential avoidance, fear of relaxation, anxiety sensitivity, perfectionism, and worrying based on the AAQ, RRAQ, ASI, FMPS, and PSWQ measures, respectively. The log-likelihood distance measure was used to compute likelihood distance between clusters with subjects assigned to the cluster leading to the largest likelihood. No restrictions were set for the number of clusters and the Bayesian information criterion was used to judge adequacy of the final solution. Differences in sample demographic characteristics were compared according to cluster membership using independent samples A total of 300 individuals with RA were eligible for inclusion, of which 227 agreed to participate in the study and completed the questionnaires . The mean = 85) was characterized by a dispositional affect comprised of patients scoring significantly higher on experiential avoidance (EA), fear of relaxation (RRAQ), anxiety sensitivity (ASI), perfectionism (FMPS), and worrying (PSWQ) as compared to Cluster 2 (n = 142). Demographic characteristics were compared between the two clusters, where it was found that patients in Cluster 1 had been diagnosed with RA for a significantly greater number of years than patients in Cluster 2 (p = 0.006). The remaining demographic variables: age, sex, education, relationship status, and average pain intensity were comparable between the two clusters . The two clusters significantly differed from each other on all clustering variables see . Clusterclusters .The two clusters were compared through a MANCOVA while controlling for mean time since RA diagnosis with Bonferroni correction. Pairwise comparisons revealed significant differences between Cluster 1 and Cluster 2 for all mood (DASS-SF), catastrophizing (PCS), and pain anxiety sensitivity (PASS) subscales. Cluster 1 reported significantly higher scores on these measures of distress and cognitive aspects related to pain. There were no significant differences between the clusters for quality of life or disability see .The present study aimed to determine if patients with RA could be differentiated based on dispositional affect. Our second aim was to determine if mood, pain catastrophizing, fear of pain, disability, and quality of life varied as a function of these patient groupings. Participants were divided into two meaningful clusters that represented one group (Cluster 1) composed of patients who reported significantly higher scores on all dispositional variables measured, including experiential avoidance, fear of relaxation, anxiety sensitivity, perfectionism, and worrying, while the second cluster of patients (Cluster 2) included those who scored significantly lower on each of these personality measures. Results also confirmed that mood, pain catastrophizing, and fear of pain measures systematically varied based on patient reports of dispositional variables studied, with those in Cluster 1 demonstrating significantly worse scores on mood, pain catastrophizing, and fear of pain compared to Cluster 2, while controlling for differences in demographic variables between clusters. There were no significant differences found between clusters on disability or quality of life measures.n = 85) than the cluster of patients who reported levels of these factors (n = 142) closer in line to normative means and community samples [Our findings revealed that the subset of patients with RA in our sample who reported higher scores on a number of dispositional variables experienced worse mood including increased depressive, anxiety, and stress symptoms, as well as increased cognitions of pain catastrophizing and fear of pain, as shown through higher scores on each pain catastrophizing and pain anxiety symptom subscale. Our results suggest that patients with RA who present with increased endorsement for the cluster of dispositional variables measured within our study may represent a group of patients who experience increased distress, pain catastrophizing, and fear of pain when living with their chronic health condition. Notably, the subset of patients reporting increased endorsement for dispositional affect encompassed fewer patients  may be impacted by a number of dispositional variables within patients with RA. Considering subgroups of patients with RA characterized by dispositional affect had not been previously studied, yet specific personality factors have been associated with psychopathology and difficulties coping in other patient samples , 47, 48.Specific limitations should be considered when interpreting the findings from this study. First, there are inherent limitations when using a cross-sectional design which inhibit causal relationships to be determined. Second, the personality factors considered were based on a number of different outcome measures rather than one specific personality measure such as the NEO Five-Factor Inventory and thus did not encompass all relevant variables that have been previously studied and linked to mood, with chronic pain. Nonetheless, the dispositional affect measures administered allowed for the analysis of a potentially challenging combination of variables. Further, an important limitation to consider when interpreting our findings is a lack of objective measure of inflammation and thus the inability for inflammation differences between patients to be adjusted for within analyses. Additionally, though the chronicity of pain was controlled for in the MANCOVA, the study demonstrated a significant difference between the two clusters in chronicity of pain. Hence, it may be that the groups differed from each other not only on the dispositional factors but also on this demographic factor. Finally, sample selection bias cannot be ruled out as our sample was recruited from a single site tertiary RA clinic which may compromise the generalizability of our findings.In conclusion, the present study identified subgroups of patients with RA based on a number of dispositional variables. The cluster characterized by significantly greater reports of dispositional affect were comprised of RA patients who experienced significantly more depression, anxiety, and stress symptoms in addition to heightened pain anxiety/fear of pain and pain catastrophizing. Ensuring that patients have access to qualified providers of appropriate multimodal treatment may be beneficial for patients with RA experiencing specific difficulties associated with their pain or adjustment including distress, pain catastrophizing, and fear of pain. Clinicians should consider that patients with specific dispositional affect may benefit from referrals for additional social support and programs that target the range of factors included in our study, beginning when they are diagnosed with RA to promote positive adjustment. Future research replicating our findings within RA patients and other samples of chronic pain patients should be carried out so that management programs can be developed to address specific needs of patients such as improving moods and decreasing ruminative styles such as pain catastrophizing and fear of pain.


The present study tested the hypothesis that recall of receiving physical activity (PA) advice would be associated with higher levels of PA in patients with a diagnosis of colorectal cancer (CRC).Colorectal cancer patients who were diagnosed in 2010 or 2011, and had been treated in the English National Health Service (NHS).>65 years and 96% were from a white ethnic group.17 753 respondents completed at least one section of the survey relevant to the current study and after exclusion of 171 with dementia , 15 254 had complete data for the current study. 60% were male, 67% were Patients completed the ‘Living with and Beyond Colorectal Cancer’ Patient-Reported Outcome Measures (PROMS) survey in 2013. The survey included questions on receiving exercise advice/information (‘PA advice’), and the frequency of currently doing at least 30 min of brisk PA per day .A third of respondents (31%) recalled receiving PA advice. Independent of demographics and treatment, patients who recalled having PA advice were more likely to be currently doing some brisk PA , and more likely to be meeting PA guidelines .Recalling being given PA advice after a diagnosis of CRC was associated with higher levels of PA. However, less than a third of patients recalled receiving advice. Future research should examine the context in which advice is given and randomised trials are required. However, encouraging clinicians working with patients with CRC to give brief PA advice is warranted and may help improve outcomes for CRC survivors. This is the first very large population-based study to explore whether physical activity advice is given to colorectal cancer patients; proportions who recalled receiving advice were low.Physical activity advice during the cancer care pathway was associated with higher levels of physical activity.The findings of this study provide strong impetus to clinicians working with colorectal cancer to recommend physical activity, a practice which does not yet appear to be routine in the UK.This study is limited in relying on patient report of physical activity levels and recall of whether they were given advice. However, the Patient-Reported Outcome Measures data are designed to collect data on patient experience on a large scale.Data on the context of the advice were not available and this should be a focus of future research.There is now a solid body of evidence that a physically active lifestyle is associated with better long-term outcomes following a diagnosis of colorectal cancer (CRC).3CRC survivors typically have lower levels of PA than the general populationClinicians dealing with patients with cancer are in a good position to offer activity advice, and they are the patients’ preferred source of information.12Brief PA advice in primary care has been shown to increase PA in sedentary adults16The current study used data collected from a very large sample of patients with CRC to test the hypothesis that recalling being given PA advice would be related to higher levels of physical activity.Living with and Beyond Colorectal Cancer survey commissioned by the UK Department of Health in 2013, as part of a programme of work designed to ensure that the needs of patients with colorectal cancer in the UK are met across a range of health, psychosocial and lifestyle domains through the recording of patient-reported outcomes (PROMS).Data were from the Did you receive any advice or information on physical activity and exercise ?’ This was within a longer list of cancer-relevant domains of information, including physical and psychological aspects of living with cancer, finance, employment, family and support services.The questionnaire section ‘Overall Support and Care’ included the question ‘Current PA was assessed by asking: ‘In the past week how many days have you done 30 min or more of brisk physical activity ?’ Responses were categorised as ‘none’ (0 days), ‘some’ (1–4 days) or ‘meeting guidelines’ (5–7 days), broadly in line with the UK Government recommendations for the general population21How has your CRC responded to treatment?’ . Length of time since treatment was also reported. Long-term health conditions (LTCs) were assessed with ‘Do you have a long-standing health condition other than cancer?’ . As the focus of this analysis was on recall of receiving PA advice, patients reporting a diagnosis of dementia were excluded. The full survey is available at cancerproms.ncr.nhs.uk. In accordance with UCL Ethics Committee guidance, additional ethical approval was not required for secondary analyses of anonymous health surveillance survey data.There were a variety of treatment questions, but for these analyses we included: ‘>1 year’, or ‘unknown’. Presence of an LTC was recorded as ‘yes’, ‘no’, or ‘unknown’.Where >75% of respondents fell into a single response category, predictor variables were dichotomised for analyses. However, full descriptive data, including the proportion of missing values, are presented in the results. Ethnic groups were categorised as ‘white’ versus ‘all other’. Since health and treatment variables were secondary to the main research question, missing data were recoded as ‘unknown’ for analyses to include as many respondents as possible. Response to treatment was categorised as ‘in remission’ versus ‘all other’. Time since treatment was coded as ‘Still having treatment’, ‘<1 year’ post-treatment, ‘Descriptive statistics and percentages in each category were calculated. Two types of logistic regression were carried out. First, to assess factors associated with whether PA advice was given, a binary logistic regression with ‘advice’ or ‘no advice’ as the outcome was carried out. Second, to assess whether advice related to activity levels, a multinomial logistic regression model with PA level (none/some/meeting activity guidelines) as the outcome was carried out. In each case, simple associations and then models adjusted for potential confounders were presented. Analyses were carried out in SPSS V.18. Given the large sample size, significance was set at p<0.01.et al.Of the 34 467 questionnaires mailed out by NCRS, 21 802 (63.3%) were returned at least partially completed and further information on this sample are provided in a recent paper by Downing 67% were >65 years old, 60% were male, and 96% identified themselves as ‘white’. Most patients reported that their cancer had fully responded to treatment and they were in remission (79%), with smaller numbers reporting that the cancer was still present (5%), had not been treated (1%), had come back after initial treatment (3%) or that they were not certain (9%); however, 4% did not respond to this question. The majority (>80%) of patients were at least 1 year since treatment. Forty-seven per cent reported a long-standing health condition other than cancer, 3% ‘couldn't say’ and 11% did not respond. Forty-five per cent of patients reported doing at least some brisk activity and 22% met the guidelines for PA, but 33% reported doing none.>85-year-olds . Patients from higher SES groups were more likely to recall advice than those from lower SES groups , but there was no significant association with ethnicity. Patients in remission were more likely to recall being given PA advice , and in the fully adjusted model, patients with a LTC were statistically more likely to recall advice, but the magnitude of this difference was extremely small  and unlikely to be clinically meaningful. Time since treatment was not associated with advice in the adjusted model.Overall, 31% of respondents recalled having received any PA advice. The proportion receiving PA advice by demographics, treatment and LTCs is shown in Consistent with our hypothesis, recalling being given PA advice was associated with higher levels of current activity. Fifty-one per cent of patients who had been given advice were doing at least some activity, with 25% meeting the guidelines, compared with 42% and 20%, respectively, in the ‘no advice’ group see . CompareThere were associations between demographic variables and activity levels  of our large sample of CRC survivors recalled having received PA advice. Women, older patients and those from lower SES backgrounds were less likely to recall having been given advice. Older patients were also less likely to have received advice in a Canadian survey, which the authors speculated could be due to them being less likely to initiate discussions about PA,Giving PA advice may not always be easy for healthcare professionals. A recent qualitative study with cancer specialists identified lack of appropriate support as a barrier to discussing lifestyle with patients with cancer.This study had limitations. Data were self-reported using single item measures, so PA may have been under-estimated or over-estimated. Additionally, no information was gathered on who gave the advice and when in the care pathway. This study was based on secondary analyses of existing large-scale PROMS data and provides an important ‘first step’. Future large-scale surveys in cancer survivors should use validated measures of PA and collect detailed information on the context of the delivery of the PA advice. Information on receiving PA advice depended on patient recall and therefore, could also be under-estimated or over-estimated. Consistency with findings from other studies, both from the patient and the health professional perspective, is reassuring.16The possibility that those recalling PA advice were already more aware of the importance of PA or had higher pretreatment levels cannot be ruled out, and longitudinal studies are warranted. However, this could also suggest the need for research on how to make important messages about PA more salient to those who are less active and less engaged. One RCT in the field suggested that clinician's brief exercise advice increased subsequent activity levels of breast cancer survivors25Recalling being given PA advice after a diagnosis of CRC was associated with higher levels of PA. However, less than a third of patients recalled receiving advice. Future research should examine the context in which advice is given. However, encouraging clinicians working with CRC patients to give brief PA advice is warranted and may help improve outcomes for CRC survivors.


The aim of this study was to compare in patients presenting with acute chest pain the clinical outcomes and cost-effectiveness of an accelerated diagnostic protocol utilizing contemporary technology in a chest pain unit versus routine care in an internal medicine department.Hospital and 90-day course were prospectively studied in 585 consecutive low-moderate risk acute chest pain patients, of whom 304 were investigated in a designated chest pain center using a pre-specified accelerated diagnostic protocol, while 281 underwent routine care in an internal medicine ward. Hospitalization was longer in the routine care compared with the accelerated diagnostic protocol group (p<0.001). During hospitalization, 298 accelerated diagnostic protocol patients (98%) vs. 57 (20%) routine care patients underwent non-invasive testing, (p<0.001). Throughout the 90-day follow-up, diagnostic imaging testing was performed in 125 (44%) and 26 (9%) patients in the routine care and accelerated diagnostic protocol patients, respectively (p<0.001). Ultimately, most patients in both groups had non-invasive imaging testing. Accelerated diagnostic protocol patients compared with those receiving routine care was associated with a lower incidence of readmissions for chest pain , and acute coronary syndromes , during the follow-up period. The accelerated diagnostic protocol remained a predictor of lower acute coronary syndromes and readmissions after propensity score analysis [OR = 0.28 (CI 95% 0.14–0.59)]. Cost per patient was similar in both groups .An accelerated diagnostic protocol is clinically superior and as cost effective as routine in acute chest pain patients, and may save time and resources. Chest pain is one of the most common causes of emergency medicine department presentation, accounting for 5–6% of emergency medicine department visits in the United States , 2. The In this comparative prospective study we compared patients with chest pain who were admitted to the Sheba Medical Center (April 2010–August 2011) either to the chest pain center or to one of the internal medicine departments. The Sheba Medical Center is a 1,800 bed tertiary medical center with approximately 192,000 emergency department visits per year, and more than 94,000 admissions annually.Inclusion criteria included: 1) age ≥18 years; 2) chest pain considered by the attending physician to be suggestive of cardiac origin or requiring admission in order to rule out ACS; 3) absence of baseline electrocardiogram (ECG) changes suggesting acute ischemia or infarction ; 4) absence of elevated cardiac troponin T or I during evaluation in the emergency department; 5) chest x-rays without new pathological findings.Exclusion criteria included: 1) any reason for chest pain other than ACS that was diagnosed in the emergency department, such as pneumonia, pulmonary embolism, pericarditis or chest trauma; 2) factors such as fever, sepsis, severe anaemia, hyperthyroidism that could exacerbate chronic coronary artery disease; 3) heart failure on admission; 4) unstable angina pectoris, non ST-elevation myocardial infarction or ST-elevation myocardial infarction on admission; 5) any other condition requiring intravenous medication or chronic nursing care; 6) pregnancy.Patients were interviewed during their admission course and additional information was collected from patient charts. Three months after discharge, each patient was interviewed by phone. Patients who were found to be eligible and who agreed to participate in the study signed a consent form.The center has 8 beds situated in an observation area adjacent to the emergency department. Patients were monitored and observed for a minimum of 8 hours, following which a repeat ECG was performed and cardiac troponin was re-assessed. Each patient was monitored continuously by an ST-segment analyzer. Patients were then referred within the first 24 hours of their admission either to 64-slice multi-detector computed tomography, stress test (exercise ECG), myocardial perfusion study (MPS) with single photon emission computed tomography (SPECT), or stress echocardiography. Discharged patients were followed-up either by a visit to the cardiac outpatient clinic or by a phone call.Patients who were suitable candidates for admittance to the chest pain center, but who were eventually admitted to an internal medicine department according to the discretion of the emergency department’s physician. Treatment in the internal medicine department was determined by local internal medicine department protocol for chest pain, at the discretion of the treating physician.Data were collected from patient interviews and from their charts, and were followed-up by a phone interview 90 days after discharge.Independent variables collected included patient history: age, gender, smoking, weight, body mass index; chronic illness ; previous percutaneous coronary intervention; previous coronary artery bypass graft.Admission variables included: ECG changes; troponin I, T elevation; percutaneous coronary intervention; coronary artery bypass graft; diagnoses at discharge; recommendations at discharge.Diagnostic imaging testing during the hospital course included: coronary multi-detector computed tomography; MPS; stress echocardiography.Dependent variables collected included cardiovascular diagnoses from the chest pain center and internal medicine department and the follow up variables: performing cardiac imaging, coronary revascularization;, readmissions due to recurrent chest pain ACS; death, cardiopulmonary resuscitation; admission and procedure costs, which were calculated using the Israeli Ministry of Health cost list for ambulatory services and admission services 2010 .Since this was an observational study without random assignment following univariant analysis, inequality was observed in the number of independent variables which could have influenced the outcome variable. Therefore, additional analysis was performed to create a propensity score by using logistic regression. A model of 20 background variables and interactions was designed to calculate predicted probability for all observations to be in the exposure group, i.e. the chest pain center patients. A new continuous variable (0–1) was divided into five strata: from stratum 1 representing low probability to stratum 5 representing high probability of being in the exposure group.Logistic regression was performed to examine differences between the groups in major adverse cardiac events adjusting for propensity score, and results are presented as odds ratio (OR) and confidence interval (CI) of 95%. In addition, Poisson regression was performed to examine differences between the groups for counting outcomes as readmissions and visits to a cardiologist adjusting for propensity score; results are presented as risk ratio (RR) and CI of 95%.The study was approved by the Sheba Medical Center Institutional Review Board and was supported by the Israel National Institute for Health Policy Research.A total of 585 patients were prospectively enrolled (95% response rate). Of them, 304 (52%) were evaluated by ADP in the chest pain center and 281 (48%) were admitted to the internal medicine department and received routine care . Of the Hospitalization stay was longer in the routine care compared with the ADP group . Nevertheless, the rate of diagnostic imaging testing was significantly higher in the ADP compared with the routine care group . Accordingly, definitive diagnostic workup for rolling out ACS and significant coronary artery disease (CAD) was achieved in significantly higher rates in the ADP group compare with the routine care group . In contrast, the number of blood laboratory tests was significantly higher in the routine care group as shown in While in the routine care 244 (87%) patients were discharged with chest pain as the primary diagnosis; 14 (5%) with ACS; 8 (3%) with CAD and 15 (5%) with other diagnoses. In the ADP group, 281 (92%) patients were discharged with non-cardiac chest pain as the primary diagnosis; 9 (3%) with ACS; 9 (3%) with CAD and 5 (2%) with other diagnoses. During the hospital course there were 5 cases of non ST-elevation myocardial infarction in the routine care and none in the ADP patient group (p = 0.025). The discharge recommendations for further ambulatory imaging testing for ruling out significant CAD, were significantly more prevalent in the routine care group ,During the 90-day post hospital discharge period, the routine care group of patients were more like to undergo diagnostic imaging tests compared with the ADP patients  . UltimatReadmissions due to recurrent chest pain during the follow-up period were three times higher in the routine care compared with the ADP group . Similarly, routine care patients compared with the ADP group were more likely to sustain ACS  during the 3-month follow-up period  It is important to note that in all ACS events and the vast majority of post discharge readmissions for recurrent chest pain [22 out of 24 (92%)] in the routine care group, occurred among patients who did not undergo complete investigation during the initial hospitalization.ADP compared with the routine care was associated with a significant reduction in the ACS rate at 3 months [OR = 0.11 (CI 95% 0.02–0.49)]. This difference remained significant after propensity score analysis [OR = 0.13 (CI 95% 0.03–0.59)]. The ADP group was also associated with a reduction in readmissions due to chest pain within 90 days post discharge compared with the routine care patients [RR = 0.47 (CI 95% 0.31–0.71)], but this difference was only of borderline statistical significant after adjustment for propensity score [RR = 0.68 (CI 95% 0.44–1.07)].The in-hospital costs  were similar for the ADP compared with the routine care group , as were the post discharge 90-day follow-up costs  were higher for the routine care compared with the ADP group . Of substantial significance were the ambulatory diagnostic test costs which amounted to $42,877 for the routine care compared with only $8854 for the ADP group. After calculating the overall costs (admission costs plus 90-day follow-up costs), the total cost per patient was $2510 in the ADP compared with $2703 in the routine care group (p = 0.9).The goal of the present study was to compare the clinical outcome and cost effectiveness of hospitalized patients with chest pain receiving either ADP treatment in a specialized chest pain center or routine care in an internal medicine department in a real-life setting. Overall, the quality of treatment for patients who were evaluated by a pre-determined ADP protocol in a dedicated chest pain center was better with respect to hospitalization length, time from symptom onset to definite diagnosis and, lower readmissions due to chest pain during a 3-month follow-up period, compared with patients treated with routine care. Treatment costs were not higher in the ADP group compared with the patients receiving routine care.While only 20% of the routine care patients had noninvasive diagnostic imaging testing during the index hospitalization, 98% of ADP patients underwent noninvasive diagnostic imaging with a high rate of coronary multi-detector computed tomography. Accordingly, while 281 (92%) patients in the chest pain center were discharged with a definite diagnosis of non-cardiac chest pain, only 15 (5%) patients who received routine care were discharged with a diagnosis of non-cardiac chest pain. This represents the essence of the ADP approach with its main role of prompt diagnosis and treatment of patients with ACS, and early discharge of patients with non-coronary chest pain , 17.Recent studies have showed that the use of coronary multi-detector computed tomography and high sensitive biomarkers, which play a pivotal role in the ADP, facilitate accelerated investigation without compromising its accuracy. It facilitates rapid evaluation, requires minimal patient cooperation (short breath hold), is fast and has high diagnostic accuracy –13, 18. Finally, the ADP treatment costs were not higher than the routine care costs, even when cost analysis for loss of workdays for patients who had to complete their diagnostic tests in the community were not included, a fact which could cause routine care costs to be even higher , 30–31. The study was a single-center study; nevertheless, it was carried out in a large tertiary medical center.The study was not randomized and hence patient baseline characteristics were different. Accordingly the reason for increased rate of ACS in the routine care group of patients may be the higher risk characteristics of patients in this arm.Although the non randomized design of the study is an important limitation, we believe that our findings suggest that fast and definitive investigation of patients with acute chest pain according to pre-specified protocol provides better quality of care with shorten hospitalization length, time to definite diagnosis and, lower readmissions rate compared with patients treated with routine care and might even reduce healthcare expenses This approach can also contribute towards lowering the workload and burden in the internal medicine department. Yet, further larger randomized studies are needed to support these findings.


This article reviews the diagnoses and treatment of temporomandibular disorders (TMD) and outlines of the role of botulinum toxin (BoNT) in the treatment of myofacial TMD. This manuscript includes a brief history of the use of BoNT in the treatment of pain, the mechanism of action of BoNT, and the techniques for injections, adverse effects and contraindications when using BoNT to treat mayofacial pain caused by TMD. The temporomandibular joint (TMJ) is a hinged synovial joint that connects the mandible to the temporal bone at the skull base, and the posterior boarder of the TMJ is the anterior boarder of the external auditory canal. The TMJ is one of the few synovial joints with an articular disc and it functions as both a hinge joint and a sliding joint. It is therefore classified as a ginglymoarthrodial joint. Adduction of the mandible, or mouth closing, is performed by the actions of the masseter, temporalis, and medial pterygoid muscles. Abduction, or mouth opening, is performed by the lateral pterygoids and digastric musculature. The lateral deviation occurs by the action of the contralateral lateral pterygoid muscles, and protrusion of the mandible occurs when right and left lateral pterygoid muscles contract simultaneously.Temporomandibular disorder (TMD) is a nonspecific term used to describe orthopedic and myofascial disorders that affect the TMJ. The prevalence of TMD is between 30% and 44%, with up to 25% of the population seeking professional care for TMD . SymptomThe diagnosis of TMD is based on history and physical exam findings. Patients should be asked about nighttime bruxism, jaw soreness, morning headaches, use of mouth orthodonitics, or history of trauma. Questions regarding the patient’s personal habits and diet should be evaluated to reduce behaviors that may place additional stress on the TMJ, like frequent gum chewing. Symptoms of depression, anxiety or recent stressors should also be assessed as these conditions often lead to unconsciously clench.Signs and symptoms of TMD may include joint or muscular pain with or without jaw opening/closing, limited jaw movement, cracking or popping sounds at the TMJ with movement, or headaches. Patients often present with otalgia, ear fullness or tinnitus which is referred from the anterior external auditory canal, and is a shared boarder with the posterior TMJ . In addiImaging studies are rarely obtained at the initial visit, and are generally used only when there is dysfunction of the articular disc or other disorders that may complicate the diagnosis like rheumatoid arthritis, osteoarthritis or trauma . If imagIn 1992, The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) was established to standardize the clinical assessment of patients with TMD. RDC/TMD classifies TMD into two categories (Axis 1 and Axis 2). Axis 1 focuses on physical symptoms like myofascial pain, temporomandibular disc displacement, and joint disorders including arthralgias, arthritis, and arthrosis. Axis 2 focuses on quality of life and psychosocial factors like depression, pain related disability and behavioral adaptions . Today, Treatments for TMD range from nonpharmacologic therapy, conservative pharmicothearpy and open surgery. The initial management consists of nonpharmacologic management and typically includes avoiding triggers, adjusting diet, pain management, physical therapy and warm compress. Patients with bruxism should be referred to a dentist and can be evaluated for an occlusal splint. Systemic pharmacotherapy for TMD may be used as adjuctive therapy and includes anti-inflammatory agents, muscle relaxants, analgesics and in some cases tricyclic antidepressants ,10,11,12The first indication that BoNT could be useful for treating pain was observed from anecdotal reports of patients treated for hyperfunctional facial lines who reported reduced frequency and severity of headache . Soon thN-ethylmaleimide sensitive factor attachment protein receptor protein (SNARE). Type B botulinum toxin (BoNT-B) cleaves synaptobravin, which is part of the vesicular-associated membrane protein (VAMP). Cleavage of these docking proteins leads to muscle weakens by inhibition of acetylcholine (Ach) release at the neuromuscular junction. In addition to blocking the activity of muscles, BoNT has been known to inhibit the release for mediators from numerous secretory glands including salivary glands, sweat glands and nasal mucosa [BoNT is a 150-Kilodalton exotoxin produced from clostridium botulinum, whose action is mediated through the cleavage of docking proteins that are responsible for membrane fusion of pre-synaptic vesicles. Type A bolulinum toxin (BoNT-A) cleaves the membrane associated protein “synaptosomal-associated protein 25” (SNAP-25) which is a member of the “soluble l mucosa ,38,39,40Chronic local muscular contracture has been known to cause inflammation and localized muscular hypoxia leading to chronic myofascial pain . HoweverThe most commonly affected muscles are the temporalis muscle, masseter muscle and lateral pterigoid muscles. The temporalis muscle and masseter muscle are almost always involved and usually manifest as direct muscle pain. Lateral pterygoids involvement usually manifests as buccal pain, lateral jaw deviation or bruxism .Although Botox (onabotulinumtoxinA), Dysport (abobotulinumtoxinA), Xeomin (incobotulinumtoxinA) or Myobloc (rimabotulinumtoxinB) have been approved for use by the U.S. Food and Drug Administration (FDA) for various other conditions including bladder dysfunction, chronic migraine, upper limb spasticity, cervical dystonia, primary axillary hyperhidrosis, blepharospasm, strabismus, glabellar rhytides and lateral canthal rhytides, no product is currently approved by the FDA to treat TMD . FurtherWe performe injections under the guidance of electromyography (EMG) using a 27-gauge monopolar electrode injection needle. The temporalis and masseter muscles are injected transcutaneously . Asking We typically use a concentration of 2.5–5.0 units per 0.1 mL of Botox witha starting dose of 10–25 units for each temporalis muscle, 25–50 units to the masseter muscles and 7.5–10 units to the lateral pterygoids. Subsequent doses are individualized and are based on the patients’ response. Botox diffuses to about 1 cm at each injection site, and affected areas may be left untreated if an inadequate number of sites are infiltrated within a single muscle group. To avoid an incomplete response, we advocate using lower concentrations at multiple sites with larger injection volumes. Approximately 3-4 weeks after the initial injection, patients will return for reevaluation and documentation any adverse effects and/or suboptimal responses. Some patients may require a booster injection at that time. Additional BoNT injections are directed by the patients’ history and clinical examination, and pain diaries are a useful guide to help in patient directed therapy. It may take several weeks before patients experience the maximum pain relief from BoNT. Althoguth the typical duration of efficacy is 12 weeks, we have noted tremendous variability among patients with respect to optimal dosing frequency. Some patients experience relief well beyond the predicted pharmacokinetic duration of the drug supporting the possibility that BoNT does not strictly act at the periphery and may be involved in neuromodulation at the level of the central nervous system. It is important to note that an individual patient’s response to toxin may change over time, which further supports the importance of patient directed dosing .BoNT injection for TMD is administered in relatively small doses and way below the estimated lethal dose of approximately 3000 units. Because of the relative low dosing profile, adverse effects are uncommon and often mild. Difficulty chewing is the most common adverse effect, which results from local muscle weakness and is usually dose dependent. Muscle atrophy may result in cosmetic alterations and is another risk of the procedure. Higher volume of BoNT increased the risk of diffusion of toxin to nearby areas which may cause brow ptosis, blepharoptosis or diplopia if the temporalis muscle is injected too close to the orbit. Facial asymmetry may result if the masseter muscle is injected too close to the zygomaticus major ,41,47,49Contraindications to BoNT use include a known allergy to BoNT, active inflammation or infection at the proposed injection site, pregnancy, breast-feeding, or chronic degenerative neuromuscular disorders like amyotrophic lateral sclerosis, myasthenia gravis, Lambert-Eaton syndrome, muscular dystrophy or multiple sclerosis. Patients taking aminoglycoside antibiotics should not receive BoNT injections because this class of antibiotics may interfere with the neuromuscular transmission of toxin and potentiate the effect of BoNT .et al reported on 46 patients with TMD treated with 150 units of BoNT-A to the masseters and termporalis muscles. They found significant reductions in their subjective and objective pain scores, and all patients with restricted mouth opening had some degree of improved range of motion. They also reported successful treatment various conditions that fall under the general category of TMD such as bruxism and clenching, oromandibular dystonias, trismus, masseter and temporalis hypertrophy, and headaches [Numerous studies have shown that BoNT provides long-term relief of myofacial TMD by decreasing the intensity, frequency, and duration of recurrent episodes. Freund eadaches . In an oeadaches . The autTemporomandibular disorder is a common cause of chronic facial pain and is known to interfere with personal relations, professional duties, and overall quality of life. Appropriate diagnosis allows physicians to identify the disorder and initiate an effective therapeutic plan. Botulinum toxin has provided long-term relief of TMD by reducing the intensity, frequency, and duration of recurrent episodes. Adverse effects from BoNT injections are uncommon, mild and transient making it an attractive option for adjunctive therapy for myofacial TMD in patients who have failed initial conservative therapy and systemic pharmacotherapy.


Symptomatic gallstone disease is one of the most common problem attended by a general surgeon. The application of minimally invasive surgical techniques for the removal of gallbladder is now an accepted and preferred method for treating this condition. The avoidance of a subcostal incision and minimal bowel handling leads to decreased postoperative pain, early returning to function and overall shorter duration of hospital stay. Nevertheless, patients do have significant postoperative pain, and newer techniques to further reduce this pain are the subject of many ongoing studies. Many intraoperative techniques for reducing postoperative pain have been described. The current practice at many institutions, including ours, is to discharge the patient on the first postoperative day on oral analgesics. Better control of postoperative pain may help establishing laparoscopic cholecystectomy as a day care procedure in selected patients. The aim of this study is to determine the effect of 0.5 % bupivacaine soaked oxidized regenerated cellulose surgical versus normal saline soaked surgical applied at the gallbladder bed on postoperative mean pain score after laparoscopic cholecystectomy for symptomatic gallstones.Patients scheduled for laparoscopic cholecystectomy were enrolled in the study after meeting the inclusion criteria. Relevant history was taken and clinical examination was done. Necessary investigations were carried out. All patients were divided to receive either 0.5 % bupivacaine soaked surgicel or normal saline soaked surgicel after laparoscopic cholecystectomy with each group having equal number of patients. The pain score was measured with a visual analogue scale (VAS) at 4, 12 and 24 h after the procedure in both groups. All data was recorded on performa and SPSS-19 was used for analysis.bupivacaine Group than Saline group. This difference was reported from 4 h till 12 h post-operatively. Bradycardia, Hypotension and Urinary retention were the most common perioperative symptoms reported, with an incidence of 28.3 % in the saline Group and 15 % in the bupivacaine group with no significant differences. Evaluation of postoperative details such as oral intake, time to walk and length of hospital stay revealed that bupivacaine group reported better outcomes as compared to saline group.The demographic characteristic of the two groups has shown that studied patients were matched as regarding gender, age, weight, ASA status and duration of surgery. Post-operative abdominal pain was significantly lower in Placing bupivacaine soaked surgicel has been shown to decrease the mean postoperative pain score in patients. No significant complication was noticed with the use of surgicel. Because adequate pain control requires intravenous medications, additional methods for pain control need to be studied before laparoscopic cholecystectomy can be routinely performed as a day care case. Although laparoscopic cholecystectomy has numerous benefits over the open method, still postoperative pain remains an issue. Postoperative pain, requiring injectable analgesics prolong the patient’s hospital stay, and is one of the hurdles in performing laparoscopic cholecystectomy as a day case. The pain reaches a maximum level within 6 h of the procedure and then gradually decreases over a couple of days, but varies considerably between patients , 2. StudMany methods have been tried to decrease the postoperative pain, like low-pressure pneumoperitoneum, gasless technique, local anesthetic infiltration, saline washout and instillation of a local anesthetic agent in the subdiaphragmatic area –8.The pain that a patient feels after laparoscopic cholecystectomy can be divided into 3 types: Visceral, parietal and shoulder pain which have different intensities . The visAccording to some studies, visceral pain accounts for most of the pain in the early postoperative period. Others state that the largest component in the total abdominal pain is from the incision sites, followed by the pneumoperitoneum and then the cholecystectomy . This isThe cause of the shoulder pain has not been determined—proposed causes include neuropraxia of the phrenic nerve, stretching of the subdiaphragmatic fibers because of the pneumoperitoneum, increased stretch on the diaphragmatic attachments of the liver due to loss of visceral surface tension and peritoneal damage from chemical, ischemic or traumatic injury , 14. ShoThere is a dearth of local studies on the above subject. This study aims to provide impetus for further research and help in performance of laparoscopic cholecystectomy as a day care procedure.This prospective observational control study was approved by the Liaquat national hospital and medical college ethical review board . Required sample size of 120 patients was calculated with 95 % confidence level and 90 % power. These patients were included consecutively in the study from June 2014 to December 2014 were recruited from the outpatient clinic after obtaining written and informed consent.Inclusion criteria was only those patients who were undergoing laparoscopic cholecystectomy and also classified as American society of anesthesiology(ASA) I and II. Patients having acute cholecystits, laparoscopic converted to open surgery, surgery requiring placement of drains and patients with contraindication to Intravenous ketorolac use were excluded from this study.All participants undergoing elective laparoscopic cholecystectomy were divided into two groups with concealment of the sequence and each group having equal number of patients. In the control group, 20 cc of normal saline solution without bupivacaine was irrigated at the surgical bed after laparoscopic cholecystectomy. The experimental group was irrigated with 20 cc of bupivacaine 0.5 % in normal saline solution. Participants were kept unaware of the treatment they received following the protocol of single blinded study.Following the anaesthetic assessment, patients were admitted to the hospital the day before the operation. All patients received the same anaesthetic technique. Usual monitoring was used including heart rate, respiratory rate, continuous ECG, SpO2 and non-invasive arterial blood pressure. Creation of CO2 pneumoperitoneum at 14 mm Hg pressure was justified in all patients and standard laparoscopic cholecystectomy using the 4-port technique was performed. All the operations were performed by one team of surgeons that is experienced in laparoscopic surgery.Application of 0.5 % bupivacaine soaked surgicel at the gall bladder bed after laparoscopic cholecystectomy will result in a lower postoperative mean pain score compared to normal saline soaked surgicel.bupivacaine group. Participants were kept unaware of the treatment they received following the protocol of single blinded study. Both groups received 2 mg/kg of 0.5 % bupivacaine infiltrated at the port sites after the procedure to minimize the local pain. The members of bupivacaine group also had a 3 x 3 inch strip of surgicel soaked in 0.5 % bupivacaine placed at the gall bladder bed, and members of saline group had a surgicel soaked in normal saline placed at the gall bladder bed. Both groups received similar postoperative analgesia, I/V Ketorolac 30 mg at 8 h intervals during the study period. The assigned researcher used the VAS to measure pain scores at 4, 12 and 24 h after the procedure. All data, including age, sex, comorbid, duration of symptoms, duration of procedure, and VAS score at 4, 12 and 24 h after procedure, and the total pain score was recorded on a performa. The study was completed at the end of 24 h with no dropouts.A performa was filled by the researcher for each patient, meeting inclusion criteria, in the ward, after taking written and informed consent and explaining him or her, the purpose of this study. The surgery was performed by a consultant having 5 years’ experience in laparoscopic cholecystectomy. Patients were allocated into two groups equally by balloting by the researcher, i.e. saline group and t test of the significance was used to compare mean pain score between groups for continuous variables like age and pain score. P value ≤0.05 was taken as significant. Confounding variables like age, gender were controlled by stratification to see the effect on outcome (mean pain score).Data was analyzed by using SPSS version-19. Descriptive statistics, frequency and percentage were computed for qualitative variables like gender and pain control. Mean ± SD was computed for presentation of age and hospital stay. Chi square test was used to compare proportion difference between groups for gender and the independent sample bupivacaine group respectively). Furthermore, mean operating time of surgery was not significantly different among the two groups . In addition, no significant differences were observed among two groups with respect to age, ASA status and weight  and at 12 h (0.022), while the difference at 24 h was not significant (p = 0.57). Verma et al. noted a mean difference in the VAS of more than 10 between the case and control group, but this difference was not significant at 4 or 8 h after surgery [The mean pain scores as calculated from the VAS were significantly less for  surgery . Khan an surgery . Only on surgery .Stratification according to gender revealed a significant difference in mean VAS in females at 4 and 12 h in females. Ure and coworkers have reported that females report more pain compared to males, therefore a significant difference in mean pain scores in females would further ascertain our hypothesis [In conclusion, there are considerable differences in the results from various studies. In our opinion, placing a surgicel soaked with bupivacaine at the gall bladder bed and infiltrating bupivacaine at the trocar insertion sites is a safe method, and decreases the postoperative pain resulting from laparoscopic cholecystectomy. We recommend that this method of analgesia be used routinely in surgery for symptomatic gall stones. Further research needs to be done to assess the efficacy and possible associated morbidity of this method in cases of acute cholecystitis.Written informed consent was obtained from the patients for publication of this article. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Approval obtained from Liaquat national hospital and medical college ethical review committee.