The recently published Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit differ from earlier guidelines in the following ways: literature searches were performed in eight databases by a professional librarian; psychometric validation of assessment scales was considered in their recommendation; discrepancies in recommendation votes by guideline panel members are available in online supplements; and all recommendations were made exclusively on the basis of evidence available until December of 2010. Pain recognition and management remains challenging in the critically ill. Patient outcomes improve with routine pain assessment, use of co-analgesics and administration as well as dose adjustment of opiates to patient needs. Thoracic epidurals help ease patients undergoing abdominal aortic surgery. Little data exists to guide clinicians as to the type or dose of co-analgesics; no opiate choice is associated with better patient outcomes. Lighter or no sedation is beneficial, and interruption is desirable in patients who require deep sedation for specific pathologic states. Delirium screening is probably useful; no treatment modality can be unequivocally recommended, and the benefit of prophylaxis is established only for early mobilization. The details of these recommendations, as well as more recent publications that complement the guidelines, are provided in this commentary. The Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit was recently published . This coFour methodological characteristics differentiate these guidelines from earlier versions. First, technical support was provided by a research librarian, Charlie Kishman, from the University of Cincinnati, who provided ongoing searches from eight distinct databases. Expertise in compiling data from a maximum of high-yield sources, and the thoroughness and methodology required to collate search terms and compile the results, impacts the quality guidelines or systematic reviews . The conBehavioral pain scales used in adult ICU patients were analyzed and compared adapting a previously published process . PsychomWe recommend…” was used. A weak recommendation indicated a less clear trade-off or weaker evidence; the phrase “We suggest…” was then used. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made.Conflict of interest declarations were left up to the individual authors; each author chose whether associations with different pharmaceutical industry partners constituted conflict. Experts with no conflicts are hard to find; some argued that being conflicted does not affect your judgment as to the quality of evidence . ConsensThe current guidelines address several new dimensions of pain assessment and management described below. Several other areas remain unexplored, largely because of a dearth in publications; these also are summarized below.We recommend performing early mobilization of adult ICU patients whenever feasible to reduce the incidence and duration of delirium (+1B); and We recommend either daily sedation interruption or a light target level of sedation be routinely used in mechanically ventilated adult ICU patients (+1B)”).The current guidelines emphasize that pain is frequent in ICU patients , with anThe association between pain in ICU patients and the development of chronic pain syndrome in ICU survivors is not addressed  as studiAs these guidelines point out, improved pain management is clearly associated with better patient outcome in the ICU ,18,19. AIn patients able to communicate, self-report is without a doubt the most reliable method to assess pain . The mosSince the review of pain measurement instruments available for ICU patients by Hamill-Ruth and Marohn  more tha…recommend that IV opioids should be considered as the first-line drug class of choice to treat nonneuropathic pain in critically ill patients (+1C).” How these opioids should be administered is not addressed. The continuous use of opioids may lead to drug and metabolite accumulation [No analgesic medication is associated with improved patient outcome. Opioids were used in up to 90% of mechanically ventilated patients in a multicenter patient-based study . Accordimulation ,41. Intrmulation ,18,20.…that nonopioid analgesics be considered to decrease the quantity of opioids administered  and to decrease opioid-related side effects (+2C).” In patients with end-stage liver disease, reduced dosing acetaminophen appears to be safe [that either enterally administered gabapentin or carbamazepine, in addition to intravenous IV opioids, should be considered for treatment of neuropathic pain (+1A).”A study performed in ICU patients  used a gradual escalation of analgesics from nonopioid drugs to incrementally powerful opioids . In that be safe . Nefopam be safe . This de be safe . This, a be safe , led to We recommend that thoracic epidural anesthesia/analgesia should be considered for postoperative analgesia in patients undergoing abdominal aortic surgery (+1B). We provide no recommendation for the use of a lumbar epidural over parenteral opioids for postoperative analgesia in patients undergoing abdominal aortic aneurysm surgery, due to a lack of benefit when these routes of administration are compared in this patient population . We provide no recommendation for the use of thoracic epidural analgesia in patients undergoing either intrathoracic or nonvascular abdominal surgical procedures, because of insufficient and conflicting evidence for this mode of analgesic delivery in these patients . We suggest that thoracic epidural analgesia may be considered for patients with traumatic rib fractures (+2B). We provide no recommendation for neuraxial/regional analgesia over systemic analgesia in medical ICU patients, due to lack of evidence in this patient population ”.Regional analgesia  is known to improve the efficacy of traditional analgesic interventions and to decrease pulmonary complications in many postoperative patients . Its intThe biology underpinning pain syndromes remains underexplored, particularly in medical ICU patients. Hyperalgesia associated with sepsis could contribute to a possible “diffuse ICU pain syndrome.” Indeed, myalgia and arthralgia are common clinical features associated with sepsis and fever , partly Barriers associated with pain not being evaluated by health caregivers should be better elucidated ,56. In pComplimentary, nonpharmacologic interventions for pain management, such as music therapy and relaxation techniques, can be considered as complementary therapies in pain management; they may be opioid-sparing and analgesia-enhancing choices, and they are low cost, easy to provide, and safe.” Although a multimodal approach to pain management in ICU patients has been recommended, few studies have demonstrated the effectiveness of nonpharmacologic interventions [Nonpharmacological adjuncts or substitutes to pharmacological intervention also are of interest. Music therapy and music are beneficial for critically ill patients. This unaddressed area in the literature is acknowledged in the current guidelines, which state: “ventions ,61,62.The current guidelines support the minimization of sedation so that patients are responsive and able to communicate. In clinical contexts where this is not possible or not desirable, daily interruption of sedation is encouraged. The recommendations take into account subsequently published data suggesting that interruption confers no additional advantage to sedation minimization ; althougShould nonbenzodiazepine-based sedation, instead of sedation with benzodiazepines, be used in mechanically ventilated adult ICU patients? (actionable) was reworded numerous times.Despite review of the literature for the 10 years preceding the inception of the guidelines and during the 7 years spent in its creation, no clear recommendation could be put forward with regard to preferred sedation agent. Few topics generated as much controversy and discussion as the use or avoidance of benzodiazepines, leading to heated debates during panel discussions and to perspective-defining publications ,70. The In parallel with the literature on continuously administered analgesic agents, few data report the pharmacokinetic properties of continuously administered benzodiazepines, propofol, and dexmedetomidine . Any comRoutine delirium assessment in all critically ill patients is recommended, in keeping with ICU guidelines published by others . This shThe importance of delirium screening is emphasized to reassure patients and provide prognostic indicators. The recommendation that screening be performed with a tool rather than with clinical assessments by intensive care physicians was based on studies where delirium screening was introduced de novo  and by tBecause continuously sedating patients with midazolam appears to be associated with a higher incidence of delirium than sedating patients with dexmedetomidine , and becShould a nonpharmacological delirium protocol in the ICU be used in the ICU to reduce the incidence or duration of delirium? (actionable),” the guidelines provide the following answer: “We recommend that performing early mobilization of adult ICU patients be performed whenever feasible to reduce the incidence and duration of delirium (+1B).” This recommendation is based on the first multicenter, randomized, controlled trial of early mobility [Delirium prophylaxis was addressed for the first time in these guidelines. To the question: “mobility  and a sumobility  are currNo recommendations were made with regard to pharmacological delirium prevention. Six randomized studies evaluating a pharmacologic intervention for ICU patients had been published at the time of review. Although a reduction in delirium was observed in five of the studies, important methodological differences and limitations may have influenced some of the results ,85, wherOne before/after study evaluated the impact of a multidisciplinary protocol for managing pain, agitation, and delirium in ICU patients.” This study demonstrated a reduction in the incidence of subsyndromal delirium (but not delirium), with improved pain control, and without compromising sedation or anxiolysis, and a 15% reduction in their total ICU costs [Given these data, no pharmacologic prophylaxis recommendation for delirium was made; a recent systematic review of delirium prophylaxis in the critically ill concurs with the lack of evidence to support this practice . HoweverCU costs ,21. SubsCU costs .p = 0.03) [After the guidelines had been written, the largest ICU delirium prophylaxis study published to date described that a low-dose, 12-hour infusion of haloperidol reduces the incidence of delirium in surgical patients from 23% to 15% ( = 0.03) . As the  = 0.03)  have sho = 0.03) .Does treatment with haloperidol reduce the duration of delirium in adult ICU patients? (descriptive) Answer: There is no published evidence that treatment with haloperidol reduces the duration of delirium in adult ICU patients (No Evidence), and Question: Does treatment with atypical antipsychotics reduce the duration of delirium in adult ICU patients? (descriptive) Answer: Atypical antipsychotics may reduce the duration of delirium in adult ICU patients (C).” A recent review of delirium treatment in ICU patients [The guidelines are clear as to the paucity of evidence supporting any pharmacologic treatment for delirium. With the possible exception of a benefit shown in a small (n = 36) study randomizing patients on as-needed haloperidol to quetiapine , where ppatients  concedesWe do not recommend administering rivastigmine to reduce the duration of delirium in ICU patients (-1B).” Although tested in only one study, when rivastigmine was compared with placebo in critically ill patients the investigation was halted because of perceived futility and potential harm by the DSMB (Data Safety Monitoring Board) [Rivastigmine use in the critically ill is specifically discouraged in the guidelines: “g Board) ; rivastig Board) .The current guidelines update the critical care clinician on the importance of pain and delirium assessments and the need to minimize or interrupt sedation. The methodological rigor with which the evidence was triaged improves the clarity and scientific basis of the recommendations; the guidelines also better identify gaps in current evidence. We hope that the current update on guideline content and process will incite critical care investigators to build on established work to address pain, sedation, and delirium issues in order to improve care and outcomes for the critically ill and to reduce the significant burden of critical illness on patients, their families, and society.The authors declare that they have no competing interests.YS was part of the Society of Critical Care Medicine’s guidelines committee. Both authors wrote sections of the manuscript, and extensively reviewed its entire content. Both authors read and approved the final manuscript.


Primary aim of this study was to compare long-term pain relief and quality of life in adults with isthmic spondylolisthesis (IS) who were treated with posterior lumbar interbody fusion (PLIF) and posterolateral fusion (PLF). Secondary aim was to compare the fusion and infection rates of PLIF- or PLF-treated groups.We searched four databases and the cited reference lists of the included studies. Inclusion criteria were pain assessment with visual analog scale (VAS), and clinical studies that compared long-term pain relief of PLF and PLIF-treated adults with IS. Exclusion criteria were use of only one treatment and non-English language.P = 0.856). The five studies together indicated that fusion rate was significantly greater in the PLIF group than that in the PLF group.Three of five included studies used VAS to assess the decline in low back pain, radicular pain, or leg pains in PLF- or PLIF-treated patients during the follow-up periods (0.5–6 years). Long-term pain relief significantly improved in both treatment groups. Pooled differences in mean improvement of Oswestry disability index after the operation revealed no significant difference in pain relief between the PLF and PLIF groups (The majority of PLIF- and PLF-treated adults with low-grade IS experienced long-term pain relief to a similar extent in most studies. PLIF treatment provided significantly better fusion rates than PLF treatment. This meta-analysis indicates that the use of separate, well-defined scales for pain relief and functional outcomes are needed in studies of PLF or PLIF-treated patients. Lower back pain of ≥3-month duration afflicts approximately 29 % of adults in the USA . SpondylTreatment of isthmic spondylolisthesis depends on the severity of symptoms. Patients with physical complaints and mild spondylolisthesis initially are treated with non-surgical modalities including prescriptions for non-steroidal anti-inflammatory drugs (NSAIDs), physical therapy, and modification of their activities that induce pain and rest for 1–2 weeks . These nAfter adults fail to respond to 3–6 months of non-surgical treatment, surgical intervention is considered for relief of continual disruptive back pain or radicular pain, loss of nerve function, as well as for symptomatic grade III or greater slip, progressive deformity, and development of cauda equine . WorkersMajor outcome criteria for surgical treatment of spondylolisthesis from the patients’ perspective would include pain relief and QOL. In addition, the fusion rate and the incidence of infection with the two procedures may influence which procedure is recommended by the surgeon and staff. Most studies compare small groups and may not have sufficient biostatistical power to detect differences. Thus, the primary objective of this meta-analysis was to determine whether PLF treatments or PLIF treatments were significantly better in improving long-term pain relief and QOL in patients with isthmic spondylolisthesis. The secondary aim included comparisons of the infection rate and the efficiency of spinal fusion of PLIF and PLF.The Medline, Embase, Current Contents, and Cochrane databases were searched using combinations of the key search terms: “posterior lumbar interbody fusion AND posterolateral fusion”; clinical trial; “comparative study and isthmic spondylolisthesis” from inception to August 31, 2012. The grey databases  were searched. The reference lists of the included studies and previous systematic reviews were searched for additional relevant articles.This meta-analysis included randomized controlled trials (RCT), non-RCT, and cohort studies that compared a group of patients with isthmic spondylolisthesis treated with PLF to a group treated with PLIF. The studies also needed to report the pain score before the surgery and at two or more points post-surgery. Fusion rate and infection were also compiled. Exclusion criteria included non-English language, no pain score, and articles reporting results of one technique but not the other.Two reviewers independently screened the titles and abstracts of the retrieved articles for adherence to criteria. The potentially relevant full length articles were screened further for the inclusion criteria, and the data were extracted using predetermined forms. Pain score measurements used the visual analog scale (VAS) and functional assessment used the Oswestry disability index (ODI) score. Any disagreements were resolved by a third reviewer.χ2-based test of homogeneity was performed and the inconsistency index (I2) statistic was determined. If I2 was >50 or >75 %, the trials were considered to be heterogeneous or highly heterogeneous, respectively. If I2 was <25 %, the studies were considered to be homogeneous. If the I2 statistic (>50 %) indicated heterogeneity existed between studies, a random effects model was calculated. Otherwise, fixed effects models were calculated. Pooled summary statistics of the difference in the mean for the individual studies are shown. Pooled differences in means were calculated and a two-sided P value < 0.05 was considered to indicate statistical significance. All analyses were performed using Comprehensive Meta-Analysis statistical software, version 2.0 .Means with standard deviations were calculated for pain score measurement (VAS) and functional measurement (ODI), and were compared between patients with PLF and PLIF. A Fifty-two articles on PLF and PLIF were retrieved from the databases, and five studies met the initial criteria Fig. . The chaThe VAS score for each study measured pain of different variables: VAS recorded the radicular pain in Farrokhi et al. , whereasn = 2), fusion rate (n = 4), and infection rate (n = 4) of the five studies that met the inclusion criteria [A total of 2–4 studies were included in the meta-analysis for pain  . The pooled mean differences in improvement of ODI ranged from −1.265 to 6.969, with the pooled mean differences being 1.265.The improvement of ODI after the operation was highly heterogeneous between the two treatment groups of these 2 studies (I2 = 0 % and the results showed PLF group had lower fusion rate than PLIF group (P < 0.001).A meta-analysis of four studies –13, 15 cI2 = 0 % and the results showed the infection rate after operation was modestly lower in the PLF group in three of the four studies [P = 0.191).A meta-analysis of four studies , 11–13 c studies , 11, 12,Taken together, the five studies indicated that both the PLF and the PLIF techniques provided similar levels of pain relief and functional activity in patients with IS after the long-term follow-up. The rate of infection was modestly less in PLF in three of four studies, but it did not reached significance. The fusion rate of PLIF was significantly greater than that of PLF.Pain relief and QOL are major outcome criteria for surgical treatment of spondylolisthesis from the patients’ perspective. VAS was used to assess the decline in low back pain, radicular pain, or leg pain in PLF- or PLIF-treated patients during the follow-up periods which ranged from 0.5 to 6 years , 13. LonSix additional clinical studies , 17–19 aThe Beaujon scale measures both pain and functional abilities such as walking and QOL : both PLThe systematic review by Jacobs et al.  indicateLimitations of this meta-analysis included the heterogeneous surveys for measuring outcomes and pain relief, the wide variation in follow-up times (0.5 to >6 years), scant reporting of pain as a distinct variable rather than as a part of the clinical outcomes, and the retrospective nature of the case series.In conclusion, the majority of PLIF- and PLF-treated adults with low-grade isthmic spondylolisthesis experienced long-term relief from low back pain, radicular pain, and leg pain to a similar extent in most studies. The data are consistent with the possibility that PLIF treatment may provide better pain relief and outcomes for adults with higher grade isthmic spondylolisthesis, but further studies are warranted. However, the fusion rate of PLIF-treated group was significantly greater than that of the PLF group. This meta-analysis also indicates that the use of separate and well-defined scales for pain relief and functional outcomes are needed in studies of PLF- or PLIF-treated patients.


The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied.This article describes the aims and design of a study to evaluate effects and costs of collaborative care with the antidepressant duloxetine for patients with pain symptoms and a depressive disorder, compared to collaborative care with placebo and compared to duloxetine alone.This study is a placebo controlled double blind, three armed randomized multi centre trial. Patients with (sub)chronic pain and a depressive disorder are randomized to either a) collaborative care with duloxetine, b) collaborative care with placebo or c) duloxetine alone. 189 completers are needed to attain sufficient power to show a clinically significant effect of 0.6 SD on the primary outcome measures (PHQ-9 score). Data on depression, anxiety, mental and physical health, medication adherence, medication tolerability, quality of life, patient-doctor relationship, coping, health resource use and productivity will be collected at baseline and after three, six, nine and twelve months.In the collaborative care conditions a) and b), a care-manager provides Problem Solving Treatment and integrated symptom management guidance with a self-help manual, monitors depressive and pain symptoms, and refers patients to a physiotherapist for treatment according to a 'Graded Activity' protocol. A psychiatrist provides duloxetine or placebo and pain medication according to algorithms, and also monitors pain and depressive symptoms. In condition c), the psychiatrist prescribes duloxetine without collaborative care. After 12 weeks, the patient is referred back to the general practitioner with a consultation letter, with information for further treatment of the patient.This study enables us to show the value of a closely monitored integrated treatment model above usual pharmacological treatment. Furthermore, a comparison with a placebo arm enables us to evaluate effectiveness of duloxetine in this population in a real life setting. Also, this study will provide evidence-based treatments and tools for their implementation in practice. This will facilitate generalization and implementation of results of this study. Moreover, patients included in this study are screened for pain symptoms, differentiating between nociceptive and neuropathic pain. Therefore, pain relief can be thoroughly evaluated.NTR1089 Patients with major depressive disorder (MDD) and co-morbid chronic pain now have a high risk of not receiving optimal care -4. The bThere is a strong correlation between pain and psychiatric distress reporting -11. PhysMoreover, depression and painful physical symptoms increase costs by increased utilization of healthcare services ,22-24. ATherefore, good detection and diagnosis of comorbid conditions is necessary in the first place to be able to treat those conditions adequately ,27. In pTreatment of chronic pain in depressed patients has been addressed , with a Collaborative care is successful in the treatment of depression, can vary in content and intensity  and combRecently, a trial explored efficacy of collaborative care for MDD and musculoskeletal pain  and anotan unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage[.According to the international Association for the study of Pain (IASP), pain is ch damage.Most pain originate from an outside stimulus (heat or a sting), but may also result from injury to sensory fibres , and follows an ascending pathway to the brain ,59. ThroSerotonin, norepinephrine, substance p, glutamate, NMDA and gamma-aminobutyric acid (GABA) play a role in pain processing in rats and mice -65 and iIn this study, in the collaborative care treatment, specific attention is paid to the management of pain by proper pain medication and adherence to pain medication. For this purpose, the pain is classified as nociceptive pain or neuropathic pain by a questionnaire, the PAINDETECT  and treaConfusion exists in terminology in describing physical symptoms and pain associated with depression: They may be somatised symptoms of MDD, or so-called associated symptoms; Medically Unexplained Symptoms, that frequently occur together with MDD; Chronic painful physical conditions that are symptoms of a chronic illness, such as diabetic neuropathy; or chronic painful conditions resulting from centralisation of a formerly peripheral pain symptom.In this trial, we aim to improve depressive symptoms of patients with MDD with concomitant subchronic or chronic pain symptoms of nociceptive, neuropathic, mixed or functional nature. As discerning nociceptive pain from neuropathic pain may have therapeutic consequences in the treatment of (sub)chronic pain , we addrThis Randomized Controlled Trial aims to evaluate effectiveness and cost effectiveness of this transmural collaborative care model with Consultation Letter (TCCCL) in patients with MDD and concomitant (sub)chronic pain.The primary objective of this randomized placebo-controlled trial is to establish effectiveness on severity of depression ) of a closely monitored integrated intervention (TCCCL + duloxetine) for concomitant depression and (sub)chronic pain compared to either TCCCL + placebo and compared to Duloxetine alone.Secondary objectives of this trial are to establish cost effectiveness in terms of Quality of Adjusted Life Years (QALY) as measured by EuroQol-5 and SF-36 and costs measured by TIC-P; and to establish improvement on pain in terms of Brief Pain inventory (BPI).Combined treatment (TCCCL + Duloxetine) is more effective than mono-treatment  in depressive symptom reduction on the PHQ-9 as main outcome for patients with MDD and (sub) chronic pain.This study is a three armed randomized Multi Centre trial led by GGz Breburg, with three collaborating mental health institutions: GGz Breburg, Arkin, and GGz inGeest, who will all include 73 patients in order to have 3 × 63 completers for the study. See Figure Three mental health institutions participate in this study. Patients will be treated at these institutions according to protocol. The participating mental health institutions are: GGz Breburg in Tilburg, GGZ inGeest in Amsterdam and Arkin/PuntP, also in Amsterdam.Care-managers and psychiatrists will be recruited at the three participating mental health centers  and form treatment teams for the trial. The care-managers are psychiatric nurses or psychologists who receive training in care management (including PST) to provide in the collaborative care interventions. The psychiatrists are trained in prescribing duloxetine and placebo medications as well as the pain medication according to the algorithm and in writing a consultation letter for the general practitioner and patient. Psychiatrists are blinded for the antidepressant medication (duloxetine/placebo), but not for the pain medication. Pain medication management will be provided by the psychiatrists in the duloxetine and placebo arm with collaborative care, but not in the treatment arm with duloxetine alone. In this study, care-managers and psychiatrists work according to a 'Case Registration Form' (CRF). In this CRF all the steps are described that a care-manager/psychiatrist has to do during an appointment with a patient.All the patients that are referred to the participating mental health centers are screened for depressive symptoms and pain complaints. This study will focus on patients with a depressive disorder and (sub)chronic pain complaints. Sub chronic pain is defined as pain of ≥ 6 weeks and chronic pain is defined as pain with a duration of at least 12 weeks. Consecutive patients that present themselves at the special mental health outpatient clinic will be screened for MDD and concomitant pain of ≥ 6 weeks duration with a questionnaire.This questionnaire will consist of the PHQ-9  and the This is a placebo controlled double blind study for the medication part of the study, which means that the allocation of duloxetine/placebo in the collaborative care arm is blinded.Patients visiting the three participating Mental Health Institutions will be randomly assigned to one of the three treatment groups. Collaborative care and Duloxetine alone will be administered in a non-blind fashion. Administration of medication within the collaborative care conditions will be double blind and placebo controlled. Outcome assessments will be performed by a blinded research assistant.After 12 weeks, the placebo-controlled part of the study will end and the patient and physician will be deblinded for this part of the intervention. This deblinding procedure is described more detailed in the intervention.Emergency deblinding of the medication condition is performed by telephone to a research associate who is not involved in treatment procedures. This happens in case of serious adverse medical events. Subjects, who are deblinded before the end of the treatment procedures, will not be incorporated in the final analysis. In case of emergency deblinding or non-compliance, the code of medication (duloxetine or placebo) in the collaborative care groups will be broken. In case of duloxetine, the medication will be reduced and stopped according to protocol. All the remaining medication of this patient will be asked back and stored in a closed cabinet, separately from the rest of the study medication. In case of non-compliance, the patient will be excluded from this study and the final analysis.Patients with pain for which by diagnostic medical assessment a structural and continuing physical cause has been found in terms of tissue damage, illness or otherwise, that requires treatment, such as pain due to cancer or recent post traumatic pain, are excluded from the study and advised to seek such treatment. Other exclusion criteria are:*a PHQ-9 < 10 or a BPI score < 3,*alcohol use >3 units (1 unit = 1 glass of ≥0.25 l) a day or drug abuse or dependence in the last 6 months, defined as current use of any hard drugs  or cannabis, as evident from history or, in case of suspicion during clinical interview, from laboratory findings;*psychotic symptoms or use of antipsychotic medication that may influence perception of pain;*use of St John’s wort (Hypericum Perforatum),*pregnancy and breastfeeding,*inability to participate in case of too severe language barrier,*dementia*history of renal and liver dysfunction for which treatment is needed*uncontrolled hypertension despite treatment for hypertension*Lastly, suicidal ideation is an exclusion criterion if this constitutes immediate danger and the need for crisis management according to the consulted psychiatrist. This will be measured with the suicidal ideation item of the PHQ-9. For this purpose, a suicide protocol is used in the study, defining degrees of suicide risk and prescribing necessary steps to be taken to advert such risk.Non-compliance is defined as not having used at least 80% of the prescribed medication (duloxetine/placebo) or no show on more than 20% of the appointments made with the psychiatrist or care-manager. The psychiatrist uses pill counts at every session to check if at least 80% of the pills have been used.This intervention contains collaborative care, duloxetine or placebo, and pain medication according to an algorithm. Collaborative care will be provided within a multidisciplinary team comprising of a care-manager, psychiatrist and a physiotherapist. They all will apply treatment simultaneously according to protocol. Only patients in the collaborative care arms will receive treatment of all three specialists. The patients in the Duloxetine alone arm will only receive treatment of the psychiatrist.The GP of the patient will be informed of the participating of the patient. Also, GP's in the same areas as the mental health centers will receive information about the study and are asked to refer patients if they have the complaints under study. The interventions will be monitored every two weeks and when needed, the doses of medication can be raised according to the algorithm shown in Figures The detailed content of the collaborative care intervention is described below:Diagnostic assessment of the nature of pain symptoms1. The nature and the extent of the pain symptoms will be explored by the psychiatrist with the BPI and the painDETECT . The 'avContracting2. During the initial visit, the care-manager informs the patient about the depressive disorder and pain symptoms, and their association. The treatment plan is then jointly formulated by the psychiatrist, the care-manager and the patient.Pain medication protocol3. In this study, pain is divided in nociceptive pain and neuropathic pain and treatment of pain will be applied based on which of these two sorts of pain a patient has. Classification as nociceptive pain, neuropathic pain or mixed pain will be done with the PainDETECT questionnaire that was specifically validated for this purpose .In all instances, patients are urged to take the medication at preset intervals, in order to medicate properly so as to prevent serious pain. In all instances, duloxetine (or placebo) is prescribed as adjuvant.The psychiatrist will use the painDETECT questionnaire to identify the pain as nociceptive or neuropathic. When it is not clear in which of these two categories the pain belongs, both the algorithms for nociceptive and for neuropathic pain are followed. The algorithm for nociceptive pain, is adapted and changed from the WHO pain ladder . It is uFigure When, after 12 weeks, the patient is referred back to the GP, the GP is advised, through a Consultation Letter, to continue the medication for a duration of 6 months, as is advised in the 'NHG standard – depression' , a guideManual guided self-help for behavioral techniques aimed at improving coping with pain4. During the treatment, the patient works through a self-help manual, guided by the care-manager. The manual is based on several existing self-help books -46. ThisProblem Solving Treatment5. Problem Solving Treatment (PST) is a brief, structured psychological intervention, guided by the care-manager, that has been shown to be effective in the management of depressive disorders and stress related disorders . The proAntidepressant medication6. In the two collaborative care conditions, patients will either receive duloxetine or placebo in a double blind fashion. The psychiatrist will monitor medication use according to protocol. In case of any adverse effects, an adverse effects protocol is followed. The pharmacists checks for possible interactions of the antidepressant medication with other medication use of the patient and instructs the doctors providing treatment accordingly.Patients will start with a dose of 30 mg once daily in the first two weeks and 60 mg once daily from the third week. From this point the PHQ-9 will be used to measure the severity of depressive symptoms. Based on the score on the PHQ-9, the dose will be raised  or stay the same (when the score on the PHQ-9 has decreased with 5 or more points or the score on the PHQ-9 is 5 or lower). This use of the PHQ9 for monitoring was used as well in other collaborative care studies in the Netherlands, with a focus on depression -87. By uMonitoring treatment outcome and motivational techniques aimed at improving adherence7. Patient adherence will be improved by contracting and psycho-education and by frequent follow-up appointments in which both adherence and progress will be evaluated. Provider adherence will be improved by instructions from the researchers. Treatment outcome is monitored with a variety of questionnaires (see section 'Outcome parameters').Referral to the physiotherapist by the care-manager according to a protocol8. Next to manual guided self-help, Problem Solving Treatment and medication, patients receive physiotherapy. The physiotherapist will treat patients according to the protocol of 'graded activity'. This treatment consists of information of physical and psychological processes and how these can be intertwined. The next step is to formulate reasonable goals on what to achieve with this therapy. According to these goals, intermediate steps are formulated that have to take into account the amount of time that is predetermined.The physiotherapist stimulates the patients with positive feedback. Also, the therapist works on a structured time schedule to optimize the course towards the determined goals. Next to the exercises, the therapist pays attention to the progress of the patients. This will be illustrated by graphs and when positive, these serve as a possible positive reinforcer and can motivate the patient.The patients also conducts the exercises at home, so these exercises generalize to situations the patients live in. In this, the patients are stimulated by their physiotherapist.Consultation Letter9. The consultation letter is written by the psychiatrist and is meant for the GP and the patient. In this letter, the symptoms of the patient are described . This letter will also contain the treatment the patient has received in this study, as well as if the patient improved or not. The expected course of the complaints will be described, and with this an advice is given how to continue treatment of the patient by the GP. An advice is given for continuing medication (antidepressants and pain medication), the number of regularly scheduled consults with the patient every 6 weeks as checkup, to perform only physical examination if the patient presents the same symptoms again, and refrain from repeated lab or diagnostic procedures as well as to avoid hospitalization, as long as the patient does not deteriorate or presents with new symptoms. Also, the GP can consult the psychiatrist if needed. This consultation letter is sent 3 months after start of treatment, when the patient is referred back to the GP.6. Antidepressant medication). No other components, i.e. PST, manual guided self-help, pain medication, physiotherapy, and a consultation letter, of collaborative care will be given here. Patients in this condition will only be prescribed Duloxetine by a psychiatrist.In the Duloxetine alone condition, patients will receive duloxetine according to the algorithm as described on page 10 (Measurement will take place at baseline (T0), and three, six, nine and twelve months after baseline, respectively T1, T2, T3 and T4.Primary outcome measure1. Primary parameter used to substantiate the study hypothesis will be severity of depression (PHQ-9) . The sevSecondary outcome measure2. Secondary parameter will be the severity of pain symptoms as measured with the total BPI. The BPI has been validated for chronic non-malignant pain . The locIn addition to the improvement in the severity of symptoms, the cost utility of the three conditions will be compared to each other. To evaluate the cost utility of each condition, the difference in direct medical costs per patient receiving collaborative care and duloxetine, collaborative care and placebo, or Duloxetine alone is related to the difference in terms of Quality Adjusted Life Years (QALY) gained. This will yield a cost per QALY estimate. These data will be collected with the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness (TiC-P), a measure commonly applied in economic evaluations of treatment in mental care ,90. The The EuroQoL (EQ-5D)  and the Additional outcome measures3. Confusion exists in terminology in describing physical symptoms and pain associated with depression ,95: TheyControlling variables4. The following demographic variables are measured at baseline and will be taken into account as possible effect modifiers: age, gender, nationality and ethnicity, marital status, living conditions, education and work status. Also, pain classification  will be taken as effect modifier. Moreover, existing somatic comorbidity will be taken as effect modifier. Co-morbid chronic medical illness will be measured with the Dutch Central Bureau for Statistics list (CBS list). The list contains 28 chronic conditions (e.g. diabetes and MS).In a former RCT on collaborative care performed in the primary care setting, the effect size of a collaborative care intervention versus no such intervention as measured by PHQ-9 was 4.64/7.6 = 0.6 (the SD on the endpoint PHQ-9 varied between 7.0 and 8.3) . In thisApart from patients that will have to be excluded because of noncompliance as described above, or patients who had to undergo emergency deblinding due to serious medical adverse events, intention to treat analysis will be performed. Multi Level Analysis will be performed which will allow us to correct for variance associated with the different sites in this Multisite RCT. Effect sizes will be estimated in terms of Cohen's d and regression analysis will be performed. Possible confounders such as age, gender, immigrant status, level of education, history of treatment and life events will be included as covariates in the analysis. An independent Helmert analysis will be performed with the following contrasts: Duloxetine alone versus TCCCL + duloxetine and TCCCL + placebo; and then TCCCL + duloxetine versus TCCCL plus placebo.To assess the cost effectiveness, we will apply a cost-utility analysis. The results will be expressed as cost per QALY. The economic evaluation will be undertaken from a societal perspective. Hence, all relevant effects and costs due to resource utilisation within the healthcare  and costs due to production losses (productivity costs) will be included.As possible effect modifiers, co morbid mental health disorders as measured with the PHQ (e.g. anxiety) will be taken into account. Another parameter will be the severity of hypochondriac tendencies (WI) as a possible effect modifier . The CBSThe goal is to enroll 219 patients in order to obtain 189 patients that will complete the study. The preparatory period is approximately 6 months. Care-managers will be recruited subsequent to the approval of the Medical Ethical Board and the care-managers will be trained. The inclusion and intervention period will be 24 months. The follow-up phase will last 12 months. Data analysis will take 6 months. The entire study period is 4 years.This study will be conducted in accordance with the code of ethics that has been established by the declaration of Helsinki (1964) and amended in Edinburgh (2000). Subjects will be informed of all procedures and asked for written informed consent. The patients will be informed that they can withdraw their consent to participate at any time without specification of reasons and without negative consequences with regard to future medical treatment. A medical adverse events protocol is established. Every session with the psychiatrist side-effects, that may have occurred since the last session, will be measured with the Dutch translation of the Antidepressant Side-Effects Checklist (ASEC-21) . When thThe study has been approved by the Medical Ethics Committee of the VU Medical Centre (reference number: 08072).This study will establish cost effectiveness of TCCCL and then make the following products available for long term implementation:– Training module of psychiatrists and psychiatric nurses working in a specialty mental health outpatient clinic to perform TCCCL integrated depression and pain treatment, and to refer the patient back to the GP with a CL letter within 3 months.– Format of a Consultation Letter to the GP.– Algorithm for psychiatrists about how to monitor and improve the pain medication of the patient according to a protocol.– A manual for the psychiatric nurses to monitor progress and to use the DVD ‘Facts on Depression’ in psycho education for the patient.– A self management manual for patients including activation and relaxation techniques.– A practical protocol for duloxetine use in patients with depression and pain.This paper describes the study protocol of a Multi-Center randomized controlled trial evaluating collaborative care, antidepressant medication and pain medication in the treatment of depressive disorders with (sub)chronic pain. The aim of this study is to compare three treatments in terms of (cost)effectiveness.A strength of this study is that the three arm design enables us to show the value of a closely monitored integrated treatment model above usual pharmacological treatment. Another strength of the study is that the comparison with a placebo arm enables us to evaluate effectiveness of duloxetine in this population in a real life setting.Also, a strong aspect of this design is that this will provide evidence-based treatments and tools for their implementation in practice. This will facilitate generalization and implementation of results of this study.Furthermore, patients included in this study are screened for pain symptoms, differentiating between nociceptive and neuropathic pain, unlike the studies of Goldstein et al. . TherefoAnother strength of the study is the structured implementation of a transmural model, aimed at better collaboration between GP and specialty mental health clinic in complex patients with depression and concomitant (sub)chronic pain.A limitation of the study is that, with this study design, we will not be able to make inferences about the effectiveness of the respective ingredients of the collaborative care model .TCCCL: Transmural collaborative care with consultation letter; CC: Collaborative care; MDD: Major depressive disorder; GP: General practitioner; PST: Problem solving treatment; CL: Consultation letter.In the past three years CFC received royalties for books that she wrote on psychiatry and her employer (EdH) received a research grant for this Investigator Initiated Trial (IIT) from Eli Lilly. JD: his employer (FK) received a research grant for this IIT from Eli Lilly. The other authors have no competing interest.CFC is the principle investigator. She supervises and facilitates EdH, facilitates data management and data handling and statistical analysis in the study. She designed this study and acquired funding for the study. She developed the algorithms for duloxetine, and for the pain medication. She recruited physiotherapists for the study, took part in the training for psychiatrists and is available for consultation by the participating psychiatrists. She facilitated and coordinates the study at GGz Breburg. She co-authored this article. EdH participated in the study design, conducts the trial, assisted in the training and supervision of the care-managers and psychiatrist, recruited physiotherapists for the study and wrote this article. JD participated in the design and acquisition of funding of this study, facilitated the study at Arkin and co-authored this article. HvM participated in acquisition of funding of this study, supervised the PST training and co-authored this article. AB facilitated the study in GGz inGeest and co-authored this article. JR participates in the trial and coordinates the trial at GGz inGeest and coauthored this article. TH participated in implementing the start of the study in the outpatient clinic of Arkin mental health care, Amsterdam and co-authored this article. PB checked all medication for interactions and coordinated the distribution, randomization and blinding of the antidepressant medication. JvEvdS tested the medication algorithms, assisted in recruiting physiotherapists in GGz Breburg and co-authored this article. LH contributed to the design of the economic evaluation of this study and coauthored this article. FK participated in conducting this trial in Arkin and assisted in the supervision of the care-managers and psychiatrist and coauthored this article. LR co-authored this article. All participants contributed their own specific expertise and read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/13/147/prepub


Low back pain (LBP) is one of the most prevalent complaints among the people worldwide. According to the medical statistics, about 80 percent of people have at least one episode of LBP during their lifetime cause them to visit a physician for treatment. LBP is the most prevalent cause of work disability and its related leaves among people under 45 years old. Numerous studies have been conducted on the connection between clinical signs, patients’ complaints, the level of lumbar disc herniation, and abnormal findings of magnetic resonance imaging (MRI). In many cases, contradictory views have been reported and even in some cases canal stenosis and herniated disc have been reported in patient without clinical sings. The aim of this study was to analyze MRI findings in patients with LBP and radicular chronic pain (RCP) attending Imam Reza Hospital .This cross-sectional study was conducted on 200 patients (100 with LBP and 100 with RCP). Following unsuccessful results of medical treatment for 1 to 48 months, the examination results, demographic information  and their complaints along with MRI findings were documented and statistically analyzed. Patients with history of lumbar surgery, infective inflammatory diseases, fractures, tumors, etc were excluded from the study. To determine the significant correlation between qualitative and quantitative variables, the Chi-Square test and the independent t-test were respectively performed using the statistical package of SPSS (Version 12) The P-value of less than 0.05 was considered significant.In the LBP group, patients complained only of posterior and inferior spinal column pain and did not have any pain distribution toward lower limbs or any other signs. However, in the RCP group, in addition to pain distribution towards the lower limbs, they were complaining about muscular myotonia and sensational disorder and 88% also had low back pain. 94 of them were men and 106 were women.106 subjects (80.5%) were urban residents and 39 (19.5%) rural residents. There were 42.5% housewife, 21.5% employee, 15% workers, 9.5% self-employed, and 8.5% were unemployed. In terms of education, 27% were uneducated, 40.5% with incomplete high school diploma, and 32.5% with high school diploma and higher levels of education. 33.5% of patients had the treatment period of one month, while for the rest this period was more than one month to 4 years. Twenty percent did not rest, 52.5% rested up to 3 weeks and 24% rested up to 3 months. In the RCP group, 41% complained of pain in the right leg, 36% in the left leg, and 23% in both legs. However, in the RCP group, 26% had limb paresis, 5% atrophy, 25% some levels of sensational disorders, and 2% had sphincter disorders. Herniated disc in the form of protrusion and extrusion at L4-L5 and L5-S1 spaces were mainly observed in patients with RCP rather than those with LBP. Twenty-six patients (13%) had spondylolisthesis of which 12 (46.2%) were in LBP group and the other 14 patients (53.8) in RCP group. Forty-eight patients (24%) had canal stenosis of which 11 patients were from LBP group and 37 from RCP group. Of these 48 patients, 11 had partial stenosis and 37 had absolute stenosis that were in the RCP group.The most prevalent herniated disc spaces were at the levels of L4-L5 (87%) and S1-S2 (65%). This is because that most of the movements occur in the mobile parts of disc surface and the stresses that are exerted on the mentioned part. Generally, a meaningful correlation between existence of canal stenosis at L4-L5 and L5-S1 levels and the existence of pressure effect on nerve in THECAL SAC and lat recess in patients with RCP was seen; and also a meaningful correlation among muscular myotonia, radicular distribution of limbs’ pain along with compressive effects on the nerve in the lat recess and the thecal sac and spinal canal stenosis were observed. A significant correlation between complaints of RCP in lower limbs and muscular myotonia with these findings was seen but in analyzing the distributing pain patterns or muscular myotonia on the base of RCP such a correlation was not seen.Low back pain, Radicular back pain, Magnetic resonance imaging


In this study we evaluate the feasibility of using a newly formed practice-based research network of nine U.S. leading integrative medicine centers, called BraveNet, to assess the utilization and costs of integrative medicine interventions used to treat patients who suffer from chronic pain.Adult patients seeking their initial treatment for chronic pain at a BraveNet center were asked to participate in a prospective, observational survey. Patient-level data collection included longitudinal measures of pain, quality of life, and integrative medicine treatment utilization. Study sites provided estimates of typical charges and insurance reimbursement amounts (when appropriate) for treatments available at each center. We computed the median charge for each service as a proxy for cost and multiplied these estimates by the quantities of specific services provided to each patient.A total of 409 patients initially enrolled in the study, with a mean duration of pain of 8 years at enrollment. A total of 322/409 (79%) patients completed a baseline visit and at least one follow-up visit at 6, 12, or 24 weeks. Over the 24 week study period these patients utilized a mean of 21.5 treatments and incurred mean costs of $2511, resulting in an average of $117 per treatment. The most frequently used therapies were acupuncture (40%) followed by massage therapy (20%), which were used an average of 11.5 and 12 times among patients receiving at least one session. Total costs varied widely by therapy, facility, and patient. Only acupuncture and integrative medicine consults were routinely reimbursed by private insurance. Mean out-of-pocket costs for acupuncture, integrative medicine consults, and massage therapy were $483, $173, and $184, respectively.Integrative medicine centers provide multiple treatment options for chronic pain. Wide variability in the cost and utilization of integrative medicine techniques poses a challenge to developing precise and generalizable estimates of cost-effectiveness.


Thoracoscopic anterior scoliosis instrumentation is a safe and viable surgical option for corrective fusion of progressive adolescent idiopathic scoliosis (AIS) and has been performed at our centre on 205 patients since 2000. However, there is a paucity of literature reporting on or examining optimum methods of analgesia following this type of surgery. A retrospective study was designed to present the authors’ technique for delivering intermittent local anaesthetic boluses via an intrapleural catheter following thoracoscopic scoliosis surgery; report the pain levels that may be expected and any adverse effects associated with the use of intrapleural analgesia, as part of a combined postoperative analgesia regime.Records for 32 patients who underwent thoracoscopic anterior correction for AIS were reviewed. All patients received an intrapleural catheter inserted during surgery, in addition to patient-controlled opiate analgesia and oral analgesia. After surgery, patients received a bolus of 0.25% bupivacaine every four hours via the intrapleural catheter. Patient’s perceptions of their pain control was measured using the visual analogue pain scale scores which were recorded before and after local anaesthetic administration and the quantity and time of day that any other analgesia was taken, were also recorded.28 female and four male patients (mean age 14.5 ± 1.5 years) had a total of 230 boluses of local anaesthetic administered in the 96 hour period following surgery. Pain scores significantly decreased following the administration of a bolus (p < 0.0001), with the mean pain score decreasing from 3.66 to 1.83. The quantity of opiates via patient-controlled analgesia after surgery decreased steadily between successive 24 hours intervals after an initial increase in the second 24 hour period when patients were mobilised. One intrapleural catheter required early removal due to leakage; there were no other associated complications with the intermittent intrapleural analgesia method.Local anaesthetic administration via an intrapleural catheter is a safe and effective method of analgesia following thoracoscopic anterior scoliosis correction. Post-operative pain following anterior thoracic scoliosis surgery can be reduced to ‘mild’ levels by combined analgesia regimes. Thoracoscopic anterior scoliosis correction is a safe and viable surgical option for corrective fusion of progressive adolescent idiopathic scoliosis -3, see Fet al. [The role of analgesia following thoracoscopy and thoracotomy for pulmonary pathology has formed an important part of the cardiothoracic literature. Intrapleural and paravertebral analgesia have been successfully used following cardiothoracic procedures involving thoracotomy -11, thoret al.  concludeFollowing spinal deformity correction, most previous literature has looked at analgesia methods after posterior instrumented fusion, particularly using patient-controlled analgesia, epidural, or local anaesthetic infiltration ,20. FollAccordingly, the aims of this retrospective case series analysis were to present the authors’ technique for delivering intermittent local anaesthetic boluses via an intrapleural catheter following thoracoscopic scoliosis surgery; report the pain levels that may be expected and any adverse effects associated with the use of intrapleural analgesia following TASF as part of a combined postoperative analgesia regime.et al.[et al.[et al.[A subset of the most recent 80 patients from a large, single centre consecutive series of 205 patients who had undergone TASF for progressive adolescent idiopathic scoliosis had their medical records reviewed. As the study involved the use of an existing database and the data being retrospectively collected from medical records was non-identifiable data, it was considered a clinical audit and exempt from requiring ethical review. The surgeries were all performed by the two senior authors (GNA and RDL) at the Mater Children’s Hospital, Brisbane, Australia. The indication for this type of surgery as opposed to a posterior selective thoracic fusion were: Lenke type 1 with thoracic Cobb angle between 40 - 70°, minimum of 50% correction of main thoracic curve on fulcrum bending radiograph, correctibility of any lumbar compensatory curve on side bending radiograph, and T5-T12 thoracic kyphosis angle of < 40°. Patient and deformity correction details were prospectively recorded in the departmental surgical database for all cases, from the larger patient series. The surgical procedure was based on the technique first described in 2001 by Picetti et al., and subl.[et al.. After dThe technique for using intrapleural analgesia was as follows: an intercostal epidural catheter was percutaneously inserted under direct vision at the end of the surgical fusion Figure , using aIn the immediate post-operative period, all patients provided self-assessment of their pain levels using a visual analogue pain score from zero to ten. This was recorded by nursing staff in the patients’ medical records every hour when awake. For inclusion in the study, patients were required to have pain scores recorded within one hour prior to local anaesthetic intrapleural bolus and between one and two hours following the bolus. These inclusion criteria were used to allow statistical analysis of changes in pain score before and after the intrapleural bolus. Details  regarding any use of opiates via patient-controlled intravenous administration and other oral analgesics were also recorded. Any adverse events related to analgesia were identified by reviewing medical and nursing entries in the patients’ medical records.Data analysis was undertaken using SPSS Version 17 . Pre- and post-bolus pain scores were compared using paired t-tests. Day to day changes in opiate usage were also assessed using paired t-tests, as was the mean hourly opiate usage before and after intrapleural catheter removal.Of the 80 medical records retrieved, 32 patients had sufficient data for inclusion in the study. There were 28 females and four males with a mean age of 14.5 ± 1.5 years . For the study cohort, a total of 230 boluses of local anaesthetic were administered via an intrapleural catheter for a period of 58.3 ± 16.4 hours  after surgery prior to its removal. One intrapleural catheter required early removal at 26 hours after surgery, due to leakage. The chest drain was removed at mean 61.1 ± 13.1  hours after surgery when the haemoserous exudate was draining at less than 150 mls per day.The remaining 48 patients  reviewed, where data was insufficient for inclusion in the analysis, were similar to the study group of 32, with mean age 16.0 ± 1.8 years . For this group, the chest drain was removed similarly at mean 60.0 ± 15.7  hours after surgery. For this group it was noted there were no adverse events or complications relating to their intrapleural analgesia.Pain scores significantly decreased following administration of an intrapleural bolus (p < 0.0001) with the overall mean pain score decreasing from 3.66 to 1.83. Figure The PCA was removed at mean 79.4 ± 16.5  hours after surgery. It remained in use for a longer duration than the intrapleural catheter in 27 patients; of the remainder, two patients had their PCA removed first, whilst three patients had the PCA removed at the same time as the intrapleural catheter. The mean quantity of opiate PCA used within each successive 24 hour interval during the post-operative period is shown in Table Research examining analgesia efficacy following surgery is essential, in order to ensure optimum post-operative care is given to patients. Due to the difficulty of insertion and placement of the thoracic epidural in patients with significant thoracic scoliotic deformities requiring instrumented fusion, the intrapleural analgesia technique was adapted at our centre to deliver local anaesthetic directly to the spine after anterior thoracic fusion surgery. This retrospective study was performed to present the authors’ technique of using intermittent analgesia via an intrapleural catheter, present patient reported pains scores after thoracoscopic scoliosis correction and identify any adverse events related to the technique.The use of an intrapleural catheter placed under direct vision in the operating theatre has several advantages; it allows the delivery of local anaesthetic directly to the site of the spinal levels involved in the instrumented fusion surgery and allows pre-emptive analgesia to be administered in these predominantly adolescent patients. Pre-emptive analgesia has been shown to have more beneficial effects and results in reduced analgesia dosages being used, as opposed to waiting for pain levels to increase prior to giving analgesia -30. EffeThe technique of giving an intermittent bolus as opposed to a continuous infusion of local anaesthetic, allows the delivery of a higher dose of anaesthetic and therefore a more concentrated effect to achieve a dense neural block and is in keeping with postoperative epidural practice. The chest drain is clamped for around 30 minutes during delivery of the bolus and at all other times functions normally to assist with the clearance of the pleural effusion. A chest drain under continuous suction would hinder the effectiveness of a continuous delivery of local anaesthetic so was considered inappropriate for patients after TASF. Postoperatively, patients don’t tend to complain of pain from the incisions/portals over their general spine pain. However the intrapleural anaesthetic bolus is able to freely flow in the pleural space so may have some effect on minimising pain originating from the portals. With the patients receiving a multi-modal analgesia approach it is difficult to attribute how much the intrapleural analgesia may ease any portal incision pain over the effects of the PCA and additional non-opiate oral analgesia.It is worth noting that for 42 of the 230 boluses 18%) assessed in the current study, the patients already had a pain score of zero before receiving a further local anaesthetic bolus, demonstrating good on-going analgesia between boluses. It is also important to note that, at our hospital, the use of intrapleural catheters and their analgesic effectiveness is carefully monitored on the ward by nursing, pharmacy and medical staff with the support of a specialised pain team. A protocol document to describe how to use the catheter, any potential complications, and the action to take in the event of any complication was developed  coincides with the patient being mobilised and sat out of bed for the first time since surgery and physiotherapy and nursing interventions commenced to achieve restoration of full lung re-expansion and volumes. Opiate usage decreased significantly between the second and third and third and fourth 24 hour periods and was lower again once the intrapleural catheter and chest drain were removed Figure . This maIt is our opinion that excellent pain management in the early couple of postoperative days with the multi-modal analgesia approach encourages rapid recovery and reduction of morphine use during the hospital stay. It also reduces the need to be prescribed prolonged usage of opiates after discharge home from hospital. In order to see if there was any association between the use of intrapleural analgesia and the required supplemental opiate analgesia, it would be necessary to perform a prospective cohort or randomised trial comparing patient-controlled analgesia with and without intrapleural catheter usage. Surgeons may wish to expand and validate the use of the intrapleural analgesia technique for use with open or minimally invasive anterior scoliosis correction or anterior release procedures prior to posterior instrumented fusion surgery.This study has demonstrated a safe method of providing effective analgesia directly onto the spinal levels involved in thoracoscopic anterior scoliosis correction using a local anaesthetic bolus via an intrapleural catheter inserted in theatre. The results found that local anaesthetic boluses significantly decrease visual analogue pain scores and, when used in conjunction with multi-modal analgesia, resulted in ‘mild’ levels of pain in the immediate post-operative period following anterior scoliosis correction. The intermittent intrapleural analgesia method was not associated with any adverse events or complications and in part this can be attributed to the educated and well-coordinated care team consisting of nursing staff, physiotherapists, anaesthetic personnel and the surgical team.All authors declare they have no competing interests.All the authors participated in the conception and design of the study. GNA and RDL performed the surgical procedures and were involved in critically reviewing the manuscript. SAC and MTI reviewed the literature, collected and collated the data and with CJA performed the statistical analysis, interpretation of the data and critically reviewing the manuscript. SAC and MTI drafted and revised the manuscript, with all authors critically reviewing the work regularly. All authors read and approved the final manuscript.


Background. Since data on pain evaluation and management in patients admitted to internal medicine wards (IMWs) are limited, we aimed to evaluate these aspects in a cohort of internistic patients. Methods. We considered all patients consecutively admitted from June to December 2011 to our unit. Age, gender, and length-of-hospital-stay (LOS) were recorded. Comorbidities were arbitrarily defined, and pain severity was evaluated by Numeric Rating Scale (NRS) on admission and discharge. Results. The final sample consisted of 526 patients . Significant pain (NRS ≥ 3) was detected in 63% of cases, and severe (NRS ≥ 7) in 7.6%. Pain was successfully treated, and NRS decreased from 4.65 ± 2.05 to 0.89 ± 1.3 (P < 0.001). Compared with subjects with NRS < 3, those with significant pain were older , and had a higher LOS . Significant pain was independently associated with age , cancer , musculoskeletal disease , biliary disease , and bowel disease . Conclusion. In an internal medicine setting, multiple diseases represent significant cause of pain. Prompt pain evaluation and management should be performed as soon as possible, in order to avoid patients' suffering and reduce the need of hospital stay. Pain is a common symptom and moderate-to-severe pain has been reported to affect up to 50% of community dwelling older adults and up to 80% of nursing home residents . In ItalA survey analyzing the quality of documentation related to pain measurement and treatment in patients discharged from hospitals of the Tuscany Region of Italy has been recently published . Out of The aim of this study was to evaluate pain prevalence and management associated with a simple pain measured by NRS, in a cohort of consecutive patients admitted to an IMW.We conducted an observational prospective study involving all adult patients consecutively admitted from 1 June to 31 December 2011 to the 30 beds IMW of Clinica Medica, Azienda Ospedaliera-Universitaria S.Anna, Ferrara, Italy. All patients received detailed information about the study and gave consent to participate. Subjects with cognitive impairments, with major sensorial deficits, or unable to understand the opposite information paper, and those who refused to participate were excluded. The study was approved by the local ethical committee .Age and gender were recorded, and length-of-hospital-stay (LOS) was calculated. Comorbidity was arbitrarily defined by classifying diseases in subgroups: cancer, heart, pulmonary, vascular, musculoskeletal, neurological, cutaneous, renal, hepatic, biliary, metabolic, pancreatic, gastric, and bowel diseases. Moreover, the presence of positive history of surgery was also evaluated.Oncologic disease included malignancy in every apparatus or organ. Cardiac disease included infectious, inflammatory, ischaemic, and valvular diseases and arrhythmias. Heart failure was excluded. Pulmonary diseases included infectious, inflammatory, and vascular disease of lungs or pleura. Vascular diseases included damage of main and medium venous or arterial vessels. Musculoskeletal diseases included all the processes leading to altered function of bone and muscles. Neurological diseases included degenerative and ischaemic damage of central nervous system. Cutaneous diseases included all processes that altered the skin. Nephrologic diseases included all processes responsible of acute or chronic reduction of renal function. Hepatic diseases included all processes producing liver dysfunction. Biliary diseases included infectious, inflammatory, and dysplastic processes with and without jaundice and gallstones. Metabolic diseases included obesity and diabetes mellitus. Pancreatic diseases included acute and chronic pancreatitis and malignancy. Gastric diseases included infectious, inflammatory, and dysplastic processes. Bowel diseases included infectious, inflammatory, and dysplastic processes. Diverticulitis were also included. Postsurgery condition included all patients who underwent any recent operation in any apparatus or organ. To evaluate comorbidities, the Charlson comorbidity index was calculated . Such scNRS was used in order to assess pain. Patients defined their pain referring to a 0 to 10 scale with “0” representing “no pain at all” and “10” representing “the worst imaginable pain.” Pain was defined as mild (1 ≤ NRS < 3), moderate (3 ≤ NRS < 7), and severe (NRS ≥ 7). Subjects were considered to have significant pain when NRS was equal or greater than 3. NRS was recorded on both admission and discharge, and administration of analgesic drugs before and during admission was also recorded.t-test, Mann Whitney U test, and Chi Squared tests, as appropriate. A two-tailed P value of <0.05 was considered significant. In order to evaluate which variables were independently associated with moderate and severe pain, logistic regression analysis was performed.Data were analyzed using SPSS ; continuous data were reported as mean and standard deviation, and categorical variables as percentage. Patients were divided into two groups: patients without pain and with mild pain (NRS < 3) and patients with moderate to severe pain (NRS ≥ 3). These two groups were compared using on admission are indicated in The final sample consisted of 524 patients (mean age 74 ± 14), 307 women and 217 men. LOS was 7.7 ± 6.4 days. Classification and frequency of comorbidities and prevalence of the different intensity of pain patients groups P < 0.001). Subjects with significant pain were older, had greater prevalence of cancer, heart, peripheral vascular, musculoskeletal, biliary, and bowel diseases, and had also higher prevalence of surgery history compared with patients with NRS < 3 (P = 0.048) (P = 0.018), cancer , musculoskeletal disease , biliary disease , and bowel disease , whereas all the other clinical characteristics were not associated to significant pain.Pain was defined as visceral and continuous in 213 patients (40.6%), burning in 146 (27.9%), cramping in 113 (21.6%), oppressive in 82 (15.6%), and lancinating in 20 (3.8%). Pain duration was reported to be less than 2 hours in 9 cases (1.7%), between 2 and 6 hours in 47 cases (9%), between 6 and 12 hours in 77 cases (14.7%), between 12 hours and 3 days in 70 cases (13.4%), and more than 3 days in 128 cases (24.4%). Patients were treated with NSAIDs in 61 cases (11.6%), paracetamol in 31 cases (5.9%), paracetamol plus codeine in 42 cases (8%), opioids in 75 cases (14.3%); 84 subjects (16%) were treated with different drugs. In  NRS < 3 . Again, = 0.048) . SignifiThis study shows that pain (moderate to severe) is present in more than 40% of patients admitted to an IMW, and attention and appropriate management may lead to a significant pain reduction. Moreover, such successful outcome might have also economic advantage, derived from a significant reduction of LOS. In 2012, Gustavsson et al.  evaluateNowadays, pain is considered not merely as a symptom but as an actual disease process , and forPain is a very important medical and social problem worldwide. In 2006 Breivik et al.  reportedTo the best of our knowledge, this is the first study that analysed all the aspects of management of pain in an Italian IMW after the introduction of the 2010 Italian specific law. However, some limitations should be underlined. First of all we did not include in our analysis pain management in the emergency department; in fact, drugs given to patients at the time of that evaluation could influence pain evaluation at the time of IMW admission. Second, we did not screen subjects with cognitive impairment, these kind of evaluation is better performed in geriatric wards where physicians are trained to manage such a patients. Third, we include in the analysis postoperative patients; however, our aim was merely do analyse pain management in an IMW, where due to shortage of hospital beds it could be that postoperative patients need to be managed. Fourth, we measured pain by ordinal scale on admission and discharge, and we have not intermediate data. On the other hand a reduction in the values of pain scale and administration of drugs for pain management underlines a careful evaluation of this parameter. Fifth, we arbitrarily defined patients without significant pain those with NRS < 3, due to the fact that such pain intensity does not require medical intervention.An appropriate knowledge of prevalence of pain, its causes and intensity, and patient satisfaction after pain management are key points for evaluating the impact of the interventions performed and the overall skill of our teams to tackle pain emergency in the hospitalized population. In our study, pain was successfully treated with standard therapy, even if moderate to severe pain was related to higher LOS, with consequent time and resources consuming. Our data showed that pain management could be considered good, and mean NSR value on discharge could be considered satisfactory. However, the use of scale for determining intensity of pain could not be completely satisfactory.In conclusion, pain is a frequent condition in subjects admitted in IMWs, and multiple diseases other than cancer represent possible causes. Since internists are familiar with these kind of diseases, a prompt pain evaluation and management should be performed as soon as possible, in order to either avoid patients' suffering and reduce the length of hospital stay.


The objective was to investigate how postural control in knee osteoarthritis (KOA) patients, with different structural severities and pain levels, is reorganized under different sensory conditions.−2, age range from 50 to 74 years) with KOA were evaluated. One minute of quiet standing was assessed on a force platform during 4 different sensory conditions, applied 3 times at random: Eyes open (EO) and eyes closed (EC) standing on firm and soft (foam) surfaces (EO-soft and EC-soft). Centre of pressure (Cop) standard deviation, speed, range and Cop mean position in both directions  were extracted from the force platform data. Structural disease severity was assessed from semiflexed standing radiographs and graded by the Kellgren and Lawrence (KL) score. Pain intensity immediately before the measurements was assessed by numeric rating scale (range: 0–10).Forty-two obese patients (BMI range from 30.1 to 48.7 kg*mP<0.01). Positive correlation between pain intensity and postural sway  was found during EC condition, indicating that the higher the pain intensity, the less effective is the postural control applied to restore an equilibrium position while standing without visual information.The patients were divided into “less severe”  and “severe”  group. The CoP range in the medial-lateral direction was larger in the severe group when compared with the less severe group during EC-soft condition (The results support that: (i) the postural reorganization under manipulation of the different sensory information is worse in obese KOA patients with severe degeneration and/or high pain intensity when compared with less impaired patients, and (ii) higher pain intensity is related to worse body balance in obese KOA patients. Knee osteoarthritis (KOA) is a progressive joint disease associated with pain in and around the knees etalWhile standing, the body sways constantly, requiring continuous correction of its position to maintain stability. Three major sensory systems provide information for constructing an internal body model that represents the different body segments relative to the surrounding environment: (i) visual, (ii) vestibular, and (iii) somatosensory The aim of the present study was to investigate: (i) posture control reorganization in obese KOA patients during different sensory conditions, (ii) the relationship between this reorganization and the KOA severity degree. We hypothesize that patients will have worst postural stability in conditions where the sensory information is altered and this impairment will be positively correlated with degeneration and/or pain intensity in these patients.−2) KOA patients were randomly included after giving their written informed consent. Eligibility criteria for the CAROT study were to be older than 50 years, with primary KOA diagnosed according to the American College of Rheumatology criteria The participants were recruited arbitrarily among patients at baseline of the CAROT study (influence of weight loss or exercise on cartilage in obese knee osteoarthritis patients (KOA) patients: a randomized controlled trial, CAROT  The study was approved by the local ethical committees of the municipalities of Frederiksberg in Copenhagen (H-B-2007-088) and conducted in accordance with the Helsinki Declaration.The patients were asked to stand as quiet as possible during one minute on a force platform measuring the ground reaction forces and moments produced by their postural sway. Four different experimental conditions were applied 3 times randomly to evaluate quiet standing balance: (i) Eyes open with firm surface, (ii) eyes closed with firm surface, (iii) eyes open with soft foam surface, and (iv) eyes closed with foam surface.−3)  placed on top of the force platform. Line grids on the foam were used to mark the patient foot position in other to match with the position used during the firm surface condition.The subjects stood barefoot and adopted a standard position with their feet comfortably positioned side-by-side (about shoulder width apart) and arms positioned along of the body, while standing on the force platform. The position of the feet was marked to ensure that the subjects always used the same position over all trials. The subjects were asked to focus on a fixation point  placed on a white wall 6 m in front of them. During the foam surface condition, the subjects stood on a 45.7×45.7×12.7 cm  foam  recorded the ground reaction forces and moments (1 kHz) through dedicated software (Vicon Nexus® 1.7.1). Prior to storage in the computer, the signals were amplified and low-pass filtered at 10 Hz. For the quiet standing sway analyses, center of pressure (CoP) standard deviation, speed, range and CoP mean position in both directions , were calculated based on 50s (first and last 5 seconds were excluded) of the quiet standing tasks. Average scores from three repeated trials were used for analysis.All patients completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) For data analysis the KL score from the most affected knee was used to separate the patients in two different groups: (i) “less severe” (KL 1 and 2) and (ii) “severe” (KL 3 and 4).disease severity  as between-group factor and four sensory conditions implemented as two repeated-measures factors: surface (firm and soft) and vision (eyes closed and open). Age, gender and body mass index (BMI) were used as covariant variables in the statistical models. In case of significant factors in the ANOVA, Newman-Keuls (NK) post-hoc tests were performed for multiple comparisons. Spearman's rank order correlation analyses were performed between pain intensity, KL score, and the CoP variables that reached significant 3-way interaction in the ANOVA. Significance was accepted at P<0.05.The data is presented as mean and standard error of the mean (SEM). T-test for independent samples was used to analyze the KOOS data between “less severe” and “severe” groups; non-parametric Mann-Whitney U-test was used for the pain intensity and KL score analyses. A 3-way mixed model analysis of variance (ANOVA) was used to analyze the data, with −2 and “severe”: 36±4 kg*m−2).Forty-two  of the initial forty five patients were included in the analyses since 3 patients were unable to finish the postural tasks. The remaining patients were classified according to their disease progression The average pain intensity was higher in the “severe” patients when compared with “less severe” patients . Correla−2 respectively.Examples of CoP excursion for representative “severe” and “less severe” patients are illustrated in The ANOVA results indicated a 2-way interaction between surface and vision, where CoP speed (Significant 2-way interaction between surface and vision indicated that eyes closed conditions compared with eyes open conditions (while standing on the foam surface), significantly: (i) increased the CoP standard deviation in the anterior-posterior direction  CoP standard deviation in the anterior-posterior direction  = 53.3, P<0.01, NK: P<0.01), (ii) CoP velocity in the medial-lateral  = 42.2, P<0.01, NK: P<0.01) and the anterior-postural direction  = 57.6, P<0.01, NK: P<0.01), and (iii) CoP range in the medial-lateral  = 61.9, P<0.01, NK: P<0.01) and anterior-posterior direction  = 79.9, P<0.01, NK: P<0.01).A significant 3-way interaction between disease severity, surface and vision indicated that the “severe” group showed significantly larger CoP range in the medial-lateral direction compared with the “less severe” group during the eyes closed with soft surface condition  at the knee joint and pain intensity affects postural sway. The severe group presented higher levels of pain immediately before the balance tests, worst scores for quality of life and symptoms and increased sway in the medial-lateral direction during eyes closed condition on soft surface when compared with less severe patients. A positive correlation between pain intensity and KL scores was found. Pain intensity was positively correlated with increased postural sway  while standing on firm surface when visual input is not available.etal.The relation between knee osteoarthritis severity and postural sway under different sensory conditions is a novel finding. Previous studies on postural stability in KOA patients have mainly focused on the difference between patients and matched control subjects and found that KOA patients have an unstable balance Shifting the CoP position forward in the anterior-posterior direction is a normal postural strategy to avoid loss of balance in healthy subjects in presence of experimental knee pain While standing on soft surface with eyes closed, the severe group swayed approximately 1.5 cm more  when compared to the less severe group . In thisIt is crucial that patients are able to reorganize their dependence on each sensory information  according to changes in the environment etalTeasdale The results support the hypothesis that, the postural reorganization under manipulation of the different sensory information is deteriorated in KOA patients with severe degeneration and/or high pain intensity when compared with less impaired patients. Vision information seems to account for the postural corrections in conditions where the sensory information from the feet's sole is affected. During these conditions, pain intensity was positively correlated with balance impairments, revealing an important role of pain in postural adjustments of obese KOA patients when the environment poses sensory challenges. There are indications that, in healthy subjects, the dynamic sensory reweighting can be optimized via specific training program and enhance balance in altered environments


It was with great interest that we read “The Effects of Bariatric Surgery Weight Loss on Knee Pain in Patients with Osteoarthritis of the Knee” by Edwards et al. . As otheWe found it valuable that the authors conducted a joint-driven and hypothesis-driven study to track pain and functional improvement in patients who underwent the three types of bariatric surgery: gastric bypass, sleeve gastrectomy, and laparoscopic adjustable gastric banding (LAGB). We agree with the authors that the existing literature is limited in examining the effect of bariatric surgery on KOA, particularly with confirmation of patients' radiographic KOA and the utilization of validated tools such as Western Ontario and McMaster Universities (WOMAC) Index of Osteoarthritis, Knee Osteoarthritis Outcome Score (KOOS).  The authors provided encouraging data, but it was unclear whether medications including acetaminophen, nonsteroidal anti-inflammatory drugs, tramadol, narcotics, topical agents, or intra-articular injections were given to patients for their knee pain during the study period. Any change in a patient's treatment regimen for KOA may contribute to the improvement of pain and function, beyond weight loss alone from bariatric surgery, and impact the findings. While it is unreasonable to ask patients to avoid any pain medication during such studies, it would be helpful to the readers to view the treatments and draw their own conclusions. In addition, the study does not report the individual ages (ranging from 18 to 70 years), demographics, or body mass indices (BMIs) of the 24 patients enrolled, or, perhaps, mean ages and BMIs of the 3 surgical subgroups. In our center we are seeing a subcohort of often younger patients with painful knee OA but only mild-moderate obesity (BMI 30–35) who would qualify for the less-invasive LAGB by recent FDA guidelines , but ins In conclusion, this study supports recent arguments –12 that


At least 50 % of female migraineurs experience migraine associated with the perimenstrual period, even though they may also suffer from attacks at other times of the cycle . MRM attacks tend to be longer and more intense than those arising in other phases of the menstrual cycle, and are often aggravated by more pronounced vegetative phenomena. In this open preliminary trial, we tested the efficacy of associating frovatriptan and dexketoprofen for the treatment of an acute attack of MRM, diagnosed according to the criteria of the International Headache Society, in 24 patients between 19 and 45 years of age (mean 31.33 ± 7.33). Twenty-one of them completed the study. Pain relief was achieved by 76 % of patients at 2 h and by 86 % at 4 h. A pain-free state was achieved by 48 % at 2 h and by 62 % at 4 h from taking the product. A pain-free state at 24 h was present in 76 % of MRM sufferers, 33 % of whom showed a sustained pain-free state at 24 h. A rescue medication was needed by eight patients. While decidedly encouraging, the data of this study obviously need confirmation with double blind studies involving a greater number of patients. Migraine predominantly affects the female sex, with a female to male ratio of approximately 3:1 . One of Menstrual migraine (MM) is a highly prevalent condition associated with considerable disability. At least 50 % of female migraineurs experience migraine associated with the perimenstrual period, even though they may also suffer from attacks at other times of the cycle  . Most ofTriptans are recommended as the first-line treatment for moderate to severe migraine attacks , includiThis was tested by combining 85 mg sumatriptan and 500 mg naproxen sodium in a single tablet, which was proposed as a way to potentiate the therapeutic effect in cases of MRM . The eff1B/1D receptors and a long half-life, both of which contribute to its distinctive clinical effect of having a more sustained and prolonged action than other triptans. Indeed, frovatriptan not only proved effective for treating the acute attack of MM, but particularly for short-term preventive therapy of MM [Frovatriptan, one of the newest triptans, has a high affinity for 5-HTpy of MM . In addipy of MM . Recent py of MM .t max and half-life of dexketoprofen are 30 min and 2 h, respectively. We have previously demonstrated in 42 women affected by migraine with or without aura that dexketoprofen very quickly reduces pain intensity and accompanying symptoms [Dexketoprofen is a NSAID that blocks the action of cyclo-oxygenase, which is involved in PGs production, thus reducing inflammation and pain . The t msymptoms .Based on the pharmacological properties of the two products, both of which have already proven to be effective in treating migraine, we decided to test the combination of frovatriptan and dexketoprofen, in an open preliminary trial, to determine the efficacy of using them together for the treatment of an acute attack of MRM.The study involved 24 patients between 19 and 45 years of age  from the Women’s Headache Center of the University of Turin, and suffering from migraine associated with menstruation , diagnosed according to the criteria of the International Headache Society . The patients were told to treat an attack of MRM by self-administering simultaneously a tablet of 2.5 mg frovatriptan and one tablet of 25 mg dexketoprofen, as soon as possible from the beginning of the migraine attack. If the frovatriptan + dexketoprofen combination proved to be ineffective, the patients were allowed to assume a rescue medication for pain, provided that it be taken at least 2 h later. The patients filled out a diary that was specially designed to highlight the characteristics of the migraine pain during the course of treatment.Reported here are the results regarding the pain relief state and the pain-free condition at 2 and 4 h from commencing treatment. In addition, data about the pain-free state at 24 h and the sustained pain-free state at 24 h are pointed out.Two patients filled in the treatment diary incorrectly and one patient failed to come to the post-treatment follow-up and were, thus, excluded from the data analysis, which therefore took into account 21 patients. Pain relief was achieved by 16 women (76 %) at 2 h and by 18 women (86 %) at 4 h  at 2 h and by 13 patients (62 %) at 4 h from taking the product  and even more remarkably at 24 h (76 %). Comparative studies of other triptans were used for treating, an acute attack of MRM showed that frovatriptan is highly effective when used alone it produced a pain-free state in 52 % of the patients at 4 h, and in 66 % of the patients at 24 h . Therefo