Proximal hamstring tendinopathy typically afflicts athletes. The poor knowledge of this pathology can lead to late diagnosis and late treatment, which in chronic cases could be challenging. Surgical treatment could resolve the symptoms and could permit the return to full sport activity also in chronic cases.We retrospectively evaluated 17 high-level athletes surgically treated for proximal hamstring tendinopathy. Symptoms lasted for an average of 23 months and were resistive to conservative treatment.The follow-up period averaged 71 months. Return to run without pain occurred at a mean of 2.4 months (range 1–4) after surgery. All patients returned to sports at their pre-symptom level at a mean of 4.4 months after surgery. Results were excellent in 15 patients (88 %) and good in two patients (12 %). No results were fair or poor.Surgical treatment to manage chronic proximal hamstring tendinopathy in high-level athletes showed excellent results in terms of relief from symptoms and return to previous sport level. Proximal hamstring tendinopathy (PHT) was firstly described by Puranen and Orava in 1988 with the name of “hamstring syndrome” .On clinical examination, there is sometimes a deep focal tenderness at the ischial tuberosity. Active stretch tests of the posterior thigh recreate a sensation of tightness or pain at the ischial tuberosity. Peripheral neurological tests are typically normal, no weakness is reported in knee flexion and hip extension , 4.Hamstring muscles overuse or previous acute hamstring strains are a common background. In most serious cases the consequent fibrosis can tether the sciatic nerve to the hamstring muscles leading to its irritation, compression or traction .The typical magnetic resonance imaging (MRI) findings of PHT are increased signal intensity on T1-weighted and proton-density images of proximal hamstring tendon intrasubstance, an increased tendon girth on axial views and asymmetric involvement of hamstring tendon in unilateral cases , 5.Biopsy specimens from the hamstring tendon of patients with PHT showed typical morphologic findings of tendinosis , absence of fibrocartilagineous metaplasia or calcification and no inflammatory cells .The PHT is often misdiagnosed; also even when diagnosis is made, decision-making can be challenging.This condition could frustrate the patient, who is often a high-level sportsman and needs to return to competition as fast as possible.As with other tendinopaties, the first option of treatment is nonoperative and includes: modified or complete rest from sporting activity, stretching of the hamstrings, local and systemic nonsteroidal anti-inflammatory drugs (NSAIDs), physiotherapy, shockwave therapy, eccentric strengthening, and local steroidal injections –8. SurgeThe goal of this study is to present the long-term results of delayed surgical treatment for chronic PHT in elite athletes, hoping to help clinicians to manage the decision-making process.We performed a retrospective chart review of 17 sportsmen presenting for surgical treatment of chronic PHT by the senior author between January 2000 and July 2009. Twelve patients (71 %) were men and 5 (29 %) were women. The average age was 26.6 years . Nine patients (53 %) were professional athletes at the international level, with an average age of 25.0 years ; eight (47 %) practiced sport at a competitive level, with an average age of 28.5 years . Thirteen (76 %) were in track and field sports, two (12 %) were long-distance runners and two (12 %) were footballers  of the thigh were routinely performed; we additionally asked the patients about their medical history and previous diagnoses. After surgery, a questionnaire, submitted through interviews at the time of follow-up, allowed us to collect further information about: time needed for walking, for running without pain and for return to competitive activity, recurrences and patient’s satisfaction. Pain was assessed by VAS : from 0 (no pain) to 10 (maximum pain experienced). Results were classified as excellent, good, fair and poor according to residual symptoms and return to sports. The result was considered excellent if the patient was asymptomatic and returned to the same pre-symptom level of sports; good if he felt pain during intense efforts, but anyway he returned to his previous level of participation. The result was fair if symptoms persisted after surgery and the athlete was forced to a lower level of participation, and poor if the patient was unable to return to sport.The study conforms to the Declaration of Helsinki and was approved by the institutional committee for medical ethics. All patients provided informed written consent.All patients had chronic pain in the lower gluteal region, mostly at the site of the ischial tuberosity; four patients 23 %) referred pain radiating along the posterior aspect of the thigh down to the popliteal fossa. Sport evoked pain in 14 patients (82 %): nine by sprinting and five also by running at constant speed; three patients (18 %) had pain irrespective of sport activity. Eight patients (47 %) felt pain also during a prolonged sitting position. At the time of clinical examination, symptoms involved only one side in all cases. Clinical assessment is resumed in Table 3 % referThere are no internationally validated score for PHT. We consider the return to preoperative level of activity as the best evaluation of the treatment proposed. The average pre-symptoms Tegner Score was 7.8 ; the average preoperative Tegner Score was 4.8 .The average VAS score for pain was 6.9 . Pain appeared and increased gradually without any acute event; however, 13 patients (76 %) had almost one previous acute hamstrings strain occurringat an average of 7.9 months (range 6–10) before the onset of symptoms. These lesions were documented by ultrasonography at the time of injury; they involved the bellies of the biceps femoris muscle in seven cases, the belly of the semitendinosus muscle in two cases, and the semimembranosus in four cases.In all patients, the pre-operative MRI of the thigh showed: signal alterations of hamstring tendons or bellies compatible with scars of distractive injuries, thickening or edema of the tendons, irregularity in the morphology of the muscle fibers and of the perineural tissue of the sciatic nerve Fig. . The comSix patients (35 %) had also ultrasonography; in all cases could be recognized scars of previous distractive injuries of the hamstring, but it didn’t clearly define them. Electroneuromyography (ENMG) was done in 14 patients (82 %), showing no abnormalities in sciatic nerve conduction.All patients were initially treated conservatively elsewhere with various non-surgical methods.local steroidal injections in seven patients (41 %);physical therapy  in eight patients (47 %);other physiotherapeutic techniques  in 12 patients (71 %);local and systemic NSAIDs in five patients (29 %);eccentric contraction exercises of hamstrings in all cases.Conservative therapy consisted of:The average duration of conservative treatment was 4.5 months .Symptoms caused limitation or interruption of sport participation;MRI findings were suggestive for hamstring tendinopathy or scars of their previous tears;Conservative treatment was not effective.Surgical treatment was performed if:The average time between the onset of symptoms to surgery was 23 months . This period lasted less than one year in three patients (18 %), between 1 and 2 years in eight patients (47 %), between two and three years in four patients (23 %) and between three and four years in two patients (12 %). Surgery was performed with the patient prone and the leg flexed to relax the hamstring muscles and the sciatic nerve; incision started from the ischial tuberosity extending 8–15 cm distally. The posterior cutaneous femoral nerve was carefully spared and the superficial fascia sectioned. The distal edge of the gluteus maximus muscle was reached and retracted superiorly; the proximal insertion of hamstring muscles was then exposed . Results were classified as excellent in 15 patients (88 %) and good in two patients (12 %). There were no fair or poor results. No recurrence was reported. Return to walk without pain occurred at an average time of 22 days after surgery . Stretching exercises were free from pain at a mean of 36 days after surgery . Running without pain occurred at a mean of 2.4 months after surgery   to 10 . Complications occurred in two patients (12 %). There was one (6 %) immediate complication (occurring in the first week after surgery), consisting in postoperative hematoma. It required surgical drainage 24 h after the first operation. The same patient had also a slower wound healing, treated with prolonged medications and it wasresolved in three weeks. The rehabilitation program was delayed about two weeks. A delayed complication occurred once (6 %); it consisted in hyperesthesia of the skin around the surgical scar, spontaneously clearing up in six weeks.The post-surgical MRI findings are shown in Fig. The most important finding of our study is that surgical treatment of PHT in competitive and high-level athletes permits return to sports at the same pre-symptom level as also in chronic situations. In our series it occurred on an average of 4.4 months, a good result comparable with recent literature , 9. CompAnother important finding is that previous hamstring strains are a common background of PHT. In our series, 76 % of patients had previous hamstring tears; others studies reported lower percentages, ranging from 19 to 34 % . HamstriIn our series, direct examination during surgical treatment confirmed pre-operative MRI findings in all patients; in two cases surgery better defined a solitary lesion of the biceps femoris muscle, previously indicated by MRI as a lesion of the common hamstring tendon. So, we consider MRI a mandatory investigation to get a correct diagnosis and satisfying preoperative planning; we do not recommend ultrasonography as the only preoperative investigation because of its low precision and sensitivity, and the need of a radiologist expert in this poorly understood but widely known injury. Due to the poor knowledge of PHT by many team physicians and sport health specialists, including orthopedic surgeons, often the time span between the onset of symptoms and the correct diagnosis is very long, and treatment is initially directed towards other pathologies , 7, 12.In our experience, differential diagnostics must consider hamstring muscle tears, piriformis syndrome, ischiatic bursitis and chronic posterior compartment syndrome of the thigh; their localization, clinical manifestations and type of patients (young adult athletes) are the same for PTH. Then, sacroiliac joint pathologies and lumbosacral sciatica should be considered. More unusual pathologies are hematomas or soft-tissue tumours of the thigh .In hamstring muscle tears, pain is acute and localized more distally in the belly; often a painful palpable defect is present. Piriformis syndrome is characterized by buttock pain, rarely sciatica, leg weakness during exercise, resulting from sciatic nerve compression by the contracted and hypertrophied piriform muscle. Pain location, specific tests (Pace’s sign and Freiberg’s sign) and MRI findings demonstrating hypertrophy of the piriformis muscle are indicative.In ischiatic bursitis, pain is located in gluteal region and evoked by palpation of the ischial tuberosity or by a prolonged sitting position. Unlike proximal hamstring tendinopathy, pain occurs at rest, disturbs sleep, and forces the patient to a continuous search for a more comfortable position.Chronic posterior compartment syndrome of the thigh is another sport pathology caused by functional overload of hamstrings leading to their fast hypertrophy not followed by distension of their fascia; pain occurs during exercise, but not in the sitting position. In proximal hamstring tendinopathy nerve conduction studies are typically negative. Anyway, adhesions between the sciatic nerve and the thickened proximal hamstring tendons could cause episodic nervous compression; it typically occurs during stretching or the forward swing phase of running –3. In ouProximal hamstring tendinopathy is an invalidating condition for patients, who are often high- level athletes that need a quick return to a complete performance status. Conservative treatment is the first therapeutic step, but its efficacy is controversial moreover because of lack of standardize treatment protocols . AccordiWhen the diagnosis has been made, if the athlete already and unsuccessfully went through different treatment protocols, time wasting with additional conservative treatment is not advisable; operative treatment seems to be the sole solution to remove the cause of the disorder , 9.Our surgical treatment lightly differs from those proposed by Young and Orava , 13. We We believe performing the tenotomy of the thickened tendon is enough to free the sciatic nerve and to release proximal hamstring at the origin. Moreover, analyzing the outcome of proximal hamstring injuries, Askling et al. found thThis study has certain limitations. It is a retrospective case series, without a control group; most data were collected from medical records, but information about the postoperative period was obtained by a later questionnaire, which permitted collecting only subjective symptoms. A randomized controlled trial is needed to assess the optimal treatment.


There has been increasing focus on factors predicting the development of chronic musculoskeletal disorders. For patients already experiencing chronic non-specific low back pain it is also relevant to investigate which prognostic factors predict recovery. We present the design of a cohort study that aims to determine the course and prognostic factors for recovery in patients with chronic non-specific low back pain.All participating patients were recruited (Jan 2003-Dec 2008) from the same rehabilitation centre and were evaluated by means of  questionnaires and physical examinations at baseline, during the 2-month therapy program, and at 5 and 12 months after start of therapy. The therapy protocol at the rehabilitation centre used a bio-psychosocial approach to stimulate patients to adopt adequate (movement) behaviour aimed at physical and functional recovery. The program is part of regular care and consists of 16 sessions of 3 hours each, over an 8-week period , followed by a 3-month self-management program. The primary outcomes are low back pain intensity, disability, quality of life, patient's global perceived effect of recovery, and participation in work. Baseline characteristics include information on socio-demographics, low back pain, employment status, and additional clinical items status such as fatigue, duration of activities, and fear of kinesiophobia. Prognostic variables are determined for recovery at short-term (5 months) and long-term (12 months) follow-up after start of therapy.In a routine clinical setting it is important to provide patients suffering from chronic non-specific low back pain with adequate information about the prognosis of their complaint. In the Netherlands, the annual incidence of back pain in the general population is estimated at 10-15% . CNLBP hA recent systematic review investigating which outcome measurements were used to define recovery of low back pain in the past 10 years, concluded that almost every study defined recovery differently . AlthougTherefore, we present the design of a cohort study that investigates the course of patients with CNLBP undergoing treatment in an outpatient rehabilitation centre. Also investigated are prognostic factors for recovery using the outcomes low back pain intensity, low back pain specific disability, generic health status, patient's global perceived effect of recovery and work participation on both the short (5 month) and long (12 month) term.This study is a prospective cohort study. Patients were recruited (from January 2003 - December 2008) in a multidisciplinary outpatient rehabilitation clinic the 'Spine & Joint Centre' (SJC) in Rotterdam. The Medical Ethics Committee of SJC approved the study protocol and all participants provided informed consent.In the present study, low back pain is defined as 'non-specific low back pain', i.e. low back pain without a specified physical cause, such as nerve root compression (the radicular syndrome), trauma, infection or the presence of a tumour. Pain in the lumbosacral region is the most common symptom in patients with non-specific low back pain. Pain may also radiate to the gluteal region or to the thighs, or to both .Patients with CNLBP (low back pain duration > 3 months) not recovering after primary and/or secondary care were referred by their general practitioner (GP) or specialist to the SJC for a diagnostic consultation.The inclusion criteria for this study are:• Men and women aged 18 years or over;• Having CNLBP (i.e. a duration of low back pain for ≥ 3 months);• Previous and insufficient treatment in primary and secondary care (e.g. physiotherapy);• Signed informed consent.Exclusion criteria are:• Insufficient knowledge of the Dutch language;• Signs indicating radiculopathy: asymmetric Achilles tendon reflex and/or (passive) straight leg raise test restricted by pain in the lower leg; positive magnetic resonance imaging findings for disc herniation;• Recent (< 6 months) fracture, neoplasm or recent previous surgery (< 6 months) of the lumbar spine, the pelvic girdle, the hip joint, or the femur;• Specific causes such ankylosing spondylitis and systemic disease of the locomotor system;• Being pregnant or ≤ 6 months post-partum at the moment of consultation.Based on a bio-psychosocial understanding of CNLBP the following steps are followed Figure :The intake is a 3-hour session in which: 1) the patient fills in psychometric questionnaires by computer; 2) a recording is made of the patient's strength (Isostation B200), a motion analysis of forward bending of the lumbar pelvic rhythm (video registration) of the trunk, and 3) the patients sees a physician for history taking and physical examination. The physician may request an additional consultation with a psychologist and/or manual physiotherapist before deciding on treatment management.Patients meeting the inclusion criteria for the SJC are invited to participate in the multidisciplinary treatment program. Those not wishing to participate in this program are referred to their GP with a letter containing appropriate recommendations.In the therapy protocol, behavioural principles are applied to encourage patients to adopt adequate normal behavioural movement aimed at physical recovery. The program consists of 16 sessions of 3 hours each, over a 2-month period  located in the SJC. During the program patients are educated to be self-supporting and to become 'their own therapist'. After this 2-month period, patients are encouraged to continue the training program independently for at least 3 months, twice a week, in a local, regular health centre located near their home environment. Five months after the start of the therapy program (2 months at SJC + 3 months self-supporting activity) the patient has a follow-up meeting.At the 5-month follow-up the patient fills in questionnaires, and discusses the recovery process with a focus on personal targets with regard to physical training, and psychological and social factors. A physical examination takes place and (if required) personal advice is provided by one of the therapists of the SJC.Via postal correspondence the patient is asked to fill in the 12-month questionnaires.At the SJC a small group of patients follow treatment once a week for 4 months (instead of twice a week for 2 months). After the program is completed they are encouraged to continue their training program for at least 3 months in a regular health centre. At 7 and 14 months after start of therapy the same follow-up procedure is performed. The reason for the 'once a week' program is that some patients are unable to visit the SJC twice a week due to travelling and/or physical problems.th and 16th sessions there is a 1:1 patient/therapist evaluation (in addition to the regular training program). The remainder of the treatment sessions consist of 1-hour training, a 1-hour group lesson, followed by another 1-hour training. The training consists of group training and/or individual coaching. Figure Patients are treated in groups of 6 accompanied by 3 therapists. In the first session a personal treatment goal/plan is established with agreement from the patient. During the 9The aim of the program is to normalise motion behaviour. This is done by modifying the patient's experience of movements and increasing the experienced quality of movements by learning about and training the reduction of compensatory mechanisms of a physical nature, e.g. increasing intra-abdominal pressure at low loads, breathing cessation during loading tasks, and extreme activity in all superficial muscles. During the program it is explained that the above-described compensatory mechanisms are present due to an interaction between biophysical and psychosocial factors  such as stress, psychological status and social factors. All these factors are treated by a multidisciplinary team.The training starts to increase awareness of excessive tension of the muscles in trunk and extremities. The patient is stimulated to take breaks during daily activities by using tools like time contingent management and learning about his/her physical load and physical capacity ,19. BreaThe lessons aim to modify the patient's cognitions with respect to their complaints, thus reinforcing well behaviours . The groIndividual coaching focuses on the specific needs/problems of the patient. The training is performed in a progressive sequence adjusted to the patient's situation and the clinical experience (estimation) of the therapist. Additional assistance (as required) is provided by a manual therapist, psychologist or therapist specialised in body awareness.Prognostic factors are assessed at intake and at start of therapy by means of an interview focusing on the patient's history, a physical examination, and on questionnaires. After the 2-month therapy program at SJC, post-treatment follow-up measurements are scheduled at 5 and 12 months after start of therapy. In the present study, the classification into domains as proposed by Pincus et al. (2008), with one additional domain 'Physical characteristics', is used to order the prognostic factors .demographic characteristics such as educational level, marital status, weight, alcohol, smoking and drug consumption; b) clinical status such as body mass index (BMI), pain below the knee, cause and duration of complaints, previous rehabilitation, degree of fatigue  visited the SJC for an intake consultation between January 2003 and December 2008. Of these, 1,760 patients  with CNLBP met the inclusion criteria, completed the 2-month therapy program, and were followed up at 5 and 12 months after start of therapy. Of this latter group, 96 followed the 'once a week' therapy program.(with a duration of 4 months). A total of 785 patients  had the intake consultation but decided not to start therapy: reasons given for this included, only wanting the consultation and/or a diagnosis and/or some advice, referred to another specialist , decided not to come, travel distance too far, and unknown reasons.The distribution of prognostic factors were similar in both the excluded and included groups regarding demographic characteristics, clinical status, psychological status, work-related parameters, and physical examination. Table Little information is available on the prognostic factors for recovery in patients with chronic non-specific low back pain. The present study is designed to provide insight into the course and prognostic factors for recovery in patients with CNLBP who are managed in a rehabilitation centre.The study population was recruited from a multidisciplinary outpatient rehabilitation clinic (part of regular care), which leads to a more pragmatic approach regarding the prognosis of patients with CNLBP. In the 6 years during which patients have been followed for 12 months after start of therapy, the procedure of data recording and the follow-up period has been consistent. This limits information bias for the outcome recovery. Another strength of this study is that use of five domains of recovery allows to describe and analyse a broader perspective of relevant health outcomes for patients with CNLBP.The study also has some limitations. First, we are unable to present the natural (untreated) course of CNLBP, because all patients receive multidisciplinary treatment during rehabilitation ,75. AlsoThis study provides information on relevant prognostic factors for recovery, and presents data on the course of patients with CNLBP following a multidisciplinary rehabilitation program.The authors declare that they have no competing interests.All authors participated in the design of the study. KV drafted the manuscript with input from the other authors. All authors read, revised and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/12/252/prepub


Substance use disorders (SUDs), whether active or in remission, are often encountered in patients with chronic nonmalignant pain. Clinicians are challenged when managing chronic pain while facing substance abuse issues during the course of chronic opioid therapy (COT). Further, the interrelated behavioral symptomatology of addiction and chronic pain suggests that if one disorder is untreated, effective treatment of the other in not possible. Incomplete understanding of the overlapping presentations of the two disorders, coupled with insufficient management of both conditions, leads to undertreated pain and premature discharge of SUD patients from pain treatment. In order to achieve pain relief and optimal functionality, both conditions need to be carefully managed. This paper reviews the prevalence of SUDs in chronic pain patents; the overlapping presentation of the two disorders; risk factors and stratification for addiction; identification of addiction in the chronic pain population; and suggestions for treating patients with COT, with an emphasis on relapse prevention. With appropriate assessment and treatment, COT for chronic pain patients with a history of SUD can be successful, leading to improved functionality and quality of life. Treating chronic pain with chronic opioid therapy (COT) in individuals with a history of a substance use disorder (SUD), whether active or in remission, presents a challenge to pain clinicians. This is, in part, due to concerns about the patient relapsing to active substance abuse in the course of COT, as analgesic treatment enables and legitimizes drug use for patients with SUDs -3. In adA review of the literature reveals that no empirical studies have been conducted to investigate the risks and benefits associated with COT in chronic pain patients with a history of SUD . This paphysical dependence and tolerance, as these are predictable physiologic consequences of chronic opioid use. Reflecting this, in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V), tolerance and withdrawal are not counted as criteria for the substance use and addictive disorder diagnosis if a patient is taking an opioid analgesic under medical supervision [In attempting to estimate the prevalence or presence of SUD in chronic pain patients, terminology becomes important Table . It is iervision .Albeit using imperfect indicators, it has been estimated that the prevalence of opioid abuse in chronic pain patients ranges between 20-24% across health-care settings . Using aChronic pain and addiction are best conceptualized as a syndrome. In some individuals with addictive disease, pain is identified as a factor contributing to their addiction. It has been hypothesized that untreated pain may be a risk factor for relapse for individuals with addiction in remission ; howeverPhysiological and psychological aspects of active addictive disease can make pain more difficult to treat. Chronic use of opioid drugs appears to affect the processing of pain stimuli through sympathetic stimulation, hypothalamic-pituitary-adrenal axis dysregulation, and proinflammatory immune-system activation, resulting in increased sensitivity to pain or decreased pain tolerance ,23. ThesSavage and Schofferman  describeMood, sleep, and personality disorders can aggravate pain symptoms and are frequently comorbid in patients with chronic pain -30. The Similarly, mood disorders, including depression and anxiety, are common sources of distress in patients with SUD -38, whicUnresolved emotional and social distress coupled with persistent pain may lead patients to self-medicate these uncomfortable feeling states with opioids. When self-medication becomes a coping mechanism, substance use can progress to a disorder, or cause relapse in patients with a history of SUD. In a recent study of 1334 patients receiving COT for noncancer chronic pain, those with moderate and severe depression were more likely to self-medicate nonpain symptoms with prescription opioids and to misuse their prescription opioid by self-increasing doses than were those without depression .Clinicians should conduct a comprehensive risk assessment for opioid abuse or misuse when considering use of COT. The assessment should include known risk factors for addiction, including a personal or family history of substance abuse, childhood adverse events , psychiatric symptoms, and functional impairment . With respect to pain symptoms, assessment in patients considered at risk for addictive disease must include careful delineation of the nociceptive and affective components of the pain syndrome; identification of associated factors that perpetuate pain; and identification of pain-related risk factors for opioid abuse and relapse. Degree of functionality Table  in the pRisk stratification approaches are indicated for selecting chronic pain patients for COT, and those with a history of SUD are considered at high risk for poor treatment response . Being aThe risk factors for opioid abuse, misuse, or other aberrant drug-related behaviors in chronic pain patients receiving COT have been well-described, with a prior history of opioid abuse being the best predictor for both current and lifetime opioid use disorder in chronic pain patients ,42. OtheBoscarino and colleagues  found thAtluri and colleagues  have sugBased on the stratification of risk, different approaches are suggested. Individuals with a history of SUD are categorized as high risk, thus, frequent monitoring of medication use, urine drug testing (UDT) every three to six months, and reviewing Prescription Monitoring Program (PMP) reports every two to four months are recommended. Although not uniformly supported in the literature, these authors suggest that opioids should be avoided or prescribed only in low doses; a >50 mg morphine-equivalent dose should be used only rarely and only in specialized settings.Building on the universal precautions, management can be tailored to the care for patients at risk for SUD. For example, in addition to the general components written in the opioid treatment agreement or contract, the clinician should stipulate that participation in ongoing addiction treatment  be required for COT prescription. More frequent office visits are required to better assess opioid use behaviors, opioid efficacy, and signs of relapse. Clinicians should prescribe opioids to these patients in smaller amounts, without refills, and conduct pill counts at each visit. If appropriate, a family member or a close friend can be included in the treatment plan .Clinicians should collect urine samples more frequently for mass spectrometry confirmatory toxicology screen . In a laBrief cognitive-behavioral interventions have been shown to reduce the risk of COT misuse in chronic pain patients. Using a randomized trial, Jamison and colleagues  tested tcontrol over drug use, compulsive use, continued use despite harm, and unmanageable drug craving [Savage and colleagues introduced the four “C” criteria for identifying opioid addiction in chronic pain population: impaired  craving . HoweverA strategy to distinguish between aberrant or misuse behaviors and addiction in chronic pain patients is to assess the relationship between opioid dose titration and functional restoration Figure . In thisConversely, should overall functionality not improve with a dose increase, addiction is considered in the differential diagnosis. Listed in Figure active addiction, regardless of type(s) of substance abused, are not candidates for COT [The authors strongly believe that patients with chronic pain and  for COT . PatientIn many primary care or pain management settings, the ability to provide the comprehensive services necessary to treat patients with both pain and current addiction are sorely lacking. Patients with an active SUD should be referred to formal addiction treatment; thus, it is incumbent upon the prescribing clinician to have available a referral network of substance abuse treatment providers willing to collaborate on providing care to patients with comorbid pain and SUD. After referral, the pain clinician should continue to work closely with the SUD treatment provider to monitor use behaviors and pain outcomes.For individuals with addiction in remission, the goal of treatment is the same as that as for all chronic pain patients: to improve pain and maintain functionality. Indicators of successful pain management include the patient’s ability to comply with regimens; engage in cognitive-behavioral pain management strategies; utilize positive coping skills to manage stress; and establish better social support systems. Further, management of comorbid neuropsychiatric complications is critical to maximize functionality.For many opioid addicts, disease remission includes opioid substitution therapy. In the context of managing pain in patients receiving methadone or buprenorphine for addiction, it is commonly assumed that the treatment opioid alone provides sufficient pain relief. Further, concerns that additional opioids put the patient at risk for untoward events, including respiratory depression and decreased level of consciousness , often lRegardless of the type(s) of substance previously abused, exposure to psychoactive medications can lead to relapse in patients with a recently or poorly treated SUD. Concerns of relapse may also contribute to clinicians’ reluctance to prescribe COT for patients whose addiction is in remission. The literature provides evidence that patients with successfully treated addiction can be effectively treated with opioids for chronic pain . Thus, wCentral to this treatment is the integration of relapse prevention strategies into the plan of care. Relapse is a predictable event in the course of addictive disease and is understood to be a process that does not occur suddenly or spontaneously and is, therefore, preventable ,71. The high-risk situation, broadly defined as “a circumstance in which an individual’s attempt to refrain from a particular behavior (ranging from any use of a substance to heavy or harmful use) is threatened” (p. 224) [The relapse prevention model is depicted in Figure (p. 224) . For pat(p. 224) .positive outcome expectancies and the abstinence violation effect are important cognitive factors in determining relapse probability. Positive-outcome expectancies refer to the anticipated positive effects of substance use , which override memories of the consequences associated with use. The abstinence violation effect refers to the patient viewing a single lapse, or “slip,” as a personal failure, leading to feelings of guilt, demoralization, and hopelessness with respect to his or her ability to maintain change. More recent conceptualizations of relapse describe it as a dynamic phenomenon, and a complex nonlinear process in which various factors act jointly and interactively to influence relapse timing and severity [Whether or not a high-risk situation results in relapse is determined by the individual's ability to engage an effective coping response to the stressor . In the severity .Central to successful relapse prevention are learned cognitive and behavioral strategies the patient can employ in the face of high-risk situations. These strategies are of two broad categories: (1) a specific intervention technique designed to assist the individual in anticipating and effectively coping with high-risk situations; and (2) global self-control approaches designed to reduce relapse risk by promoting positive lifestyle changes. In that high-risk situations vary among individuals, it is critical to conduct a comprehensive assessment of substance use patterns, high-risk situations, coping skills, self-efficacy, outcome expectancies, and readiness to change, as well as to document coexisting conditions that may complicate the relapse-prevention process. To increase insight into, and self-monitoring of, problematic behaviors, the patient is encouraged to identify immediate precipitants and distal lifestyle factors related to relapse and to evaluate his or her own coping responses to high-risk situations.Specific intervention strategies include enhancing self-efficacy by setting achievable behavioral goals and purposeful dispelling of positive outcome expectancies. With respect to global self-control strategies, patients are encouraged to incorporate stress-reduction activities into their daily life, such as exercise or meditation. The overall purpose is lifestyle balancing, which increases self-efficacy across life domains and therefore minimizes the risk of relapse.Preventing relapse is central to effective COT in patients with SUD in remission. Clinicians must continuously assess the patient’s relative risk for it and monitor for its emergence. Further, the ability to manage a relapse episode, if one should occur, is a necessary skill of the COT prescriber. With addiction in remission, optimal functioning with appropriate opioid use can be appreciated.A series of questions should be asked of the chronic pain patient regarding the status of SUD remission Table . Asking The identification of relapse in chronic pain patients receiving COT is complicated by their tendency to hide problematic use for the fear of losing access to medications. A careful monitoring plan including general and additional precautions (as described above) is critical. A relapse contract can be developed with the patient in early treatment, which is individualized to the patient and specifies steps or actions that will be taken by both the patient and clinician if relapse occurs. The patient’s behaviors with respect to the opioid-analgesic regimen provide the best evidence for the presence of active addiction. Evidence of relapse in chronic pain patients includes the presence of adverse consequences associated with opioid use, a loss of control over the use of opioids, preoccupation with obtaining opioids, and a lack of improvement in function .An objective indicator of medication use is adherence to a treatment contract or medication agreement, which clearly outlines acceptable and unacceptable medication use behaviors. However, engaging in unacceptable medication-taking behaviors cannot be considered a definitive indicator of addictive disease, and rather may reflect an untreated psychiatric disorder or misunderstanding of dosing instructions. Similarly, unexpected UDT results may indicate patients’ nonadherence to opioid regimen or problematic use of medications, but it is not a specific indicator of relapse to addictive disease. Thus, clinicians should not summarily discharge SUD patients from COT based on behavioral indicators or UTD results; neither are specific to exacerbation of addiction. Rather, these findings should prompt a dialogue between the patient the clinician. Patients with a history of SUD who are nonadherent to the prescribed opioid regimen should be strongly encouraged to increase recovery efforts, and their access to opioids should be more tightly controlled. Evaluation by an addiction specialist is warranted if behaviors do not quickly resolve.If relapse is identified, it is critical to continue to support patients’ efforts towards recovery and maintain high levels of controls over opioid access. If attempted, opioid detoxification should be gradual so as not to elicit opioid withdrawal symptoms . It is important not to characterize the relapse as a treatment failure but to frame it as a part of the process of recovery from an addictive disease and successful pain treatment.Studies indicate that exposure to specific high-risk situations alone does not predict relapse, but the way in which people cope with those situations is a strong predictor of subsequent relapse or continued abstinence -78. FollIf relapse is identified, discharging the patient from pain treatment without providing addiction intervention is not only premature, but sets the patient up for the progression of addictive disease. It is important that clinicians who prescribe COT for chronic pain are prepared with a relapse management strategy and have addiction expertise or support in place. It is critical that COT providers maintain a thoughtful and working partnership with addiction treatment providers so that pain treatment can continue while supporting addiction remission. As opposed to discharge, it is incumbent upon the pain-management practitioner to take more of an advocacy role in the management of addiction.Management of chronic pain in patients with a history of SUD with COT can be challenging, but with appropriate assessment and management, can be successful, leading to enhanced functionality and quality of life. Albeit imperfect, data suggest that up to one-quarter of chronic pain patients have an SUD history. The interrelated behavioral symptomatology of addiction and chronic pain suggests that the untreated presence of one precludes effective treatment of the other. Demographic correlates and risk factors for SUD have been well-described, and COT management is most successful when based upon risk stratification with increased control of opioid access for those classified as high risk.The evidence is good that COT can be effective in patients with chronic pain whose SUD is in remission, suggesting that a primary goal of treatment, in addition to improving pain and maximizing functionality, is to prevent a relapse or exacerbation of addictive disease. Expanding the pain treatment plan to include specific relapse-prevention strategies and directed relapse management, if needed, is critical to appreciate the benefits of COT for patients with a history of SUD. Identifying relapse in this population can be challenging and should not be based on a single indicator. Premature discharge of the SUD patient from pain treatment provides an opportunity for addiction to worsen. It is suggested that the best chronic pain outcomes occur when the pain clinician and addiction treatment provider work in concert using a syndromal approach to treat pain and addiction.The authors declare that they have no competing interests.YPC and PC collaborated on the conception of the manuscript and YPC wrote the first draft. Both authors read, edited and approved the final manuscript.


In recent years, a battery-powered bone marrow biopsy system was developed and cleared by the U.S. Food and Drug Administration to allow health care providers to access the bone marrow space quickly and efficiently. A multicenter randomized clinical trial was designed for adult patients to determine if the powered device had advantages over traditional manually-inserted needles in regard to length of procedure, patient pain, complications, user satisfaction, and pathological analysis of the specimens.Adult patients requiring marrow sampling procedures were randomized for a Manual or Powered device. Visual Analog Scale (VAS) pain scores were captured immediately following the procedure and 1 and 7 days later. Procedure time was measured and core specimens were submitted to pathology for grading.3; Manual: 20.4 ± 9.0 mm3; p = 0.039). Two non-serious complications were experienced during Powered procedures (4%); but none during Manual procedures (p = 0.495).Ten sites enrolled 102 patients into the study . Mean VAS scores for overall procedural pain were not significantly different between the arms . A day later, more patients who underwent the Powered procedure were pain-free (67%) than those patients in the Manual group . One week later, there was no difference  Mean procedure time was 102.1 ± 86.4 seconds for the Powered group and 203.1 ± 149.5 seconds for the Manual group (p < 0.001). Pathology assessment was similar in specimen quality, but there was a significant difference in the specimen volume between the devices (Powered: 36.8 ± 21.2 mmThe results of this first trial provide evidence that the Powered device delivers larger-volume bone marrow specimens for pathology evaluation. In addition, bone marrow specimens were secured more rapidly and subjects experienced less intermediate term pain when the Powered device was employed. Further study is needed to determine if clinicians more experienced with the Powered device will be able to use it in a manner that significantly reduces needle insertion pain; and to compare a larger sample of pathology specimens obtained using the Powered device to those obtained using traditional manual biopsy needles. Bone marrow evaluation is often essential to determine the efficacy of treatment in hematological disorders and to monitor the recovery process in patients undergoing bone marrow transplantation or marrow-ablative chemotherapy ,2. It isSince the introduction of the Jamshidi needle in 1971, there has been no substantial advancement in marrow sampling technology . Biopsy et al found that the duration of the procedure  was the sole independent factor for patients' pain intensity ). Assessment of needle insertion pain was done on the last 28 patients enrolled in the study. VAS pain scores were not different between the arms . One day after the procedure, more patients who underwent the Powered procedure were pain-free (67%) than those patients in the Manual group . One week following the procedure, there was no difference in the proportion of patients who were pain-free . Notably, mean procedure time was shorter for the Powered group (102.1 ± 86.4 seconds) than for the Manual group . Biopsy core acquisition success rate was similar between the arms . Assessment by pathology showed equivalence in core specimen quality parameters and length and width, but the specimen volume was larger in the Powered group (36.8 mm3 ± 21.2) than the Manual group . There was no difference between the two devices for operator satisfaction, nor for patient satisfaction. There were two non-serious complications for the Powered (3.8%). In one case, the patient's skin became wrapped around the shaft of the rotating biopsy needle; and in the other case, the clinician's glove became wrapped for a very brief time around the rotating biopsy needle. There were no complications for the Manual procedure (p = 0.495). See Table Mean VAS scores for overall procedural pain were not significantly different between the arms . Patients undergoing bone marrow biopsy procedures most likely expect some level of pain. Most patients are willing to undergo the procedure and a reasonable level of pain, providing the procedure time is relatively short. Assuming the validity of Kuball et al study using the Manual procedure, only 36% of patients were without pain after 24 hours, very similar to the results in the Manual group in our study [Another important finding from our study is that whereas patients generally expect pain during any invasive procedure, they may not expect or tolerate persistent residual pain afterwards. In our study, 67% of the patients who received the bone marrow biopsy procedure using the Powered device were pain-free within 24 hours compared to only 33% of patients who received the procedure with the Manual device, a statistically and clinically significant finding. In the Liden ur study .As expected, there were few complications in our study with either the Powered or Manual bone marrow biopsy procedures. The two observed complications occurred with a single operator's use of the Powered device. In one case, a small portion of the patient's skin wrapped around the rotating needle. This could have been avoided by holding the skin tautly at the needle insertion site. In the other case, the operator's latex glove became wrapped around the rotating needle, which could have been avoided by not placing the gloved finger too close to the rotating needle. It is recognized that these types of complications are potentially serious and not likely to occur with manual devices. But it is felt that complications of this type can be avoided by emphasizing this potential problem and methods to avoid the problem during operator training. Moreover, considering that both these problems were experienced by only one of 13 operators participating in the study, their prevalence is not felt to be wide-spread.et al found only 42% of bone marrow biopsy specimens were adequate for accurate diagnosis in a study involving 767 patients [Clinicians attempt to conduct bone marrow sampling procedures quickly and safely with as little pain and discomfort to the patient as possible; however, the ultimate goal of the procedure is to acquire a bone marrow specimen that is adequate for diagnosis by pathologists. Adequate specimens need to be of adequate size and free of crush trabecular distortion and other artifact. Inadequate specimens can diminish the clinician's ability to make an accurate diagnosis and/or assessment of the patient's clinical status. Bishop patients . In the The cost of using the Powered device must be considered in decisions regarding its use in the clinic. While the powered driver can be used up to 500 times, the needle and other components are for single use and part of a tray that generally costs $60 to $70 more than the Manual device. Although needle-for-needle, the cost of the Powered system is higher, the total cost for the disposable needle tray is covered by insurance reimbursement under most plans. While the seemingly high cost of the Powered device might negatively influence a decision to adopt its use, the concerns of most clinicians and patients are not simply the costs of the material and equipment required to do the procedure but the costs of these items together with their quality and patient outcome. Our study and other recent studies ,18, suggThere were several limitations in this study. As with any new device, there is a learning curve that must be negotiated before operators can gain proficiency. While our study protocol stipulated that the operator complete 3 to 5 Powered device uses in non-study subjects before performing the procedure on study patients, in hindsight perhaps those numbers should have been higher. Another limitation was initially capturing patient pain scores as an "overall" event that included the aspiration portion of the bone marrow sampling procedure. Generally, bone marrow aspiration is painful regardless of the needle-type used to withdraw the liquid bone marrow specimen. This extreme pain during the aspiration phase may obscure any differentiation in pain levels between the two device types during the less painful phases of the procedure. This phenomenon was realized after the interim analysis. By the time the study protocol could be revised to include recording needle insertion pain, patient accrual was 72% complete. Thus, we were unfortunately able to collect very little data specifically on needle insertion pain. A final limitation was that relatively few core specimens were available for pathology analysis. Our initial plan was to conduct quality analysis for each specimen at a central laboratory, but some investigators were reluctant to send specimens to the central laboratory following analysis at their local laboratory. The compromise was that two specimens from each center were analyzed, one for each device type.The results of this first multicenter randomized controlled trial evaluating the Powered bone marrow biopsy system suggest that use of the Powered bone marrow biopsy device may deliver larger-volume bone marrow core specimens for analysis, markedly shorten the procedure time, and reduce intermediate-term pain--important considerations for both the medical provider and the patient when determining how best to obtain bone marrow specimens. Further study is needed to determine if clinicians more experienced with the Powered device will be able to use it in a manner that significantly reduces needle insertion pain; and to compare a larger sample of pathology specimens obtained using the Powered device to those obtained using traditional manual biopsy needles.All authors, or their respective organizations, received research grant funds from the sponsor of the study, Vidacare Corporation, for their participation in the study.JRB and OY participated in the design of the study, collected clinical data, and helped draft the manuscript. BB participated in the design of the study and performed the statistical analysis. DB, JC, DA, GU collected clinical data and helped draft the manuscript. CS participated in the design of the pathology portion of the study and helped draft the manuscript. All authors read and approved the final manuscript.


Maquet III procedure, unloved due to its complications (2% to 59%), has been progressively abandoned. At long-term follow-up, what happens to patients with complications that exceeded the initial ones ? We retrospectively studied patients who were submitted to Maquet III procedure, by functional and radiologic long-term outcomes, in order to determine if this surgery has or has not fulfilled its initially proposed objectives. From 1970 to 1991, 116 patients benefit from the Maquet III procedure. From this, we were able to review in 2011, 23 patients (25 knees) who went through a single Maquet III procedure. Of these patients, 52% were males. Age at surgery was 39.7 ± 11.4, with a postoperative follow-up of 27.2 ± 3.1 years.A questionnaire has been prepared for collecting data, and it has been supplemented by clinical records. We evaluated the preoperative complaints, postoperative complications, and range of motion during the recovery time, as well as the postoperative pain-absence period. All patients underwent an objective assessment using the visual analog scale (VAS) at rest and activity, and the Kujala patellofemoral scoring system. A radiological assessment was also made in order to evaluate the arthrosis degree. The bicondylo-patellar angle described by Delgado-Martins  was used to measure patellar tilt, and the Caton-Deschamps index to calculate the patellar height.Only one knee had benefited from a total knee arthroplasty (20 years after the Maquet III procedure). Preoperative complains were mainly anterior knee pain, crepitus, and patellar instability. Nowadays, 10 patients (40%) still are pain free. Others had an average period without pain of 19.1 ± 6.1 years. VAS at rest was 1.7 ± 0.7 and in activity 4.4 ± 3.0. KPS was 61.9 ± 22.3 points. X-ray shows that 40% had a Kellgren-Lawrence grade of 1 at the patellofemoral joint.Maquet proposed this technique for knee-pain relief, maintenance of the knee range of motion, and for slowly progressive osteoarthritic development. Viewed in a dispassionately way, we could notice that the initial objectives of this procedure were completely achieved. A part of 80% of the initial population was lost during follow-up, which may compromise the conclusions, perhaps, it is time to reflect again on this solution, so unloved by so many. Isolated patellofemoral osteoarthritis is rare, being present in 3.8% of the osteoarthritic knees ,2. AmongIdeal treatment for chondromalacia and/or patellofemoral osteoarthritis on younger patients still remains unknown and a controversial topic. Conservative treatment with rest, strengthening of the quadriceps femoralis muscle, and intake of nonsteroidal anti-inflammatory drugs is a successful treatment in a significant number of patients ,4.When conservative treatment fails, a surgical approach may be the solution. Several surgical options have been proposed ranging from Pridie's holes  to a patMaquet  proposedThe aim of this study is to evaluate the long-term results of the patients with osteoarthritis and/or patellofemoral chondromalacia, who underwent a single Maquet III osteotomy -13.n = 116), 37 had no record in the National Health Service; 29 cases, in spite of having records, do not had phone numbers for contact to make an interview, and 16 patients had already died. The other patients were contacted by telephone call and were invited for medical evaluation. Six refused because they were suffering from other severe diseases. The remaining patients accepted to come to our hospital, but only 23 were really present for clinical and radiological evaluation. Since two patients were bilaterally operated, we had included 25 knees in this evaluation.All surgical records of the Orthopedic Department between 1970 and 1991 were reviewed. Patients (116) who underwent Maquet III procedure for the treatment of chondromalacia and/or patellofemoral osteoarthritis were found. Surgical procedures were performed by or under the supervision of one of the senior authors (PM). Of these patients , with the lowest score of 0 that corresponds to ‘pain free’ and highest of 10 which means ‘intolerable pain’. The patients were asked to mark at the line a point that corresponded to the exact level of pain they experienced currently at rest and a point that corresponded to the exact level of pain during daily life activities (DLA). For correlation, we use the Cox assessment scale  and the Additionally, a radiographic study of the knee was made: antero-posterior view with a profile at 30° of flexion and sky view of patella at 30° of flexion. On radiographic evaluation, we tried to identify the existence of patellofemoral conflict, patellar subluxation, and osteoarthritis, classified according Kellgren-Lawrence criteria . Patellat test for the continuum variables. A p value <0.05 was considered statistically significant. All the patients included in the study consented, and an approval from an ethics committee of our Hospital to retrieve the clinical data has been obtained.We considered an absolute surgery failure when patient is to undergo total knee arthroplasty (TKA) and a relative failure when patient relates pain that affects daily life activities. Patients' records were registered into a database and processed statistically; Chi-squared test was used for the categorical variables, and Student's n = 20; 80%). The main reason for the surgery was patellofemoral osteoarthritis , as shown in Table Pain was the most frequent preoperative complaint . The mean time of hospitalization was 22.8 ± 22.4 days. Only 23.5% of the patients benefitted from physiotherapy procedures.n = 19); the remaining 6 patients were distributed between levels 2 and 3. With daily life activity, 76% (n = 19) of the patients were also pain-free, 12% (n = 3) had pain intensity between 3 and 4, and 12% (n = 3) with more than 5. Cox score showed 68% (n = 17) as good/excellent, and 32% (n = 8) as fair/poor. Kujala patellofemoral scoring revealed an average of 61.8 ± 22.3 points.On the 2011 review, the mean postoperative follow-up was 27.2 ± 3.1 years with a mean pain-free time of 19.1 years. Tables n = 12) of the patients had an osteoarthritis grade of I-II, and 40% (n = 10) had a grade of III-IV. The remaining three (12%) patients still do not have patello-femoral osteoarthritis, independently of the long term follow-up. Patellar tilt measurement using the Delgado-Martins angle [n = 10) had a normal angle (6° to 17° at 30° knee flexion), 4% (n = 1) had more than 17°, and the remaining 56% (n = 14) had less than 6°. Figure Based on the radiographic study, 48% , Ferguson et al. [n = 48 patients), and Radin [n = 42 patients).What happens to patients with a Maquet III procedure 20 years or more after the surgery? As we know, there is no paper describing such long follow-up result. Maquet  reportedn et al.  92% (n =nd Radin  79% (n =n = 25), and even with this long term follow-up, we were able to review by clinical and radiological exams 23 of the 116 cases (19.8%) registered in our hospital. Our long-term results show only 1 (4%) case of absolute surgery failure with 48% (n = 12) of excellent results (pain-free with DLA until now) with good Kujala patellofemoral scoring score. Apart from this, the remaining patients who complained of pain tolerate it and had good Cox score.Our study has more than 20 years of follow-up (Have patellofemoral arthroplasty and other procedures resulted to such a performance at long term? Dejour and Allain  reportedMaquet III had three purposes: pain relief, maintenance of mobility, and prevention of osteoarthritis. The patients evaluated with a minimum of 20 years, after having pain relief for at least 15 years after surgery, also had good range of motion. Prevention of osteoarthritis was the only purpose that has not been totally achieved, but a delay of 15 years should be taken into account. Taking into consideration the loss of 80.2% of the patients during follow-up may compromise the final conclusions.First of all, apart from skin complications, evidence supports that Maquet III is a reliable procedure with good results, better than other procedures which have results in less follow-up time. Second, in Maquet III procedure is important to prevent skin complications, as reported on a significant number of cases. Bandi and Brennwald  and FergTaking into account the loss of 80.2% of the initial population, in this long-term follow-up, we showed that patients who do not have skin problems after a single Maquet III procedure also have a long free-pain period with functional good outcomes. Avoiding skin problems, Maquet III procedure may be rehabilitated and rise again as a surgical option to treat isolated patello-femoral osteoarthritis.The authors declare that they have no competing interests.FF designed the study, reviewed the patients, wrote the paper, and supervised the research. JPO reviewed the patients and recorded the patients' data. PM wrote the paper and gave research advices. All authors read and approved the final manuscript.


Pain is one of the most frequent and most distressing symptoms in the course of cancer. The management of pain in cancer patients is based on the concept of the World Health Organization (WHO) analgesic ladder and was recently updated with the EAPC  recommendations. Cancer pain may be relieved effectively with opioids administered alone or in combination with adjuvant analgesics. Corticosteroids are commonly used adjuvant analgesics and play an important role in neuropathic and bone pain treatment. However, in spite of the common use of corticosteroids, there is limited scientific evidence demonstrating their efficacy in cancer patients with pain. The use of corticosteroids in spinal cord compression, superior vena cava obstruction, raised intracranial pressure, and bowel obstruction is better established than in other nonspecific indications. This review aims to present the role of steroids in pain and management of other symptoms in cancer patients according to the available data, and discusses practical aspects of steroid use. Pain is a vital problem in cancer as it occurs in 30–50 % patients in earlier stages and in 70–90 % of these patients with advanced disease. The management of this symptom is generally based on the concept of the World Health Organization (WHO) analgesic ladder. This three-step framework was published for the first time in 1986 by the WHO to promote rational use of analgesic medications in the treatment of cancer pain. Step I recommends nonopioid analgesics for mild pain. Step II specifies the use of weak opioids for moderate pain. Step III comprises the use of strong opioids for severe pain , 3••. ThN-methyl-D-aspartate receptor (NMDA) antagonists, namely ketamine, is recommended [To achieve better pain relief, apart from the use of the analgesics recommended by the WHO ladder, an appropriate application of adjuvant analgesics , supportive drugs (for the prevention and treatment of opioid adverse effects) , and nonommended . Patientommended .Steroids can reduce pain intensity by inhibiting prostaglandin synthesis and reducing vascular permeability. Their role in controlling cancer pain and other indications in the course of cancer and some practical aspects of steroid use will be discussed in this article. According to the WHO and EAPC pain management recommendations, an adjuvant pain medication should be considered at each step of the WHO analgesic ladder, especially when the anti-inflammatory effect is needed.Endogenous steroids, depending on their nature, site of synthesis, and specific clinical features, can be divided into four groups: corticosteroids , progestogens, androgens, and estrogens. Generally, steroids are produced in the adrenals and gonads, and some other tissues such as the bowel, liver, prostate, and nervous system (neurosteroids) may synthesize or metabolize them . CorticoThe anti-inflammatory effect and vascular permeability reduction are the clinical results of steroid use. Because the mineralocorticoid properties of steroids may lead to a higher risk of sodium excess, potassium loss, and water retention , cortisone or hydrocortisone are rarely employed for long-term anti-inflammatory therapy (due to the highest sodium-retaining potency). The negative feedback of the HPA axis by endogenous and synthetic steroids is well established. It is a dose- and time-dependent process. Consequently, a sudden cessation of corticosteroid therapy may result in adrenal failure. Clinically significant HPA axis suppression is rare if a steroid is administered for less than 3 weeks. Such patients can withdraw from steroids suddenly, with no harmful effects . There aVarious syndromes may occur when the glucocorticoid is withdrawn or reduced. The first is relapse of the disease for which the steroids were prescribed. The second is a combination of nonspecific symptoms of steroid withdrawal syndrome . This syndrome must be distinguished from the suppressed HPA axis or relapse of the underlying disease. The third syndrome is acute adrenal insufficiency, which could be precipitated by surgery, intercurrent disease, or stress and may result in a hemodynamic collapse . CliniciThe process of pain origination is called nociception. It consists of four stages: transduction , transmission (via neurons), modulation, and pain perception. The possible role of steroids on every step of nociception has been raised even though the exact mechanisms remain unclear. The variety of proinflammatory cytokines synthesized or/and released during tissue injury are responsible for peripheral sensitization. This process leads to an increase in pain perception. The reduction in inflammation involved in this process decreases nociceptors activation, and thus, can diminish pain intensity. A decrease in pathological electrical activity of damaged neurons is also suggested . The antAs a consequence, corticosteroids are considered to be the most effective strategy against inflammatory pain. Steroids also have an anti-swelling effect. The reduction of peritumoral edema by the shrinkage of tumor in response to steroid therapy may lead to the improvement in analgesia in brain metastases  and spinThe receptors of various steroid hormones are expressed in several neural structures, allowing steroids to control the development, growth, maturation, differentiation, and plasticity of the CNS and PNS. By modulating neural activity and plasticity, the steroids are suspected to play an important role in pain sensation. Sex steroids (androgens and estrogens) are key factors accounting for the gender difference in pain and analgesia. Androgens, particularly testosterone, exert an analgesic effect in humans while estrogens were found to have both the hyperalgesic and analgesic effects, depending on the experimental conditions , 20. SexThe most often prescribed corticosteroid for pain treatment is dexamethasone. Long-acting dexamethasone causes less fluid retention than other steroids because it has less mineralocorticoid effect. However, betamethasone (equipotent to dexamethasone), prednisone, and prednisolone also may be used . DexametCorticosteroids are commonly prescribed in cancer patients for a variety of symptoms , 25. TheCorticosteroids display short- and long-term toxicities. The immediate adverse effects include immunosuppression, which may manifest as candidosis, hyperglycemia, and psychiatric disorders. Long-term effects comprise myopathy, peptic ulceration, osteoporosis, and Cushing’s syndrome . TherefoIn an uncontrolled study, oral candidosis and proximal myopathy were the most frequent adverse effects attributable to steroid therapy. The most common reason for discontinuation of dexamethasone treatment was death or general deterioration. A total of four (4 %) out of the 106 treated patients discontinued the treatment due to adverse effects such as restlessness, sleep disturbance, dyspepsia, and skin rash . In anotP < 0.02) and hyperactivity (P < 0.05) were observed in patients treated with dexamethasone [A comparison of prednisolone with dexamethasone showed that adverse effects of both drugs were similar, although more psychological changes . The studies presented below attempted to answer these important queries.Nauck et al. , in a muAccording to the previously presented data, corticosteroids were suspected to improve pain control. Bruera et al.  conducteIn a Swedish survey, out of a total of 147 patients with pain, 50 (34 %) had very good effect, 71 (48 %) had some effect, 4 (3 %) had no effect, and the effect of the treatment with corticosteroids could not be assessed in 22 patients (15 %). The positive response came within a week and lasted for more than 4 weeks. Of these patients, 81 % used corticosteroids for more than 4 weeks and 90 % were on betamethasone, with daily doses less than 3 mg in most of the patients [Della Cuna et al.  reportedGreenberg et al.  reportedSturdza et al.  reportedn = 7; 8 mg, n = 4, 16 mg, n = 2) compared with the doses of prednisolone  [Hanks et al.  observed n = 11) .Several case reports demonstrated the effectiveness of corticosteroids in bone pain treatment. Arkel et al.  demonstrCorticosteroids are commonly used for quality of life and symptom control improvement. Hardy et al.  conducteBeneficial effects of steroid use on appetite, vomiting, general well-being, and social interaction in the Dellacuna et al.  study weThe problem of appropriate steroid dose and its efficacy is raised in the literature and clinical practice. In a randomized double-blind trial Vecht et al.  comparedLundström and Fürst  assertedn = 121) or dexamethasone (n = 95) in starting doses of 10–30 mg and 4–16 mg daily, respectively. The maintenance daily doses varied considerably from 5–20 mg of prednisolone and from 0.5 mg on alternate days to 4 mg twice daily of dexamethasone. There was no difference in response rates between the two drugs.Hanks et al.  reportedThe beginning and duration time of the clinical effect of corticosteroids is another unclear problem. In the Swedish study, the authors noted that positive effect of steroids lasted from 3 to 6 weeks. Of the questioned doctors, 83 % stated that more than 50 % of their patients had a positive effect from the treatment, and 97 % of the respondents observed the positive effect within 5 days .Corticosteroids have an established role in specific indications in cancer patients such as spinal cord compression, superior vena cava syndrome, brain metastases with raised intracranial pressure and bowel obstruction. Their role in non-specific indications is not well proved. Clinical practice and several studies suggest that corticosteroids may be effective in the treatment of bone and neuropathic pain, when administered along with opioids and with other adjuvant analgesics. The decrease in pain intensity is probably connected with both the anti-inflammatory and anti-swelling effects as well as modulation of neuroimmune interactions. The sex-steroid dependent differences in pain sensitivity were also found.It seems that dexamethasone may be commonly used for cancer pain management due to its high potency, long duration of action and minimal mineralocorticoid effect. A proposed starting daily dose is 8 mg  with subsequent adjustment to the analgesia achieved and adverse effects. The lowest effective dose should be used and patients must be followed up regularly to assess benefits and risks associated with the therapy. In the situation when the general condition of a patient deteriorates and the patient is no longer able to swallow medications that are taken orally, it is rather recommended not to stop the treatment abruptly but to continue dexamethasone administration by the subcutaneous route.Patients with severe pain intensity of bone and neuropathic origin should also be considered for the use of analgesic ladder step 3 opioids  without climbing up the analgesic ladder. Other co-analgesics appropriate for bone and neuropathic pain should also be considered. Future studies that would take patients’ quality of life into consideration and could establish the role of corticosteroids in pain and other symptom treatment, are urgently needed.


Objective. Drip infusion during long-term tocolysis causes mechanical and infectious vasculitis and increases the frequency of peripheral venous catheter exchange (PVC), thereby placing a burden on patients. Our study aim is to confirm whether heparin ameliorates pain due to vasculitis during long-term tocolysis and reduces the frequency of peripheral venous catheter exchange. Design. Prospective study. Setting and Sample. All the patients requiring admission because of the presence of uterine contraction or progressive cervical dilatation from August 2009 to June 2011 at Juntendo University in Japan. Methods. Heparin was used for patients at the time the total number of peripheral venous catheter exchanges exceeded 5 in two weeks, and we evaluated whether heparin reduced the frequency of peripheral venous catheter exchange and improved the visual analog scale (VAS) for patients. The main outcome measures frequency of PVC exchange and VAS. Results. This study demonstrated that heparin reduced the frequency of peripheral venous catheter exchange (P = 0.0069) and VAS (P = 0.042). No side effects were noted. Conclusion. Heparin could satisfy patients during long-term tocolysis in terms of ameliorating pain due to vasculitis and reducing the PVC exchange frequency. Preterm labor is considered differently in Japan and USA. Continuous tocolysis for more than 48 hours is not recommended in the USA. But in Japan Ritodrine hydrochloride is usually used for long-term tocolysis under the presence of uterine contraction or progressive cervical dilatation. This therapy leads to the lower premature delivery rate in Japan  than the other country (10.6% in north America). But drip infusion therapy during long term tocolysis causes pain due to vasculitis, and the PVC must be exchanged often.Three kinds of vasculitis mechanism have recently been proposed . One is The observation period was from August 2009 to June 2011. We obtained a written informed consent from patients. All patients required admission for long term tocolysis were eligible for enrollment in this prospective study, if consent was obtained.Vasculitis increases the pain, where peripheral venous catheter (PVC) placed, and the frequency of PVC exchange. So we used PVC exchange frequency and VAS of the patients to assess the objective scale in this study.t-test was selected and a predictive value <0.05 was regarded as indicating a statistically significant difference.  The frequency of PVC exchange was counted for two weeks after drip infusion tocolysis being started in admission. When PVC exchange exceeded 5 times in two weeks, heparin was administered with patient consent. We used the PVC, . The amount of heparin in the bottle was set at almost 6000 IU per day. The precise amount regulated by the velocity of drip infusion is described in P = 0.0069).There was a significant difference in the frequency of PVC exchange between before and after inducement of heparin . There was a significant difference before versus after heparin rescue  is used instead of total parenteral nutrition. With PPN, however, peripheral vein thrombophlebitis and vascular pain are problems. Inoue et al. reported that a 1 IU/mL heparin injection into the bottle reduced both vascular pain and the rate of peripheral venous catheter exchange . A prospective study on prolonging the usability of peripherally placed percutaneous central venous catheters in neonates demonstrated the beneficial effects of heparin on these catheters –16.Our study confirmed heparin's beneficial effect on the pain during long term tocolysis. By ameliorating inflammation and coagulation, patients can maintain the peripheral venous catheter less painful. During this study, most of our patients felt less painful after heparin induction. Heparin inducement can mitigate pain, and thereby improve VAS. In this study, neither drug induced hepatitis nor anti-coagulant abnormalities occurred. However, heparin induced thrombocytopenia (HIT) develops in approximately 0.5% of patients during heparin-induction therapy , 18. In The risk of heparin's side effects is unacceptable. However, the benefits of heparin should also be considered. The stress on patients during therapy is considerable. Even if complications such as HIT occur, simply discontinuing heparin is enough to achieve recovery.Some groups have suggested that a lower dose of heparin than that of our study would be effective. Our study is the effective dose for curing coagulant abnormalities. Thus, a lower dose of heparin might be enough to improve the pain. The next survey must consider the lower effective dose of heparin. Furthermore, a larger subject number and in vitro experiments would be needed for the next survey to prove that heparin ameliorates vasculitis itself in patients.Key Message. Heparin can ameliorate the pain due to vasculitis during long term tocolysis and reduce the frequency of peripheral venous catheter exchange. This method lifts the burden from patients during admission.


Cancer-related pain continues to be a major healthcare issue worldwide. Despite the availability of effective analgesic drugs, published guidelines and educational programs for Health Care Professionals (HCPs) the symptom is still under-diagnosed and its treatment is not appropriate in many patients. The objective of the study is to evaluate the efficacy of the Pac-IFicO programme in improving the quality of pain management in hospitalised cancer patients.This is a before-after cluster phase II study. After the before assessment, the experimental intervention – the Pac-IFicO programme – will be implemented in ten medicine, oncology and respiratory disease hospital wards. The same assessment will be repeated after the completion of the intervention. The Pac-IFicO programme is a complex intervention with multiple components. It includes focus group with ward professionals for identifying possible local obstacles to optimal pain control, informative material for the patients, an educational program performed through guides from the wards, and an organisational intervention to the ward. The primary end-point of the study is the proportion of cancer patients with severe pain. Secondary end-points include opioids administered in the wards, knowledge in pain management, and quality of pain management. We plan to recruit about 500 cancer patients. This sample size should be sufficient, after appropriate statistical adjustments for clustering, to detect an absolute decrease in the primary end-point from 20% to 9%.This trial is aimed at exploring with an experimental approach the efficacy of a new quality improvement educational intervention.NCT02035098ClinicalTrials.gov:  Pain is one of the most common reasons for requesting health care service attention. The World Health Organization (WHO) estimates that 20% of individuals worldwide have some degree of chronic pain ,2.Despite the availability of effective analgesic drugs and of published guidelines -8 as welData from a systematic revision of the literature show that pain prevalence in cancer patients ranges from 33% in patients after curative treatment to 59% in patients on anticancer treatment, up to 64% in patients with advanced or terminal phase of disease .Pain was undertreated in about 50% of the cancer patients evaluated in 26 trial by means of the Pain Management Index (PMI)  which evSince 2010 pain assessment has been required by law for all patients in all Italian hospitals . Major cThe systematic management of cancer related pain is not included in the standard educational programs for clinicians in the Italian schools of medicine, whereas specific courses are available for nurses, who may also access a larger number of training courses on pain assessment and management, compared to clinicians -25. On tAs indicated in the international guidelines, the optimal treatment of pain in cancer patients has recently been acknowledged as a major goal to guarantee the quality of care in hospitalized patients.The availability of an effective protocol to improve the quality of pain control in hospitalized patients is mandatory in the daily practice in hospital units.There is enough evidence supporting the potential effectiveness of the single issues  of a program for the improvement of the quality of pain control in hospitalized patients -40. The A group of health professionals from different institutions developed a complex educational intervention aimed at improving pain control in hospitalized cancer patients. The acronym of the programme is Pac-IficO . The Pac-IficO Programme includes a number of integrated interventions and is targeted to hospital wards, with the aim to significantly improve pain control in cancer patients.The general aim of this study is assessing the effectiveness of the Pac-IFicO Programme in improving the quality of pain management in hospitalised cancer patients.In this manuscript we report in detail the protocol used.The primary aim of this trial is to evaluate the effectiveness of the Pac-IFicO programme in improving the control of severe pain in cancer patients admitted to general medicine, oncology and respiratory disease wards of three Italian regions.The secondary aims of this study include the assessment of:○ type and quantity of opioids administered in the wards;○ knowledge of the ward professionals in pain management;○ quality of pain management in cancer patients.This is a multicentre uncontrolled before–after cluster trial performed within hospital wards participating in the assessment of the Pac-IFicO programme.The main objective of the Pac-IFicO programme is improving the quality of pain management in hospitalised cancer patients. The targets of the intervention are the professionals working in the hospital ward, but the outcomes of interest are assessed in clusters of patients from the hospital wards before and after the implementation of the Pac-IFicO programme.The study is organised in different phases:Preliminary phase○ Identification of the eligible wards“Before” assessment in the selected wards○ Before evaluation according to the procedures of assessmentImplementation of the experimental intervention in the selected wards○ Implementation of the PAC-IFicO programme“After” assessment in the selected wards○ After evaluation according to the procedures of assessmentThe three regional coordinators of the study obtained from local health authorities the list of all hospitals and wards of the region. For each ward the following information was collected: denomination and classification, number of beds, number of ordinary admissions per year with a primary or secondary diagnosis of tumour (ICD-IX 140-239) and their average length of stay in ward. An approximation of the punctual prevalence of the oncological patients was estimated for each ward from the last two information.The process of identification of the eligible wards participating to this study is performed according to the following procedures:➣ identification of all potential eligible units from the list of the hospital wards of each region (criteria 2-6 of the ward-level inclusion criteria);➣ phone interview with the nurse coordinators on previous training on pain management received by the wards (criteria 1 of the ward-level exclusion criteria);➣ random sampling, for each region, of the first eligible ward and subsequent evaluation of the consent from the Hospital management and the head of the ward to participate in the study. The procedure were repeated until two eligible units per region were identified.The procedures and the dimensions of assessment for each identified ward include three levels:Ward level○ Information about the total consumption of opioids of the ward in the 6 months before and in the 6 months after the implementation of the Pac-IFicO programme were collected from the Hospital pharmacy.Staff level○ For all physicians and nurses of the ward information about qualification, years of service, training in pain management were collected.○ Knowledge of the ward professionals in pain management were assessed before and after the implementation of the intervention by administering the Italian version of the Pain Attitudes and Knowledge Scale (PAK) ,42;Patient level○ The quality of pain management is assessed before and after the implementation of the intervention by administering the APS-POK  to all e○ For all eligible cancer patient demographic and clinical information were collected. Moreover, date and time of evaluation, and causes for failed evaluation were also registered.The primary end-point of the study is the percentage of hospitalized cancer patients with average severe pain (score 7-10) within the latest 24 hours in the after sample as compared to the before sample.Ward level○ Indicators about opioids administration includes: type and total amount of opioids administered in the wards to all patients;Staff level○ Knowledge and attitudes of the ward professionals in pain management were assessed with the Italian version of the Pain Attitudes and Knowledge Scale (PAK). The questionnaire was developed and validated by Lebovitz et al , and subPatient level○ The quality of pain management was assessed with the APS-POK. The questionnaire was originally developed and validated with the aim of assessing pain and pain control as perceived and rated by the patient . The APSHospital level1. consent from the Hospital Management to participate to the studyWard levelIncluding criteria1. consent from the head of the ward to participate in the study;2. ward classified as oncology, medicine, respiratory disease ward according to the regional classification of hospitals;3. number of beds;4. number of ordinary admissions with primary or secondary diagnosis of tumour (ICD-IX 140-239) >180 per year;5. yearly average stay in hospital between 4 and 19 days;6. punctual prevalence of patients with primary or secondary diagnosis of tumour (ICD-IX 140-239) ≥ 8 patients.Excluding criteria1. the ward had received or is receiving quality improvement programmes of staff education for improving pain control.Staff level1. affiliation to the ward;2. informed consent to participate in the study.Patient levelIncluding criteria1. patients admitted in the ward for at least 24 hours;2. age ≥ 18 years3. able to fill in the questionnaire according the health care professionals judgment;4. informed consent to participate to the study.Excluding criteria1 patient already assessed in one of the previous assessments.PAC-IFicO programme shows significant differences if compared to previous Italian “Pain-free Hospital” experiences. Such differences can be listed as follows:In all selected wards the PAC-IFicO programme will be implemented. The ➣ a rigorous research in terms of methods and subsequent phases of the project;➣ the use within hospital units of a “Program” with the same modalities of implementation;➣ comprehensive employment of all the components of the “Program”;peer-to-peer training among colleagues;➣ training based on adult education programs: education based on local barrier clearing (pre-education focus) and ➣ local organizational support interventions following the training phase;➣ the involvement of both clinicians and nurses into the project ;Pac-IFicO Protocol [Additional file Protocol ,49.Within each involved units, two Guides (a physician and a nurse) will be appointed, who will attend a four-day training course, with the aim to be enabled, in turn, to train and educate their colleagues in their unit relating to the “standard implementation” of the Program.All the patients in the involved units will receive an information pack on pain control, during the whole protocol .After the training course for all the health professionals, the following organizational support interventions will be performed:crucial clinical case within the unit with the support of both the appointed Guides and a regional coordinator;1. Monthly debate (for three months) on a 2. Peer to peer learning interviews among the unit staff with the Guides3. Audit interview to the nurse coordinator of the unit three months after the completion of the training phase.The Program includes a procedure for the evaluation of the quality of the implementation process. In particular, the following evaluations will be carried out:➣ Evaluation of the training program; the whole process of design, implementation and learning assessment will be evaluated according to the Quality Improvement Programs. Process indicators will be used concerning the subsequent phases of both the training program for the Guides and of the standard implementation process.➣ Evaluation of the organizational support program: all the critical clinical cases discussed within the unit will be analysed; all the support interviews among colleagues will be tracked and collected; all the audit interviews to the nurse coordinator and to the unit chief will be also analysed., and from the Ethics committees of all participating centres.The protocol was approved by the Ethics Committee of the Promoting Center, The primary outcome measurement in the present study is the percentage of hospitalized cancer patients with severe pain within the latest 24 hours (score 7-10).To address the effectiveness of the Pac-Ifico Programme, a clustered sample size was estimated with an alpha error of 0.05 and a power of 80%, assuming an intraclass correlation coefficient (ICC) for the primary endpoint equal to 0.01. According to these assumptions we estimated that 10 hospital wards, with cluster size equal to 25 pre-intervention and 25 post-intervention patients corresponding to overall 500 patients, would be sufficient to detect an absolute decrease in the primary endpoint from 20% to 9%, corresponding to an odds ratio of 0.4.Patients’ characteristics by pre and post-intervention groups and/or by centres were reported as means, frequency and percentage, for continuous and categorical variables, respectively. Student t-test for continuous variables and Pearson chi-square for categorical variables were used to compare pre-intervention vs. post-intervention group.To account for the nested nature of the study design (i.e. patients clustered within wards), primary and secondary endpoints were analysed with a generalized hierarchical linear model ,51.Results comparing pre-intervention vs. post-intervention group were expressed in terms of mean differences and odds ratios (OR) along with their 95% confidence intervals (95% CI) for hierarchical linear and logistic models, respectively. Some analyses were adjusted for known confounders as reported in details in the specific tables.Two-sided P-values < 0.05 were considered statistically significant. All the analyses were performed using the SAS Statistical Package Release 9.1 .Although pain evaluation and management is codified both in available guidelines and, in Italy, also in the Law 38/2010, pain is still often uncontrolled both in cancer patients and in patients with non oncological chronic diseases.Our Study aims to improve the quality of pain management in patients admitted to medicine, oncology and pneumology units in three Italian Regions: Liguria, Piemonte and Veneto.By means of consolidated educational and organizational methodologies, the Pac-IFicO Programme actually reinforces current strategies for cancer related pain control according to international guidelines in some medicine, oncology and respiratory disease wards. Not only does the present study aim to consolidate scientific knowledge relating to clinical and non clinical recommendations contained in the object Program, but it also aims to assess the effectiveness of the whole Program as a tool to improve health care in cancer patients in pain.The aim of this study was to assess whether the implementation of the programme may determine effective changes in the attitudes and behaviour of health professionals in view of a better practice, and whether these changes have a positive impact on the control of pain in cancer patients. The results will be analysed and interpreted at three levels: the ward level, the staff level, and the patient level, the last to evaluate the effectiveness of the induced changes in terms of an improved quality of health care.One of the most innovative features of the present programme is the appointment of two Guides in the unit  who will first attend a 4-day long training course, after which they will reproduce a “standard implementation” training to all their colleagues, including all the physicians and nurses within the involved unit. The hospital staff will thus become a source of continuous training, which multiplies by involving new professionals. Moreover, the monthly grand rounds on critical clinical cases, along with the peer to peer learning assessment interviews among the unit health professionals with the Guides strengthen and improve any educational initiative by including the whole involved staff.The authors declare that they have no competing interests.CR, MS, CP, wrote the paper after having planned the study protocol with all the other Authors. All the Authors revised the study protocol critically. EP and FP gave their contribution in the statistical section. Moreover CP and EP were the Coordinating Research Group of the Study Protocol. CP was the Scientific Responsable of the Study Protocol. All the Authors gave final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All the Authors read and approved the final manuscript.Carla Ida Ripamonti, MD specialized in medical oncology and clinical pharmacology , Head of Supportive Care in Cancer Unit at the Fondazione IRCCS, Istituto Nazionale dei Tumori, Milano (INT), and in the past Vice Director of Pain Therapy and Palliative Care Unit of INT. Member of: European Society Medical Oncology (ESMO) Faculty Member Educational Committee; Supportive and Palliative Care; Co-Chair of the ESMO Palliative Care Working Group (PCWG); ESMO Media Ambassador; Italian Member of Multinational Association Supportive Care Cancer (MASCC); the life-time Board of Directors of the International Association Hospice Palliative Care (IAHPC).Maria Adelaide Pessi, a medical oncologist mainly involved in the treatment of ovarian and gastrointestinal cancers. She actively participated in the development of national and international clinical trials, specially related with adjuvant and palliative treatment of gastrointestinal cancers and treatment of nausea and vomiting from chemotherapy. Since 2009 she is part of the supportive care team.Massimo Costantini, a physician specializing in oncology, is Head of the Palliative Care Unit at the IRCCS S. Maria Nuova Hospital of Reggio Emilia . His research interests are in the areas of palliative care and quality of life. Since 2007, he is Visiting Professor in Palliative Care at the Department of Palliative Care, Rehabilitation and Policy, King’s College London (UK). He is author or co-author of more than 100 peer reviewed publications.Carlo Peruselli, President of Italian Society of Palliative Care (SICP).Cesarina Prandi, Research Nurse, Secretary of Italian Society of Palliative Care (SICP).Lorenza Garrino, actively involved in Educational programs at the Department of Pubblic Health and Pediatrics Sciences University of Turin Italy.Elisa Perfetti is a pharmacist working as Clinical Trial Coordinator at the Oncology Unit of a Hospital in the North of Italy. Anna De Luca, Marco Visentin are Directors of Pain Therapy and Palliative Care Units and Educational programs in the 2 comprehensive Hospitals in the North of Italy.Fabio Pellegrini, is a statistician working at the Biostatistic Unit, Fondazione Mario Negri Sud. He published more than 150 papers.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-684X/13/15/prepubPhases of the PACIFICO Program.Click here for file