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Background and Objectives: This prospective randomized controlled trial investigated the clinical efficacy of stimulating catheters for continuous femoral nerve block in patients who underwent anterior cruciate ligament reconstruction.Methods: Seventy patients were randomized to either a stimulating catheter (SC, n = 35) or a nonstimulating catheter (NSC, n = 35) for femoral nerve block using 25 mL ropivacaine 7.5 mg/mL and clonidine 50 microg injected through the catheter. A single-injection sciatic block was also given to ensure surgical anesthesia. The time to loss of sensation to cold and pinprick of the femoral nerve was registered as the onset time. Data were registered intra- and postoperatively regarding pain scores, adverse effects, and need for supplemental anesthesia and analgesia other than a continuous postoperative infusion of ropivacaine 2 mg/mL through the continuous femoral nerve catheter set at 7 mL/h.Results: Onset time was faster in the SC group (SC: 6.4 +/- 2.5, NSC: 8.3 +/- 2.9 min, P = .006). Visual analog scale pain scores were similar in both groups. The number of patient-controlled regional analgesia boluses (SC: 14.6 +/- 12.6, NSC: 23.2 +/- 13.6 mg ropivacaine 2 mg/mL, P = .008) as well as intravenous rescue ketorolac (SC: 34.3 +/- 35.7, NSC: 54 +/- 39.7 mg, P = .033) administered were higher in the NSC group.Conclusion: Although the use of a stimulating catheter was associated with faster onset time for the femoral nerve block and lower additional analgesics postoperatively, the clinical superiority (analgesia; lateral femoral cutaneous, and obturator nerve block) of stimulating catheters was not evident in this clinical setting. [ABSTRACT FROM AUTHOR]

A survey was conducted in the largest hospital in Albania to estimate the prevalence and risk factors for nosocomial infections (NIs). A one-day prevalence survey was carried out between October and November 2003 in medical, surgical and intensive care wards. Centers for Disease Control and Prevention definitions were used. Study variables included patient and hospital characteristics, surgical procedures, invasive devices, antibiotic treatment, microbiological and radiological examinations, infection signs and symptoms. Risk factors were determined using logistic regression. In all, 185 NIs were found in 163 of 968 enrolled patients. Urinary tract infections (33.0%), surgical site infections (24.3%), pneumonia (13.0%) and venous infections (9.2%) were the most frequent NIs. The prevalence of NIs was higher in intensive care units (31.6%) than in surgical (22.0%) and medical wards (10.3%). Overall, 132 NIs (71.4%) were confirmed by microbiological examination; the single most frequently isolated micro-organism was Staphylococcus aureus (18.2%). By means of logistic regression, the following independent risk factors were identified: age >40 years, length of hospital stay, 'trauma' diagnosis at admission, and invasive devices. Even though comparisons must be made with great caution, the prevalence of NIs was higher than in western European countries and in some developing countries. Copyright © 2007 The Hospital Infection Society [ABSTRACT FROM AUTHOR]

Introduction: An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here., Methods: Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity., Results: Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids., Conclusions: These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients' satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients., Funding: Molteni Farmaceutici, Italy.

The study's aim was to examine safety and efficiency of citrate anticoagulated continuous renal replacement therapies (CRRT) in cardiac surgery patients with acute kidney injury and associated liver dysfunction. The study was conducted on critical ICU patients, hospitalized after cardiac surgery, who developed renal and liver acute failures due to low-flow syndrome. CRRT in continuous veno-venous hemodiafiltration with regional citrate anticoagulation (RCA) was prescribed to address renal failure and avoid bleeding-risk. Patient Ca(++) was measured to monitor RCA safety, while thromboelastography (TEG) and circuit Ca(++) were used to verify efficacy. CRRT effectiveness was evaluated through creatinine and urea levels, while liver function was monitored through bilirubin, aspartate aminotransferase, glutamic oxaloacetic transaminase (AST GOT) and gamma glutamyl transferase (GT) levels. The study did not require ethical approval. Hepatic and renal failures were confirmed by baseline levels (total bilirubin=3.1 ± 3.37 mg/dL, AST GOT=153 ± 147 U/L and gamma GT=93.3 ± 86 IU/L, creatinine=1.97 ± 0.88 and blood urea nitrogen [BUN] 98.13 ± 71.34) assessed in 15 patients. During treatment, Ca(++) (patient and circuit) remained stable and within range for the whole therapy thanks to low citrate dose (2.8 ± 0.3 mmol/L of blood), while hepatic markers did not show any significant changes the therapy, although treatment with citrate is contraindicated in patients with hepatic failure. RCA quality was confirmed by TEG values, which showed an anticoagulated circuit with no effects on patients. These results involved a high filter lifespan (49.76 ± 22.10 h) and with an effective creatinine and BUN clearance. No episodes of citrate intoxication were reported (total/ionized calcium ratio remained stable and physiologic). RCA during CRRT with dilute solutions proved both effective and safe, even in patients with acute liver failure., (© 2015 The Authors. Therapeutic Apheresis and Dialysis © 2015 International Society for Apheresis.)

Objective: A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU), seven oncology departments (ONC), and nine pain clinics (OPC)., Methods: A standard algorithm was used to confirm the diagnosis of BTP of patients refereed to different settings., Results: 1,412 evaluable cancer patients were enrolled. 53.9% were males and the mean age was 63.7±13.1 years. The mean intensity of background pain was 2.8±0.73. Patients reported 2.4±1.1 BTP episodes/day with a mean intensity of 7.37±1.28. 80.6% patients reported that the BTP had a significant negative impact in everyday life. The majority of patients reported a fast onset of BTP, which was predictable in 50.7% of cases, while BTP with a gradual onset (>10 min) was less predictable (29%) (P=0.001). PCU patients were older, had lower Karnofsky levels, a lower number of BTP episodes/day, a slow onset of BTP onset, and a less predictable BTP. Cancer diagnosis was performed a mean of 23.5 months (SD±32.8) before the assessment. The mean duration of background pain was 3.5 months (SD±3.5), and the mean duration of any analgesic treatment was 2.5 months (SD±3). BTP started a mean of 2.2 months (SD±1.9) before the assessment. Characteristics of BTP were influenced by the course of disease, as well as the duration of background pain and initiation of BTP. Most patients took rapid onset opioids and were satisfied with the treatment. BTP diagnosis was prevalently made by ONC and OPC physicians, and rarely by GPs., Conclusion: This survey performed by an Italian observatory expert review group, has confirmed that the BTP represents a clinically relevant condition with a negative impact on the patient's quality of life. BTP was detected in all settings involved. A number of factors are associated with the BTP. Also factors regarding the course of disease and setting of care have been assessed. This information may help in stratifying patients or predicting the risk of development of BTP with specific characteristics.

Background: Breakthrough pain (BTP) is traditionally defined as a pain exacerbation in patients with chronic controlled pain. However, this definition has recently been challenged., Objectives: To evaluate the prevalence of unsatisfactory control in patients with chronic cancer pain, and investigate the frequency and intensity of BTP episodes., Methods: A total of 665 patients with chronic cancer pain attending 21 pain therapy units in Italy were evaluated for baseline pain intensity and number of BTP episodes over a 30-day period. All patients started, continued or modified treatment for BTP at enrollment, according to medical judgment., Results: The number of BTP events was higher in patients with uncontrolled baseline pain, although the intensity and duration of episodes were similar. In patients with uncontrolled baseline pain, the number of events decreased with time and reached values comparable with those reported in patients with controlled pain. Both the intensity of the pain and the duration of the BTP events exhibited similar values in the two groups at all time points, following increased monitoring and the prescription of analgesic medication., Conclusion: Patients with uncontrolled baseline pain experienced BTP flares with higher frequency, but similar intensity and duration with respect to patients with controlled pain at baseline. Notably, a close follow-up and adequate management of the BTP episodes led to an improvement of BTP in the observed patients.

Background: Recent information on epidemiology and management of post-herpetic neuralgia (PHN), a painful complication of zoster, is scarce., Methods: This study was conducted at the Pain Clinic of the Policlinico Tor Vergata, Rome, Italy, on eighty-five immunocompetent patients with a clinical diagnosis of PHN. At enrollment (time 0, T0), the patients were interviewed by physicians to obtain demographic data and information about their zoster clinical history and underwent a blood test for VZV-DNA research. DN4 and SF-12 questionnaires were used to assess the neuropathic nature of pain and the overall health status, respectively. A one-year follow-up was planned for enrolled cases, who were visited at regular intervals of at least 3 months., Results: At T0 all the patients were at least 6 months from the episode of acute zoster and still presented with intense pain (mean VAS =6.7; mean DN4 = 5.7). Using antivirals within 72 hours from the rash onset was associated to a significant reduction of pain at T0 (p = 0.006 vs untreated patients). Only 2.6% of patients treated with antivirals during acute zoster but 18.6% of the untreated ones presented with neuropathic pain at T12 (p =0.007), even though the two groups were similar at T0. VZV-DNA was found in 5 out of the 50 available blood samples. At the last follow-up visit, PCS and MCS scores of the PHN patients were found to be recovered over those of the historical age-matched healthy controls. Undesirable side effects of analgesic therapies were observed in 15.3 to 28.8% of the patients., Conclusions: Patients who six months after acute zoster still have significant neuropathic pain, have a high probability of suffering from chronic pain in the subsequent months/years. The initial antiviral treatment has a significant impact on the pain. Current strategies of analgesic therapy are effective to achieve relief of pain in PHN patients, but they are burdened with heavy and undesirable side effects.

Background and Objectives: Treatment for chronic non-cancer neuropathic pain can be complicated by side effects and drug interactions. Combining opioid analgesics and calcium channel modulators may overcome these and improve efficacy. The objective of the present study was to evaluate the efficacy and safety of OROS® hydromorphone combined with pregabalin in patients with chronic non-cancer neuropathic pain., Methods: This retrospective observational study was conducted on clinical records from patients aged ≥18 years with chronic non-cancer neuropathic [>4 on the Douleur Neuropathique en 4 questions (DN4) scale] pain of ≥6 months duration, with severe intensity [>4 on the Numerical Rating Scale (NRS); range 0-10], who attended all visits and had ≥12 months of follow-up at the Tor Vergata University Polyclinic Hospital, from November 2008 to February 2011. Patients received an oral combination of OROS® hydromorphone and pregabalin. Pain was evaluated at each visit (months 1, 3, 6, 9, and 12) using the NRS and DN4 scale; Patients' Global Impression of Change (PGIC) was administered at months 1, 6, and 12. Dosage and side effects were recorded at each visit., Results: Of 1,292 patients (32 % men, mean ± SD age 67.6 ± 11.9 years), 1,126 attended all visits. Seventeen percent (n = 224) had purely neuropathic pain. Initial mean dosage was 6.06 ± 2.00 mg/day for OROS® hydromorphone, 113.02 ± 21.94 mg/day for pregabalin. Dosages increased up to month 6, and returned to near initial dosages at month 12 (range 4-120 mg/day for OROS® hydromorphone; 75-600 mg/day for pregabalin). NRS pain scores (mean ± standard deviation) were 7.25 ± 1.34 at baseline and 1.85 ± 1.36 at 12 months (p < 0.0001); DN4 scores were 6.19 ± 1.65 at baseline, reduced to 1.84 ± 1.25 at 12 months (p < 0.0001), reductions of 74.4 and 70.2 %, respectively. More than 90 % of patients had a ≥50 % score reduction on both scales after 12 months. The PGIC scale showed that >75 % of patients felt improvement at 1 month, increasing to 91 % and 93 % at 6 and 12 months. The incidence of side effects was similar between elderly (aged >65 years) and younger subjects; there were no cases of addiction., Conclusions: The OROS® hydromorphone and pregabalin combination was efficacious for chronic non-cancer neuropathic pain and well tolerated, providing significant pain reduction without the risk of addiction and with a good tolerability profile, regardless of age.

Background: Opioids may alleviate chronic neuropathic pain (NP), but are considered second/third-line analgesia due to their poor gastrointestinal (GI) tolerability. A fixed combination of prolonged-release oxycodone and naloxone (OXN) has been developed to overcome the GI effects. The aim of this analysis was to evaluate analgesic effectiveness and tolerability of low-dose OXN in patients with moderate-to-severe noncancer NP despite analgesia., Methods: This retrospective observation of consecutive adult patients, treated open-label for 8 weeks at a single Italian centre, evaluated effectiveness (pain intensity numerical rating scale [NRS], Patients' Global Impression of Change [PGIC], Douleur Neuropathique 4 inventory [DN4] and Chronic Pain Sleep Inventory [CPSI]), doses of daily OXN and adjuvant medication, rescue paracetamol use, bowel function index (BFI), laxative use, and safety., Results: Of 200 patients (mean age 65.9 years; 54% female) with NP included in the analysis; 97% completed 8 weeks' treatment. At the observation start, all patients were taking anticonvulsants and complained of constipation, and 60% were receiving opioids. Pain intensity and DN4 score decreased significantly by endpoint (NRS p < 0.0001; DN4 p < 0.0001) and need for rescue analgesics abated. Reduction in pain intensity throughout the observation was similar regardless of NP aetiology. According to PGIC, 87.8% of patients were much/extremely improved, CPSI (p < 0.0001) and BFI were significantly improved (p < 0.0001) and laxative use decreased. No differences were found between patients <65 years vs those ≥65 years. OXN was generally well tolerated., Study Limitations: Study limitations including the retrospective observational design, the lack of a control group and the single-centre design may limit the generalizability of our findings., Conclusions: Low-dose OXN (25.0 ± 12.5 mg/day) added to anticonvulsants was highly effective in controlling noncancer NP of varied aetiology, with reduced need for rescue analgesia and improved quality of sleep, and was well tolerated, with improved bowel function and reduced laxative use. The efficacy and tolerability of OXN demonstrated in this real-world setting suggest its utility in this difficult to manage patient population.

Informed consent is part of a process of communication useful to obtain an agreement (conscious, voluntary and free) between doctors and patients. Mesotherapy is based on the introduction of drugs by intradermal route in order to obtain a dose-sparing effect with respect to deeper administration. Opioids are the most appropriate therapy for patients who do not respond to other therapies. Proper communication between doctor and patient, including an explanation of the potential benefits, limitations and risks (even mild), is recommended both in clinical practice and research. Active participation of the patient has the advantage of better control of adverse events, both of mesotherapy and opioid-based therapy. This information-education process returns to the fundamental concept of "first do no harm" and set a "therapeutic partnership" with patients.

According to Italian legislation to diagnose brain death (BD) after the initial documentation of the clinical signs, repetition of clinical testing and confirmation of the loss of bioelectrical activity of the brain (EEG) is required. However, when EEG is unreliable it is necessary to demonstrate cerebral circulatory arrest (CCA). Accepted imaging techniques to demonstrate CCA include: cerebral angiography, cerebral scintigraphy, transcranial Doppler (TCD) and computed tomography angiography (CTA). This latter technique, due to its large availability, low invasivity and easy and fast acquisition is widely used over the country. Nevertheless its diagnostic reliability is affected by some limitations in patients with decompressive craniectomy. Here we report two cases of brain injury with clinical signs of BD and at the same time, opacification of intracranial arteries on CTA and a pattern consistent with flow arrest on the corresponding insonable arteries on TCD. The discrepancy between CTA and TCD results points out a methodology limitation that could be overcome by updating Italian legislation according to other European Countries legislation.

Introduction: Breakthrough pain (BTP) is traditionally defined as a transitory pain flare in opioid-treated patients with chronic background pain. This definition has, however, been challenged in recent years. This study aimed to analyze BTP prevalence in different pain conditions., Methods: This was a prospective, non-interventional, observational study conducted from June to September 2011 in two Italian pain treatment reference centres. Consecutive patients aged >18 years with oncological or non-oncological pain were eligible for this study; background pain was acute/ subacute (<3 months) or chronic (>3 months). The characteristics of pain were evaluated by means of a structured interview by physicians, and patients were asked to complete a dedicated clinical study form. The following outcomes were assessed: chronic pain duration (in patients with chronic pain), BTP prevalence, and number and severity of daily BTP episodes. All outcomes were assessed in four populations of patients with: (a) chronic oncological pain; (b) chronic non-oncological pain; (c) non-chronic oncological pain; (d) non-chronic non-oncological pain. The correlation between BTP and gender was also investigated., Results: Of 1,270 patients with chronic pain, 1,086 had non-oncological pain (85.5%). Most patients (68.6%) with non-oncological pain were female (P = 0.001). Pain duration was significantly longer in non-oncological pain versus oncological pain groups (P = 0.002). BTP prevalence was lower in non-oncological patients (P < 0.001). No differences were reported in terms of number and severity of daily BTP episodes. BTP was more frequent in females with non-oncological pain (P = 0.04). Females had a significantly higher pain severity (P = 0.02) than males., Conclusion: BTP is frequently reported in patients who do not have BTP according to the traditional definition. BTP frequency and severity is similar in oncological and non-oncological pain.

Introduction: Opioid treatment for chronic malignant and nonmalignant pain of moderateto-severe intensity is associated with bowel dysfunction leading to constipation; this often requires opioid dose reduction or interruption. Combination opioid agonist/antagonist therapy can restore normal bowel function. A prolonged-released (PR) fixed-dose combination of oxycodone and naloxone has been developed and efficacy has been demonstrated in phase 3 clinical trials., Methods: This 2-month, retrospective, singlecenter, observational study assessed the effectiveness and safety of PR oxycodone/naloxone in consecutive nononcological patients with constipation and chronic pain despite analgesic treatment; specific subgroup analyses were performed in opioid-experienced or opioid-naïve patients and in age subgroups. Efficacy was assessed by: intensity of pain; bowel function; effective oxycodone/naloxone dose; Patients' Global Impression of Change (PGIC) scale; rescue paracetamol; and laxative use. Safety evaluations were also performed., Results: Of 1,051 patients starting on the oxycodone/naloxone combination (32.0% male; mean age 67 ± 13 years, 53.9% opioid naïve), 1,012 completed 2 months of treatment. Overall, PR oxycodone/naloxone was associated with a significant decrease in pain intensity (P < 0.001), a reduced need for rescue paracetamol (P < 0.001), and PGIC score of "very much improved" or "much improved" in 84.0% of patients. Constipation markedly decreased (P < 0.001) despite reduced laxative use (P < 0.001 vs. baseline). The most frequent treatment-emergent adverse events were somnolence (2.0%), dizziness (1.1%), and confusion (1.0%). Clinical differences in endpoints were seen between opioid-naïve and opioid-experienced patients, and among agestratified groups, but efficacy was similar to the overall population., Conclusions: Fixed combination PR oxycodone/naloxone was effective and well tolerated in moderate-to-severe chronic pain in patients with constipation, providing analgesia and relief from bowel dysfunction. Consistent efficacy across patient subgroups provides guidance for daily management of chronic pain when therapy options are limited due to bowel dysfunction, regardless of age or previous medication. Supplementary material belonging to this paper is available on SpringerLink.

Objective: To assess the efficacy and safety of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the N-acylethanolamines family, in reducing pain severity in patients with pain associated to different pathological conditions., Methods: This was an observational study conducted on 610 patients who were unable to effectively control chronic pain with standard therapies. PEA (600 mg) was administered twice daily for 3 weeks followed by single daily dosing for 4 weeks, in addition to standard analgesic therapies or as single therapy. The primary outcome measure was the mean score pain severity evaluated by the numeric rating scale. Safety was also evaluated., Results: PEA treatment significantly decreased the mean score pain intensity evaluated in all patients who completed the study. The PEA effect was independent of the pain associated pathological condition. PEA-induced decrease of pain intensity was present also in patients without concomitant analgesic therapy. Importantly, PEA showed no adverse effects., Conclusions: In this study, PEA was effective and safe in the management of chronic pain in different pathological conditions., (Wiley Periodicals, Inc.)

Introduction: Despite breakthrough pain (BTP) being one of the most severe forms of pain, there are no definitive data on its prevalence., Methods: The authors performed a retrospective survey of the prevalence of BTP in consecutive patients in four Italian pain clinics, subsequent to application of an Italian law mandating detailed clinical records on pain characteristics, treatment, and results. Mean pain intensity was assessed with a numerical rating scale from 0 to 10., Results: The authors analyzed records of 1,401 patients (58% women, 33.1% patients with cancer). Transient episodes of severe pain or BTP were referred by 790 patients (56.4%), including 58.2% of the men (342 of 588) and 55.1% of the women (448 of 813). Among the 464 patients with cancer, 70.3% reported daily exacerbation of pain. The mean BTP intensity was 8.31 ± 1.58 and 31.1% of patients reported experiencing three episodes per day., Conclusion: Despite some limitations of the study, the authors show that transient episodes of severe pain or BTP are significantly present both in cancer and other diseases, and that many patients are not yet receiving appropriate opioid therapy. The authors need validated tools at international level for the diagnosis and treatment of BTP in patients with cancer and for transitory and patients with severe non-cancer pain. A survey at national level is needed to estimate the prevalence of BTP in different settings, to plan specific medical education.

Opioids are one of the most widely used therapies for the palliative treatment of cancer pain; however, despite their proven analgesic efficacy, they are associated with several adverse effects. Associated with psychological distress and multiple concomitant clinical concerns, constipation is the most commonly occurring adverse effect of chronic opioid therapy in cancer patients. Whilst prophylaxis remains the first-line management option, methylnaltrexone is a recommended treatment option for opioid-related constipation if administration of laxatives is ineffective. Due to its inability to cross the blood-brain barrier, methylnaltrexone exerts a peripheral inhibition of opioid-related effects without influencing the opioid-induced central effects; as a result, the analgesic effect of opioids is unaffected. Moreover, multiple clinical trials, albeit not always conducted specifically in cancer patients, have demonstrated that up to 4 months' treatment with either intravenous or subcutaneous methylnaltrexone provides effective relief from opioid-related constipation and is well tolerated. Preliminary evidence indicates that the addition of methylnaltrexone to standard care for opioid-related constipation may also be advantageous from a pharmacoeconomic perspective. In addition, preliminary data suggest that methylnaltrexone could be associated with some further clinical benefits other than the treatment of opioid-related constipation, such as the improvement of gastric emptying, the relief of nausea/vomiting, and the reduction of the risk of regurgitation and pulmonary aspiration. This narrative review examines the most recent evidence and evaluates the current role of methylnaltrexone in the management of opioid-related constipation, and its potential efficacy in cancer patients. The pharmacokinetics, pharmacodynamics, efficacy and tolerability of methylnaltrexone are discussed.

Mesotherapy is the injection of active substances into the surface layer of the skin. This method allows a slower spread, higher levels, and longer lasting effects of drugs in the tissues underlying the site of injection (skin, muscle, and joint) compared with those following intramuscular injection. This technique is useful when a local pharmacological effect is required and relatively high doses of drug in the systemic circulation are not. Mesotherapy should only be undertaken following a complete clinical workup and subsequent diagnosis. Encouraging results have been reported in randomized, controlled clinical trials and in observational studies involving patients with various forms of musculoskeletal pain. Recommendations by experts from the Italian Society of Mesotherapy for appropriate use of mesotherapy in musculoskeletal pain and an algorithm for treating localized painful conditions are provided.

Objective: Since its introduction in the 1950s, the use of mesotherapy has generated much interest among clinicians and patients. The Italian Society of Mesotherapy (SIM) brought together a panel of experts to review available evidence and to draw up a series of recommendations on the use of intradermal therapy (LIT) in clinical practice., Consensus Report: There was overwhelming agreement among Consensus Group members that, when used correctly, LIT is a valuable therapeutic option in the treatment of painful, loco-regional conditions. They also emphasised that the clinical efficacy of LIT has been demonstrated in the management of chronic venous lymphatic insufficiency, oedematous fibrosclerotic panniculopathy and facial skin aging. The experts were unanimous on the use of LIT in vaccination. Mesotherapy is not a substitute for other therapeutic options and should only be used when the patient has been fully informed of its advantages and limitations. Likewise the procedure should only be carried out by an experienced qualified physician., Conclusions: Although there was widespread agreement among the Consensus Group on the place of LIT in several indications, the Authors reiterated the need for more large-scale clinical trials to determine the specific benefits and limitations in some areas of the application of intradermal therapy.

Introduction: Long-term administration of opiates in patients with chronic noncancer pain (CNCP) is subject to debate due to insufficient clinical evidence to support efficacy and tolerability., Methods: This retrospective analysis used hospital records to investigate the effects of low doses of the combination of oxycodone/paracetamol on CNCP in an outpatient clinic setting to verify adherence to therapy and long-term efficacy. All patients receiving therapy for CNCP were examined between May and September 2010 and information was collected on medication, duration of therapy, and static and dynamic pain measured using numeric rating scales (NRS) from relevant charts., Results: Two hundred and thirty-one patients (157 men, 68%) with a mean (± SD) age of 66.4±15.5 years were analyzed. Pain indexes at baseline revealed a mean (± SD) static NRS (sNRS) of 3.5±1.77 and a mean dynamic NRS (dNRS) of 7.24±1.33. At last follow-up, mean (± SD) pain reductions versus baseline were 1.58±1.42 for sNRS and 3.04±1.43 for dNRS (P<0.0001 for both). Regarding the duration of therapy, 54 patients (23.4%) were treated for <4 months, and 177 patients (76.6%) for 4 months up to 23 months. Pain reduction was significant in all groups (P<0.0001) but was greatest in patients who had been receiving therapy for ≥4 months. Improvements in pain relief were not associated with an increase in daily dose, which remained stable or decreased slightly over time., Discussion: The results of this study support the hypothesis that an opiate-based combination at low doses improves tolerability and adherence and results in patients obtaining long-term efficacy. Larger studies of the use of opiates in this setting and clinical monitoring on the regional and national level may convince clinicians to view opiates as efficacious analgesics and not as dangerous substances of abuse.

In this paper, we propose the use of black box models for the system identification of the cardiopulmonary baroreflex control of arterial resistance and of ventricular contractility and of arterial baroreflex control of heart rate (HR) from invasive, continuous measurements of arterial blood pressure (ABP) and central venous pressure (CVP), and non invasive, continuous recordings of ECG and respiration. Two crucial phases of the abdominal aortic aneurism (AAA) repair were investigated: the clamping and declamping of aorta. The objective of the present work is to evaluate and to test the ability to monitor baroreflex responses to clamping and declamping maneuvers preceding and following aneurism removal.

In critical care patient management, extensive and invasive patient monitoring is routinely performed in order to quantify patient status in view of therapeutic interventions. Little quantitative integration is performed when collecting information from multiple monitors, and processing algorithms are often based on little physiological understanding. Mechanistic modeling can offer insight into the mechanisms underlying patient stability and sensitivity to alterations in physiological variables. Starting from existing models, we construct an integrated model which combines detailed neural cardiovascular regulation with realistic circulation modeling, using Monte-Carlo techniques for reparameterisation when merging the two models. The combined model is analyzed in terms of its dynamical stability and sensitivity to parameter perturbations under simulated conditions of fluid deficit, anaesthesia, and dilatative cardiomyopathy. The results exemplify how a structural model can serve as a quantitative guide in assessing how different underlying patient states can alter the haemodynamics impact of external therapeutic intervention.

Aims: This study evaluates the efficacy and tolerability of long-term controlled-release (CR) oxycodone + pregabalin in patients with non-cancer pain, in a real-life setting., Methods: Patients (n = 1,051) with chronic uncontrolled non-cancer pain received CR oxycodone + pregabalin for 1 year. Pain intensity was rated on an 11-point numerical rating scale (NRS) at months 1, 2, 4, 6, 9 and 12., Results: Throughout the study period, the NRS score decreased significantly (baseline: 7.02 ± 1.26; 12 months: 1.45 ± 0.92; p = 0.00001). Following an initial increase in the mean daily doses of CR oxycodone (starting dose: 12.5 ± 8.4 mg) and pregabalin (starting dose: 121.7 ± 97.2 mg), dose reductions were seen for both drugs with the trend particularly evident for CR oxycodone. 23% of patients withdrew from the study, mainly due to adverse events (67.9% of withdrawn subjects). However, 19.7% of withdrawn patients were removed from the study due to complete relief from chronic pain. The combination was generally well tolerated and there were no reports of addiction., Conclusion: The combination of CR oxycodone + pregabalin could represent a valuable long-term therapeutic addition to existing pharmacological options for the treatment of non-cancer pain., (Copyright © 2011 S. Karger AG, Basel.)

This paper presents the analysis of the autonomic nervous system (ANS) control and cardiac baroreflex sensitivity in patients undergoing general anesthesia for major surgery, with the goal of evaluating the effects of anesthesia bolus induction with propofol on autonomic control of heart rate (HR) and arterial blood pressure (ABP). The increase in baroreflex gain in the LF band observed through two different methods hints at the fact that the baroreflex may increase heart period (HP) following a transient ABP decrease, but its response displays a larger amplitude, to compensate for the blunting of the sympathetic action on heart rate and vascular resistance.

Background and Objectives: Opioid-bowel dysfunction (OBD) is a broad range of symptoms potentially associated with opioid therapy. This prospective, multicentric study assesses the prevalence of OBD in patients on analgesic therapy for the treatment of pain from any cause and identifies the factors associated with the onset of this side effect., Materials and Methods: Consecutive patients aged > 18 years, on analgesic treatment with opioids, non-steroidal anti-inflammatory drugs (NSAIDs) or other therapies for chronic pain of any aetiology were included in the study. The association of OBD with gender, age, pain aetiology and analgesic treatment was analyzed by multivariate analysis and logistic analysis., Results: In total, 2324 patients were included in the study. The prevalence of OBD symptoms was 63.5%, despite that the wide majority of patients (89.5%) were receiving laxatives. OBD symptoms were judged as directly correlated with analgesic therapy in 85.1% of cases. The highest prevalence of constipation was reported with morphine, whereas the lowest was observed in patients on oxycodone CR and buprenorphine TTS. Statistical analysis showed that patients on opioids have a higher likelihood of experiencing OBD symptoms than those on NSAIDs or other treatments (66.2% vs 37.0%), and this probability is even higher in those with cancer-related pain (69.3%). Female gender and age > 70 years also appeared as risk factors. The logistic analysis indicated that cancer-related pain, increased age and the use of fentanyl are positive predictors of the presence of OBD, whereas the administration of oxycodone CR was associated with a decreased incidence of these symptoms., Discussion: Even with the limitation of any observational experience, this study suggests, for the first time, the existence of some factors predictive of the onset of OBD symptoms in patients on analgesic treatment. Moreover, different opioids seem to be associated with a different risk of experiencing these symptoms.

Little is known about reactivation of latent varicella zoster virus as herpes zoster in individuals with no underlying immunosuppression. Risk factors include age, sex, ethnicity, exogenous boosting of immunity from varicella contacts, underlying cell-mediated immune disorders, mechanical trauma, psychological stress, and immunotoxin exposure. An association between herpes zoster and family history of zoster has been proposed. A case-control study involving patients affected by post-herpetic neuralgia, which usually follows more severe acute herpes zoster, was performed. The patients with post-herpetic neuralgia were enrolled at the Pain Clinic of the Policlinico Tor Vergata in Rome, Italy, within 1 year from the onset of acute zoster. The controls matched for sex and age were chosen among healthy subjects without a history of herpes zoster presenting at the Internal Medicine Outpatient Clinic for hypertension in the same time period. All the participants in the study gave informed consent and were interviewed by medically trained and blinded investigators using a questionnaire. Similar proportions of the patients and the controls reported a family history of herpes zoster irrespective of the degree of relationship, i.e., 17.4% and 18.2%, respectively, by analyzing only the first-degree relatives [RR 1.03 (CI 95%: 0.78-1.37)], and 28.4% and 29.6%, respectively, by analyzing the total number of relatives [RR 1.03 (CI 95%: 0.81-1.31)]. Further and larger prospective cohort studies are needed to ascertain whether a family history of herpes zoster is really an independent predictor of zoster in different geographical settings., ((c) 2010 Wiley-Liss, Inc.)

The combination of two analgesic agents offers several advantages in the treatment of chronic pain. Paracetamol (acetaminophen) has central analgesic activity without a nonsteroidal anti-inflammatory drug (NSAID)-like or opioid-like effect. Oxycodone is a semisynthetic opioid agonist. The oral fixed-dose combination of oxycodone and paracetamol immediate-release formulation has a synergistic mechanism of action that is useful for moderate-to-severe pain and for nonresponders to NSAIDs or paracetamol alone. This fixed-dose combination offers several advantages: lower individual drug doses can be used because of their synergistic mechanisms of action, its opioid-sparing effect and it has a good efficacy and tolerability profile. Efficacy and safety of this fixed-dose combination were assessed in a wide range of clinical settings: in patients with osteoarthritis or chronic musculoskeletal pain, including when complicated by a neuropathic component; for chronic pain in elderly patients; cancer-related pain; postoperative pain; and for neuropathic pain, in the latter case usually given in combination with an NSAID or other drugs. The large variety of indications for which this fixed-dose combination may be useful can be attributed to the pharmacological synergy between oxycodone and paracetamol and because lower individual drug dosages can be used, suggesting that this should be a first-line agent for the treatment of chronic moderate-to-severe pain.

Background: Opioid rotation is currently the subject of considerable debate for two reasons: firstly as a strategy for pain treatment, and secondly because of the difficulty in determining equianalgesic doses. Switching from one slow-release (SR) opioid analgesic to another raises a number of critical issues, and there are no widespread studies that support a standard protocol. Initiation of opioid therapy must consider gradual dose titration of the drug until the minimum effective and maximum tolerated dosage for each patient is found., Objective: This study aimed to evaluate the effects of SR opioid rotation after a stabilization period with normal-release (NR) morphine ('start therapy') in patients with cancer or non-cancer pain not controlled with their current SR opioid., Methods: This is a multicentre, open-label, prospective study. A total of 326 consecutive patients were enrolled who were affected by chronic cancer or non-cancer pain that was not controlled by an SR opioid administered as either monotherapy or in combination with other analgesic drugs. Following start therapy with oral NR morphine at a dosage of 5 mg or 10 mg every 4 hours, rotation to an SR opioid of a different type from that previously administered was carried out., Results: After about 3 days of start therapy with NR morphine, rotation to an SR opioid allowed a significant decrease of both baseline pain and daily episodes of breakthrough pain. No significant difference was detected between dosages and type of opioid administered, both prior to and after the start therapy period with NR morphine., Conclusions: Rotation to another opioid preceded by a brief period of opioid receptor resetting by start therapy with NR morphine allows a good level of pain control and avoids rotation to inappropriate opioid dosages or combinations analgesics.