Role of the informed consent, from mesotherapy to opioid therapy.

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.

Decompressive craniectomy may cause diagnostic challenges to assess brain death by computed tomography angiography.

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.

Effectiveness and tolerability of low-dose oral oxycodone/naloxone added to anticonvulsant therapy for noncancer neuropathic pain: an observational analysis.

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.

Mesotherapy, definition, rationale and clinical role: a consensus report from the Italian Society of Mesotherapy.

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.

Long-term controlled-release oxycodone and pregabalin in the treatment of non-cancer pain: an observational study.

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.

Postoperative pain treatment SIAARTI Recommendations 2010. Short version.

The aim of these recommendations is the revision of data published in 2002 in the "SIAARTI Recommendations for acute postoperative pain treatment". In this version, the SIAARTI Study Group for acute and chronic pain decided to grade evidence based on the "modified Delphi" method with 5 levels of recommendation strength. Analgesia is a fundamental right of the patient. The appropriate management of postoperative pain (POP) is known to significantly reduce perioperative morbidity, including the incidence of postoperative complications, hospital stay and costs, especially in high-risk patients (ASA III-V), those undergoing major surgery and those hospitalized in a critical unit (Level A). Therefore, the treatment of POP represents a high-priority institutional objective, as well as an integral part of the treatment plan for "perioperative disease", which includes analgesia, early mobilization, early enteral nutrition and active physiokinesitherapy (Level A). In order to improve an ACUTE PAIN SERVICE organization, we recommend: --a plan for pain management that includes adequate preoperative evaluation, pain measurement, organization of existing resources, identification and training of involved personnel in order to assure multimodal analgesia, early mobilization, early enteral nutrition and active physiokinesitherapy (Level A); --the implementation of an Acute Pain Service, a multidisciplinary structure which includes an anesthetist (team coordinator), surgeons, nurses, physiotherapists and eventually other specialists; --referring to high-quality indicators in establishing an APS and considering the following key points in its organization (Level C): --service adoption; --identifying a referring anesthetist who is on call 24 hours a day; --patient care during the night and weekend; --sharing, drafting and updating written therapeutic protocols; --continuous medical education; --systematic pain assessment; --data collection regarding the efficacy and safety of the implemented protocols; --at least one audit per year. --a preoperative evaluation, including all the necessary information for the management of postoperative analgesia (Level C); --to adequately inform the patient about the risks and benefits of drugs and procedures used to obtain the maximum efficacy from the administered treatments (Level D). We describe pharmacological and loco-regional techniques with special attention to day surgery and difficult populations. Risk management pathways must be the reference for early identification and treatment of adverse events and chronic pain development.

No evidence of family history as a risk factor for herpes zoster in patients with post-herpetic neuralgia.

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.

Opioid-related bowel dysfunction: prevalence and identification of predictive factors in a large sample of Italian patients on chronic treatment.

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.

Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences.

BACKGROUND: Gabapentin and pregabalin inhibit Ca(2+) currents via high-voltage-activated channels containing the alpha2delta-1 subunit, reducing neurotransmitter release and attenuating the postsynaptic excitability. They are antiepileptic drugs successfully used also for the chronic pain treatment. A large number of clinical trials indicate that gabapentin and pregabalin could be effective as postoperative analgesics. This systematic-narrative review aims to analyse the most recent evidences regarding the effect of gabapentinoids on postoperative pain treatment. METHODS: Medline, The Cochrane Library, EMBASE and CINHAL were searched for recent (2006-2009) randomized clinical trials (RCTs) of gabapentin-pregabalin for postoperative pain relief in adults. Quality of RCTs was evaluated according to Jadad method. Visual analogue scale (VAS), opioid consumption and side-effects (nausea, vomiting, dizziness and sedation) were considered the most important outcomes. RESULTS: An overall of 22 gabapentin (1640 patients), 8 pregabalin (707 patients) RCTs and seven meta-analysis were involved in this review. Gabapentin provided better post-operative analgesia and rescue analgesics sparing than placebo in 6 of the 10 RCTs that administered only pre-emptive analgesia. Fourteen RCTs suggested that gabapentin did not reduce PONV when compared with placebo, clonidine or lornoxicam. Pregabalin provided better post-operative analgesia and rescue analgesics sparing than placebo in two of the three RCTs that evaluated the effects of pregabalin alone vs placebo. Four studies reported no pregabalin effects on preventing the PONV. CONCLUSION: Gabapentin and pregabalin reduce pain and opioid consumption after surgery in confront with placebo, but comparisons with other standard post-operative regimens are not sufficient. Gabapentin and pregabalin seem not to have any influence on the prevention of PONV.

Pregabalin in the treatment of chronic pain: an overview.

Chronic 'pathological' pain is sustained by mechanisms of peripheral and central sensitization, which are being increasingly investigated at the molecular and cellular levels. The molecular determinants of nociceptive sensitization are natural targets for potential analgesic drugs used in the treatment of different forms of pain. Most of these determinants are common to all forms of chronic pain, and it is therefore not surprising that drugs specifically targeted for the treatment of neuropathic pain are effective in relieving nociceptive inflammatory pain and vice versa. The molecular mechanisms of sensitization that occur in peripheral nociceptors and the dorsal horns of the spinal cord are putative targets for context-dependent drugs, i.e. drugs that are able to discriminate between 'normal' and 'pathological' pain transmission. Among these, pregabalin and gabapentin bind to the alpha(2)delta subunit of voltage-sensitive Ca2+ channels, which sustain the enhanced release of pain transmitters at the synapses between primary afferent fibres and second-order sensory neurons under conditions of chronic pain. Pregabalin in particular represents a remarkable example of a context-dependent analgesic drug that acts at a critical step of nociceptive sensitization. Preclinical and clinical data suggest that pregabalin is more than a structural and functional analogue of gabapentin and may be effective in the treatment of nociceptive inflammatory pain that is resistant to gabapentin.

Clinical and psychosocial correlates of post-herpetic neuralgia.

Post-herpetic neuralgia is the most challenging and debilitating complication of herpes zoster in the immunocompetent host. Because the effect of treatment is disappointing once the syndrome has developed, it is important to know which factors predict post-herpetic neuralgia occurrence to facilitate selection of herpes zoster patients with a higher risk of developing neuralgia and undertake preventative strategies. The present study aimed at identifying demographic, clinical and psychosocial correlates of post-herpetic neuralgia in a sample of 219 immunocompetent patients, who were examined by dermatologists in private practice in Italy and who completed a questionnaire designed to evaluate their clinical and psychosocial profile at the time of clinical diagnosis of herpes zoster and at a follow-up visit 6 months later. In a univariate analysis, post-herpetic neuralgia was associated significantly with older age, longer duration of prodromal pain, greater acute pain intensity, greater extent of rash, presence of abnormal sensations and use of systemic antiviral therapy. Compared to the values at herpes zoster onset, at the follow-up visit patients with post-herpetic neuralgia presented with similar high mean scores of pain intensity, anxiety and depression and greatly reduced quality of life, whereas patients without neuralgia presented with improved scores. In a multivariate model, older age, greater acute pain intensity, greater extent of rash and longer duration of prodromal pain were independently associated with post-herpetic neuralgia. The results of this study may help physicians to identify patients with a higher risk of developing post-herpetic neuralgia and undertaking preventative strategies.

The first prevalence survey of nosocomial infections in the University Hospital Centre 'Mother Teresa' of Tirana, Albania.

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.

The first point prevalence survey of nosocomial infections in Albania: pilot study.

In May 2003, investigators were trained and prevalence pilot study was conducted at the University Hospital of Tirana, Albania. Investigators were trained to assess the organizational problems of the first prevalence survey of nosocomial infections (NIs) in Albania. Twelve investigators were trained in 2 days. After the training, the pilot study was conducted in 3 wards. The investigators collected data using a standard form and the definitions of the Centers for Disease Control, USA. The training improved the investigators' knowledge of NI epidemiology and surveillance. The pilot study underlined the lack of information in the clinical documentation and lack of collaboration between clinicians and the laboratory: microbiological examinations were performed only in 13 (16.5%) patients and none of the 11 NIs reported was confirmed in the laboratory. This led to a review of the survey protocol, above all in order to increase the use of microbiological laboratory.

Scrambler therapy.

UNLABELLED: In neuropathies there are complex reactions that modify the homeostatic equilibrium of pain system. In such a context the Scrambler Therapy (ST5) interferes with pain signal transmission, by ''mixing'' a ''non-pain'' information into the nerve fibres. The aim of this study is to evaluate the effectiveness of ST5 in the treatment of neuropathic pain. The ST5 consists of a multiprocessor apparatus able to simulate 5 artificial neurons by the application of surface electrodes on skin pain areas. A total of 226 patients, all suffering from intense drug-resistant neuropathic pain, were recruited for this trial in 2004. INCLUSION CRITERIA: neuropathic pain, very high baseline visual analogue scale (VAS). EXCLUSION CRITERIA: pacemaker users, neurolithic blocks or neurolesive pain control treatment. The treated neuropathic pain syndromes were: failed back surgery syndrome (FBSS), sciatic and lumbar painpost-herpetical (PHN), trigeminal neuralgia, post-surgery nerve lesion neuropathy, pudendal neuropathy, brachial plexus neuropathy, low back pain (LBP), others. The trial programme: 1 to 6 therapy sessions of 5 treatments, each one lasting 30 min. Pain intensity was evaluated using VAS before and after each treatment. The statistical significance of VAS was measured using the paired t-test. The total results show 80.09% of responders (pain relief>50%), 10.18% of partially responders (pain relief from 25% to 49%) and 9.73% of no responders (patients with pain relief<24% or VAS>3). The CONCLUSIONS: is draen that ST5 produced a statistically significant (P<0.0001) pain relief in all treated neuropathies.