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Mesotherapy (local intradermal therapy, LIT) is a technique used to slowly spread drugs in tissues underlying the site of injection to prolong the pharmacological effect with respect to intramuscular injection. Recommendations for proper medical use of this technique have been made for pain medicine and rehabilitation, chronic venous disease, sport medicine, musculoskeletal disorders, several dermatological conditions, skin ageing, and immune-prophylaxis. Although mesotherapy is considered a valid technique, unresolved questions remain, which should be answered to standardize methodology and dosing regimen as well as to define the right indications in clinical practice. New randomized controlled trials are needed to test single products (dose, frequency of administration, efficacy and safety). Even infiltration of substances for dermo-cosmetic purposes must be guided by safety and efficacy tests before being proposed by mesotherapy. In this article, we put forth a preclinical and clinical research plan and a health technology assessment as a call to action by doctors, researchers and scientific societies to aid national health authorities in considering mesotherapy for prevention, treatment and rehabilitation paths., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/bIuRhGQsUjs

Axillary web syndrome (AWS) is defined as a visible and palpable network of cords in the skin of the axillary cavity that are tensed by shoulder abduction following surgery for breast cancer, causing significant functional limits of the ipsilateral upper limb (UL) and pain. The purpose of this narrative review is to discuss rehabilitation approaches for greater efficacy with respect to pain and novel suggestions. AWS is a frequent complication of axillary lymphadenectomy that necessitates a thorough follow-up in the medium to long term. Physiotherapy is effective in the treatment of functional limb deficits, the management of pain, and the treatment of upper limb disability. The best management approach involves the use of soft tissue techniques to slow the natural course of the syndrome, in association with therapeutic exercises for functional recovery and muscle strengthening. AWS is linked secondary lymphedema, requiring integration with manual lymphatic drainage. The physiotherapy management of AWS is currently fragmented, and insufficient information is available on the nature of the disease. Thus, randomized and controlled studies that compare rehabilitation approaches in AWS are desirable, including the possibility of using mesotherapy in the treatment of axillary and upper limb pain.

Despite the existence of protocols for effective pain control, pediatric pain is still high, due to scarce knowledge of its treatment, especially regarding opioids. This study aimed to evaluate doctors and nurses' knowledge of pain treatment and the use of opioids in children, before and after the implementation of Law 38/2010, that represented an important step in guaranteeing patients' rights to gain access to appropriate services for pain control and palliative care in Italy and in establishing the obligation of specific training programs in this matter for health professionals. An

Drugs injected intradermally spread slowly into the underlying tissues and produce a drug-saving effect. The Italian society of mesotherapy suggested that intradermal therapy obtains analgesic effect on localized pain, with a lower risk of systemic drug interactions. We report a case of post-herpetic pain successfully treated by this technique. This case confirms that the intradermal administration technique (mesotherapy), which is based on the pathophysiology of the disorder, according to the recommendations, can contribute to the management of patients who do not tolerate standard therapies.

Stefano De Santis,1 Maria Domenica Simone,2 Sebastiano Mercadante,3 Rocco Domenico Mediati,4 Renato Vellucci,4 Paolo Marchetti,5 Giuseppe Tonini,6 Arturo Cuomo,7 Augusto Caraceni,8 Silvia Natoli,9 Grazia Armento,6 Livio Blasi,10 Massimo Mammucari11 On behalf of the IOPS-MS Study Group1Palliative Care and Oncologic Pain Service, S. Camillo-Forlanini Hospital, Rome, Italy; 2Hematology and BMT Unit, S. Camillo-Forlanini Hospital, Rome, Italy; 3Anesthesia and Intensive Care & Pain Relief and Supportive Care, La Maddalena, Palermo, Italy; 4Palliative Care and Pain Therapy Unit, Careggi Hospital, Florence, Italy; 5Molecular and Clinical Medicine Medical Oncology, La Sapienza University of Rome, Rome, Italy; 6Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy; 7Anesthesiology, Resuscitation, and Pain Therapy Department, National Cancer Institute, IRCCS Foundation, Naples, Italy; 8Palliative Care, Pain Therapy and Rehabilitation, National Cancer Institute, IRCCS Foundation, Milan, Italy; 9Department of Clinical Science and Translational Medicine – University of Rome Tor Vergata and Department of Emergency, Admission and Critical Area – Policlinic of Tor Vergata, Rome, Italy; 10Medical Oncology Unit, ARNAS Ospedale Civico Di Cristina Benfratelli, Palermo, Italy; 11Primary Care Unit, ASL RM1, Rome, 00165, ItalyCorrespondence: Stefano De Santis Email sdesantis@scamilloforlanini.rm.itBackground: International guidelines recommend moderate-to-severe cancer pain to be treated with strong opioids. However, pain management remains an unsolved matter, at least in the demanding oncology and palliative care setting. Although cancer pain consists of multiple components, which interact in complex ways where combination therapy can better intercept multiple pain characteristics, few studies have used a non-opioid/opioid association to exploit possible synergistic actions. Even the efforts of a recent approach emphasizing appropriate pain assessment and accurate classification to obtain personalized pain management have not produced a satisfactory analgesic strategy.Objective: This analysis was intended to evaluate the effectiveness of the immediate release fixed combination of oxycodone/acetaminophen (OxyIR/Par) for the treatment of moderate-to-severe intensity background pain used alone or in combination with other strong opioids in cancer patients with breakthrough cancer pain (BTcP). This is a secondary analysis of a wider observational, prospective, multicenter study [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] performed on 179 patients treated with opioids for cancer pain who received the fixed combination of oxycodone/acetaminophen (OxyIR/Par) for the treatment of background pain (BGP).Results: Cancer patients with breakthrough cancer pain and controlled BGP (Background Pain) were classified according to the presence of analgesic therapy with tablets of fixed combination OxyIR/Par alone (group A, n=120) or tablets of fixed combination OxyIR/Par combined with other strong opioids (group B, n=59). Clinical features of group A were different to group B: higher mean Karnofsky Performance Status Index 70.3% (95% CI=67.2– 73.5; median=70, CI=60– 80) vs 58.3 (95% CI=53.4– 63.2; median=50, CI=45– 70) (P< 0.001), and mainly group A patients were treated in an ambulatory setting (55.0% group A vs 33.9% group B) (p< 0.001). Both groups had managed BGP with similar mean dosages (group A: 12.0, CI=10.5– 13.4; group B: 13.1, CI=11.0– 15.1) and frequencies of OxyIR/Par alone for group A and in association to other opioids for group B, but Breakthrough cancer Pain (BTcP) exhibited different characteristics in the two groups, showing a lower mean intensity numerical rating scale (NRS) of 7.5 (95% CI=7.2– 7.7; median=7, CI=7– 8 group A) vs 7.9 (95% CI=7.6, 8.2; median= 8, CI=7– 9 group B) (P=0.04) and a higher percentage of patients had a faster onset, defined as the maximum intensity reached in less than 10 minutes, 81.7% (N=98) in group A vs 59.3% (n=35) in group B (P=0.002).Conclusion: This is the first analysis about the efficacy of an immediate-release fixed combination of OxyIR/Par in the real world for moderate-to-severe background cancer pain and breakthrough cancer pain. The oral fixed combination OxyIR/Par provided an adequate level of analgesia for moderate–severe background cancer pain, in a different cohort of cancer patients with different performance status, both in ambulatory and palliative settings. The low dosage of fixed combination OxyIR/Par was effective alone or in association with other opioids.Keywords: analgesia, combination of oxycodone/acetaminophen, cancer pain, breakthrough cancer pain

The aim of this study was to longitudinally assess the characteristics of background pain and breakthrough pain (BTcP), analgesic treatment, and satisfaction with treatment four weeks after the first assessment. Methods: Adult cancer patients with a diagnosis of BTcP were included. At T0, age, gender, visit setting, cancer diagnosis, the extent of the disease, ongoing anticancer treatments, and Karnofsky level were recorded. The background pain intensity in the last 24 h (on a numerical scale 0–10), opioids used for background pain, and their doses, expressed as oral morphine equivalents (OME), as well as other analgesic drugs, were recorded. The number of BTcP episodes, their intensity, predictability and precipitating factors, onset duration of untreated episodes, and interference with daily activities were collected. Analgesics and doses used for BTcP, and the mean time to meaningful pain relief after taking medication, were assessed. The level of satisfaction with BTcP medication was also assessed. Adverse effects to be attributed to these medications were also recorded. At T4, the same data were evaluated. Results: After one-month follow-up, patients had a lower number of BTcP episodes and peak intensity, possibly due to the optimization of background analgesia. The principal characteristics of BTcP did not change significantly. Conclusion: A careful and continuous assessment should be guaranteed to all patients to limit the burden induced by BTcP, other than treating BTcP episodes with short-onset opioids.

Intradermal therapy, known as mesotherapy, is a technique used to inject a drug into the surface layer of the skin. In particular, it involves the use of a short needle to deposit the drug in the dermis. The intradermal microdeposit modulates the drug’s kinetics, slowing absorption and prolonging the local mechanism of action. It is successfully applied in the treatment of some forms of localized pain syndromes and other local clinical conditions. It could be suggested when a systemic drug-sparing effect is useful, when other therapies have failed (or cannot be used), and when it can synergize with other pharmacological or nonpharmacological therapies. Despite the lack of randomized clinical trials in some fields of application, a general consensus is also reached in nonpharmacological mechanism of action, the technique execution modalities, the scientific rationale to apply it in some indications, and the usefulness of the informed consent. The Italian Mesotherapy Society proposes this position paper to apply intradermal therapy based on scientific evidence and no longer on personal bias.

Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that “breaks through” a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) is a subtype of BTcP that occurs in the absence of any specific activity. Since NP-BTcP has an important clinical impact, this analysis is aimed at characterizing the NP-BTcP phenomenon through a multidimensional statistical technique. This is a secondary analysis based on the Italian Oncologic Pain multiSetting—Multicentric Survey (IOPS-MS). A correlation analysis was performed to characterize the NP-BTcP profile about its intensity, number of episodes per day, and type. The multiple correspondence analysis (MCA) determined the identification of four groups (phenotypes). A univariate analysis was performed to assess differences between the four phenotypes and selected covariates. The four phenotypes represent the hierarchical classification according to the status of NP-BTcP: from the best (phenotype 1) to the worst (phenotype 4). The univariate analysis found a significant association between the onset time &gt, 10 min in the phenotype 1 (37.3%)’ vs. the onset &gt, 10 min in phenotype 4 (25.8%) (p &lt, 0.001). Phenotype 1 was characterized by the gastrointestinal type of cancer (26.4%) with respect to phenotype 4, where the most frequent cancer affected the lung (28.8%) (p &lt, 0.001). Phenotype 4 was mainly managed with rapid-onset opioids, while in phenotype 1, many patients were treated with oral, subcutaneous, or intravenous morphine (56.4% and 44.4%, respectively, p = 0.008). The ability to characterize NP-BTcP can offer enormous benefits for the management of this serious aspect of cancer pain. Although requiring validation, this strategy can provide many indications for identifying the diagnostic and therapeutic gaps in NP-BTcP management.

Breakthrough cancer pain (BTcP) is a common condition in oncological patients. However, its management is still suboptimal. Improved knowledge of BTcP and its management in clinical practice may have immediate importance for all physicians involved in the supportive care of cancer patients. This review critically discusses the most important concepts for the correct diagnosis of BTcP and presents some intriguing cases of the management of this condition in clinical practice. Overall, the most appropriate therapeutic choice appears to be a rapid-onset opioid (ROO), and in particular, the nasal route of administration is the quickest and most convenient mode of administration for the management of BTcP, especially when the patient needs rapid resolution of pain. To this end, intranasal fentanyl spray may have a particular relevance in clinical practice. Future research should focus on accepted definitions of BTcP to investigate the optimal management of this highly heterogeneous pain condition. Therapeutic decision-making of patients, clinicians, and payers will likely be driven from results of well-designed clinical trials of ROOs., Video abstract

Oxycodone is one of the most commonly used opioid analgesics in the clinical management of pain. The present retrospective analysis aimed to determine the dose of oxycodone that could achieve effective control of moderate pain when combined with a fixed dose of acetaminophen, and the time required to reach a clinically relevant reduction in intensity of pain.Data of patients treated with a combination of oxycodone (5, 10, and 20 mg) and acetaminophen (325 mg) were evaluated for gender, current disease condition, basal pain intensity, total daily dose, days of controlled pain at the initial low dose, and pain intensity after treatment using a numeric pain rating scale.Data from a total of 491 patients were assessed; of these 93.5% of patients experienced persistent non-cancer pain and had an average baseline pain score of 5.68 ± 1.35. For the overall population, the pain score was reduced to 2.49 ± 1.71 with a mean dose of 8.68 ± 4.96 mg oxycodone after 21.60 ± 6.12 days of treatment with the combination. Almost 97% of the patients who reported relief of pain received 1.61 ± 0.67 doses of oxycodone 5 mg combined with 325 mg of acetaminophen.A low-dose combination of oxycodone with acetaminophen can be effective in the management of moderate pain and may help in reducing the treatment-associated adverse reactions and drug dependence.Sponsorship for article processing charges was provided by Molteni Farmaceutici, Florence, Italy.

Background: The aim of this study was to identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP). Methods: Cancer patients with a diagnosis of BTP were enrolled. Demographic and clinical characteristics, as well as background pain and BTP characteristics were collected. Multivariate analyses were conducted to assess the correlation between BTP characteristics and the variables examined. Results: Data of 4016 patients were analysed. Average daily number of BTP episodes was 2.4, mean intensity was 7.5, and a mean duration was 43.3 min. A short onset BTP was observed in 68.9% of patients. In 30.5% of patients BTP was predictable. There were 86.0% of participants who reported a marked interference of BTP with their daily activities. Furthermore, 86.8% of patients were receiving opioids for the management of BTP. The average time to meaningful pain relief was 16.5 min and 70.9% of patients were satisfied with their BTP medications. Age, head and neck cancer, Karnofsky, background pain intensity, predictable and fast onset BTP were independently associated with the number of BTP episodes. BTP pain intensity was independently associated with background pain intensity, fast onset BTP, and Karnofsky. Neuropathic pain mechanism was independently associated with unpredictable BTP. Variables independently associated with a longer duration of BTP were age, place of visit, cancer diagnosis, disease-oriented therapy, background pain intensity and mechanism, and unpredictable BTP. Age, Karnofsky, background pain intensity, fast onset, and long duration of BTP were independently associated with interference with daily activity. Conclusions: BTP has a variable presentation depending on interdependent relationships among its different characteristics.

Aims: Modern medicine has recently faced the need to consider the existential qualities of patients during the process leading to diagnosis and choice of therapy, in addition to relying on technological progress. Materials & methods: Narrative medicine has gradually entered the routine of clinical work, aiming at improving patient–physician relationships and adherence to therapy and reducing direct and indirect health cost. Results: The Local Health Authority of Firenze (Italy) has launched an innovative process for the integration of narrative practices into the health services. This initiative’s aim was to spread the culture of narrative-based medicine among health professionals and increase the quality and appropriateness of care (NaMe project). Conclusion: This article describes the experience through which a model of narrative medicine was implemented into the clinical practice.

Chronic venous insufficiency (CVI) induces alterations that cause fibrosclerotic edema of the subcutaneous tissue. This study examined the effects of a complex naturopathic compound with vasoactive and antiedema activities (Lymdiaral®) administered intradermally.40 patients with signs and symptoms of CVI and associated fibrosclerotic edema of the subcutaneous tissue.Efficacy was assessed by using clinical investigation, subjective and objective measures, and ultrasonography performed at baseline and after treatment.Thirty-four patients completed the study; 6 of the original 40 (15%) had stopped for reasons unrelated to study treatment. The treatment was well tolerated. Fifteen adverse reactions were reported among a total of 378 doses administered (3.97%). None of these reactions were severe or required discontinuation of treatment. Subjective symptoms and objective measures improved, and ultrasonography showed statistically significant changes in hypodermal thickness of the medial aspect of the knees.Its open-label design and small sample size notwithstanding, this study indicates that intradermal therapy, according to the recommendation of the Italian Society of Mesotherapy, may provide a valuable contribution to the treatment of CVI and related fibrosclerotic edema of the subcutaneous tissue by prolonging the local effect of the pharmacologically active compounds. Comparative studies are needed to identify the broader clinical and economic benefits of local therapy compared with other systemic therapies.

Responsible use of analgesic drugs is crucial to the management of pain. Proper diagnosis and classification of pain, measurement of its intensity with a validated scale, determination of the type of pain, information on its duration, and identification of comorbidities are essential when selecting analgesics. The …

The management of patients with chronic osteoarticular pain requires a comprehensive clinical evaluation and a multidisciplinary approach. Thirty specialists (orthopedic specialists, rheumatologists, physiatrists), members of the National Association of Osteoarticular Specialists (ASON), attended a specific training course in the use of a standardized medical record designed for the management of osteoarticular pain in outpatients. An audit on 888 medical records was later conducted and it showed that use of this instrument led to an improvement in the diagnostic-therapeutic approach.A complete and accurate medical record compilation process may also promote collaborative interaction among the healthcare practitioners involved and this can result in greater efficiency and continuity of care. ASON recommends expediting the use of electronic tools to facilitate information-sharing among pain care specialists. This study shows that the use of electronic tools facilitates the exchange of information between healthcare providers. ASON supports the adoption of similar instruments in order to improve the management of chronic pain. Level of evidence: Level III, cross-sectional survey.

Background: Musculoskeletal pathologies are among the most frequent causes of long-term non-oncological severe pain and consequent physical impairment. Aims of pharmacological and physical therapy are to reduce pain, promote functional recovery and improve overall quality of life. Pharmacological therapy may include the use of opioids. Objective: To evaluate the efficacy and tolerability of transdermal buprenorphine (TDS) in the long-term management of non-oncological, chronic, moderate-to-severe musculoskeletal pain. Study Design: An open-label, prospective, single-centre, 6-month study. Setting: A ‘real world’ outpatient setting. Patients: Adult patients with chronic moderate-to-severe musculoskeletal pain were enrolled consecutively. Intervention: Patients initially received buprenorphine TDS 11.7 µg/h (onethird of 35 µg/h patch) every 72 hours. If required, patients could be uptitrated to 17.5 µg/h (one-half of 35µg/h patch), 23.4 µg/h (two-thirds of 35 µg/h patch) or 35 µg/h. Concomitant antiemetics were allowed. Main Outcome Measures: The primary endpoint was percentage mean reduction in static and dynamic pain visual analogue scale (VAS) scores at study end (10 being worst pain, 0 being no pain). Quality of life and tolerability were also assessed. Results: We enrolled 146 patients aged 41–94 years; their baseline mean± SD static and dynamic pain VAS scores were 6.87±1.89 and 7.70 ± 1.74, respectively. Buprenorphine TDS initial dosages were 11.7 µg/h (n=139), 17.5 µg/h (n = 4), 23.4 µg/h (n= 1) and 35 µg/h (n = 2). At 6 months, 89 patients were under treatment; 11% (n=10) were receiving 11.7µg/h, 30% (n = 27) 17.5 µg/h, 6% (n = 5) 23.4 µg/h and 53% (n = 47) 35µg/h. Patients achieved a nonsignificant reduction in pain at rest and in movement; mean ± SD static and dynamic pain VAS scores decreased to 1.56 ± 2.05 and 3.54 ± 2.02, respectively. The quality of life improved as shown by significant (p< 0.01) increases from baseline in all items relating to physical and mental health on the Short-Form 36 health survey. Patients experienced recovery of daily and social activities according to the significant (p

Background: Multimodal pain is comprised of nociceptive/inflammatory and neuropathic components. Pharmacological pain therapies from different classes provide pain relief using different mechanistic actions; often a combination of such therapies provides more effective pain relief than monotherapy. To assess whether pain management is adequate requires a comprehensive pain scoring system. Objective: To evaluate the adequacy of a low-dose combination of oxycodone and paracetamol (acetaminophen) in patients with multimodal, chronic, non-malignant pain using the Pain Management Index (PMI). Methods: During this prospective, observational study, consecutive patients were classified according to the presence of prevalent osteoarticular pain (group A, n = 78) or prevalent neuropathic pain (group B, n = 72). Existing pain-relief medications were discontinued and both groups received oxycodone 5 mg and paracetamol 325 mg up to 8 hourly for a planned duration of ≥6 weeks. Patients in group B who were receiving gabapentin continued this treatment up to a maximum daily dosage of 2400 mg during the observation period. Pain intensity was evaluated using a visual analogue scale (VAS from 0 to 10). Functional limitation for patients in group A was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The intensities of dynamic allodynia and hyperalgesia in patients in group B were evaluated by a VAS. Results from the WOMAC, dynamic allodynia, and hyperalgesia assessments were evaluated using the PMI. Results: In group A, 64.3% of patients showed improvements in pain symptoms after 15 days of treatment in the WOMAC categories of “pain preventing sleep” and “walks with aid”. The PMI showed that the oxycodone/paracetamol therapy was adequate in patients with osteoarticular pain. In group B, 83.3% of patients reported improvement in the category of “pain preventing sleep”, and all patients rated the remaining four categories (“spontaneous pain”, “burning pain”, “painful paresthesia”, and “pinprick”) as either stable or improved after 15 days of treatment. Using the PMI, hyperalgesia resolved with oxycodone/paracetamol therapy. 37.1% and 58.3% of patients did not complete the study in group A and B, respectively. Conclusion: The PMI was an effective tool for assessment of pain management efficacy. Oxycodone/paracetamol improved pain symptoms in the majority of compliant patients. In patients with neuropathic pain, rescue therapy with oxycodone/paracetamol showed a lesser, but significant, improvement of pain symptoms.

Controversies exist about the definition and epidemiology of breakthrough cancer pain (BTcP), the pharmacological treatment options, drug dosing, and how to select the medications for BTcP among the new fentanyl products. Existing data were critically evaluated to provide recommendations by an expert group. An algorithm to diagnose BTcP should be used followed by a careful assessment. Fentanyl products provide efficacy and rapidity of action to counteract the temporal pattern of BTcP. The doses of opioids used for background pain should guide the choice of the doses of fentanyl products. The choice of fentanyl products should be based on individual clinical conditions.

As recognized by law no. 38 of March 15, 2010 patients with chronic pain should have access to an appropriate diagnostic and therapeutic path with continuity of care. In addition to clinical guidelines it is necessary to implement a multidisciplinary care to manage patients with osteoarticular chronic pain to start an early analgesic treatment and to optimize the health system resources. Through a triage territorial of patients with pain we identify the most complex cases to be sent to the network of pain (Spoke and Hub), and we differentiate those that must be managed in a territorial path. The proposal by National Association Osteoarticular Specialists (ASON) suggests a multidisciplinary personalized path, coordinated by general practitioners and specialists, aims to improve patient-health system relationship.

A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU), seven oncology departments (ONC), and nine pain clinics (OPC).A standard algorithm was used to confirm the diagnosis of BTP of patients refereed to different settings.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.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.

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.

Our aim was to evaluate retrospectively the role of the radiotherapy in the multi-disciplinary management of pain due to bone metastases.A total of 305 patients received radiotherapy with or without bisphosphonate and antalgic drugs. Tolerability and efficacy were evaluated using a Numerical Rating Scale, Pain Intensity Difference evaluation scale related to administration of the drug, a 5-point verbal scale of the patients' general impression.We found differences in some patient subgroups: pain reduction was significantly more evident in patients treated with a single-fraction radiotherapy scheme. Overall, 68% of patients experienced an improvement in pain control using concomitant drugs during radiotherapy.Our study underlines the role of radiotherapy in the management of metastatic bone pain. The use of rapid-onset opioids to prevent predictable pain is a crucial step in managing radiotherapy. An interdisciplinary approach is recommended.

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.This was a prospective, non-interventional, observational study conducted from June to September 2011 in two Italian pain treatment reference centres. Consecutive patients aged18 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.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 (P0.001). 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.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.

Heart failure (HF) is one of the leading causes of hospitalization and medical expenditure, especially in elderly patients. Cooperation between specialists and general practitioners may improve outcomes. A 1-year hospital-territory disease management program was designed in collaboration with the Tuscany Region and the Ministry of Health involving specialists, general practitioners and nurses to investigate the impact of our model on healthcare organization and hospitalization rates in patients with HF.The program used a web-based clinical report form, and monitoring of patients from specialists and nurses was coordinated by the general practitioners. We enrolled 106 patients (78.3% male, mean age 74.6 years), with a mean left ventricular ejection fraction 49% and mean Charlson index 2.2.A statistically significant reduction was observed in the number of hospitalizations and emergency calls compared with the previous year. HF severity did not substantially changed in 69.8% of patients, whereas it improved in 17.0% and worsened in 13.2% (NYHA class).Our preliminary data suggest that cooperation between hospitals and medical systems in the territory by means of a web-based clinical report may result in better management of healthcare interventions in the territory with subsequent reduction of hospitalizations. An extension of this model is now ongoing for collecting data from different areas, both within and outside Tuscany.

Despite breakthrough pain (BTP) being one of the most severe forms of pain, there are no definitive data on its prevalence.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.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.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.

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.

Radiotherapy is crucial in the management of cancer patients in both the curative and palliative settings. However, patients often report pain both during positioning for, and execution of, radiotherapy and this may be a reason for interrupting the radiotherapy session. This observation is common even if the patient is undergoing baseline drug therapy for cancer pain. Recent data suggest that orally administrated immediate-release morphine (MIR) is able to reduce pain in patients with predictable pain. The authors tested a rescue dose of MIR 10 or 20 mg, 20 to 60 minutes before radiotherapy, to verify the effectiveness of MIR in this setting and also to assess the patient's ability to receive the full course of radiotherapy. One hundred forty consecutive patients were evaluated during radiotherapy treatment and visual analogue scale (VAS) and positioning VAS scores were assessed. All patients completed the course of scheduled radiotherapy and pain was well controlled, despite the fact that previous pharmacological treatment had not been able to completely control chronic cancer pain. These data strongly suggest a role for MIR pretreatment in patients with pain due to positioning during radiotherapy.

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. 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. 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

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: Cancer-related and non-cancer chronic pain embodies the most frequent challenge in clinical practice. Management of chronic pain and breakthrough pain (BTP) requires adjustments to the analgesic regimen to achieve adequate pain control. Objective: To examine the time to achieve pain relief in patients who experienced intense episodic pain breakouts despite baseline therapy with analgesics. Methods: This study was based on a 14-day observation period. Patients with either cancer-related or non-cancer pain who experienced >2 intensive episodic pain breakouts per day were prescribed immediate-release (IR) morphine sulphate (10 mg to 20 mg as needed) every 4 hours (around-the-clock) and allowed one rescue dose of IR morphine (equal to one additional administration of the dosage taken at fixed times) for any episodic pain breakouts. Patients recorded time of administration and time taken to achieve partial or total relief of episodic pain breakout in daily diaries; in one study centre the diary was managed with the help of specialized medical attendants. Pain intensity and general wellbeing were assessed by a Numerical Rating Scale (NRS) and Karnofsky Performance Scale, respectively. Adverse events and sleep patterns were also recorded. Results: Of 85 patients (mean age 62.67 ± 14.3 years) enrolled, 14 experienced pain from non-cancer degenerative diseases, and 71 had cancer-related pain. Following stabilization of background pain, the intensity of daily pain improved; NRS decreased from baseline to day 14 for cancer (from 5.63 to 1.98) and non-cancer (from 8.00 to 1.00) groups (both p < 0.0001). Patients’ general wellbeing increased concomitantly. Around-the-clock therapy resulted in an immediate decrease in the number of intense episodic pain breakouts per day, with 11.8% of patients achieving total pain relief within 24 hours. The mean number of intense episodic pain breakouts per day decreased steadily in the cancer group, reaching significance at day 14 (p < 0.001 vs baseline). Moreover, the time to achieve partial and total pain relief of intense episodic pain breakouts improved significantly. Adverse events and sleep patterns improved over the 14-day observation period. Conclusions: Stabilization of background cancer-related or non-cancer pain with around-the-clock IR morphine therapy resulted in fewer intense episodic pain breakouts, which were more quickly managed with rescue-dose IR morphine, suggesting that ‘end-dose’ pain should not be classified as BTP.

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.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.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.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.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.

Wide variations in the types of pain and response to analgesic pharmacotherapy mean that a variety of treatment strategies are needed. One approach is mesotherapy (intradermal therapy). This consists of microinjections into the skin and is ideally suited to the management of localized pain. Advantages include increasing the duration of drug activity, reduced risk of adverse events and interactions, and possible synergy with other therapies. Mesotherapy provides general practitioners with another tool for the treatment of local pain. However, it is important to provide patients with full details of the pros and cons of this approach and obtain informed patient consent.

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.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.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.