Mesotherapy: From Historical Notes to Scientific Evidence and Future Prospects.

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 pain and its treatment: critical review and recommendations of IOPS (Italian Oncologic Pain Survey) expert group.

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.

[Role of intensive medical training on Law 38 to improve pain management in primary care]. / La gestione del dolore nella medicina primaria: esiti di un progetto di fomazione sulla Legge 38/2010.

The Italian Law no. 38/2010 requires that the physician reports in the medical record the type and the intensity of pain, analgesic therapies and clinical results. We developed a training model for 256 primary care physicians (GPs). After a period of intensive training on the content of the law no. 38, diagnostic and pharmacological approach of pain, we carried out a clinical audit by a web based clinical record to assess doctor's compliance to Law no. 38 and the use of opioids. 2631 patients were assessed (age 71,5±13,7 years; median 74). The mean of chronic non oncologic pain intesity was 5.41±2.0 (static) and 6.10±2.32 (dynamic). After a systematic measurement of pain, a better control of patients was achieved (2.22±2.12 points lower for static, 2.37±2.34 lower for dynamic pain (p<0.001 vs basal time). An increased use of opioids have been detected. GPs have also used strong opioids in opioid-naïve patients, avoiding the first or the second step if intensity of pain detected was severe. In fact, a greater pain control was achieved with oxycodone compared to tramadol or codeine (all of them with normal release and combined with acetaminophen). Chronic non cancer pain remains one of the major clinical problems in the primary care setting, especially in the elderly. The standard measurement of parameters related to pain and the proper use of opioids depends on the scientific update and how this is delivered. GPs are crucial to implement the Law 38 and to increase the degree of complexity of the patient to be properly admitted to a SPOKE/HUB center.

[Informed consent and experimental treatments: the case of mesotherapy]. / Consenso informato e trattamenti sperimentali: il caso della mesoterapia.

Mesotherapy is a minimally invasive technique based on the introduction of pharmacologically active compounds in the surface layer of the skin. The intradermal route has been known for many years and it has the aim of reducing the dose and slowing the diffusion into the underlying tissues. Mesotherapy requires a clinical diagnosis and informed consent. Patient should be well informed about potential benefits, limitations, and risks (even mild). The process of doctor-patient interaction in mesotherapy is an example of compliance with the basic concept: "first do no harm" and, at the same time, the advantage for the patient to conclude a "therapeutic alliance". We propose a draft form to facilitate the decision-making process.

Role of mesotherapy in musculoskeletal pain: opinions from the italian society of mesotherapy.

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.

Intradermal Vaccination: A Potential Tool in the Battle Against the COVID-19 Pandemic?

This narrative review is the final output of an initiative of the SIM (Italian Society of Mesotherapy). A narrative review of scientific literature on the efficacy of fractional intradermal vaccination in comparison with full doses has been conducted for the following pathogens: influenza virus, rabies virus, poliovirus (PV), hepatitis B virus (HBV), hepatitis A virus (HAV), diphtheria-tetanus-pertussis bacterias (DTP), human papillomavirus (HPV), Japanese encephalitis virus (JE), meningococcus, varicella zoster virus (VZV) and yellow fever virus. The findings suggest that the use of the intradermal route represents a valid strategy in terms of efficacy and efficiency for influenza, rabies and HBV vaccines. Some systematic reviews on influenza vaccines suggest the absence of a substantial difference between immunogenicity induced by a fractional ID dose of up to 20% and the IM dose in healthy adults, elderly, immunocompromised patients and children. Clinical studies of remaining vaccines against other pathogens (HAV, DTP bacterias, JE, meningococcal disease, VZV, and yellow fever virus) are scarce, but promising. In the context of a COVID-19 vaccine shortage, countries should investigate if a fractional dosing scheme may help to save doses and achieve herd immunity quickly. SIM urges the scientific community and health authorities to investigate the potentiality of fractionate intradermal administration in anti-COVID-19 vaccination.

A Longitudinal Study of Breakthrough Cancer Pain: An Extension of IOPS-MS Study.

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.

Web Axillary Pain Syndrome-Literature Evidence and Novel Rehabilitative Suggestions: A Narrative Review.

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.

Oxycodone/Acetaminophen: The Tailoring Combination Treatment for Specific Clinical Profile of Opioid Well-Responsive Cancer Pain.

BACKGROUND: 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.

Multidimensional Statistical Technique for Interpreting the Spontaneous Breakthrough Cancer Pain Phenomenon. A Secondary Analysis from the IOPS-MS Study.

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 >10 min in the phenotype 1 (37.3%)' vs. the onset > 10 min in phenotype 4 (25.8%) (p < 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 < 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.

A Call to Action by the Italian Mesotherapy Society on Scientific Research.

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.

Time to pain relief after immediate-release morphine in episodic pain: the TIME study.

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.

Oxycodone/paracetamol: a low-dose synergic combination useful in different types of pain.

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.

Transdermal buprenorphine in non-oncological moderate-to-severe chronic pain.

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 microg/h (one-third of 35 microg/h patch) every 72 hours. If required, patients could be up-titrated to 17.5 microg/h (one-half of 35 microg/h patch), 23.4 microg/h (two-thirds of 35 microg/h patch) or 35 microg/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 microg/h (n = 139), 17.5 microg/h (n = 4), 23.4 microg/h (n = 1) and 35 microg/h (n = 2). At 6 months, 89 patients were under treatment; 11% (n = 10) were receiving 11.7 microg/h, 30% (n = 27) 17.5 microg/h, 6% (n = 5) 23.4 microg/h and 53% (n = 47) 35 microg/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 < 0.01) increase in Karnofsky Performance Status sub-item scores. Twenty-three patients discontinued treatment because of adverse events, which were mainly gastrointestinal or CNS-related. CONCLUSIONS: Low-dose buprenorphine TDS had good analgesic efficacy, and quality of life improved as early as 1 month after treatment initiation. Our results suggest that buprenorphine TDS is a well tolerated long-term analgesic for patients experiencing chronic musculoskeletal pain of moderate-to-severe intensity.

Effects of opioid rotation in chronic pain patients: ORTIBARN study.

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.

Breakthrough Cancer Pain Clinical Features and Differential Opioids Response: A Machine Learning Approach in Patients With Cancer From the IOPS-MS Study.

PURPOSE: A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice. METHODS: Partitioning around a k-medoids algorithm on a large data set of patients with BTcP, previously collected by the Italian Oncologic Pain Survey group, was used to identify possible subgroups of BTcP. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features, and use of basal pain and rapid-onset opioids. Opioid dosages were converted to a unique scale and the BTcP opioids-to-basal pain opioids ratio was calculated for each patient. We used polynomial logistic regression to catch nonlinear relationships between therapy satisfaction and opioid use. RESULTS: Our algorithm identified 12 distinct BTcP clusters. Optimal BTcP opioids-to-basal pain opioids ratios differed across the clusters, ranging from 15% to 50%. The majority of clusters were linked to a peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients' cluster computation to validate these clusters in future studies and provide handy indications for personalized BTcP therapy. CONCLUSION: This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values that are possibly useful for future trials. These results will allow us to target BTcP therapy on the basis of patient characteristics and to define a precision medicine strategy also for supportive care.

Adequacy assessment of oxycodone/paracetamol (acetaminophen) in multimodal chronic pain : a prospective observational study.

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.

Standard therapy with opioids in chronic pain management : ORTIBER study.

OBJECTIVE: Moderate to severe pain is commonly experienced by cancer and non-cancer patients. Although opioids are generally the most important drugs in chronic pain management, their use in Italy remains low. We designed a prospective open trial to assess the efficacy and safety of a standard therapy clinically available for a large range of patients. METHODS: A total of 172 consecutive patients (89 women and 83 men) with chronic pain (daily mean visual analogue scale (VAS) score > 4) that was not adequately managed by their existing pain regimen were enrolled to receive an immediate release (IR) dose of morphine: 30 mg/day (opioid-naive patients) or 60 mg/day (non-naive patients) for 5 days. After this period (start therapy), all patients were switched to slow release (SR) opioid therapy for 30 days (steady therapy). Each breakthrough pain (BTP) episode was treated with a single dose of IR morphine (20% of the daily dose) during all study periods. RESULTS: Daily VAS score was reduced from 7.4 +/- 1.3 at baseline to 3.8 +/- 1.5 (p < 0.0001) after 30 days of steady therapy in cancer and non-cancer patients. Fewer patients reported BTP events by study end (55% of patients with BTP at basal time had no BTP at last follow up), and the number of daily BTP events experienced by patients was reduced by therapy to 1-2 per day in 75% of patients reporting BTP. Further, the time delay to reach pain relief following administration of a rescue dose of IR morphine was 15 minutes or less in 52.1% of patients at study end. The standard therapy was well tolerated and fewer adverse effects were recorded at the end of the study period compared with baseline, with the exception of constipation, which showed a moderate increase (from 18.2% to 25.0%). CONCLUSION: Start therapy with IR morphine followed by conversion to SR opioid therapy could be implemented as a standard therapy to manage moderate to severe chronic pain in patients with cancer or non-cancer pain. ORamorph in TIBER study (ORTIBER).

Doctors and Nurses' Knowledge and Attitudes Towards Pediatric Pain Management: An Exploratory Survey in a Children's Hospital.

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 ad hoc questionnaire was developed and administered before (investigation A) and after (investigation B) the issuance of the Law. In B both doctors and nurses showed a slight but significant increase in correct answers and a reduction in incorrect ones, mainly concerning the category Myths and Prejudices. In both investigations doctors and nurses showed adequate general knowledge, yet there were some gaps regarding the specific knowledge of opioid drugs. Most of the participants were not familiar with the Law and its provisions.Investigation B showed an improvement in health professionals' knowledge, perhaps due to a hospital environment that followed the provisions of Law 38/2010. Nevertheless, the establishment of training courses according to the Law is needed to improve the knowledge of opioids, as well as to dispel deeply rooted myths and prejudices on pediatric pain.