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Massimo Mammucari,1 Teresa Paolucci,2 Domenico Russo,3 Enrica Maggiori,1 Raffaele Di Marzo,4 Alberto Migliore,5 Umberto Massafra,5 Gianpaolo Ronconi,6 Paola Emilia Ferrara,6 Fabio Gori,7 Barbara Bifarini,7 Stefano Brauneis,8 Renato Vellucci,9 Rocco Domenico Mediati,9 Bartolomeo Violo,10 Silvia Natoli,11 Carmen Pediliggieri,12 Cristiana Di Campli,12 Maria Chiara Collina12 1Primary Care Unit, ASL RM 1, Rome, Italy; 2Unit of Physical Medicine and Rehabilitation, G. D’ Annunzio University of Chieti-Pescara, Department of Oral Medical Science and Biotechnology (DSMOB), Chieti, Italy; 3“San Marco” Hospice and Palliative Care, Latina, Italy; 4Member of the Italian Society of Mesotherapy, Rome, Italy; 5Unit of Rheumatology, San Pietro Fatebenefratelli Hospital, Rome, Italy; 6Physical Medicine and Rehabilitation Unit, IRCCS, Catholic University of Sacred Heart, Rome, Italy; 7Section of Anaesthesia, Intensive Care, and Pain Medicine, University Hospital Santa Maria Della Misericordia, Perugia, Italy; 8Pain Centre “Enzo BorzomatI”, University Hospital of Rome “Policlinico Umberto I”, Rome, Italy; 9Anaesthesiology Department, University Hospital Careggi, Florence, Italy; 10Pain Therapy Unit, S. Spirito Nuovo Regina Margherita Hospital, Rome, Italy; 11Department of Clinical Science and Translational Medicine, Tor Vergata University, Rome, Italy; 12Department of Vascular Surgery, Limb Salvage and Diabetic Foot, IDI-IRCCS, Rome, ItalyCorrespondence: Massimo MammucariPrimary Care Unit, Local Health, ASL RM 1, Rome, 00165, ItalyTel +39-06-61560695 Email massimo.mammucari@libero.itAbstract: 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.Keywords: mesotherapy, intradermal therapy, research plan

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

Renato Vellucci,1 Rocco Domenico Mediati,1 Silvia Gasperoni,1 Massimo Mammucari,2 Franco Marinangeli,3 Patrizia Romualdi4 1Palliative Care and Pain Therapy Unit, University Hospital of Careggi, Florence, 2Primary Care Unit, ASL RM 1, Rome, 3Department of Life, Health and Environmental Sciences, University of L’Aquila, l’Aquila, 4Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy Abstract: 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. Keywords: breakthrough cancer pain, rapid-onset opioid, intranasal fentanyl spray

Background. Mesotherapy is a technique through which active ingredients are administered into the thickness of the skin in order to increase the local analgesic effect. Methods. 141 patients with spinal pain not responding to systemic therapy with NSAIDs were randomized to receive one or more intracutaneous drugs on a weekly basis. Results. All patients achieved a pain reduction of at least 50% compared to baseline, and all tolerated the therapy without having to resort to systemic drug dose increases. Conclusions. The data from our study show that the active ingredients infiltrated into the skin induce a mesodermal modulation between the infiltrated liquid and the cutaneous nervous and cellular structures from which the typical drug-saving effect of mesotherapy arises. Although further studies are needed to establish how to integrate mesotherapy in various clinical settings, it appears to be a useful technique available to the practicing physician. This research is also useful in guiding future clinical research. [ABSTRACT FROM AUTHOR]

Background. Intradermal therapy (mesotherapy) is a technique used to inject drugs into the surface layer of the skin. The intradermal micro deposit allows to modulate the kinetics of drugs, slowing down its absorption and prolonging the local mechanism of action. This technique is applied in the treatment of some forms of localized pain when a systemic drug-saving effect is useful, when it is necessary to synergize with other pharmacological or non-pharmacological therapies, when other therapies have failed or cannot be used. Aim. The purpose of our study was to evaluate the effect of a mixture with respect to its lower concentration. We also wanted to evaluate the number of sessions needed to reach the therapeutic goal (50% reduction in pain from baseline) in patients with acute or chronic neck pain. Method. We analyzed retrospectively data from 62 patients with cervicobrachial pain treated with intradermal drugs. Group A received a mixture of drugs; group B received half the dose of drugs. Results. Patients who received a lower concentration of drugs achieved similar results to those who received a higher dose. The therapeutic goal was achieved on average with 3.5 + 1.7 sessions on a weekly basis (min 1; max 9). Subjects in group A required 4±1.7 treatments (min 1; max 9), while subjects in group B required 3±1.5 treatments (min 1; max 7). Conclusions. Our study confirms that even a lower dose of drugs can induce a clinically useful result. This study confirms that the useful effect of mesotherapy is only partly due to the pharmacological action. Further randomized prospective studies are needed to standardize the technique in the various pain syndromes, but it is recommended to follow the guidelines of the Italian Society of Mesotherapy to ensure patients receive appropriate treatment. [ABSTRACT FROM AUTHOR]

Introduction. Mesotherapy, also known as local intradermal therapy, widely used all over the world, is a technique used to inject substances into the surface layer of the skin. There are no international guidelines for the correct use of this technique and in many countries, it is still applied empirically without valid patient consent. The Italian society of mesotherapy has planned a study to assess the rationale and clinical applications based on current evidence. Methods. An independent steering committee, based on the available scientific literature, has formulated a series of clinical questions. 21 experts responded by writing an evidence-based document. From this document 30 statements were obtained which were presented to 114 experts using the Delphi method. Results. 28 statements reached a broad agreement on definition, technique, pharmacological rationale, indications and some crucial ethical aspects. Conclusions. Although further studies are needed to establish the clinical role of this technique in each field of application, our statements recommend the correct application according to the needs of the individual patient in full respect of ethics. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Chronic pain is one of the most common complaints for people seeking medical care, with a series of potential detrimental effects on the individual and his social texture. Despite the heavy impact of chronic pain on patients' quality of life, epidemiological data suggest that chronic pain is often untreated or undertreated. An accurate diagnostic flow and appropriate treatment should be considered as key factors for optimal management of patients with chronic pain. Opioids are recommended for treatment of chronic cancer pain (CCP) and chronic non-cancer pain (CNCP) in guidelines and can safely and effectively relieve pain in a number of patients with chronic pain. Conversely, fears of addiction and adverse events could result in ineffective pain management. Recent epidemiological and clinical data demonstrate that only low percentages of patients treated with opioids for chronic pain have a risk to develop addiction, with a prevalence rate similar to that observed in the general population. METHODS: Despite the iatrogenic risk can be considered as low, validated tools for the early identification of patients at higher risk of addiction can help health professionals in the overall management of chronic pain. CONCLUSIONS: Due to the increasing relevance of primary care physicians in chronic pain management, we propose a 28-item questionnaire to validate specifically conceived for GPs' and aimed at the preliminary evaluation of the risk of addiction in patients with chronic pain. [ABSTRACT FROM AUTHOR]

Background: Mesotherapy is a technique through which active ingredients are administered into the thickness of the skin in order to increase the local analgesic effect., Methods: 141 patients with spinal pain not responding to systemic therapy with NSAIDs were randomized to receive one or more intra-cutaneous drugs on a weekly basis., Results: All patients achieved a pain reduction of at least 50% compared to baseline, and all tolerated the therapy without having to resort to systemic drug dose increases., Conclusions: The data from our study show that the active ingredients infiltrated into the skin induce a mesodermal modulation between the infiltrated liquid and the cutaneous nervous and cellular structures from which the typical drug-saving effect of mesotherapy arises. Although further studies are needed to establish how to integrate mesotherapy in various clinical settings, it appears to be a useful technique available to the practicing physician. This research is also useful in guiding future clinical research.

Objective: Due to its opioid and non-opioid mechanism of action, tapentadol is considered an atypical opioid with improved gastrointestinal tolerability versus traditional opioids. As for all opioid analgesics it is important to understand how to discontinue a treatment when it is not needed anymore. The aim of this article was to provide an overview of opioid therapy in non-cancer pain, with a specific focus on tapering of tapentadol in patients with chronic non-cancer pain, and suggestions on how to achieve tapering., Methods: Studies for this narrative review were identified via PubMed using a structured search strategy, focusing on management of chronic non-cancer pain with opioids, and the efficacy, tolerability, and pharmacology of tapentadol prolonged release. Publications were limited to English-language articles published within the last ∼10 years., Results: The review discusses the use and discontinuation of opioids in general, as well clinical data on discontinuation of tapentadol specifically. We provide a flow chart, which can be used by clinicians in the context of their own clinical experience to appropriately taper tapentadol in patients with chronic non-cancer pain. The flow chart can be easily tailored to individual patient characteristics, duration of tapentadol treatment, response to progressive dosage reduction, and likelihood of withdrawal symptom occurrence., Conclusions: While tapentadol is associated with a low frequency of opioid withdrawal symptoms after abrupt discontinuation, use of a tapering strategy is prudent. Tapering strategies developed for opioids in general can potentially be safely individualized in tapentadol-treated patients, although research on tapering strategies for tapentadol is required.

Telemedicine represents a major opportunity to facilitate continued assistance for patients with chronic pain and improve their access to care. Preliminary data show that an improvement can be expected of the monitoring, treatment adherence, assessment of treatment effect including the emotional distress associated with pain. Moreover, this approach seems to be convenient and cost-effective, and particularly suitable for personalized treatment. Nevertheless, several open issues must be highlighted such as identification of assessment tools, implementation of monitoring instruments, and ability to evaluate personal needs and expectations. Open questions exist, such as how to evaluate the need for medical intervention and interventional procedures, and how to define when a clinical examination is required for certain conditions. In this context, it is necessary to establish dynamic protocols that provide the right balance between face-to-face visits and telemedicine. Useful tips are provided to start an efficient experience. More data are needed to develop precise operating procedures. In the meantime, the first experiences from such settings can pave the way to initiate effective care pathways in chronic pain.

Introduction: A previous Delphi survey from the Rational Use of Analgesics (RUA) project involving Italian palliative care specialists revealed some discrepancies between current guidelines and clinical practice with a lack of consensus on items regarding the use of strong opioids in treating cancer pain. Those results represented the basis for a new Delphi study addressing a better approach to pain treatment in patients with cancer., Methods: The study consisted of a two-round multidisciplinary Delphi study. Specialists rated their agreement with a set of 17 statements using a 5-point Likert scale (0 = totally disagree and 4 = totally agree). Consensus on a statement was achieved if the median consensus score (MCS) (expressed as value at which at least 50% of participants agreed) was at least 4 and the interquartile range (IQR) was 3-4., Results: This survey included input from 186 palliative care specialists representing all Italian territory. Consensus was reached on seven statements. More than 70% of participants agreed with the use of low dose of strong opioids in moderate pain treatment and valued transdermal route as an effective option when the oral route is not available. There was strong consensus on the importance of knowing opioid pharmacokinetics for therapy personalization and on identifying immediate-release opioids as key for tailoring therapy to patients' needs. Limited agreement was reached on items regarding breakthrough pain and the management of opioid-induced bowel dysfunction., Conclusion: These findings may assist clinicians in applying clinical evidence to routine care settings and call for a reappraisal of current pain treatment recommendations with the final aim of optimizing the clinical use of strong opioids in patients with cancer.

Background: Poor sleep may predict the increase and intensification of pain over time with increased insomnia symptoms being both a predictor and an indicator of worse pain outcomes and physical functioning status over time. However, the impact of different analgesic therapies on quality of life, functional recovery and sleep has been poorly assessed to date, whereas these evaluations may greatly help clinicians in the selection of treatment when dealing with patients with chronic pain (CP)., Methods: To explore whether tapentadol-induced pain relief may drive improved sleep quality, we carried out a pooled analysis of real-world data collected from 487 patients with CP (mean age, 68.3 years; 57.7% women) suffering from a wide range of chronic musculoskeletal pain conditions and treated with tapentadol., Results: Following tapentadol treatment, patients experienced an 80% reduction in the frequency of very disturbed sleep as well as a 50% reduction in the predominant sleep complaint reported by patients with CP - that is, nocturnal awakenings. A significantly greater proportion of patients reported good/restful sleep at the end of the study period compared to baseline (72.4% versus 25.3%; p <0.01). This benefit was observed regardless of the clinical setting, treatment duration, posology or patient age and was associated with a higher proportion of patients reporting an improved global health status and good tolerability., Conclusion: The reduction in pain intensity provided by tapentadol fosters sleep quality and favours a better quality of life. Therefore, our findings provide the rationale for addressing sleep quality as a relevant outcome, complementary to pain relief in CP management., Competing Interests: Disclosure and potential conflicts of interest: R Vellucci and E Piraccini report no conflicts of interest in this work. G De Rosa is an employee of Grünenthal Italia Srl. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2021/03/dic.2020-12-9-COI.pdf, (Copyright © 2021 Vellucci R, De Rosa G, Piraccini E.)

Introduction: Mesotherapy, also known as local intradermal therapy, widely used all over the world, is a technique used to inject substances into the surface layer of the skin. There are no international guidelines for the correct use of this technique and in many countries, it is still applied empirically without valid patient consent. The Italian society of mesotherapy has planned a study to assess the rationale and clinical applications based on current evidence., Methods: An independent steering committee, based on the available scientific literature, has formulated a series of clinical questions. 21 experts responded by writing an evidence-based document. From this document 30 statements were obtained which were presented to 114 experts using the Delphi method., Results: 28 statements reached a broad agreement on definition, technique, pharmacological rationale, indications and some crucial ethical aspect., Conclusions: Although further studies are needed to establish the clinical role of this technique in each field of application, our statements recommend the correct application according to the needs of the individual patient in full respect of ethics.

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., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Paolo MancaPatents, Royalties, Other Intellectual Property: Patent for a method for the identification of gene panels optimal for TMB estimation (Inst)Grazia ArmentoConsulting or Advisory Role: Novartis Travel, Accommodations, Expenses: TevaBruno VincenziSpeakers' Bureau: PharmaMarPaolo MarchettiHonoraria: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Incyte, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Roche Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche Research Funding: AstraZeneca (Inst), Bristol Myers Squibb (Inst), Incyte (Inst), Eli Lilly (Inst), Merck Serono (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), NanoString Technologies (Inst), Pierre Fabre (Inst), Pfizer (Inst), Roche (Inst), Takeda (Inst) Travel, Accommodations, Expenses: Boehringer Ingelheim, Bristol Myers Squibb, Incyte, Merck Sharp & Dohme, RocheAugusto CaraceniConsulting or Advisory Role: Angelini Pharma, Shionogi Molteni, Kyowa Hakko KirinRocco Domenico MediatiSpeakers' Bureau: Angelini Pharma, Kyowa Hakko KirinRenato VellucciTravel, Accommodations, Expenses: Grünenthal GroupSilvia NatoliConsulting or Advisory Role: Grünenthal Italia, Sandoz, Angelini Pharma Speakers' Bureau: Mylan Travel, Accommodations, Expenses: AMS Group, SandozGiuseppe AzzarelloConsulting or Advisory Role: MerckVittorio GuardamagnaConsulting or Advisory Role: Istituto GentiliStefano MorosoConsulting or Advisory Role: Novartis, Janssen-CilagGiuseppe ToniniConsulting or Advisory Role: Novartis, Molteni Farmaceutici, Roche, Pierre Fabre, Italfarmaco Research Funding: PharmaMar (Inst), Novartis (Inst) No other potential conflicts of interest were reported., (© 2020 by American Society of Clinical Oncology.)

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., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Massimo Mammucari et al.)

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.

Background: Opioids provide effective relief from moderate-to-severe pain and should be prescribed as part of a multifaceted approach to pain management when other treatments have failed. Fixed-dose oxycodone/naloxone prolonged-release tablets (OXN PR) were designed to address the opioid class effect of opioid-induced constipation (OIC) by combining the analgesic efficacy of oxycodone with the opioid receptor antagonist, naloxone, which has negligible systemic availability when administered orally. This formulation has abuse-deterrent properties, since systemic exposure to naloxone by parenteral administration would antagonize the euphoric effects of oxycodone., Methods: A literature search was conducted to assess the evidence base for OXN PR to treat moderate-to-severe pain and its impact on bowel function, based on published clinical trials and observational studies., Results: Extensive data demonstrate that OXN PR provides effective analgesia and clinically relevant improvements in bowel function in patients with OIC and moderate-to-severe cancer-related pain and noncancer pain types such as low back pain, neuropathic pain, and musculoskeletal pain. OXN PR has also been found to improve bowel function in patients with OIC refractory to multiple types of laxatives, and improve Parkinson's disease-related pain. No unanticipated safety concerns have been reported in elderly patients., Conclusions: Evidence from clinical trials and observational studies confirms that for selected patients OXN PR significantly improves moderate-to-severe chronic pain and provides relief from OIC. Treatment should be tailored to individual patients to establish the lowest effective dose. An absence of analgesic ceiling effect was seen across the clinically relevant dose range investigated (≤ 160/80 mg/day)., (© 2017 The Authors. Pain Practice published by Wiley Periodicals, Inc. on behalf of World Institute of Pain.)