Effects of an Intrathecal Drug Delivery System Connected to a Subcutaneous Port on Pain, Mood and Quality of Life in End Stage Cancer Patients: An Observational Study.

BACKGROUND: In cancer patients with limited life expectancy, an implant of an intrathecal (IT) drug delivery system connected to a subcutaneous port (IDDS-SP) has been proposed as a successful strategy, but conflicting results are reported on quality of life (QoL). The aim of this prospective observational study is to report the effects on pain, mood and QoL of an IT combination therapy delivered by an IDDS-SP in malignant refractory pain. METHODS: Adult patients in which IT therapy was recommended were recruited. An IT therapy with morphine and levobupivacaine was started: VASPI score, depression and anxiety (evaluated by the Edmonton Symptom Assessment System -ESAS-), the Pittsburgh Sleep Quality Index (PSQI), the 5-level EuroQol 5D version (EQ-5D-5L) and the requirements of breakthrough cancer pain (BTcP) medications were registered, with adverse events rate and the satisfaction of patients scored as Patient Global Impression of Change (PGIC). RESULTS: Fifty patients, (16 F/34 M) were enrolled (age 69 ± 12). All had advanced cancer with metastasis. The median daily VASPI score was 75, the median depression score was 6, and the median anxiety score was 4, median PSQI was 16. At 28 days, a significant reduction in VASPI score was registered as well as in depression and anxiety item. Also, PSQI decreased significantly. The EQ-5D-5 L showed a significant improvement in all components at 14 and 28 days. Patient Global Impression of Change scores showed high level of satisfaction. A low incidence of adverse events and a reduction in BTCP episodes were also registered. CONCLUSION: Intrathecal combination therapy delivered by an IDDS-SP could ensure adequate control of cancer related symptoms, such as pain, depression, anxiety and sleep disturbances. These effects, with low rate of AEs and reduced BTcP episodes, could explain the improvement in QoL and the overall high levels of patients' satisfaction.

The central role of the gut in intensive care.

Critically ill patients undergo early impairment of their gut microbiota (GM) due to routine antibiotic therapies and other environmental factors leading to intestinal dysbiosis. The GM establishes connections with the rest of the human body along several axes representing critical inter-organ crosstalks that, once disrupted, play a major role in the pathophysiology of numerous diseases and their complications. Key players in this communication are GM metabolites such as short-chain fatty acids and bile acids, neurotransmitters, hormones, interleukins, and toxins. Intensivists juggle at the crossroad of multiple connections between the intestine and the rest of the body. Harnessing the GM in ICU could improve the management of several challenges, such as infections, traumatic brain injury, heart failure, kidney injury, and liver dysfunction. The study of molecular pathways affected by the GM in different clinical conditions is still at an early stage, and evidence in critically ill patients is lacking. This review aims to describe dysbiosis in critical illness and provide intensivists with a perspective on the potential as adjuvant strategies (e.g., nutrition, probiotics, prebiotics and synbiotics supplementation, adsorbent charcoal, beta-lactamase, and fecal microbiota transplantation) to modulate the GM in ICU patients and attempt to restore eubiosis.

Acute Kidney Injury in Coronavirus Disease 2019 Infected Patients: A Meta-Analytic Study.

INTRODUCTION: In clinical reports on coronavirus disease 2019 (COVID-19), the incidence of acute kidney injury (AKI) is extremely variable, although AKI is described as an independent risk factor for mortality. A meta-analysis was performed to clarify the incidence and the impact of COVID-19-related AKI on mortality. METHODS: All trials reporting the incidence of AKI in COVID-19 patients were searched using MEDLINE, the Cochrane Library, and EMBASE databases (last update April 26, 2020). RESULTS: Ten trials with a sample of 5,166 patients were included. AKI occurred in 947 out of 5,166 (18.3%) patients. AKI incidence was higher in severe cases: 62/305 severe patients developed AKI (20%) versus 27/1,268 nonsevere patients (2%) (p = 0.00001). AKI occurred in 475 out of 915 (52%) deceased patients versus 183 out of 2,678 (7%) survivors (p = 0.00001). Continuous renal replacement therapy was significantly more frequent in severe cases and in dead patients. CONCLUSION: A significant increase in mortality rate was observed in COVID patients who developed AKI, and AKI incidence was also higher in severe cases. Any supportive strategies to protect kidney could represent valuable intervention to reduce mortality in severe COVID-19 patients.

Hemodynamic goal-directed therapy and postoperative kidney injury: an updated meta-analysis with trial sequential analysis.

BACKGROUND: Perioperative goal-directed therapy (GDT) reduces the risk of renal injury. However, several questions remain unanswered, such as target, kind of patients and surgery, and role of fluids and inotropes. We therefore update a previous analysis, including all studies published in the meanwhile, to clarify the clinical impact of this strategy on acute kidney injury. MAIN BODY: Randomized controlled trials enrolling adult patients undergoing major surgery were considered. GDT was defined as perioperative monitoring and manipulation of hemodynamic parameters to reach normal or supranormal values by fluids alone or with inotropes. Trials comparing the effects of GDT and standard hemodynamic therapy were considered. Primary outcome was acute kidney injury, whichever definition was used. Meta-analytic techniques (analysis software RevMan, version 5.3) were used to combine studies, using random-effect odds ratios (OR) and 95% confidence intervals (CI). Trial sequential analyses were performed including all trials and considering only low risk of bias trials. Sixty-five trials with an overall sample of 9308 patients were included. OR for the development of renal injury was 0.64 (95% CI, 0.62-0.87; p = 0.0003), with no statistical heterogeneity. Trial sequential analyses and sensitivity analysis including studies with low risk of bias confirmed the main results. A significant decrease in renal injury rate was observed in studies that adopted cardiac output and oxygen delivery as hemodynamic target and that used both fluids and inotropes. The postoperative kidney injury rate was significantly lower in trials enrolling "high-risk" patients and major abdominal and orthopedic surgery. SHORT CONCLUSION: The present meta-analysis suggests that targeting GDT to perioperative systemic oxygen delivery, by means of fluids and inotropes, can be the best way to improve renal perfusion and oxygenation in high-risk patients undergoing major abdominal and orthopedic surgery.

Colistin-associated Acute Kidney Injury in Severely Ill Patients: A Step Toward a Better Renal Care? A Prospective Cohort Study.

BACKGROUND: Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy. METHODS: A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD)-based dosing approach. RESULTS: Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87-11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9-9.2; P < .001) and age (1.03; 1.0-1.05; P = .028), whereas a strong independent renal-protective role emerged for ascorbic acid (0.27; .12-.57; P < .001). CONCLUSIONS: In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin.

Gut Microbiota Modulation and Its Implications on Neuropathic Pain: A Comprehensive Literature Review.

Neuropathic pain (NP) is a chronic pain disorder arising from somatosensory nervous system impairment. Extensive evidence supports the notion that the gut microbiota (GM) is crucial in maintaining human health by performing vital tasks. At the same time, its disruption has been linked to the emergence and advancement of an expanding range of disorders, including NP, in which GM could play a role in its pathophysiology. The crosstalk between the nervous system and GM happens through immune mediators, metabolites, and nervous structures and involves both central and peripheral nervous systems. This literature review aims to thoroughly investigate the function of modulating GM in the treatment of NP. It will achieve this by integrating existing knowledge, identifying underlying mechanisms, and evaluating the possible clinical consequences of exploiting the gut-brain axis. We will cover the main therapeutic applications of the described GM-modulators, such as probiotics, faecal microbiota transplantation, dietary supplements and emotional support, to the main kinds of NP in which any evidence, even if only pre-clinical, has been unravelled in recent years. The explored NP areas include chemotherapy-induced peripheral neuropathy, diabetic neuropathy, trauma-induced neuropathic pain, trigeminal neuralgia, postherpetic neuralgia and low back pain.

Microbial Symphony: Exploring the Role of the Gut in Osteoarthritis-Related Pain. A Narrative Review.

One of the most common musculoskeletal disorders, osteoarthritis (OA), causes worldwide disability, morbidity, and poor quality of life by degenerating articular cartilage, modifying subchondral bone, and inflaming synovial membranes. OA pathogenesis pathways must be understood to generate new preventative and disease-modifying therapies. In recent years, it has been acknowledged that gut microbiota (GM) can significantly contribute to the development of OA. Dysbiosis of GM can disrupt the "symphony" between the host and the GM, leading to a host immunological response that activates the "gut-joint" axis, ultimately worsening OA. This narrative review summarizes research supporting the "gut-joint axis" hypothesis, focusing on the interactions between GM and the immune system in its two main components, innate and adaptive immunity. Furthermore, the pathophysiological sequence of events that link GM imbalance to OA and OA-related pain is broken down and further investigated. We also suggest that diet and prebiotics, probiotics, nutraceuticals, exercise, and fecal microbiota transplantation could improve OA management and represent a new potential therapeutic tool in the light of the scarce panorama of disease-modifying osteoarthritis drugs (DMOADs). Future research is needed to elucidate these complex interactions, prioritizing how a particular change in GM, i.e., a rise or a drop of a specific bacterial strain, correlates with a certain OA subset to pinpoint the associated signaling pathway that leads to OA.

Low Back Pain and Radiofrequency Denervation of Facet Joint: Beyond Pain Control-A Video Recording.

Chronic low back pain is often due to L5S1 instability resulting in facet joint syndrome. Patients suffering from low back pain may also have a gait pattern characterized by a reduced speed and a shorter, asymmetrical step in order to reduce pain. This case is of a patient with L5S1 instability that occurred after L1 to L5 lumbar stabilization who was treated with radiofrequency (RF) denervation of the medial branch of L5S1 bilaterally. RF ablation outcome was tested by comparing its impact on pain, function, quality of life, and on gait pattern, before and 1 month after the procedure. To objectify the impact of a good pain control on gait, a video recording was performed (see Video 1).

Effect of Preoperative Music Therapy Versus Intravenous Midazolam on Anxiety, Sedation and Stress in Stomatology Surgery: A Randomized Controlled Study.

BACKGROUND: Patients undergoing surgery and general anesthesia often experience anxiety, fear and stress, with negative bodily responses. These may be managed by the pre-procedural application of anxiolytic, analgesic, and anesthetic drugs that have, however, potential risks or side effects. Music therapy (MT) can be used as a complementary no-drug intervention alongside standard surgical care before, during and after medical procedures. The aim of this study was to evaluate the effects of preoperative MT intervention compared to premedication with midazolam on levels of anxiety, sedation and stress during general anesthesia for elective stomatology surgery. METHODS: A two-arm randomized and controlled single-center, parallel-group, pre-post event study was conducted. In total, 70 patients affected by stage I or II (both clinically and instrumentally N0) micro-invasive oral cancer and undergoing elective surgery under general anesthesia were assigned to the control group (CG) or to the music therapy group (MTG). MTG patients received preoperative music therapy intervention (MT) from a certified music therapist before surgery, while the CG patients did not receive MT but instead received premedication with intravenous midazolam, 0.02 mg/kg. Anesthesia was the same in both groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded at the entrance to the operating room, just before the induction of anesthesia and every 5 min until the end of surgery. An anxiety visual analogues scale (A-VAS) was used to evaluate the level of anxiety. The bispectral index (BIS) monitor was used to measure the depth of sedation just before and 10 min after both music intervention and midazolam administration. Stress response was assessed 5 min before and 20 min after surgery via the control of plasma prolactin (PRL), growth hormone (GH), and cortisol levels. The patient global impression of satisfaction (PGIS) was tested 1 h after surgery. Participants in the MTG were asked to answer 3 questions concerning their experience with MT. RESULTS: No statistical differences among the PRL, GH and cortisol levels between the two groups were registered before and after the treatment, as well as for PAS, PAD and HR. Significant differences in the A-VAS scores between the MTG and CG (p < 0.01) was observed. Compared to the CG, MTG patients had a statistically significantly lower BIS score (p = 0.02) before induction. A PGIS score of 86.7% revealed that patients in the MTG were very satisfied, versus 80% in the CG (p < 0.05). CONCLUSION: Preoperative music therapy could be an alternative to intravenous midazolam when aiming to promote a preoperative and post-operative state of anxiolysis and sedation in stomatology surgery, even if no differences were found in terms of the surgery-related stress response according to physiological and hormonal determinations.

High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? A preliminary study.

BACKGROUND: Gram-negative bacteria susceptible only to colistin (COS) are emerging causes of severe nosocomial infections, reviving interest in the use of colistin. However, consensus on the most effective way to administer colistin has not yet been reached. METHODS: All patients who had sepsis due to COS gram-negative bacteria or minimally susceptible gram-negative bacteria and received intravenous colistimethate sodium (CMS) were prospectively enrolled. The CMS dosing schedule was based on a loading dose of 9 MU and a 9-MU twice-daily fractioned maintenance dose, titrated on renal function. For each CMS course, clinical cure, bacteriological clearance, daily serum creatinine clearance, and estimated creatinine clearance were recorded. RESULTS: Twenty-eight infectious episodes due to Acinetobacter baumannii (46.4%), Klebsiella pneumoniae (46.4%), and Pseudomonas aeruginosa (7.2%) were analyzed. The main types of infection were bloodstream infection (64.3%) and ventilator-associated pneumonia (35.7%). Clinical cure was observed in 23 cases (82.1%). Acute kidney injury developed during 5 treatment courses (17.8%), did not require renal replacement therapy, and subsided within 10 days from CMS discontinuation. No correlation was found between variation in serum creatinine level (from baseline to peak) and daily and cumulative doses of CMS, and between variation in serum creatinine level (from baseline to peak) and duration of CMS treatment. CONCLUSIONS: Our study shows that in severe infections due to COS gram-negative bacteria, the high-dose, extended-interval CMS regimen has a high efficacy, without significant renal toxicity.

Oral nystatin prophylaxis in surgical/trauma ICU patients: a randomised clinical trial.

INTRODUCTION: Candida prophylaxis in ICU is still a matter of debate. Oral chemoprophylaxis has been advocated to reduce the incidence of Candida colonisation and infection. METHODS: We performed a randomised trial studying a single drug (nystatin) versus control in surgical/trauma ICU patients. Multiple-site testing for fungi was performed in each patient on ICU admission (T0) and subsequently every 3 days (T3, T6, T9, and so forth). The primary evaluation criterion was the time course of the corrected colonisation index. RESULTS: Ninety-nine patients were enrolled. At admission, 69 patients exhibited Candida colonisation: the most frequently colonised body sites were the stomach and the pharynx. The most frequent isolated species was Candida albicans. The corrected colonisation index was similar in the two groups at T0 (P = 0.36), while a significant statistical difference was observed between the treatment and control groups at T6 (median 0.14 and 0.33, respectively; P = 0.0016), at T9 (median 0.00 and 0.28, respectively; P = 0.0001), at T12 (median 0.00 and 0.41, respectively; P = 0.0008), and at T15 (median 0.00 and 0.42, respectively; P < 0.0003). The same results were obtained in the subgroup of patients already colonised at ICU admission. CONCLUSION: This trial shows that nystatin prophylaxis significantly reduces fungal colonisation in surgical/trauma ICU patients, even if already colonised. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01495039.

Real-Time Muscle Activity and Joint Range of Motion Monitor to Improve Shoulder Pain Rehabilitation in Wheelchair Basketball Players: A Non-Randomized Clinical Study.

Wheelchair basketball (WB) involves sports gestures that expose the shoulder to high biomechanical stress and frequently lead to shoulder pain (SP). Due to their physical peculiarities and sporting performance, these athletes require specific rehabilitation programs that are as fast, personalized and effective as possible. However, there are few studies specifically dedicated to these purposes. Surface electromyography (sEMG) seems a promising tool for better customization and achieving more targeted rehabilitation results. The aim of this study was to evaluate the usefulness of sEMG to monitor SP rehabilitation outcomes in WB players. Thirty-three athletes were enrolled in this non-randomized clinical study and divided into two groups. Both groups underwent a shoulder rehabilitation protocol, but only the experimental group was monitored in real time with sEMG on the shoulders. At enrollment (T0), at the end of 4 weeks of the rehabilitation program (T1), and 8 weeks after T1 (T2), the following outcome measures were collected: Wheelchair User's Shoulder Pain Index (WUSPI), 20 m straight line test, shoulder abduction range of motion (ROM). There was a statistically significant difference for WUSPI and ROM scores in the comparison between groups (p < 0.001), and for all outcomes in the comparison between times and in the interaction between time and group (p < 0.001). Therefore, the experimental group showed a better improvement at all detection times compared to the control group. sEMG seems a useful tool for improving the monitoring of SP rehabilitation outcomes in WB players. This monitoring speeds up and improves the rehabilitative results, limiting the risk of sport abandonment and increasing the possibility for people with disabilities to quickly return to practice physical activity.

New Perspectives on the Adverse Effects of NSAIDs in Cancer Pain: An Italian Delphi Study from the Rational Use of Analgesics (RUA) Group.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs for cancer pain. We used the Delphi methodology to evaluate the opinions of clinicians on NSAIDs and paracetamol, with a specific focus on their safety profile. Consensus was reached on seven statements. A high level of consensus was reached regarding the use of NSAIDs and gastrointestinal, cardiovascular, and renal risk in patients taking low-dose aspirin and assessment of liver function during long-term treatment with paracetamol. Consensus was also reached that assessment and monitoring of eGFR are important in the elderly being administered NSAIDs. It was further agreed that NSAIDs can often play a key role in association with opioids in the treatment of cancer pain and that paracetamol is the analgesic of first choice for patients with mild chronic pain. When NSAIDs are administered in combination with steroids, it was agreed that the risk of gastrointestinal damage is increased since steroids delay the healing of ulcers and that paracetamol can be used during pregnancy and does not affect the health of the fetus. This Delphi study highlights that there is poor agreement on how these drugs are routinely prescribed. However, a consensus was reached for seven key statements and may represent a valid contribution to daily practice.

Efficacy of Radiofrequency as Therapy and Diagnostic Support in the Management of Musculoskeletal Pain: A Systematic Review and Meta-Analysis.

Radiofrequency (RF) is a minimally invasive procedure used to interrupt or alter nociceptive pathways for treating musculoskeletal pain. It seems a useful tool to relieve chronic pain syndromes, even if, to date, solid evidence is still needed about the effectiveness of this therapy. By this systematic review and meta-analysis, we aimed to evaluate the efficacy of RF in treating musculoskeletal pain. PubMed, Medline, Cochrane, and PEDro databases were searched to identify randomized controlled trials (RCTs) presenting the following: patients with chronic musculoskeletal pain as participants; RF as intervention; placebo, anesthetic injection, corticosteroid injection, prolotherapy, conservative treatment, physiotherapy, and transcutaneous electrical nerve stimulation as comparisons; and pain and functioning as outcomes. Continuous random-effect models with standardized mean difference (SMD) were used to compare the clinical outcomes. Overall, 26 RCTs were eligible and included in the systematic review. All of them analyzed the efficacy of RF in four different regions: cervical and lumbar spine, knee, sacroiliac (SI) joint, shoulder. The outcomes measures were pain, disability, and quality of life. A medium and large effect in favor of the RF treatment group (SMD < 0) was found for the shoulder according to the Visual Analogical Scale and for the SI joint according to the Oswestry Disability Index. A small effect in favor of the RF treatment group (SMD > 0) was found for the spine according to the 36-item Short Form Survey. Non-significant SMD was found for the other outcomes. RF represents a promising therapy for the treatment of chronic musculoskeletal pain, especially when other approaches are ineffective or not practicable. Further studies are warranted to better deepen the effectiveness of RF for pain and joint function for each anatomical region of common application.

Haemodynamic goal-directed therapy and postoperative infections: earlier is better. A systematic review and meta-analysis.

INTRODUCTION: Infectious complications are the main causes of postoperative morbidity. The early timing of their promoting factors is the rationale for perioperative strategies attempting to reduce them. Our aim was to determine the effects of perioperative haemodynamic goal-directed therapy on postoperative infection rates. METHODS: We performed a systematic review and meta-analysis. MEDLINE, EMBASE, The Cochrane Library and the DARE databases were searched up to March 2011. Randomised, controlled trials of major surgery in adult patients managed with perioperative goal-directed therapy or according to routine haemodynamic practice were included. Primary outcome measure was specific type of infection. RESULTS: Twenty-six randomised, controlled trials with a combined total of 4,188 participants met our inclusion criteria. Perioperative goal-directed therapy significantly reduced surgical site infections (pooled OR 0.58, 95% CI 0.46 to 0.74; P < 0.0001), pneumonia (pooled OR 0.71, 95% CI 0.55 to 0.92; P = 0.009), and urinary tract infections (pooled OR 0.44, 95% CI 0.22 to 0.84; P = 0.02). A significant benefit was found regarding total infectious episodes (OR 0.40, 95% CI 0.28 to 0.58; P < 0.00001). CONCLUSIONS: Flow-directed haemodynamic therapy designed to optimise oxygen delivery protects surgical patients against postoperative hospital-acquired infections and must be strongly encouraged, particularly in the high-risk surgical population.

Candida colonization index in patients admitted to an ICU.

Multiple-site colonization with Candida spp. is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At admission (T0) and every three days for two weeks, different samples (pharynx swab, tracheal secretions, stomach contents, etc.) were collected for mycological surveillance. Candida mannan antigen and Candida anti-mannan antibodies were assayed. The Colonization Index (CI) and Corrected Colonization Index were calculated for each time point. Of all patients 70% was already colonized by Candida spp. at T0 and six of them had CI ≥ 0.5. Three patients developed candidemia; they had CI ≥ 0.5 before infection. Positive values of Candida mannan antigen and anti-mannan antibodies were found only in the patients with candidemia. The sensitivity and specificity of the Candida mannan test were 66.6% and 100%, respectively, while the sensitivity and specificity of the anti-mannan antibody test were 100%. In accordance with other authors, we find the surveillance cultures are useful to monitor the Candida colonization in ICU patients. In addition, the sequential observation of anti-mannan antibodies could contribute to early diagnosis of candidiasis more than Candida mannan antigen in immunocompetent patients.

The Routes of Administration for Acute Postoperative Pain Medication.

Effective treatment of postoperative acute pain, together with early mobilization and nutrition, is one of the perioperative strategies advocated to improve surgical outcome and reduce the costs of hospitalization. Moreover, adequate pain control reduces perioperative morbidity related to surgical stress and can also prevent the incidence of chronic postoperative pain syndromes, whose treatment is still a challenge. The choice of the most appropriate analgesics depends not only on the drug class, but also on the most suitable route of administration, the best dosage for that route, and unique limitations and contraindications for every patient. In the present review, a comprehensive analysis was performed on the different routes of administration of acute postoperative pain medications and their indications and limitations, focusing on recent evidence and international recommendations.

An Italian Expert Consensus on the Use of Opioids for the Management of Chronic Non-Oncological Pain in Clinical Practice: Focus on Buprenorphine.

PURPOSE: The aim of the present work was to evaluate the knowledge and prescriptive habits of clinicians involved in the management of chronic non cancer pain (CNCP), with a special focus on the use of opioids. METHODS: A Delphi method was used. A Board of specialists elaborated and discussed a series of statements, based on available literature and personal clinical expertise, about particularly controversial topics on pain pathophysiology and treatment. A Panel of experts in the field of pain management, selected by the Board, was invited to vote the proposed statements, indicating the level of agreement on a 5-point Likert scale (1: strongly disagree; 2: disagree; 3: partially agree; 4: agree; 5: strongly agree). The threshold for consensus was set at minimum 66.6% of the number of respondents with a level of agreement ≥4 (Agree or Strongly agree). RESULTS: The Board included 5 pain therapists, 1 pharmacologist and 1 methodology expert and drew up a total of 36 statements (for a total of 40 requested answers)". A total of 100 clinicians were included in the Expert Panel. Respondents were 89 (89%). Consensus was achieved for 32 out of 40 answers. Most of the lack of consensus was recorded for statements regarding opioids use, and resulted from a low level of agreement (3 on the Likert scale), suggesting a neutral position deriving from a lack of knowledge rather than a strong contrary opinion. CONCLUSION: Most of the proposed items reached consensus, suggesting a generally homogeneous approach to CNCP management. However, the lack of consensus recorded for several items regarding opioid use confirms the need to fill important gaps in the knowledge of available agents. A clear explanation of the peculiar pharmacological properties of drugs associated with potential clinical advantages (such as buprenorphine) will help optimize pain treatment in both primary care and hospital settings and improving pain control in CNCP patients.

Personalizing Cancer Pain Therapy: Insights from the Rational Use of Analgesics (RUA) Group.

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.