Radiofrequency for chronic lumbosacral and cervical pain: Results of a consensus study using the RAND/UCLA appropriateness method.

BACKGROUND: Despite the routine use of radiofrequency (RF) for the treatment of chronic pain in the lumbosacral and cervical region, there remains uncertainty on the most appropriate patient selection criteria. This study aimed to develop appropriateness criteria for RF in relation to relevant patient characteristics, considering RF ablation (RFA) for the treatment of chronic axial pain and pulsed RF (PRF) for the treatment of chronic radicular pain. METHODS: The RAND/UCLA Appropriateness Method (RUAM) was used to explore the opinions of a multidisciplinary European panel on the appropriateness of RFA and PRF for a variety of clinical scenarios. Depending on the type of pain (axial or radicular), the expert panel rated the appropriateness of RFA and PRF for a total of 219 clinical scenarios. RESULTS: For axial pain in the lumbosacral or cervical region, appropriateness of RFA was determined by the dominant pain trigger and location of tenderness on palpation with higher appropriateness scores if these variables were suggestive of the diagnosis of facet or sacroiliac joint pain. Although the opinions on the appropriateness of PRF for lumbosacral and cervical radicular pain were fairly dispersed, there was agreement that PRF is an appropriate option for well-selected patients with radicular pain due to herniated disc or foraminal stenosis, particularly in the absence of motor deficits. The panel outcomes were embedded in an educational e-health tool that also covers the psychosocial aspects of chronic pain, providing integrated recommendations on the appropriate use of (P)RF interventions for the treatment of chronic axial and radicular pain in the lumbosacral and cervical region. CONCLUSIONS: A multidisciplinary European expert panel established patient-specific recommendations that may support the (pre)selection of patients with chronic axial and radicular pain in the lumbosacral and cervical region for either RFA or PRF (accessible via https://rftool.org). Future studies should validate these recommendations by determining their predictive value for the outcomes of (P)RF interventions.

Consensus practice guidelines on interventions for cervical spine (facet) joint pain from a multispecialty international working group.

BACKGROUND: The past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial. METHODS: In August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4-5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement. RESULTS: Twenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation. CONCLUSIONS: Cervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.

The Use of Contrast Agents in Interventional Pain Procedures: A Multispecialty and Multisociety Practice Advisory on Nephrogenic Systemic Fibrosis, Gadolinium Deposition in the Brain, Encephalopathy After Unintentional Intrathecal Gadolinium Injection, and Hypersensitivity Reactions.

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.

The Effect of Peripheral Neuromodulation on Pain from the Sacroiliac Joint: A Retrospective Cohort Study.

We report here a retrospective review of the longer-term results of peripheral neuromodulation in 12 patients with significant chronic sacroiliac joint pain who had previously failed multiple conservative and interventional pain therapies. To allow for the assessment of meaningful longer-term outcome, implants for all 12 patients had been in place for a minimum of 18 months to a maximum of 36 months prior to the formal review. Compared to the preimplantation baseline, the longer-term follow-up revealed a significant and sustained reduction in visual analog scale pain scores from 8.7 ± 1.1 to 1.1 ± 1.0 (P < 0.001), with a 75% reduction in analgesia requirement, and improvement in pain impact on daily function from 94.1% ± 5.9% to 5.8% ± 6.0% (P < 0.001). These preliminary results merit a prospective randomized trial of peripheral neuromodulation.

A systematic review and network meta-analysis of pharmaceutical interventions used to manage chronic pain.

It is estimated 1.5 billion of the global population suffer from chronic pain with prevalence increasing with demographics including age. It is suggested long-term exposure to chronic could cause further health challenges reducing people's quality of life. Therefore, it is imperative to use effective treatment options. We explored the current pharmaceutical treatments available for chronic pain management to better understand drug efficacy and pain reduction. A systematic methodology was developed and published in PROSPERO (CRD42021235384). Keywords of opioids, acute pain, pain management, chronic pain, opiods, NSAIDs, and analgesics were used across PubMed, Science direct, ProQuest, Web of science, Ovid Psych INFO, PROSPERO, EBSCOhost, MEDLINE, ClinicalTrials.gov and EMBASE. All randomised controlled clinical trials (RCTs), epidemiology and mixed-methods studies published in English between the 1st of January 1990 and 30th of April 2022 were included. A total of 119 studies were included. The data was synthesised using a tri-partied statistical methodology of a meta-analysis (24), pairwise meta-analysis (24) and network meta-analysis (34). Mean, median, standard deviation and confidence intervals for various pain assessments were used as the main outcomes for pre-treatment pain scores at baseline, post-treatment pain scores and pain score changes of each group. Our meta-analysis revealed the significant reduction in chronic pain scores of patients taking NSAID versus non-steroidal opioid drugs was comparative to patients given placebo under a random effects model. Pooled evidence also indicated significant drug efficiency with Botulinum Toxin Type-A (BTX-A) and Ketamine. Chronic pain is a public health problem that requires far more effective pharmaceutical interventions with minimal better side-effect profiles which will aid to develop better clinical guidelines. The importance of understanding ubiquity of pain by clinicians, policy makers, researchers and academic scholars is vital to prevent social determinant which aggravates issue.

Pulsed Radiofrequency Increases Nestin and Matrix Metalloproteinase-2 Expression in Porcine Lumbar Dorsal Root Ganglion.

Background: Pulsed radiofrequency (PRF) has been used for the treatment of chronic lumbar radicular pain and other chronic pain states. The dorsal root ganglion (DRG) consists of primary afferent somatic and visceral nerve cell bodies that transduce sensory signals from the periphery to the central part of the nervous system. It is a very important part of acute nociception, as well as the development and maintenance of chronic pain. Methods: A total of seven domestic pigs were investigated. All pigs underwent a PRF procedure while under general anesthesia and with X-ray imaging. Four lumbar DRGs were randomly treated. We used the opposite side of the DRGs as controls. The lumbar region of the spine was placed in 10% formaldehyde for one month. After this fixation, DRG samples were prepared for slide analysis. Results: Nestin (Nes, code-Nr. AB 5968, dilution 1:250, rabbit, Abcam, United Kingdom) and matrix metallopeptidase 2 (MMP-2, code-Nr. DUB 03, dilution 1:100, goat) expressions were detected by immunohistochemical staining. The cell numbers with Nes (28.4 ± 3.3 vs. 16.1 ± 3.4; P < 0.05) and MMP-2 (26.2 ± 3.2 vs. 14.1 ± 2.3; P < 0.05) expressions were larger on the PRF side compared to the control side. The glial cells in the spinal ganglia on both sides showed immunoreactivity. Conclusions: The increase of MMP-2-containing gangliocytes one month after PRF procedures highlights active neural cell proliferation. Increased Nes factor expression in spinal gangliocytes of the lumbar region indicates neural remodeling and regeneration.

Consensus practice guidelines on interventions for cervical spine (facet) joint pain from a multispecialty international working group.

BACKGROUND: The past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial. METHODS: In August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4-5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement. RESULTS: Twenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation. CONCLUSIONS: Cervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.

Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process.

BACKGROUND: Globally, medical cannabis legalization has increased in recent years and medical cannabis is commonly used to treat chronic pain. However, there are few randomized control trials studying medical cannabis indicating expert guidance on how to dose and administer medical cannabis safely and effectively is needed. METHODS: Using a multistage modified Delphi process, twenty global experts across nine countries developed consensus-based recommendations on how to dose and administer medical cannabis in patients with chronic pain. RESULTS: There was consensus that medical cannabis may be considered for patients experiencing neuropathic, inflammatory, nociplastic, and mixed pain. Three treatment protocols were developed. A routine protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg CBD twice daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 2.5 mg and titrate by 2.5 mg every 2 to 7 days until a maximum daily dose of 40 mg/day of THC. A conservative protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg once daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 1 mg/day and titrate by 1 mg every 7 days until a maximum daily dose of 40 mg/day of THC. A rapid protocol where the clinician initiates the patient on a balanced THC:CBD variety at 2.5-5 mg of each cannabinoid once or twice daily and titrates by 2.5-5 mg of each cannabinoid every 2 to 3 days until the patient reaches his/her goals or to a maximum THC dose of 40 mg/day. CONCLUSIONS: In summary, using a modified Delphi process, expert consensus-based recommendations were developed on how to dose and administer medical cannabis for the treatment of patients with chronic pain.

Cancer pain: part 1: Pathophysiology; oncological, pharmacological, and psychological treatments: a perspective from the British Pain Society endorsed by the UK Association of Palliative Medicine and the Royal College of General Practitioners.

OBJECTIVE: This discussion document about the management of cancer pain is written from the pain specialists' perspective in order to provoke thought and interest in a multimodal approach to the management of cancer pain, not just towards the end of life, but pain at diagnosis, as a consequence of cancer therapies, and in cancer survivors. It relates the science of pain to the clinical setting and explains the role of psychological, physical, interventional and complementary therapies in cancer pain. METHODS: This document has been produced by a consensus group of relevant health care professionals in the United Kingdom and patients' representatives making reference to the current body of evidence relating to cancer pain. In the first of two parts, pathophysiology, oncological, pharmacological, and psychological treatment are considered. CONCLUSIONS: It is recognized that the World Health Organization (WHO) analgesic ladder, while providing relief of cancer pain towards the end of life for many sufferers worldwide, may have limitations in the context of longer survival and increasing disease complexity. To complement this, it is suggested that a more comprehensive model of managing cancer pain is needed that is mechanism-based and multimodal, using combination therapies including interventions where appropriate, tailored to the needs of an individual, with the aim to optimize pain relief with minimization of adverse effects.

Interventional pain management in patients with cancer-related pain.

Invasive interventional procedures for managing pain in cancer patients are often underutilized following the popularization of the WHO analgesic ladder. The procedures that were successfully used until then were relegated away from mainstream palliative care practice, with the advent of newer opioids and adjuvants. Even though nerve blocks, intrathecal pumps and spinal cord stimulation were reintroduced as the fourth step of the WHO ladder, often referrals for these procedures are too late to produce a meaningful effect on quality of life. At this point most patients have advanced disease and are requiring end of life care. Additionally, it is becoming evident that at least 10% of patients do not achieve good quality analgesia with oral opioids and are often troubled by unacceptable side effects. There is an increasing public awareness of the problems with long-term opioid therapy and some of these patients would certainly benefit from invasive procedures to alleviate their pain and improve their quality of life. Improving life quality and expectancy with better treatment options and increasing number of cancer survivors should be heralding a change and hence neurolytic procedures are to be used only in patients with limited life expectancy. ITDDs, neuromodulation and ever-increasing use of procedures routinely used in treating chronic nonmalignant pain would be the mainstay of interventional management until AI and nanotechnology would open doors for novel treatment options. Interventions should not be used as a last resort after multiple failed attempts at opioid therapy, but as an integral part of a management strategy including medical management, psychological and emotional welfare, and supportive care of the patient in a holistic manner. The curriculum of specialists should include appropriate training to safely perform and produce better quality evidence to validate the efficacy and safety of these challenging procedures.

ARTSENS® Pen-portable easy-to-use device for carotid stiffness measurement: technology validation and clinical-utility assessment.

OBJECTIVE: The conventional medical imaging modalities used for arterial stiffness measurement are non-scalable and unviable for field-level vascular screening. The need for an affordable, easy-to-operate automated non-invasive technologies remains unmet. To address this need, we present a portable image-free ultrasound device-ARTSENS® Pen, that uses a single-element ultrasound transducer for carotid stiffness evaluation. APPROACH: The performance of the device was clinically validated on a cohort of 523 subjects. A clinical-grade B-mode ultrasound imaging system (ALOKA eTracking) was used as the reference. Carotid stiffness measurements were taken using the ARTSENS® Pen in sitting posture emulating field scenarios. MAIN RESULTS: A statistically significant correlation (r > 0.80, p < 0.0001) with a non-significant bias was observed between the measurements obtained from the two devices. The ARTSENS® Pen device could perform highly repeatable measurements (with variation smaller than 10%) on a relatively larger percentage of the population when compared to the ALOKA system. The study results also revealed the sensitivity of ARTSENS® Pen to detect changes in arterial stiffness with age. SIGNIFICANCE: The easy-to-use technology and the automated algorithms of the ARTSENS® Pen make it suitable for cardiovascular risk assessment in resource-constrained settings.

Safety Considerations in Cannabinoid-Based Medicine.

Cannabinoids are a diverse class of chemical compounds that are increasingly recognized as potential therapeutic options for a range of conditions. While many studies and reviews of cannabinoids focus on efficacy, safety is much less well reported. Overall assessment of the safety of cannabinoid-based medicines is confounded by confusion with recreational cannabis use as well as different study designs, indications, dosing, and administration methods. However, clinical studies in registered products are increasingly available, and this article aims to discuss and clarify what is known regarding the safety profiles of cannabinoid-based medicines, focusing on the medical and clinical safety evidence and identifying areas for future research. The two most well-studied cannabinoids are Δ9-tetrahydrocannabinol (THC), or its synthetic variants (dronabinol, nabilone), and cannabidiol (CBD). Across diverse indications, dizziness and fatigue are generally the most common adverse events experienced by patients receiving THC or combined THC and CBD. Patients receiving THC may experience adverse cognitive effects and impairment in psychomotor skills, with implications for driving and some occupations, while CBD may help to lower the psychotropic effects of THC when used in combination. Studies on dependency and addiction in a medical context are limited, but have shown inconsistent findings regarding misuse potential. Generally, the recommended route of administration is oral ingestion, as smoking medicinal cannabinoid products potentially releases mutagenic and carcinogenic by-products. There are several potential drug-drug interactions and contraindications for cannabinoid-based medicines, which physicians should account for when making prescribing decisions. The available evidence shows that, as with any other class of pharmaceuticals, cannabinoid-based medicines are associated with safety risks which should be assessed in the context of potential therapeutic benefits. Each patient should be assessed on an individual basis and physicians must rely on informed, evidence-based decision-making when determining whether a cannabinoid-based medicine could be an appropriate treatment option.

Consensus and Controversies Between Pain and Addiction Experts on the Prevention, Diagnosis, and Management of Prescription Opioid Use Disorder.

OBJECTIVES: Prescription opioid use disorder (POUD) is an established public health crisis in many countries, and current evidence indicates it is a growing problem in Europe. Many specialists play a role, including pain and addiction medicine specialists, in the diagnosis and management of POUD, but neither group can fully address these patients' needs alone. The purpose of this consensus process was to bring together experts from pain and addiction medicine to examine the positions of both specialties. METHODS: In all, 13 international pain medicine, addiction medicine, and addiction psychiatry experts convened a meeting to formulate a set of consensus statements on the diagnosis and management of POUD. The statements were further refined by a wider group of 22 European expert clinicians. At a second meeting of all 35 participants, a set of controversy statements was also developed to recognize some of the key areas of divergent opinion. RESULTS/CONCLUSIONS: There was a high level of agreement between pain and addiction specialists. Key themes that emerged were the need to strengthen interdisciplinary communication, a desire for greater education and training for clinicians in both specialties, and mutual acknowledgment of the importance of multidisciplinary management of POUD. The blurred line between poorly managed pain and POUD was also a subject of much discussion, reflecting the difficulties in defining and diagnosing this complex condition.

Consensus practice guidelines on interventions for lumbar facet joint pain from a multispecialty, international working group.

BACKGROUND: The past two decades have witnessed a surge in the use of lumbar facet blocks and radiofrequency ablation (RFA) to treat low back pain (LBP), yet nearly all aspects of the procedures remain controversial. METHODS: After approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, letters were sent to a dozen pain societies, as well as representatives from the US Departments of Veterans Affairs and Defense. A steering committee was convened to select preliminary questions, which were revised by the full committee. Questions were assigned to 4-5 person modules, who worked with the Subcommittee Lead and Committee Chair on preliminary versions, which were sent to the full committee. We used a modified Delphi method, whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chair, who incorporated the comments and sent out revised versions until consensus was reached. RESULTS: 17 questions were selected for guideline development, with 100% consensus achieved by committee members on all topics. All societies except for one approved every recommendation, with one society dissenting on two questions (number of blocks and cut-off for a positive block before RFA), but approving the document. Specific questions that were addressed included the value of history and physical examination in selecting patients for blocks, the value of imaging in patient selection, whether conservative treatment should be used before injections, whether imaging is necessary for block performance, the diagnostic and prognostic value of medial branch blocks (MBB) and intra-articular (IA) injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for a prognostic block, how many blocks should be performed before RFA, how electrodes should be oriented, the evidence for larger lesions, whether stimulation should be used before RFA, ways to mitigate complications, if different standards should be applied to clinical practice and clinical trials and the evidence for repeating RFA (see table 12 for summary). CONCLUSIONS: Lumbar medial branch RFA may provide benefit to well-selected individuals, with MBB being more predictive than IA injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of more false-negatives. Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.

Interventions for myofascial pain syndrome in cancer pain: recent advances: why, when, where and how.

PURPOSE OF REVIEW: Pain is one of the most feared and most common symptoms of cancer, experienced by 38-85% of patients. Pain in terminally ill cancer patients is a multidimensional experience caused by a diverse array of factors - cancer itself, its treatment or other causes. Studies have shown a high incidence of myofascial pain syndrome (MPS) in patients with cancer and the knowledge of myofascial trigger points (MTrPs) is important to address and manage existing pain, and to prevent the recurrence of pain. This review aims to summarize recent advances in interventions for managing MPS in patients with cancer. RECENT FINDINGS: Database searches were conducted on MEDLINE, CINAHL, and Google Scholar to locate all studies published from inception until April 2019 using the keywords cancer pain, myofascial pain, TrPs with emphasis of any methodological quality that included interventions for MPS. MPS in advanced cancer patients are more commonly observed along with other cancer pains rather than independently with a prevalence of 11.9-48% in those patients diagnosed with cancer of head and neck and breast cancer. SUMMARY: Interventional therapies employing ultrasound guided injection of the MTrPs is gaining popularity in the management of MPS in cancer pain and may be a better alternative than the use of opioid analgesics in the multidisciplinary management.

Ethical justification of single-blind and double-blind placebo-controlled response tests in neuropathic pain and N-of-1 treatment paradigm in clinical settings.

At our center in the Netherlands, patients, who very often are treatment resistant to the analgesics recommended in the guidelines, suffering from symmetrical peripheral neuropathic pain are treated exclusively. We have developed a number of compounded topical formulations containing classical co-analgesics such as ketamine, baclofen, amitriptyline, and phenytoin for the treatment of neuropathic pain in treatment-resistant patients. In order to identify putative responders and exclude an (initial) placebo-response, we developed single-blind and double-blind placebo-controlled response tests. The test can be performed when the patient has a symmetrical polyneuropathy with a pain score difference of not more than 1 point on the 11-point numerical rating scale (NRS) between bilateral pain areas. On one area (eg, left foot) the placebo cream and on the other area (eg, right foot) the active cream will be applied. Within a time frame of 30 minutes, patients are considered responders if they rate a pain difference of at least 2 points on the NRS between the bilateral areas on which the active cream and placebo cream are applied. Response tests can be easily conducted during the first consultation. In this paper, we explore the ethical context of using a placebo in clinical practice in a single-blind and double-blind fashion to improve and individualize treatment of neuropathic pain outside a context of a formal clinical trial.

Standards for the management of cancer-related pain across Europe-A position paper from the EFIC Task Force on Cancer Pain.

BACKGROUND AND OBJECTIVE: Pain is a common symptom in patients who survive cancer and in those who live with progressive advanced disease. Evidence from meta-analyses suggests that pain remains poorly controlled for a large proportion of patients; barriers to good management include poor assessment of pain, inadequate support for patient self-management and late or inadequate access to strong opioid analgesia in those with advanced disease. METHODS: The European Pain Federation (EFIC) established a Task Force in 2017 which convened a European group of experts, drawn from a diverse range of relevant clinical disciplines, to prepare a position paper on appropriate standards for the management of cancer-related pain. The expert panel reviewed the available literature and made recommendations using the GRADE system to combine quality of evidence with strength of recommendation. The panel took into account the desirable and undesirable effects of the management recommendation, including the cost and inconvenience of each when deciding the recommendation. RESULTS AND CONCLUSIONS: The 10 standards presented are aimed to improve cancer pain management and reduce variation in practice across Europe. The Task Force believes that adoption of these standards by all 37 countries will promote the quality of care of patients with cancer-related pain and reduce unnecessary suffering. SIGNIFICANCE: Pain affects up to 40% of cancer survivors and affects at least 66% of patients with advanced progressive disease, many of whom experience poor pain control. These 10 standards are aimed to improve cancer pain management, promote the quality of care of patients and reduce variation across Europe.

Chronic postsurgical pain and cancer: the catch of surviving the unsurvivable.

PURPOSE OF REVIEW: Chronic postsurgical pain (CPSP) is an important and well recognized cause of much long-term suffering, which in some cases may be preventable and affects many people living with cancer. Unfortunately, general consensus is lacking as to how best reduce the risk of developing CPSP. RECENT FINDINGS: Cancer is now not always a short-lived, fatal disease and is now moving towards a chronic illness. Poorly managed perioperative pain is the greatest risk factor for CPSP. Recent trials have examined preventive strategies for CPSP associated with breast surgery and thoracotomy, two operations used in cancer treatment. Standard antinociceptive drugs, 5% lidocaine patches and ketamine do not prevent CPSP. The evidence for gabapentinoids is conflicting. Intravenous lidocaine and, separately, regional anaesthesia appear beneficial. SUMMARY: Well-managed pain, irrespective of technique, reduces the risk of CPSP. The literature is inconclusive regarding an 'optimal approach.' Regional anaesthesia, intravenous lidocaine and the aggressive management of perioperative pain using multimodal analgesia including antineuropathic pain agents such as gabapentinoids and certain antidepressants are recommended. Clinicians should not rely on general anaesthesia, opioids, NSAIDs and ketamine to prevent CPSP. A blanket approach using gabapentinoids for all patients undergoing major surgery is not indicated. Instead, the presence of perioperative neuropathic pain should be checked for regularly.

Nasopharyngeal Pneumococcal Colonization and Impact of a Single Dose of 13-Valent Pneumococcal Conjugate Vaccine in Indian Children With HIV and Their Unvaccinated Parents.

BACKGROUND: Human immunodeficiency virus (HIV) infection increases risk of invasive disease from Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV) prevent invasive disease and acquisition of vaccine type (VT) pneumococcus in the nasopharynx. OBJECTIVE: To look at the safety and impact of one dose of PCV13 on acquisition of VT pneumococcal carriage in Indian children with HIV. METHOD: We conducted a cohort study in families of HIV-infected children (CLH) and families of HIV-uninfected children (HUC) in West Bengal. All children received one dose of PCV13. Nasopharyngeal swabs were collected from children and parents at baseline and 2 months after vaccination. RESULT: One hundred and fifteen CLH and 47 HUC received one dose of PCV13. Fifty-eight percent of CLH were on antiretroviral therapy (ART), and the median nadir CD4 count was 287. There were no significant adverse events in either group. HUC had more VT colonization than CLH-55% versus 23% of all pneumococcal isolates. HIV infection doubled the risk of nonvaccine serotype colonization (P = 0.03). There was no difference in acquisition of VT isolates in CLH (4.4%) and HUC (4.5%) post-PCV13; however, older CLH (>5 years) had decreased clearance of VT strains. ART made no difference in pneumococcal colonization at baseline or after PCV13; however, CLH with higher nadir CD4 counts before starting ART were less likely to have VT colonization post-PCV13 (prevalence ratio, 0.2; 95% confidence interval: 0.1-0.5). CONCLUSION: While there was no difference in acquisition of VT nasopharyngeal carriage of pneumococcus in CLH and HUC after one dose of PCV13, earlier access to ART may impact response to PCV13 in CLH.

Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics.

Treatment of neuropathic pain using topical formulations is still in its infancy. Only few topical analgesic formulations have become available for clinical use, and among these, analgesic creams are still rare. This is unfortunate because analgesic creams offer a number of advantages over patches, such as convenience, ease of adapting the frequency of application, and dose, and "rubbing cream where it hurts" involves the patient much more in the therapeutic process compared to patches and other localized treatment modalities. Although the literature supporting the efficacy and safety of analgesic creams (mostly compounded) is growing since the last decade, most pain physicians have not yet noticed and appreciated the therapeutic potential and clinical value of these creams. This is most probably due to a prejudice that topical application should need to act transdermally, more or less as a slow-release formulation, such as in patches delivering opioids. We will discuss this prejudice and show that there are multiple important targets in the skin to be reached by topical analgesic or anti-inflammatory compounds, and that the keratinocyte is one of those targets. By specifically targeting the keratinocyte, analgesia seems possible, effective, and safe, and thus topical analgesic creams may hold promise as a novel treatment modality for neuropathic pain.