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Chronic low back pain can be caused by impaired control and degeneration of the multifidus muscles and consequent functional instability of the lumbar spine. Available treatment options have limited effectiveness and prognosis is unfavorable. We conducted an international randomized, double-blind, sham-controlled trial at 26 multidisciplinary centers to determine safety and efficacy of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms (clinicaltrials.gov identifier: NCT02577354). Two hundred four eligible participants with refractory mechanical (musculoskeletal) chronic LBP and a positive prone instability test indicating impaired multifidus control were implanted and randomized to therapeutic (N = 102) or low-level sham (N = 102) stimulation of the medial branch of the dorsal ramus nerve (multifidus nerve supply) for 30 minutes twice daily. The primary endpoint was the comparison of responder proportions (≥30% relief on the LBP visual analogue scale without analgesics increase) at 120 days. After the primary endpoint assessment, participants in the sham-control group switched to therapeutic stimulation and the combined cohort was assessed through 1 year for long-term outcomes and adverse events. The primary endpoint was inconclusive in terms of treatment superiority (57.1% vs 46.6%; difference: 10.4%; 95% confidence interval, -3.3% to 24.1%, P = 0.138). Prespecified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related adverse events (3.9%) compared favorably with other neuromodulation therapies for chronic pain.

Intrathecal trialing is used as a screening prognostic measure prior to intrathecal drug delivery system implant. The purpose of this study was to determine the efficacy of a continuous intrathecal infusion of an admixture of bupivacaine and fentanyl in patients with chronic low back pain. Patients with refractory chronic low back pain in the setting of previous lumbar spine surgery and/or chronic vertebral compression fracture(s) were enrolled in a randomized double blind cross-over study comparing saline infusion to infusion of a solution containing bupivacaine combined with low-dose fentanyl over a 14–18 hour period. The primary outcome measure was the change in pain intensity at the end of the screening trial. Patients who experienced significant pain reduction from either infusion relative to baseline pain were offered a permanent implant. In total, 36 patients were enrolled, with 31 patients trialed and 25 implanted. At the end of the screening trial, pain scores, at rest or with activity, decreased appreciably in both groups; however, significantly better improvements occurred in the fentanyl/bupivacaine group compared to saline both with activity and at rest (P = .016 and .006, respectively). Treatment order appeared to affect outcome with saline demonstrating a placebo response. At 12 months following implant, primary and secondary outcome measures continued to be significantly reduced from baseline. Continuous intrathecal delivery of a combination of low-dose fentanyl with bupivacaine is superior to saline in screening intrathecal trialing for back pain reduction. With longer term delivery, a sustained reduction of chronic low back pain was also observed.

This systematic review assessed design characteristics and reporting quality of published randomized clinical trials of spinal cord stimulation (SCS) for treatment of pain in adults and adolescents. The study protocol was registered with PROSPERO (CRD42018090412). Relevant articles were identified by searching the following databases through December 31, 2018: MEDLINE, Embase, WikiStim, The Cochrane Database of Systematic Reviews, and The Cochrane Central Register of Controlled Trials. Forty-six studies were included. Eighty-seven percent of articles identified a pain-related primary outcome. Secondary outcomes included physical functioning, health-related quality of life, and reductions in opioid use. Nineteen of the 46 studies prespecified adverse events as an outcome, with 4 assessing them as a primary outcome. Eleven studies stated that they blinded participants. Of these, only 5 were assessed as being adequately blinded. The number of participants enrolled was generally low (median 38) and study durations were short (median 12 weeks), particularly in studies of angina. Fifteen studies employed an intention-to-treat analysis, of which only seven specified a method to accommodate missing data. Review of these studies identified deficiencies in both reporting and methodology. The review's findings suggest areas for improving the design of future studies and increasing transparency of reporting. Perspective This article presents a systematic review of research methods and reporting quality of randomized clinical trials of SCS for the treatment of various pain complaints. The review identifies deficiencies in both methodology and reporting, which may inform the design of future studies and improve reporting standards.

Supplemental Digital Content is Available in the Text., Spinal cord stimulation (SCS) is an interventional nonpharmacologic treatment used for chronic pain and other indications. Methods for evaluating the safety and efficacy of SCS have evolved from uncontrolled and retrospective studies to prospective randomized controlled trials (RCTs). Although randomization overcomes certain types of bias, additional challenges to the validity of RCTs of SCS include blinding, choice of control groups, nonspecific effects of treatment variables (eg, paresthesia, device programming and recharging, psychological support, and rehabilitative techniques), and safety considerations. To address these challenges, 3 professional societies (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials, Institute of Neuromodulation, and International Neuromodulation Society) convened a meeting to develop consensus recommendations on the design, conduct, analysis, and interpretation of RCTs of SCS for chronic pain. This article summarizes the results of this meeting. Highlights of our recommendations include disclosing all funding source and potential conflicts; incorporating mechanistic objectives when possible; avoiding noninferiority designs without internal demonstration of assay sensitivity; achieving and documenting double-blinding whenever possible; documenting investigator and site experience; keeping all information provided to patients balanced with respect to expectation of benefit; disclosing all information provided to patients, including verbal scripts; using placebo/sham controls when possible; capturing a complete set of outcome assessments; accounting for ancillary pharmacologic and nonpharmacologic treatments in a clear manner; providing a complete description of intended and actual programming interactions; making a prospective ascertainment of SCS-specific safety outcomes; training patients and researchers on appropriate expectations, outcome assessments, and other key aspects of study performance; and providing transparent and complete reporting of results according to applicable reporting guidelines.

BackgroundCombining neuraxial opioids and local anesthetics in acute pain results in improved duration of analgesia and reduced dosages and adverse effects. Although commonly used in intrathecal drug delivery systems (IDDS) for chronic pain, the effectiveness of this admixture has not been examined specifically in relation to patient-controlled intrathecal analgesia (PCIA).MethodsIDDS-implanted chronic noncancer pain patients receiving opioids with bupivacaine (O + B) were randomized to receive either opioids without bupivacaine (O) or O + B in a double-blind manner, at IDDS refills, for one week and then crossed over to the other solution for another week. Primary outcome measures included numeric rating scale (NRS) pain scores before and within 30 minutes after PCIA boluses. Secondary outcome measures included average NRS scores and functional outcome measures.ResultsSeventeen patients were enrolled, and 16 patients completed the study. There were no differences in NRS scores before and after PCIA boluses between the O and O + B conditions, though pain scores improved significantly (average decrease in NRS scores: O 1.81 ± 1.47 vs O + B 1.87 ± 1.40, P = 0.688). No differences were noted in speed of onset or duration of analgesia. Although more patients subjectively preferred the O + B treatment, the difference was not statistically significant. No differences were noted in secondary outcome measures, with the exception of global impression of change having higher scores in O compared with O + B.ConclusionsAcutely removing bupivacaine from a chronic intrathecal infusion of opioids and bupivacaine in patients with chronic noncancer pain did not adversely affect PCIA effectiveness, nor did it affect speed of onset or duration of effect. These findings are divergent from those in acute pain and may have to do with study conditions and pain phenotypes.

BackgroundIt is nearly impossible to overestimate the burden of chronic pain, which is associated with enormous personal and socioeconomic costs. Chronic pain is the leading cause of disability in the world, is associated with multiple psychiatric comorbidities, and has been causally linked to the opioid crisis. Access to pain treatment has been called a fundamental human right by numerous organizations. The current COVID-19 pandemic has strained medical resources, creating a dilemma for physicians charged with the responsibility to limit spread of the contagion and to treat the patients they are entrusted to care for.MethodsTo address these issues, an expert panel was convened that included pain management experts from the military, Veterans Health Administration, and academia. Endorsement from stakeholder societies was sought upon completion of the document within a one-week period.ResultsIn these guidelines, we provide a framework for pain practitioners and institutions to balance the often-conflicting goals of risk mitigation for health care providers, risk mitigation for patients, conservation of resources, and access to pain management services. Specific issues discussed include general and intervention-specific risk mitigation, patient flow issues and staffing plans, telemedicine options, triaging recommendations, strategies to reduce psychological sequelae in health care providers, and resource utilization.ConclusionsThe COVID-19 public health crisis has strained health care systems, creating a conundrum for patients, pain medicine practitioners, hospital leaders, and regulatory officials. Although this document provides a framework for pain management services, systems-wide and individual decisions must take into account clinical considerations, regional health conditions, government and hospital directives, resource availability, and the welfare of health care providers.

A main cause of biodiversity loss is artificialization of the marine environment (IPBES 2019). With 39,400 km2 of coastal and marine areas already encroached upon by human infrastructure and an increasing demand on space due to the growing global population – projected to reach 9 billion by 2050 – it is clear that humanity needs to find ways to prevent its activities from endangering biodiversity. To this end, since the 1990s ecologists have been trying to develop a win-win approach that unites ecological engineering with civil engineering. Today, civil engineers have a responsibility to incorporate eco-design processes in all construction projects underway to ensure that the latter benefit both humans and nature. Then, the new challenge of the 21st century is to develop eco-designed concretes that, in addition to their usual properties, provide improved bioreceptivity in order to enhance marine biodiversity without affecting the structure durability. The aim of this study is to master, clarify and classify the intrinsic parameters that influence the bioreceptivity (biocolonization) of cementitious materials in the marine environment. By using biofilm-culture-method (biofilm quantification), this study shows that the use of rough surface or slag cement CEM III and the surface treatment with green formwork oil enhance the biocolonization of cementitious materials in the marine environment whereas the application of curing agent (hydrophobic surface coating) has the opposite effect. Among the influent parameters, surface roughness proved to be the factor that promotes biocolonization most effectively.

Since its original introduction several decades ago, peripheral nerve stimulation (PNS) of the craniofacial region has been traditionally performed using devices intended for spinal cord stimulation applications with inevitably high rate of technical challenges and procedural complications. The lower invasiveness of recently developed wireless neurostimulation systems makes them much better suited for craniofacial applications. Here, we discuss the preliminary clinical data from several published reports and the ongoing multicenter prospective study of wireless PNS in the craniofacial region. Advances in wireless transmission of electrical signals may make wireless neurostimulation even more attractive in the future. Since most of the evidence supporting PNS for facial pain comes from small subsets of the population, case series and case reports, there will need to be larger, randomized controlled trials with cost efficacy analyses in order to validate the role of wireless PNS as the standard of care.

ObjectiveTargeted intrathecal drug delivery (TIDD) is an effective interventional pain management modality often used in postlaminectomy patients with refractory chronic low back pain. A combination of intrathecal bupivacaine with an opioid is often used. However, intrathecal catheter tip granulomas have occurred with use of morphine or hydromorphone but generally not with fentanyl. The objective of this study was to compare the efficacy of TIDD using bupivacaine/fentanyl vs bupivacaine/hydromorphone in patients with chronic intractable low back pain postlaminectomy.Materials and MethodsA retrospective comparative analysis of consecutive patients with lumbar postlaminectomy syndrome who were trialed and later received TIDD with a combination of bupivacaine/hydromorphone or bupivacaine/fentanyl between June 2009 and May 2016 at a single tertiary medical center.ResultsWe identified a cohort of 58 lumbar postlaminectomy patients receiving a TIDD admixture of either hydromorphone/bupivacaine (30 patients) or low-dose fentanyl/bupivacaine (28 patients) with at least two years of follow-up. The fentanyl group had significantly lower baseline opioid consumption and a lower rate of intrathecal opioid dose escalation. Both groups had similar and significant reductions in pain scores over the two-year follow-up period. No granulomas were observed.ConclusionTIDD using a low-dose fentanyl admixture with bupivacaine in patients with postlaminectomy syndrome and refractory chronic low back pain results in similar pain relief to TIDD with hydromorphone and bupivacaine. Low-dose intrathecal fentanyl leads to a lower rate of opioid escalation and may be safer than hydromorphone.

Background and importance The implementation of an antimicrobial stewardship programme (AMSP) is very important but it has to be accompanied by personnel resources. It is therefore necessary to effectively use the time spent in the AMSP reviewing only those treatments that can be improved. Aim and objectives To implement a screening alert system (SAS) that shows only those antibiotic treatments that could be improved by meeting predefined conditions and to evaluate the SAS. Material and methods This was a quasi-experimental study. Using the information available in the electronic health record (EHR) and in the pharmacy and microbiology applications, we developed a computer tool that analysed hundreds of situations under pre-established conditions. For one month, before each AMSP team meeting, we recorded the total number of patients and prescribed antibiotics in the hospital compared with the number of treatments and patients that our system proposed to review. The main variable of our study was number of patients to check before and after the tool. Secondary variables included number of antibiotics to review. For the statistical analysis, the paired t test was used to determine if there were differences in the mean number of patients reviewed before and after using the SAS. The analyses were performed using SPSS/PC statistical programme (V.24.0 for Windows, SPSS Inc, Chicago, Illinois, USA). Results Seven services were included in the study: vascular surgery, cardiology, general surgery, geriatrics, internal medicine, neurology and traumatology. The number of antibiotics to review without the SAS in each AMSP team meeting was 21 (7–22) compared with 7 (3–9) when we used the SAS. Mean differences were found for patients to theoretically check before using the SAS (14±7 patients) compared with those who were actually checked after using the tool (5±3 patients) (mean difference 9 (95% CI 5 to 12 patients); p=0.000124). Conclusion and relevance This software allows the collection of information contained in different systems and displays only the relevant one in an organised view for the user. Limited personnel resources make the development of screening systems essential to optimise time and to prioritise which treatments need to be reviewed. References and/or acknowledgements 1. Rodriguez-Banos J, et al. Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH-SEIMC, SEFH and SEMPSPH consensus document. Farm Hosp 2012;36(1). No conflict of interest.

Since its original introduction several decades ago, peripheral nerve stimulation (PNS) of the craniofacial region has been traditionally performed using devices intended for spinal cord stimulation applications with inevitably high rate of technical challenges and procedural complications. The lower invasiveness of recently developed wireless neurostimulation systems makes them much better suited for craniofacial applications. Here, we discuss the preliminary clinical data from several published reports and the ongoing multicenter prospective study of wireless PNS in the craniofacial region. Advances in wireless transmission of electrical signals may make wireless neurostimulation even more attractive in the future. Since most of the evidence supporting PNS for facial pain comes from small subsets of the population, case series and case reports, there will need to be larger, randomized controlled trials with cost efficacy analyses in order to validate the role of wireless PNS as the standard of care.

Resume Introduction L’objectif principal de ce travail est d’etudier les facteurs personnels et familiaux intervenant dans le developpement de l’ennui et du risque d’addiction chez les adolescents libanais appartenant a un milieu socioeconomique eleve. Methodologie Quatre-cent quatorze eleves ont ete selectionnes pour repondre a 6 echelles en rapport avec l’ennui, le risque d’addiction, la recherche de sensations fortes, l’estime de soi, l’efficacite personnelle et les pratiques de parentage. Resultats et discussion L’ennui et le risque d’addiction ne sont pas lies (p = 0,259). La relation entre la recherche de sensations et le risque d’addiction est forte (p = 0,001). Le controle parental n’est pas directement correle au risque d’addiction (p = 0,317). C’est l’affection qui le diminue significativement (p = 0,096). Conclusion L’autorite et l’affection des parents sont des facteurs familiaux qui interviennent positivement dans le developpement des adolescents.

Summary Background Quality approach within a mental health facility is essential to enhance safety of care. Among the determinants of quality of care are: patient participation, assessment methods, and appreciate vulnerability. Methods A survey with psychiatrists using a questionnaire and semi-directive interviews aiming to determine the assimilation of the concept of informed consent in psychiatric care and identification of the obstacles that might hinder care. This was coupled with the auditing of patients’ medical records in the Lebanese psychiatric care centres. Results & discussion Data analysis revealed a discrepancy of the value of the human person as potential patient. Our study showed: (i) a misunderstanding of the principle of autonomy endorsed by the marginalization practiced on the vulnerable patients, (ii) absence of a written form of informed consent, (iii) absence of feasible capacity assessment policies and a complete reliance on clinical judgment and/or tools not adapted to the Lebanese patient, (iv) absence of protective legislations or guidelines that target psychiatric patients, (v) a lack of doctor–patient information exchange and follow-up. Conclusion Informed consent can be challenging in psychiatric disorders. We have moved to a new concept of the Human Person being capable of making his/her own decisions. Vulnerability is rejected in the current practice.

Highlights • Trichobezoar is a rare disorder that almost exclusively affects young females. • We present a review of the main characteristics of this disease with a case of gastric outlet obstruction. • A treatment should be coupled to psychiatric evaluation and therapy to prevent recurrence., Introduction Bezoars are concretions of foreign indigestible material accumulating in the gastrointestinal tract leading to intraluminal mass formation that impairs the gastrointestinal motility and can lead to gastric obstruction of the small or the large bowel. There are different types of bezoars, named according to the material they are made of. These include phytobezoar, lactobezoar, pharmacobezoar, trichobezoar, and polybezoar. Trichobezoars (hair ball) are usually located in the stomach but may extend through the pylorus into the duodenum and small bowel (Rapunzel syndrome). Case presentation Herein, we report a case of a young adult female known to have a long-standing trichophagia who presented with gastric outlet obstruction due to a large trichobezoar. Endoscopy revealed a large and hard gastric trichobezoar not amenable to endoscopic retrieval leading to surgical extraction as a last resort. Discussion They are almost always associated with trichotillomania and trichophagia or other psychiatric disorders. Trichobezoar can be treated either surgically by laparotomy/laparoscopy or by endoscopic intervention. Conclusion Treatment should be coupled to psychiatric evaluation and therapy to prevent recurrence.

Massage, in the form of cyclic compressive loading (CCL), is associated with multiple health benefits, but its potential anabolic effect on atrophied muscle has not been investigated. We hypothesized that the mechanical activity associated with CCL induces an anabolic effect in skeletal muscle undergoing regrowth after a period of atrophy. Fisher/Brown Norway rats at 10 months of age were hind limb unloaded for a period of 2 weeks. The rats were then allowed reambulation with CCL applied at a 4.5 N load at 0.5 Hz frequency for 30 min every other day for 4 bouts during a regrowth period of 8 days. Muscle fibre cross sectional area was enhanced by 18% with massage during regrowth compared to reloading alone, and this was accompanied by elevated myofibrillar and cytosolic protein as well as DNA synthesis. Focal adhesion kinase (FAK) phosphorylation indicated that CCL increased mechanical stimulation, while a higher number of Pax7+ cells likely explains the elevated DNA synthesis. Surprisingly, the contralateral non-massaged limb exhibited a comparable 17% higher muscle fibre size compared to reloading alone, and myofibrillar protein synthesis, but not DNA synthesis, was also elevated. We conclude that massage in the form of CCL induces an anabolic response in muscles regrowing after an atrophy-inducing event. We suggest that massage can be used as an intervention to aid in the regrowth of muscle lost during immobilization. This article is protected by copyright. All rights reserved

Introduction Intrathecal therapy is an important part of the pain treatment algorithm for chronic disease states. The use of this option is a viable treatment strategy, but it is inherent for pain physicians to understand risk assessment and mitigation. In this manuscript, we explore evidence and mitigating strategies to improve safety with intrathecal therapy. Methods A robust literature search was performed covering January 2011 to October 9, 2016, in PubMed, Embase, MEDLINE, Biomed Central, Google Scholar, Current Contents Connect, and International Pharmaceutical Abstracts. The information was cross-referenced and compiled for evidence, analysis, and consensus review, with the intent to offer weighted recommendations and consensus statements on safety for targeted intrathecal therapy delivery. Results The Polyanalgesic Consensus Conference has made several best practice recommendations to improve care and reduce morbidity and mortality associated with intrathecal therapy through all phases of management. The United States Prevention Service Task Force evidence level and consensus strength assessments are offered for each recommendation. Conclusion Intrathecal therapy is a viable and relatively safe option for the treatment of cancer- and noncancer-related pain. Continued research and expert opinion are required to improve our current pharmacokinetic and pharmacodynamic model of intrathecal drug delivery, as this will undoubtedly improve safety and efficacy.

Pain is a frequently reported symptom in dry eye disease (DED). We examine the factors associated with ocular pain severity and patient-reported improvement in ocular pain to commonly used dry eye and pain treatments.Cross-sectional study of patients presenting for dry eye management. Demographics, ocular and medical history, OSDI, numeric pain scale, pain descriptors, and subjective response to tried eye drop, systemic, and non-pharmacologic treatments were collected. Statistical analysis was performed to identify differential treatment response in patients with various pain levels using the non-parametric test for trend.144 patients were categorized into 4 groups according to reported pain severity. Increasing pain was significantly associated with younger age, history of refractive surgery, higher OSDI score, and less likelihood of corneal staining. Patients with higher pain intensity were more likely to report a history of fibromyalgia, depression, anxiety, and migraine. Patients with greater pain severity were less responsive to treatment with artificial tears (p 0.001), lubricating ointment (p = 0.002), steroid eye drops (p = 0.03), cyclosporine 0.05% (p = 0.03), 20% autologous serum tears (p = 0.01), hot compresses (p = 0.04), lid hygiene (p = 0.002) and punctal occlusion (p = 0.03).Dry eye patients with severe ocular pain often have associated psychological and systemic pain conditions. Treating the underlying DED is beneficial in reducing ocular pain, however the low rate of a satisfactory response highlights the need for further investigation of effective therapies. Cross-sectional studies can provide guidance in the treatment of patients with dry eye-related ocular pain and guide future prospective studies on potentially effective therapies.

Chronic low back pain (CLBP) conditions are highly prevalent and constitute the leading cause of disability worldwide. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the US Food and Drug Administration and the American Pain Society (APS), have combined to create the ACTTION-APS Pain Taxonomy (AAPT). The AAPT initiative convened a working group to develop diagnostic criteria for CLBP. The working group identified 3 distinct low back pain conditions which result in a vast public health burden across the lifespan. This article focuses on: 1) the axial predominant syndrome of chronic musculoskeletal low back pain, 2) the lateralized, distally-radiating syndrome of chronic lumbosacral radicular pain 3) and neurogenic claudication associated with lumbar spinal stenosis. This classification of CLBP is organized according to the AAPT multidimensional framework, specifically 1) core diagnostic criteria; 2) common features; 3) common medical and psychiatric comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors. PERSPECTIVE: An evidence-based classification of CLBP conditions was constructed for the AAPT initiative. This multidimensional diagnostic framework includes: 1) core diagnostic criteria; 2) common features; 3) medical and psychiatric comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors.

OBJECTIVES The local anesthetic bupivacaine is a common analgesic adjuvant medication used in combination with opioids in intrathecal drug delivery systems (IDDSs). While the acute effects of spinal bupivacaine injection on blood pressure (BP) have been studied, there is a dearth of data regarding long-term effects of continuous intrathecal bupivacaine infusion. MATERIALS AND METHODS A retrospective review of all noncancer pain patients receiving bupivacaine through IDDSs from January 2013 to November 2017 was performed. Blood pressure values before implantation, and after implant at the 1-week, 3-month, 6-month and 1-year time points are recorded as well as corresponding bupivacaine and opioid doses in the IDDS. RESULTS Eighty-two patients were included in the study; median patient age was 64 years and intrathecal catheter tips were located predominantly in the lower thoracic spine. Significant decreases in systolic blood pressure (SBP) and mean arterial pressure (MAP) relative to baseline occurred in patients receiving chronic lower thoracic intrathecal bupivacaine delivery at 3, 6, and 12 months post-implant (-12.96 ± 18.21; p < 0.001 and - 6.38 ± 12.04; p < 0.001, respectively). The only significant decrease in DBP was observed at 1 year post-implant (-3.09 ± 11.76; p < 0.05). Similar decreases in BP values occurred in patients with or without hypertension. CONCLUSIONS Long-term thoracic intrathecal infusion of bupivacaine likely exerts a lowering effect on BP, primarily because of a significant decrease in SBP. This effect is likely due to efferent sympathetic blockade by bupivacaine.

Pain medicine is a growing and evolving field, yet one of the most challenging aspects continues to be treating patients with cancer related pain. These patients’ pain is often complex and may be a result of different processes. Cancer pain may either be nociceptive, resulting from damage to tissues, or neuropathic, due to damage or dysfunction of the nervous system. In many cases it is a combination of the two. Analgesia can be accomplished in several ways, including systemic analgesic medications, surgical intervention, radiation, neurolysis or other interventional radiologic techniques. In this chapter we will focus on surgical options as well as non-neurolytic radiologic approaches.

Ziconotide is a non-opioid, potent intrathecal analgesic with mechanism of action involving interruption of spinal neurotransmission approved by the Food and Drug Administration in 2004 for the treatment of severe refractory chronic pain. Presented are pertinent diagnoses and proper patient selection for ziconotide therapy, guidelines for treatment, and current evidence for analgesic efficacy and safety for intrathecal use.

Tuberculosis (TB) presents new challenges as a global public health problem, especially at a time of increasing threats to some particular patients due to Human Immunodeficiency Virus (HIV) infection and multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. The World Health Assembly strives to reduce TB deaths by 95% and to decrease TB incidence by 95% by 2035. However, new approaches are necessary in order to attain these objectives. Such approaches include active ascertainment of cases in high risk populations, increasing the availability of accurate point-of-care testing, rapid detection of drug resistance, novel vaccines, and new prophylaxis and treatment regimens (particularly for MDR and XDR TB). The ultimate objective of those programs is to develop highly effective drug regimens that can achieve high cure rates regardless of strains’ resistance patterns.

Background Intrathecal drug delivery therapy has been used effectively in treating patients with intractable chronic pain. The development of an intrathecal catheter tip granuloma (ICTG) related to delivery of intrathecal opiates is a relatively infrequent, but potentially devastating complication. While there are many morphine-related ICTG cases described, reports of hydromorphone-related ICTG are limited. In addition, studies suggest a strong correlation between the use of higher doses and concentrations of intrathecal opiates and ICTG formation. Objective The objective of this study is to determine the incidence and the association of intrathecal hydromorphone dose, concentration, duration of treatment and concomitant agents with ICTG formation. Study Design This is a retrospective analysis of 101 consecutive patients implanted with intrathecal infusion delivery devices. Data were collected from chart review, and records of pump refills from the division of Pain Medicine of University Hospitals or outsourced to a home pump refill service. Results From a cohort of 101 consecutively implanted patients, 69 were treated with intrathecal hydromorphone and followed up postimplant for an average of 33.5 ± 24 months (range 0–93 months; 95% CI of 27–39 months). The incidence of ICTG in our patient population was 8.7% during this period of time postimplant with mean time to granuloma detection 35.1 ± 7.9 months. Patients developing granuloma (n = 6) were treated with a combination of intrathecal hydromorphone and bupivacaine infusion. Exposure time to intrathecal agents was not different between the granuloma and nongranuloma group. Monthly dose increase of hydromorphone was higher in granuloma group vs. non-granuloma group (58 ± 34 mcg/month n = 6 vs. 25 ± 8 mcg/month n = 63). Four out of six granuloma cases occurred with low dose and concentration of IT hydromorphone (160–370 mcg/day; 0.75–1.0 mg/mL concentration). Intrathecal bupivacaine dose was not different between groups. A subset of patients was treated with intrathecal fentanyl and bupivacaine. No intrathecal granulomas occurred in this patient cohort. Conclusion This is the first clinical report demonstrating an association of hydromorphone with intrathecal granulomas, particularly at low doses and concentrations of hydromorphone. This study supports the notion that using low dose of IT opioids might not protect against ICTG development but that the level of exposure and type of opioid used in IT space might be highly correlated with ICTG development. Further research and recommendations related to chronic intrathecal opioid infusions are necessary to raise awareness of significant incidence of ICTG and development of tests to isolate patient populations at high risk.

Introduction Intrathecal therapy [IT] has become an important modality for treatment of intractable cancer and noncancer pain although adverse events limit its effectiveness. Objective The purpose of this case series was to report and discuss the lower limb edema from IT hydromorphone and morphine therapy and its resolution or nonrecurrence upon rotating the IT solution to fentanyl. Methods Case series. Results Five patients, 4 women and 1 man, 55 to 67 years old implanted with IT delivery device systems [IDDS] were treated with continuous infusion of hydromorphone [4 subjects] at 95 ± 40 mcg/24 hours and morphine [1 subject] at 0.67 mg/24 hours. They developed peripheral edema of the lower extremities at an average of 4.2 months [mean, range 1 to 8 months] after implant. In 4 subjects, peripheral edema resolved by changing the IT agent to fentanyl. The mean time for complete resolution of edema was 50 ± 20 days while patients were treated with continuous infusion of fentanyl. It should be noted that all patients were receiving bupivacaine in addition to the IT opioid. In one subject, infusion of IT saline resulted in faster resolution of peripheral edema. Conclusion Peripheral lower extremity edema may occur in patients treated with IT infusion of hydromorphone or morphine, even at low doses. This report presents, to the best of our knowledge, the first case series describing the benefit of IT opioid rotation to fentanyl in alleviating challenging lower extremity edema from IT hydromorphone and morphine.

Treatment of noncancer pain with intrathecal opioids in patients with chronic intractable pain has been an important breakthrough in the pain management field over the past four decades [1]. It has been increasingly used in patients with chronic intractable pain in whom conservative therapies have failed, or those who cannot tolerate side effects of oral opioid medications. Delivering opioids within the cerebrospinal fluid allows the administration of only a small amount of opioid to provide analgesia without the overt systemic side effects that may be experienced when the drugs are given orally or intravenously. A number of reviews have documented the safety and efficacy of intrathecal drug delivery (IDD) therapy in patients with chronic pain. IDD therapy for noncancer pain is effective, cost-neutral, and appropriate [1]. Although the overall safety of IDD systems has been documented, there have been case reports of adverse events. Most notably, respiratory depression with concomitant use of central nervous system depressant medications such as benzodiazepines has been implicated in IDD-related fatalities [1]. Potential problems also can occur during the pump refill, such as a pocket fill. Although respiratory depression is rare in patients who are opioid tolerant, missed refill dates may predispose the patient to an opioid-naive state in which a medication refill of morphine at the same concentration and dose may result in delayed respiratory depression [2]. (Early respiratory depression has not been reported with morphine.) A number of other important matters need particular care and attention during the refill and maintenance process to avoid likely complications. Proper physician training and understanding of the pharmacology and dosing of intrathecal medications is imperative to limit life-threatening complications including pocket fills and respiratory depression.

Implantation of an intrathecal drug delivery system (IDDS) requires a comprehensive knowledge of the process, including selection of appropriate patients and indications for implantation, the method of performing a trial, the surgical procedure of implantation, and the choice of pharmacologic agents. Additionally, knowledge of cerebrospinal fluid (CSF) dynamics plays an important role in determining IDDS success. This chapter addresses the pharmacologic fundamentals of the intrathecal agents that are typically used in an IDDS.

This chapter covers the troubleshooting management of an intrathecal drug delivery system (IDDS) when it loses its efficacy. The potential scenarios to consider when IDDS efficacy is lost are problems with the pump device or the catheter system, or the development of tolerance. Of the first two situations, catheter-related dysfunction is more frequent. Potential catheter-related problems include catheter tip migration, kink or occlusion, fracture of the catheter, inadvertent puncture, or loosening of connections. Long-term follow-up studies have shown 37–55% malfunction for catheter and/or pump malfunction [1]. The relative frequency of catheter-related complications include disconnection from the pump (6–10%); leak from breakage, cut, or puncture (5–16%); and catheter tip migration (3–11%) [1]. The same study reported pump malfunction in less than 14%. A more recent study of intrathecal therapy showed that 15.8% had catheter-related problems within 2 years. Of these, 5% were catheter migrations, 5% were kinks, and 5% were leaks [2]. The same study also showed 10.5% pump malfunction. In another recent series of 144 pumps, there was pump failure in 9.03% [3].

Detection of environmental threats and noxious stimuli is vital to an organism’s survival and well-being. Without this ability, protective behaviors could not be formed against potentially harmful situations, which may become life threatening. The role of nociceptors as specialized sensory neurons is to detect the environmental threats presented as intense stimuli and relay the information to neural circuits to formulate a reaction to avoid them. Nociceptive pain serves as an alarm system. Acute nociceptive pain serves not only to trigger early withdrawal responses and enhance wound healing but also to initiate affective responses and modify future behaviors. Perception of pain is a complex experience, involving transduction of various noxious environmental stimuli (thermal, mechanical, environmental, and chemical) through polymodal peripheral receptors; action potentials ensue and relay the signal to the central nervous system to be processed into cognitive and emotional experiences by the brain. Noxious stimuli generating nociceptive pain are generally temporary. However, persistent pain beyond the resolution of initial stimuli and tissue healing is maladaptive and could lead to chronic pain. Intense and prolonged pain transmission associated with chronic pain is associated with sensory neuronal plasticity which results in changes in pain transmission pathways of both the peripheral and central nervous systems. This chapter focuses on the neurophysiology of pain transmission and processing. Particular emphasis is directed to receptors, sensory neurons, and mechanisms modulating noxious stimulation.

Neuralgia is defined as an intense burning or stabbing pain caused by irritation of or damage to a nerve. Neuralgia usually follows an injury to the structure of the nerve that can result in atypical firing, neuroma formation, reorganization of nerve fiber interconnections, or central neuroplasticity that leads to chronic neuropathic pain. The medical concept of neuralgia was initially discussed by Francois Chaussier in 1801 as the term “nevralgie” to indicate “an affection of one or more nerves causing pain which is usually of intermittent but frequently intense character.” Peripheral neuralgias and entrapment neuropathies are often diagnosed on clinical grounds. Just as there are multifactorial etiologies, there are many treatment modalities directed to the pathophysiology. A discussion of common peripheral neuralgias and entrapment neuropathies ensues.

The management of chronic pain is a clinically complex and challenging task for practitioners. A strategy for chronic pain management begins with a thorough understanding of the pathophysiology of different types of pain. A careful evaluation of the patient with a history and physical exam will be helpful to differentiate types of pain, identify biopsychosocial contributing factors, assess the functional and emotional burden of pain, devise a multimodal treatment plan, and develop goals of therapy. Commonly employed management strategies include physical therapy, behavioral techniques, complementary approaches, medications, interventional procedures, and neuromodulation modalities. With healthcare costs estimated at over $300 billion for chronic pain in America, it is important that we only offer patients treatment that is efficient, safe, patient centered, and produces outcomes that can be measured.

The appropriate selection of medications is key to the accomplishment of symptom control when using an intrathecal drug delivery system (IDDS). Medications must be preservative-free, safe for intrathecal use, and efficacious. For control of chronic pain, a number of intrathecal agents are commonly used, including opioids, the local anesthetic bupivacaine, the peptide ziconotide, and clonidine. Morphine and ziconotide are the only medications approved by the US Food and Drug Administration (FDA) for the intrathecal treatment of chronic pain. Baclofen is the only FDA-approved medication for treatment of spasticity using intrathecal drug delivery (IDD).

Background Occipital neuralgia (ON) is a disorder characterized by sharp, electrical, paroxysmal pain, originating from the occiput and extending along the posterior scalp, in the distribution of the greater, lesser, and/or third occipital nerve. Occipital nerve stimulation (ONS) constitutes a promising therapy for medically refractory ON because it is reversible with minimal side effects and has shown continued efficacy with long-term follow-up. Objective To conduct a systematic literature review and provide treatment recommendations for the use of ONS for the treatment of patients with medically refractory ON. Methods A systematic literature search was conducted using the PubMed database and the Cochrane Library to locate articles published between 1966 and April 2014 using MeSH headings and keywords relevant to ONS as a means to treat ON. A second literature search was conducted using the PubMed database and the Cochrane Library to locate articles published between 1966 and June 2014 using MeSH headings and keywords relevant to interventions that predict response to ONS in ON. The strength of evidence of each article that underwent full text review and the resulting strength of recommendation were graded according to the guidelines development methodology of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Guidelines Committee. Results Nine studies met the criteria for inclusion in this guideline. All articles provided Class III Level evidence. Conclusion Based on the data derived from this systematic literature review, the following Level III recommendation can be made: the use of ONS is a treatment option for patients with medically refractory ON.

Objectives Intrathecal (IT) trial is a prognostic interventional pain management procedure employed to determine the potential success of treating intractable pain with an implantable infusion device system. There is a dearth of data regarding trials with continuous infusion of combination therapy (e.g. opioid combined with local anesthetic). The objective of the this study was to determine the overall outcomes of continuous infusion IT trials and factors influencing long-term success of IT therapy in patients with chronic intractable pain post-laminectomy. Materials and methods This is a retrospective analysis of all patients with lumbar failed back surgery syndrome (FBSS) who were trialed with a combination of hydromorphone and bupivacaine with a temporary externalized IT catheter from March 2007 to June 2014. Results From a cohort of 62 patients fulfilling the inclusion criteria, 54 (87.10%) patients had successful IT trials. No significant differences were found between successful and failed trial patients with regards to age, sex, pre-trial pain numeric rating scale scores, pre-trial morphine equivalent daily dose, or trial dosages. Significant positive correlations were found between pretrial oral opioid intake and end of trial hydromorphone dose and hydromorphone dose escalation at 12 months and 24 months. Conclusions Patients with refractory low back pain due to FBSS who underwent successful combination IT trial with hydromorphone and bupivacaine infused through a temporary IT catheter had significantly improved pain intensity scores following permanent implant. Higher pre-trial MEDD was correlated with higher trial and post-implant opioid doses and higher rates of opioid dose escalation post-implant.

Introduction Surgical site infection is a potential complication of spinal cord stimulator (SCS) implantation. Current understanding of the epidemiology, diagnosis, and treatment of these infections is based largely on small clinical studies, many of which are outdated. Evidence-based guidelines for management of SCS-related infections thus rely instead on expert opinion, case reports, and case series. In this study, we aim to provide a large scale retrospective study of infection management techniques specifically for SCS implantation. Methods A multicenter retrospective study of SCS implants performed over a seven-year period at 11 unique academic and non-academic institutions in the United States. All infections and related complications in this cohort were analyzed. Results Within our study of 2737 SCS implant procedures, we identified all procedures complicated by infection (2.45%). Localized incisional pain and wound erythema were the most common presenting signs. Laboratory studies were performed in the majority of patients, but an imaging study was performed in less than half of these patients. The most common causative organism was Staphylococcus aureus and the IPG pocket was the most common site of an SCS-related infection. Explantation was ultimately performed in 52 of the 67 patients (77.6%). Non-explantation salvage therapy was attempted in 24 patients and was successful in resolving the infection in 15 patients without removal of SCS hardware components. Discussion This study provides current data regarding SCS related infections, including incidence, diagnosis, and treatment.