Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes.

PURPOSE: In patients with metastatic prostate cancer (mPC), ATM and BRCA2 mutations dictate differences in PARPi inhibitor response and other therapies. We interrogated the molecular features of ATM- and BRCA2-mutated mPC to explain the divergent clinical outcomes and inform future treatment decisions. EXPERIMENTAL DESIGN: We examined a novel set of 1,187 mPCs after excluding microsatellite-instable (MSI) tumors. We stratified these based on ATM (n = 88) or BRCA2 (n = 98) mutations. As control groups, mPCs with mutations in 12 other homologous recombination repair (HRR) genes were considered non-BRCA2/ATM HRR-deficient (HRDother, n = 193), whereas lack of any HRR mutations were considered HRR-proficient (HRP; n = 808). Gene expression analyses were performed using Limma. Real-world overall survival was determined from insurance claims data. RESULTS: In noncastrate mPCs, only BRCA2-mutated mPCs exhibited worse clinical outcomes to AR-targeted therapies. In castrate mPCs, both ATM and BRCA2 mutations exhibited worse clinical outcomes to AR-targeted therapies. ATM-mutated mPCs had reduced TP53 mutations and harbored coamplification of 11q13 genes, including CCND1 and genes in the FGF family. BRCA2-mutated tumors showed elevated genomic loss-of-heterozygosity scores and were often tumor mutational burden high. BRCA2-mutated mPCs had upregulation of cell-cycle genes and were enriched in cell-cycle signaling programs. This was distinct from ATM-mutated tumors. CONCLUSIONS: Tumoral ATM and BRCA2 mutations are associated with differential clinical outcomes when patients are stratified by treatments, including hormonal or taxane therapies. ATM- and BRCA2-mutated tumors exhibited differences in co-occurring molecular features. These unique molecular features may inform therapeutic decisions and development of novel therapies.

A Complex Regional Pain Syndrome Imaging Journal: Case Report.

Complex regional pain syndrome (CRPS) poses a diagnostic and management challenge for many clinicians, particularly when disease symptomatology waxes and wanes. Monitoring symptom variations with digital and infrared thermal images allows for more accurate evaluation of disease progression overtime. We present the case of a patient who developed CRPS and catalog his symptoms using a digital and infrared thermal imaging diary. The images were instrumental toward establishing the initial diagnosis of CRPS, monitoring disease progression, and assessing response to treatment. We discuss the present understanding of infrared thermography in CRPS and advocate for its routine use at the beside.

Rise of multiattribute decision-making in combating COVID-19: A systematic review of the state-of-the-art literature.

Considering the coronavirus disease 2019 (COVID-19) pandemic, the government and health sectors are incapable of making fast and reliable decisions, particularly given the various effects of decisions on different contexts or countries across multiple sectors. Therefore, leaders often seek decision support approaches to assist them in such scenarios. The most common decision support approach used in this regard is multiattribute decision-making (MADM). MADM can assist in enforcing the most ideal decision in the best way possible when fed with the appropriate evaluation criteria and aspects. MADM also has been of great aid to practitioners during the COVID-19 pandemic. Moreover, MADM shows resilience in mitigating consequences in health sectors and other fields. Therefore, this study aims to analyse the rise of MADM techniques in combating COVID-19 by presenting a systematic literature review of the state-of-the-art COVID-19 applications. Articles on related topics were searched in four major databases, namely, Web of Science, IEEE Xplore, ScienceDirect, and Scopus, from the beginning of the pandemic in 2019 to April 2021. Articles were selected on the basis of the inclusion and exclusion criteria for the identified systematic review protocol, and a total of 51 articles were obtained after screening and filtering. All these articles were formed into a coherent taxonomy to describe the corresponding current standpoints in the literature. This taxonomy was drawn on the basis of four major categories, namely, medical (n = 30), social (n = 4), economic (n = 13) and technological (n = 4). Deep analysis for each category was performed in terms of several aspects, including issues and challenges encountered, contributions, data set, evaluation criteria, MADM techniques, evaluation and validation and bibliography analysis. This study emphasised the current standpoint and opportunities for MADM in the midst of the COVID-19 pandemic and promoted additional efforts towards understanding and providing new potential future directions to fulfil the needs of this study field.

Comparison between acupuncture therapy and gabapentin for chronic pain: a pilot study.

BACKGROUND: We examined whether the effect of true electroacupuncture on pain and functionality in chronic pain participants can be differentiated from that of medication (gabapentin) by analyzing quantitative sensory testing (QST). METHODS: We recruited chronic back and neck pain participants who received six sessions (twice weekly) of true electroacupuncture versus sham electroacupuncture or 3 weeks of gabapentin versus placebo treatment. QST profiles, pain scores, and functionality profile were obtained at baseline (visit 1) and after three sessions (visit 4) or six sessions (visit 7) of acupuncture or 3 weeks of gabapentin or placebo. RESULTS: A total of 50 participants were analyzed. We found no differences in QST profile changes (p = 0.892), pain reduction (p = 0.222), or functionality (p = 0.254) between the four groups. A major limitation of this pilot study was the limited number of study participants in each group. CONCLUSION: This pilot study suggests that a large-scale clinical study with an adequate sample size would be warranted to compare acupuncture and medication therapy for chronic pain management. TRIAL REGISTRATION NUMBER: NCT01678586 (ClinicalTrials.gov).

Fantastic Four: Age, Spinal Cord Stimulator Waveform, Pain Localization and History of Spine Surgery Influence the Odds of Successful Spinal Cord Stimulator Trial.

BACKGROUND: There is a dearth in our understanding of the factors that are predictive of successful spinal cord stimulator (SCS) trials and eventual conversion to permanent implants. Knowledge of these factors is important for appropriate patient selection and treatment optimization. OBJECTIVES: Although previous studies have explored factors predictive of trial success, few have examined the role of waveform in trial outcomes. This study sought to establish the relationship of neuraxial waveform and related measures to trial outcomes. STUDY DESIGN: This study used a retrospective chart review design. METHODS: Data were retrospectively collected on 174 patients undergoing SCS trials upon institutional review board approval of the study protocol. Indications for SCS were: complex regional pain syndrome, failed back surgery syndrome with radicular symptoms, peripheral neuropathy, and axial low back pain. Descriptive statistics and logistic regression analyses were used to assess the association of demographic and clinical variables with SCS trial outcomes. RESULTS: The study population comprised 56% women, had a median age of 55 (interquartile range [IQR], 44-64), and 32 of 174 (18%) patients failed SCS trials. Individuals with successful trials (>= 50% pain relief) were significantly younger and had a median age of 54 years (IQR, 42-60) compared to those who failed SCS trials (median age 66 years; IQR, 50-76; P = .005). Adjusting for age, gender, number of leads, pain category, and diagnoses: surgical history (odds ratio [OR] = 4.4; 95% confidence interval [CI], 1.3-15.8) and paresthesia-based tonic-stimulation (OR = 10.3; 95% CI, 1.7-62.0), but not burst or high frequency, were significantly associated with successful trials. Of note, the number of leads (whether dual or single), pain duration, characteristics, and category (nociceptive vs neuropathic) were not significant factors. An interaction between surgical spine history and lower extremity pain was significantly associated with a positive trial (P = .005). LIMITATIONS: This study was limited by its retrospective nature and focus on a patient population at a single major academic medical center. CONCLUSIONS: Paresthesia-based tonic stimulation, age, and surgical history have significant effects on SCS trials. Prospective and randomized controlled studies may provide deeper insights regarding impact on costs and overall outcomes.IRB Approval #: 2018P002216. KEY WORDS: Pain duration, pain location, spinal cord stimulator trial, stimulator waveform, surgical history.

Management of incidental lumboiliac hernia during spinal cord stimulator implant: a case report.

Lumboiliac or lumbar hernia is a rare defect in the posterolateral abdominal wall that may be inadvertently misidentified and interfere with the implantable pulse generator (IPG) portion of spinal cord stimulator (SCS) implants. We report the case of a 54-year-old Caucasian man with an incidental finding of a lumboiliac hernia in the inferior lumbar triangle of Petit with placement of an IPG in a SCS implant. With the assistance of surgical colleagues, the correct diagnosis was made intraoperatively. We describe the operative repair of the lumboiliac hernia with a synthetic mesh. A new IPG pocket was created above the mesh prior to proceeding with IPG placement. No recurrence of the hernia defect was observed on 2-month follow-up. It is important that pain physicians and neurosurgeons who perform SCS implants are aware of lumboiliac hernias to avoid potential diagnostic or management errors. Lumboiliac hernias should be included on the differential diagnosis of lumbar or flank masses. Confirmation with imaging may be necessary and definitive surgical treatment should be pursued.

Spinal Cord Stimulation vs Conventional Therapies for the Treatment of Chronic Low Back and Leg Pain: A Systematic Review of Health Care Resource Utilization and Outcomes in the Last Decade.

OBJECTIVE: The purpose of this review is to critically appraise the literature for evidence supporting the health care resource utilization and cost-effectiveness of spinal cord stimulation (SCS) compared with conventional therapies (CTs) for chronic low back and leg pain. METHODS: The PubMed, MEDLINE, Embase, CINAHL, and Rehabilitation & Sports Medicine databases were searched for studies published from January 2008 through October 2018, using the following MeSH terms: "spinal cord stimulation," "chronic pain," "back pain," "patient readmission," "economics," and "costs and cost analysis." Additional sources were added based on bibliographies and consultation with experts. The following data were extracted and analyzed: demographic information, study design, objectives, sample sizes, outcome measures, SCS indications, complications, costs, readmissions, and resource utilization data. RESULTS: Of 204 studies screened, 11 studies met inclusion criteria, representing 31,439 SCS patients and 299,182 CT patients. The mean age was 53.5 years for SCS and 55.6 years for CT. In eight of 11 studies, SCS was associated with favorable outcomes and found to be more cost-effective than CT for chronic low back pain. Compared with CT, SCS resulted in shorter hospital stays and lower complication rates and health care costs at 90 days. SCS was associated with significant improvement in health-related quality of life, health status, and quality-adjusted life-years. CONCLUSIONS: For the treatment of chronic low back and leg pain, the majority of studies are of fair quality, with level 3 or 4 evidence in support of SCS as potentially more cost-effective than CT, with less resource expenditure but higher complication rates. SCS therapy may yet play a role in mitigating the financial burden associated with chronic low back and leg pain.

A randomized trial to assess the immediate impact of acupuncture on quantitative sensory testing, pain, and functional status.

In this randomized clinical trial, we examined whether the effect of true acupuncture can be differentiated from sham acupuncture (pain and functionality) by analyzing quantitative sensory testing (QST) profiles in chronic pain participants. We recruited 254 healthy or chronic back and neck pain participants. Healthy subjects were included to control for a possible effect of acupuncture on baseline QST changes. Study participants received 6 sessions (twice weekly) of true acupuncture, sham acupuncture, or no acupuncture treatment (routine care). Quantitative sensory testing profiles, pain scores, and functionality profile were obtained at baseline (visit 1) and after 3 (visit 4) or 6 sessions (visit 7). A total of 204 participants were analyzed. We found no QST profile changes among 3 groups (P = 0.533 and P = 0.549, likelihood ratio tests) in either healthy or chronic pain participants. In chronic back and neck pain participants, true acupuncture reduced pain (visit 4: difference in mean [DIM] = -0.8, 95% confidence interval [CI]: -1.4 to -0.1, adjusted P = 0.168; visit 7: DIM = -1.0, 95% CI: -1.7 to -0.3, adjusted P = 0.021) and improved functional status including physical functioning (DIM = 14.21, 95% CI: 5.84-22.58, adjusted P = 0.003) and energy/fatigue (DIM = 12.28, 95% CI: 3.46-21.11, adjusted P = 0.021) as compared to routine care. Our results indicate that QST was not helpful to differentiate between true acupuncture and sham acupuncture (primary outcome) in this study, although true acupuncture reduced pain and improved functionality (secondary outcomes) when compared with routine care.

Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients.

Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (eg, microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far, the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain. Here, we show that patients suffering from a common chronic pain disorder (lumbar radiculopathy), compared with healthy volunteers, exhibit elevated levels of the neuroinflammation marker 18 kDa translocator protein, in both the neuroforamina (containing dorsal root ganglion and nerve roots) and spinal cord. These elevations demonstrated a pattern of spatial specificity correlating with the patients' clinical presentation, as they were observed in the neuroforamen ipsilateral to the symptomatic leg (compared with both contralateral neuroforamen in the same patients as well as to healthy controls) and in the most caudal spinal cord segments, which are known to process sensory information from the lumbosacral nerve roots affected in these patients (compared with more superior segments). Furthermore, the neuroforaminal translocator protein signal was associated with responses to fluoroscopy-guided epidural steroid injections, supporting its role as an imaging marker of neuroinflammation, and highlighting the clinical significance of these observations. These results implicate immunoactivation at multiple levels of the nervous system as a potentially important and clinically relevant mechanism in human radicular pain, and suggest that therapies targeting immune cell activation may be beneficial for chronic pain patients.

Ultrasmall Superparamagnetic Iron Oxide Imaging Identifies Tissue and Nerve Inflammation in Pain Conditions.

Objective: Correlation between radiologic structural abnormalities and clinical symptoms in low back pain patients is poor. There is an unmet clinical need to image inflammation in pain conditions to aid diagnosis and guide treatment. Ferumoxytol, an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle, is clinically used to treat iron deficiency anemia and showed promise in imaging tissue inflammation in human. We explored whether ferumoxytol can be used to identify tissue and nerve inflammation in pain conditions in animals and humans. Methods: Complete Freud's adjuvant (CFA) or saline was injected into mice hind paws to establish an inflammatory pain model. Ferumoxytol (20 mg/kg) was injected intravenously. Magnetic resonance imaging (MRI) was performed prior to injection and 72 hours postinjection. The changes in the transverse relaxation time (T2) before and after ferumoxytol injection were compared between mice that received CFA vs saline injection. In the human study, we administered ferumoxytol (4 mg/kg) to a human subject with clinical symptoms of lumbar radiculopathy and compared the patient with a healthy subject. Results: Mice that received CFA exhibited tissue inflammation and pain behaviors. The changes in T2 before and after ferumoxytol injection were significantly higher in mice that received CFA vs saline (20.8 ± 3.6 vs 2.2 ± 2.5, P = 0.005). In the human study, ferumoxytol-enhanced MRI identified the nerve root corresponding to the patient's symptoms, but the nerve root was not impinged by structural abnormalities, suggesting the potential superiority of this approach over conventional structural imaging techniques. Conclusions: Ferumoxytol-enhanced MRI can identify tissue and nerve inflammation and may provide a promising diagnostic tool in assessing pain conditions in humans.

Neuropathic Pain Medication Use Does Not Alter Outcomes of Spinal Cord Stimulation for Lower Extremity Pain.

INTRODUCTION: Spinal cord stimulation (SCS) for the treatment of lower extremity pain is believed to the result of increased activity in the descending inhibitory and decreased activity in the ascending excitatory tracts. Evidence suggests that the analgesia afforded by SCS may be altered using certain neuropathic pain medications that also modulate neurotransmitters in these sensory tracts. We hypothesize that neuropathic pain medications may alter the response to SCS therapy. METHODS: One hundred and fifteen subjects undergoing SCS therapy for lower extremity pain were retrospectively examined. The pharmacologic profile, including stable use of neuropathic and opioid medications, were recorded. Three separate logistic regression models examined the odds ratio of primary outcomes; a successful SCS trial, a 50% decrease in pain or a 50% reduction in opioid use one year after implant. RESULTS: Neither the use of opioids or neuropathic pain medications were associated with changes in the odds of a successful SCS trial or a 50% pain reduction. A higher dose of chronic opioids use prior to a trial was associated with greater odds of having a 50% reduction in opioid use following implant. OR 1.02, 95% CI 1.01-1.02, p-value < 0.01). CONCLUSIONS: The use of neuropathic pain medications did not change the odds of either a successful SCS trial, or of experiencing a 50% reduction in pain at one year. The association between higher opioid doses and greater odds of a 50% reduction in opioid use may be the reflective of SCS's ability to reduce opioid reliance in chronic pain patients.

Loss of Efficacy to Spinal Cord Stimulator Therapy: Clinical Evidence and Possible Causes.

BACKGROUND: Although spinal cord stimulation (SCS) therapy has been shown to be efficacious in various pain conditions, the ability for SCS therapy to maintain long-term efficacy has been questioned. OBJECTIVE: The purpose of this study was to investigate whether a loss of efficacy (LOE) phenomenon exists with SCS therapy and to investigate if this phenomenon is more apparent in any specific patient population. STUDY DESIGN: A retrospective, observation chart review was conducted to evaluate the patient response to SCS therapy over time. SETTING: Massachusetts General Hospital, Boston, Massachusetts. METHODS: Patients who received a SCS at the Massachusetts General Hospital, between January 1, 2002 and December 31, 2012, were invited to participate. A total of 62 patients were included in this study. Various models were created to analyze pain score changes over time using 2-tailed statistical analysis. Additionally, one-way ANOVA and Pearson's chi-square tests were used to determine if certain patient characteristics were associated with LOE. RESULTS: Compared to the visual analog scale (VAS) score at one month after device implantation, pain scores increased 1.95 points after 2 years (95% CI: 1.06 to 2.84, P = < 0.001). There were no significant differences in baseline characteristics between the groups of patients who did and did not lose efficacy of their therapy. However, those who experienced LOE had a baseline SCS therapy VAS score 3.09 points lower than those who did not (95% CI: 1.69 to 4.48, P = < 0.001). LIMITATIONS: This study had several limitations including the retrospective nature of its design, confounders to VAS scores, small sample size, missing data points, and the evaluation of only conventional, low-frequency SCS therapy. CONCLUSIONS: Patients who received a SCS had a significant increase in VAS scores over time. Our data did not show any baseline patient characteristic that helped predict LOE. However, patients who have significant baseline response to therapy may be more likely to experience LOE. KEY WORDS: Spinal cord stimulation, chronic pain, retrospective study, low frequency electrical stimulation, efficacy, chronic pain therapy.

Chronic Opioid Therapy Modifies QST Changes After Ketamine Infusion in Chronic Pain Patients.

The long-term effects of opioids on sensitization processes are believed to be mediated through the N-methyl-D-aspartate receptor. Quantitative sensory testing (QST) changes observed after a ketamine infusion have been previously described but the effect that chronic opioids will have is not known. The results of this prospective randomized factorial trial compared the thermal QST changes observed after a .05 mg/kg ketamine infusion or a saline placebo in chronic pain subjects who were either opioid-naive or were chronically using opioids for chronic noncancer pain are presented. No baseline QST differences were noted between the 4 groups at baseline. Comparison of changes preinfusion with postinfusion QST measurements resulted in decreased average change in temporal summation response between opioid subjects who received a placebo compared with those who received a ketamine infusion (-5.22, SD = 9.96 vs 13.81, SD = 19.55; P = .004). Additionally, the average change in temporal summation was decreased among subjects who received a ketamine infusion and were not chronically using opioids compared with subjects who were using chronic opioids and received a placebo infusion (-1.91, SD = 13.25 vs 13.81, SD = 19.55; P = .007). The results indicate that low-dose ketamine infusions produce subtle changes in QST phenotypes that are modified by the chronic use of opioids. This illustrates the potential diagnostic and therapeutic value of ketamine in the setting of chronic opioid use. PERSPECTIVE: The presented data further our understanding of modulation of sensory perception in the setting of chronic opioid use and the role of the N-methyl-D-aspartate receptor. The use of low-dose ketamine infusions may be useful for the treatment as well as diagnosis of opioid-related neuropathic conditions.

Thermal QST Phenotypes Associated with Response to Lumbar Epidural Steroid Injections: A Pilot Study.

OBJECTIVE: Response to lumbar epidural steroid injection in lumbar radicular pain varies. The purpose of this study is to characterize the changes in quantitative sensory testing (QST) phenotypes of subjects and compare the QST characteristics in patients who do respond to treatment of radicular pain with a lumbar epidural steroid injection (ESI). DESIGN: Prospective, observational pilot study. SETTING: Outpatient pain center. METHODS: Twenty subjects with a lower extremity (LE) radicular pain who were scheduled to have an ESI were recruited. At the visit prior to and four weeks following an ESI, subjects underwent QST measurements of both the affected LE and the contralateral unaffected UE. RESULTS: Following an ESI, nine subjects reported a greater than 30% reduction in radicular pain and 11 reported a less than 30% reduction in radicular pain. Subjects who had less than 30% pain reduction response (nonresponders) to an ESI had increased pre-injection warm sensation threshold (37.30 °C, SD = 2.51 vs 40.39, SD = 3.36, P = 0.03) and heat pain threshold (47.22 °C, SD = 1.38, vs 48.83 °C, SD = 2.10, P = 0.04). Further, the nonresponders also showed increased pre-injection warm sensation threshold as measured in the difference of warm sensation detection threshold difference in the affected limb and the unaffected arm (2.68 °C, SD = 2.92 vs 5.67 °C, SD = 3.22, P = 0.045). Other QST parameters were not affected. CONCLUSIONS: The results show that the nonresponders to ESIs have increased detection threshold to heat pain and warm sensation, suggesting that a preexisting dysfunction in the C fibers in this group of subjects who can be detected by QST. Such altered QST characteristics may prognosticate the response to ESIs.

High-Frequency Spinal Cord Stimulation for Chronic Pain: Pre-Clinical Overview and Systematic Review of Controlled Trials.

OBJECTIVE: To assess the evidence base for high-frequency spinal cord stimulation (HFSCS). HFSCS has the potential to provide paresthesia-free pain relief for patients with chronic pain, in contrast to conventional spinal cord stimulation, which produces distracting and potentially unpleasant paresthesias. DESIGN: A systematic review following standard methodological guidelines (Prospero #CRD42015029215). METHODS: We searched PubMed to March 14, 2016 without language restriction and hand-checked reference lists. Two authors independently performed study selection, bias evaluations, and data extraction. The pre-clinical review selected studies focusing on the mechanism and non-human experience with HFSCS. Clinically, any prospective study of adults using HFSCS (≥ 1000 Hz) was included. RESULTS: Pre-clinical studies have characterized many aspects underlying the mechanism of HFSCS. For the clinical systematic review, eight trials (236 participants randomized or 160 followed prospectively) met inclusion criteria. All trials of HFSCS focused on patients with chronic low back pain with one exception, which included patients with chronic migraine. All but one trial documented funding by industry. Performance bias due to unmasked participants, physicians, and outcome assessors limited the quality of all but one study. CONCLUSIONS: Significant growth in the preclinical and clinical evidence base for HFSCS suggests that HFSCS may differ from conventional SCS in mechanism of action and efficacy of treatment, respectively. Addressing current knowledge gaps in clinical evidence will require standardization in trial reporting and leveraging the paresthesia-free characteristic of HFSCS to enable masking in high-quality randomized controlled trials.

Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity.

Nanoparticles found in air pollutants can alter neurotransmitter profiles, increase neuroinflammation, and alter brain function. Therefore, the assay described here will aid in elucidating the role of microglia in neuroinflammation and neurodegenerative diseases. The use of microglia, resident immune cells of the brain, as a surrogate biosensor provides novel insight into how inflammatory responses mediate neuronal insults. Here, we utilize an immortalized murine microglial cell line, designated BV2, and describe a method for nanoparticle exposure using silver nanoparticles (AgNPs) as a standard. We describe how to expose microglia to nanoparticles, how to remove nanoparticles from supernatant, and how to use supernatant from activated microglia to determine toxicity, using hypothalamic cell survival as a measure. Following AgNP exposure, BV2 microglial activation was validated using a tumor necrosis factor alpha (TNF-α) enzyme linked immunosorbent assay (ELISA). The supernatant was filtered to remove the AgNP and to allow cytokines and other secreted factors to remain in the conditioned media. Hypothalamic cells were then exposed to supernatant from AgNP activated microglia and survival of neurons was determined using a resazurin-based fluorescent assay. This technique is useful for utilizing microglia as a surrogate biomarker of neuroinflammation and determining the effect of neuroinflammation on other cell types.

Profiles of Urine Drug Test in Clinical Pain Patients vs Pain Research Study Subjects.

OBJECTIVE: To examine similarities and differences in urine drug test (UDT) results in clinical pain patients and pain subjects participating in pain research studies. DESIGN: An observational study with retrospective chart review and data analysis. METHODS: We analyzed 1,874 UDT results obtained from 1) clinical pain patients (Clinical Group; n = 1,529) and 2) pain subjects consented to participate in pain research studies (Research Group; n = 345). Since several medications such as opioids used in pain management are drugs of abuse (DOA) and can result in a positive UDT, we specifically identified those cases of positive UDT due to nonprescribed DOA and designated these cases as positive UDT with DOA (PUD). RESULTS: We found that 1) there was a higher rate of PUD in clinical pain patients (41.3%) than in pain research study subjects (14.8%); 2) although subjects in the Research Group were informed ahead of time that UDT will be conducted as a screening test, a substantial number (14.8%) of pain research study subjects still showed PUD; 3) there were different types of DOA between clinical pain patients (cannabinoids as the top DOA) and research study subjects (cocaine as the top DOA); and 4) a common factor associated with PUD was opioid therapy in both Clinical Group and Research Group. CONCLUSION: These results support previous findings that PUD is a common finding in clinical pain patients, particularly in those prescribed opioid therapy, and we suggest that UDT be used as routine screening testing in pain research studies.

Cervical epidural blood patch--A literature review.

OBJECTIVE: Epidural blood patches (EBP) are rarely performed at the cervical levels, primarily due to fear of neurological complications such as spinal cord compression. We reviewed the literature to provide an evidence-based review of performance of cervical EBPs, with a specific focus on indication, technique, safety, and efficacy. DESIGN: A comprehensive electronic literature search was done to include studies that reported on performance of cervical EBPs in patients with CSF leak at the cervical level. Data regarding indication, level of CSF leak, level of cervical EBP, volume of blood used, efficacy, and complications were collected. RESULTS: A total of 15 studies, reporting on 19 patients were included. All patients presented with a headache that increased in the standing position, and improved in the supine position. All patients were identified to have a CSF leak at the cervical level. Eight patients first underwent a lumbar EBP, without complete, long-term relief. All these patients, along with 11 patients who did not undergo a lumbar EPB prior to cervical EBP, reported complete, long-term pain relief. EBPs were mostly done in the prone position, using imaging guidance. An average of 5-8 mL of autologous blood was injected in the epidural space. No major neurological complications were reported in any patient. CONCLUSION: The review suggests that cervical EBP can be performed for cervical CSF leaks associated with positional headache without a significant risk of serious adverse events. CLASSIFICATION OF EVIDENCE: Our review provides Class II level of evidence that cervical EBPs are safe and effective in reliving positional headache due to CSF leak.

Effects of Spinal Cord Stimulation on Pain Thresholds and Sensory Perceptions in Chronic Pain Patients.

OBJECTIVE: Spinal cord stimulation (SCS) has been in clinical use for nearly four decades. In earliest observations, researchers found a significant increase in pain threshold during SCS therapy without changes associated with touch, position, and vibration sensation. Subsequent studies yielded diverse results regarding how SCS impacts pain and other sensory thresholds. This pilot study uses quantitative sensory testing (QST) to objectively quantify the impact of SCS on warm sensation, heat pain threshold, and heat pain tolerance. MATERIALS AND METHODS: Nineteen subjects with an indwelling SCS device for chronic pain were subjected to QST with heat stimuli. QST was performed on an area of pain covered with SCS-induced paresthesia and an area without pain and without paresthesia, while the SCS was turned off and on. The temperature at which the patient detected warm sensation, heat pain, and maximal tolerable heat pain was used to define the thresholds. RESULTS: We found that all three parameters, the detection of warm sensation, heat pain threshold, and heat pain tolerance, were increased during the period when SCS was on compared with when it was off. This increase was observed in both painful and non-painful sites. CONCLUSION: The observed pain relief during SCS therapy seems to be related to its impact on increased sensory threshold as detected in this study. The increased sensory threshold on areas without pain and without the presence of SCS coverage may indicate a central (spinal and/or supra-spinal) influence from SCS.

Effect of 1.5% Topical Diclofenac on Clinical Neuropathic Pain.

BACKGROUND: Neuropathic pain is a condition resulting from injury to the peripheral and/or central nervous system. Despite extensive research over the last several decades, neuropathic pain remains difficult to manage. METHODS: The authors conducted a randomized, placebo-controlled, double-blinded, and crossover clinical trial to examine the effect of 1.5% topical diclofenac (TD) on neuropathic pain. The authors hypothesized that 1.5% TD would reduce the visual pain score and improve both quantitative sensory testing and functional status in subjects with neuropathic pain. The authors recruited subjects with postherpetic neuralgia and complex regional pain syndrome. The primary outcome was subject's visual pain score. RESULTS: Twenty-eight subjects completed the study (12 male and 16 female) with the mean age of 48.8 yr. After 2 weeks of topical application, subjects in 1.5% TD group showed lower overall visual pain score compared with placebo group (4.9 [1.9] vs. 5.6 [2.1], difference: 0.8; 95% CI, 0.1 to 1.3; P = 0.04) as well as decreased burning pain (2.9 [2.6] vs. 4.3 [2.8], difference, 1.4; 95% CI, 0.2 to 2.6; P = 0.01). There were no statistical differences in constant pain, shooting pain, or hypersensitivity over the painful area between the groups. This self-reported improvement of pain was corroborated by the decreased pain summation detected by quantitative sensory testing. There were no statistically significant changes in functional status in these subjects. There were no complications in both groups. CONCLUSION: The findings indicate that 1.5% TD may serve as an effective treatment option for patients with neuropathic pain from postherpetic neuralgia and complex regional pain syndrome.