Michael Leong

All Publications

• Research designs for proof-of-concept chronic pain clinical trials: IMMPACT recommendations. Pain Gewandter, J. S., Dworkin, R. H., Turk, D. C., McDermott, M. P., Baron, R., Gastonguay, M. R., Gilron, I., Katz, N. P., Mehta, C., Raja, S. N., Senn, S., Taylor, C., Cowan, P., Desjardins, P., Dimitrova, R., Dionne, R., Farrar, J. T., Hewitt, D. J., Iyengar, S., Jay, G. W., Kalso, E., Kerns, R. D., Leff, R., Leong, M., Petersen, K. L., Ravina, B. M., Rauschkolb, C., Rice, A. S., Rowbotham, M. C., Sampaio, C., Sindrup, S. H., Stauffer, J. W., Steigerwald, I., Stewart, J., Tobias, J., Treede, R., Wallace, M., White, R. E. 2014; 155 (9): 1683-1695

  Abstract

  Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine whether a treatment is likely to be efficacious for a given indication and thus whether it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge in designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost-effective manner. An IMMPACT consensus meeting was convened to discuss design considerations for POC trials in analgesia, with a focus on maximizing power with limited resources and participants. We present general design aspects to consider including patient population, active comparators and placebos, study power, pharmacokinetic-pharmacodynamic relationships, and minimization of missing data. Efficiency of single-dose studies for treatments with rapid onset is discussed. The trade-off between parallel-group and crossover designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages of more recent trial designs, including N-of-1 designs, enriched designs, adaptive designs, and sequential parallel comparison designs, are summarized, and recommendations for consideration are provided. More attention to identifying efficient yet powerful designs for POC clinical trials of chronic pain treatments may increase the percentage of truly efficacious pain treatments that are advanced to confirmatory trials while decreasing the percentage of ineffective treatments that continue to be evaluated rather than abandoned.

  View details for DOI 10.1016/j.pain.2014.05.025

  View details for PubMedID 24865794

• The Appropriate Use of Neurostimulation: Avoidance and Treatment of Complications of Neurostimulation Therapies for the Treatment of Chronic Pain NEUROMODULATION Deer, T. R., Mekhail, N., Provenzano, D., Pope, J., Krames, E., Thomson, S., Raso, L., Burton, A., DeAndres, J., Buchser, E., Buvanendran, A., Liem, L., Kumar, K., Rizvi, S., Feler, C., Abejon, D., Anderson, J., Eldabe, S., Kim, P., Leong, M., Hayek, S., McDowell, G., Poree, L., Brooks, E. S., McJunkin, T., Lynch, P., Kapural, L., Foreman, R. D., Caraway, D., Alo, K., Narouze, S., Levy, R. M., North, R. 2014; 17 (6): 571-597

  Abstract

  The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes.The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks.The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician.The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly.

  View details for DOI 10.1111/ner.12206

  View details for Web of Science ID 000340500200006

  View details for PubMedID 25112891

• CT-Guided Percutaneous Infrazygomatic Radiofrequency Neurolysis Through Foramen Rotundum to Treat V2 Trigeminal Neuralgia PAIN MEDICINE Huang, B., Yao, M., Feng, Z., Guo, J., Zereshki, A., Leong, M., Qian, X. 2014; 15 (8): 1418-1428

  Abstract

  Percutaneous radiofrequency thermocoagulation or neurolysis of Gasserian ganglion through foramen ovale (FO) is the classical approach to treat trigeminal neuralgia (TN). However, it has been technically challenging when individual trigeminal sub-branch nerve block is desired through this approach. We have thus developed a novel computed tomograph-guided technique to block the V2 trigeminal nerve through foramen rotundum (FR). With this technique, we have conducted a study of 27 patients with isolated V2 TN. We hypothesize that this new technique will have comparable clinical outcome with the conventional FO approach.Prospective study.Academic hospitals.Twenty-seven patients with isolated classical V2 TN were enrolled and divided into FO group (N?=?12) and FR group (N?=?15).Numeric Rating Scale (NRS) scores for facial pain, at pretreatment, immediate postoperative, postoperative 1 day, and 1, 6, and 12 months were recorded. The primary clinical outcome (successful pain relief with 50% or more reduction in NRS) and secondary adverse clinical outcome (hematoma, facial numbness, masticatory weakness, and corneal involvement) were compared and analyzed.Both groups have good immediate and sustained pain relief. However, when compared with the FO group, the FR group is associated with shorter procedural time (29.2?±?9.3 vs 45.4?±?22.13 minutes, P?

  View details for DOI 10.1111/pme.12440

  View details for Web of Science ID 000342630800025

  View details for PubMedID 24716880

• The Appropriate Use of Neurostimulation: New and Evolving Neurostimulation Therapies and Applicable Treatment for Chronic Pain and Selected Disease States NEUROMODULATION Deer, T. R., Krames, E., Mekhail, N., Pope, J., Leong, M., Stanton-Hicks, M., Golovac, S., Kapural, L., Alo, K., Anderson, J., Foreman, R. D., Caraway, D., Narouze, S., Linderoth, B., Buvanendran, A., Feler, C., Poree, L., Lynch, P., McJunkin, T., Swing, T., Staats, P., Liem, L., Williams, K. 2014; 17 (6): 599-615

  Abstract

  The International Neuromodulation Society (INS) has determined that there is a need to provide an expert consensus that defines the appropriate use of neuromodulation technologies for appropriate patients. The Neuromodulation Appropriateness Consensus Committee (NACC) was formed to give guidance to current practice and insight into future developments.The INS executive board selected members of the international scientific community to analyze scientific evidence for current and future innovations and to use clinical experience to fill in any gaps in information. The NACC used PubMed and Google Scholar to obtain current evidence in the field and used clinical and research experience to give a more complete picture of the innovations in the field.The NACC has determined that currently approved neurostimulation techniques and technologies have expanded our ability to treat patients in a more effective and specific fashion. Despite these advances, the NACC has identified several additional promising technologies and potential applications for neurostimulation that could move this field forward and expand the applicability of neuromodulation.The NACC concludes that the field of neurostimulation is an evolving and rapidly changing one that will lead to improved patient access, safety, and outcomes.

  View details for DOI 10.1111/ner.12204

  View details for Web of Science ID 000340500200008

  View details for PubMedID 25112892

• The Appropriate Use of Neurostimulation of the Spinal Cord and Peripheral Nervous System for the Treatment of Chronic Pain and Ischemic Diseases: The Neuromodulation Appropriateness Consensus Committee NEUROMODULATION Deer, T. R., Mekhail, N., Provenzano, D., Pope, J., Krames, E., Leong, M., Levy, R. M., Abejon, D., Buchser, E., Burton, A., Buvanendran, A., Candido, K., Caraway, D., Cousins, M., DeJongste, M., Diwan, S., Eldabe, S., Gatzinsky, K., Foreman, R. D., Hayek, S., Kim, P., Kinfe, T., Kloth, D., Kumar, K., Rizvi, S., Lad, S. P., Liem, L., Linderoth, B., Mackey, S., McDowell, G., McRoberts, P., Poree, L., Prager, J., Raso, L., Rauck, R., Russo, M., Simpson, B., Slavin, K., Staats, P., Stanton-Hicks, M., Verrills, P., Wellington, J., Williams, K., North, R. 2014; 17 (6): 515-550

  Abstract

  The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications.The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar.Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated.Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation.

  View details for DOI 10.1111/ner.12208

  View details for Web of Science ID 000340500200002

  View details for PubMedID 25112889

• Acute Cardiovascular Toxicity of Low-Dose Intrathecal Ziconotide. Pain medicine (Malden, Mass.) Heifets, B. D., Smith, S. M., Leong, M. S. 2013

  View details for PubMedID 23855951

• Polyanalgesic Consensus Conference-2012: Recommendations on Trialing for Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel NEUROMODULATION Deer, T. R., Prager, J., Levy, R., Burton, A., Buchser, E., Caraway, D., Cousins, M., De Andres, J., Diwan, S., Erdek, M., Grigsby, E., Huntoon, M., Jacobs, M., Kim, P., Kumar, K., Leong, M., Liem, L., McDowell, G., Panchal, S. J., Rauck, R., Saulino, M., Staats, P., Stanton-Hicks, M., Stearns, L., Sitzman, B. T., Wallace, M., Willis, K. D., Witt, W., Yaksh, T., Mekhail, N. 2012; 15 (5): 420-435

  Abstract

  Trialing for intrathecal pump placement is an essential part of the decision-making process in placing a permanent device. In both the United States and the international community, the proper method for trialing is ill defined.The Polyanalgesic Consensus Conference (PACC) is a group of well-published experienced practitioners who meet to update the state of care for intrathecal therapies on the basis of current knowledge in the literature and clinical experience. Anexhaustive search is performed to create a base of information that the panel considers when making recommendations for best clinical practices. This literature, coupled with clinical experience, is the basis for recommendations and for identification of gaps in the base of knowledge regarding trialing for intrathecal pump placement.The panel has made recommendations for the proper methods of trialing for long-term intrathecal drug delivery.The use of intrathecal drug delivery is an important part of the treatment algorithm for moderate to severe chronic pain. It has become common practice to perform a temporary neuroaxial infusion before permanent device implantation. On the basis of current knowledge, the PACC has developed recommendations to improve care. The need to update these recommendations will be very important as new literature is published.

  View details for DOI 10.1111/j.1525-1403.2012.00450.x

  View details for Web of Science ID 000309744800003

  View details for PubMedID 22494357

• Polyanalgesic Consensus Conference-2012: Consensus on Diagnosis, Detection, and Treatment of Catheter-Tip Granulomas (Inflammatory Masses) NEUROMODULATION Deer, T. R., Prager, J., Levy, R., Rathmell, J., Buchser, E., Burton, A., Caraway, D., Cousins, M., De Andres, J., Diwan, S., Erdek, M., Grigsby, E., Huntoon, M., Jacobs, M. S., Kim, P., Kumar, K., Leong, M., Liem, L., McDowell, G. C., Panchal, S., Rauck, R., Saulino, M., Sitzman, B. T., Staats, P., Stanton-Hicks, M., Stearns, L., Wallace, M., Willis, K. D., Witt, W., Yaksh, T., Mekhail, N. 2012; 15 (5): 483-496

  Abstract

  Continuous intrathecal infusion of drugs to treat chronic pain and spasticity has become a standard part of the algorithm of care. The use of opioids has been associated with noninfectious inflammatory masses at the tip of the intrathecal catheter, which can result in neurologic complications.The Polyanalgesic Consensus Conference is a meeting of a group of well-published and experienced practitioners; the purpose of the meeting is to update the standard of care for intrathecal therapies to reflect current knowledge gleaned from literature and clinical experience. An exhaustive literature search was performed, and information from this search was provided to panel members. Analysis of the published literature was coupled with the clinical experience of panel participants to form recommendations regarding intrathecal inflammatory masses or granulomas.The panel has made recommendations for the prevention, diagnosis, and management of intrathecal granulomas.The use of chronic infusions of intrathecal opioids is associated with the formation of inflammatory masses at the intrathecal catheter tip in a small minority of treated patients. Nonetheless, the appearance of these space-occupying lesions can lead to devastating neurologic sequelae. The prevention, early detection, and successful treatment of intraspinal granulomas are important considerations when offering intrathecal drug therapy to patients with chronic intractable pain.

  View details for DOI 10.1111/j.1525-1403.2012.00449.x

  View details for Web of Science ID 000309744800006

  View details for PubMedID 22494332

• Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel NEUROMODULATION Deer, T. R., Prager, J., Levy, R., Rathmell, J., Buchser, E., Burton, A., Caraway, D., Cousins, M., De Andres, J., Diwan, S., Erdek, M., Grigsby, E., Huntoon, M., Jacobs, M. S., Kim, P., Kumar, K., Leong, M., Liem, L., McDowell, G. C., Panchal, S., Rauck, R., Saulino, M., Sitzman, B. T., Staats, P., Stanton-Hicks, M., Stearns, L., Wallace, M., Willis, K. D., Witt, W., Yaksh, T., Mekhail, N. 2012; 15 (5): 436-466

  Abstract

  The use of intrathecal (IT) infusion of analgesic medications to treat patients with chronic refractory pain has increased since its inception in the 1980s, and the need for clinical research in IT therapy is ongoing. The Polyanalgesic Consensus Conference (PACC) panel of experts convened in 2000, 2003, and 2007 to make recommendations on the rational use of IT analgesics based on preclinical and clinical literature and clinical experiences.The PACC panel convened again in 2011 to update the standard of care for IT therapies to reflect current knowledge gleaned from literature and clinical experience. A thorough literature search was performed, and information from this search was provided to panel members. Analysis of published literature was coupled with the clinical experience of panel members to form recommendations regarding the use of IT analgesics to treat chronic pain.After a review of literature published from 2007 to 2011 and discussions of clinical experience, the panel created updated algorithms for the rational use of IT medications for the treatment of neuropathic pain and nociceptive pain.The advent of new algorithmic tracks for neuropathic and nociceptive pain is an important step in improving patient care. The panel encourages continued research and development, including the development of new drugs, devices, and safety recommendations to improve the care of patients with chronic pain.

  View details for DOI 10.1111/j.1525-1403.2012.00476.x

  View details for Web of Science ID 000309744800004

  View details for PubMedID 22748024

• Polyanalgesic Consensus Conference-2012: Recommendations to Reduce Morbidity and Mortality in Intrathecal Drug Delivery in the Treatment of Chronic Pain NEUROMODULATION Deer, T. R., Levy, R., Prager, J., Buchser, E., Burton, A., Caraway, D., Cousins, M., De Andres, J., Diwan, S., Erdek, M., Grigsby, E., Huntoon, M., Jacobs, M. S., Kim, P., Kumar, K., Leong, M., Liem, L., McDowell, G. C., Panchal, S., Rauck, R., Saulino, M., Sitzman, B. T., Staats, P., Stanton-Hicks, M., Stearns, L., Wallace, M., Willis, K. D., Witt, W., Yaksh, T., Mekhail, N. 2012; 15 (5): 467-482

  Abstract

  Targeted intrathecal drug infusion to treat moderate to severe chronic pain has become a standard part of treatment algorithms when more conservative options fail. This therapy is well established in the literature, has shown efficacy, and is an important tool for the treatment of both cancer and noncancer pain; however, it has become clear in recent years that intrathecal drug delivery is associated with risks for serious morbidity and mortality.The Polyanalgesic Consensus Conference is a meeting of experienced implanting physicians who strive to improve care in those receiving implantable devices. Employing data generated through an extensive literature search combined with clinical experience, this work group formulated recommendations regarding awareness, education, and mitigation of the morbidity and mortality associated with intrathecal therapy to establish best practices for targeted intrathecal drug delivery systems.Best practices for improved patient care and outcomes with targeted intrathecal infusion are recommended to minimize the risk of morbidity and mortality. Areas of focus include respiratory depression, infection, granuloma, device-related complications, endocrinopathies, and human error. Specific guidance is given with each of these issues and the general use of the therapy.Targeted intrathecal drug delivery systems are associated with risks for morbidity and mortality that can be devastating. The panel has given guidance to treating physicians and healthcare providers to reduce the incidence of these problems and to improve outcomes when problems occur.

  View details for DOI 10.1111/j.1525-1403.2012.00486.x

  View details for Web of Science ID 000309744800005

  View details for PubMedID 22849581

• Intrathecal Ziconotide for Complex Regional Pain Syndrome: Seven Case Reports PAIN PRACTICE Kapural, L., Lokey, K., Leong, M. S., Fiekowsky, S., Stanton-Hicks, M., Sapienza-Crawford, A. J., Webster, L. R. 2009; 9 (4): 296-303

  Abstract

  Ziconotide is a nonopioid analgesic currently indicated as monotherapy, but frequently used in combination with opioids, for the management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted and who are intolerant of, or whose pain is, refractory to other treatments. There is a paucity of information regarding ziconotide use in patients with complex regional pain syndrome (CRPS). Seven cases in which IT ziconotide was used in patients with CRPS were analyzed. All patients (4 male, 3 female; age range, 14 to 52 years) had experienced inadequate pain relief with multiple conventional and interventional treatments. Three patients received ziconotide monotherapy exclusively; 4 patients received ziconotide monotherapy initially, then combination IT therapy. The mean ziconotide dose was 5.2 mcg/d (range, 0.5 to 13 mcg/d) at initiation and 24.7 mcg/d (range, 0.06 to 146 mcg/d) at the last available assessment. The mean duration of ziconotide therapy was 3.1 years (range, 26 days to 8 years). At ziconotide initiation, the mean visual analog scale (VAS) score was 89.3 mm (range, 75 to 100 mm); VAS scores decreased by a mean of 47.5% (range, 5% to 100%) at last assessment. Of the 5 patients who experienced substantial improvement in pain, edema, skin abnormalities, and/or mobility with ziconotide therapy, 2 have discontinued ziconotide and are pain free. Another patient experienced marked reversal of both edema and advanced skin trophic changes. Adverse events included urinary retention, depression, anxiety, and hallucinations. Adverse events generally resolved spontaneously, with treatment, or with ziconotide discontinuation/dose reduction. Although further studies are required, ziconotide holds promise as an effective treatment for CRPS.

  View details for DOI 10.1111/j.1533-2500.2009.00289.x

  View details for Web of Science ID 000208107800008

  View details for PubMedID 19500276

• Phase II, open-label, multicenter study of combined intrathecal morphine and ziconotide: Addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain PAIN MEDICINE Wallace, M. S., Kosek, P. S., Staats, P., Fisher, R., Schultz, D. M., Leong, M. 2008; 9 (3): 271-281

  Abstract

  To assess the safety and efficacy of adding intrathecal ziconotide to intrathecal morphine in patients being treated with a stable intrathecal morphine dose.Phase II, multicenter, open-label study with a 5-week titration phase and an extension phase.Outpatient clinics.Patients with suboptimal pain relief receiving stable intrathecal morphine doses (2-20 mg/day).Intrathecal morphine dosing remained constant during the titration phase. Ziconotide therapy began at 0.60 microg/day and was titrated to a maximum of 7.2 microg/day. During the extension phase, ziconotide and intrathecal morphine dosing were adjusted at the investigator's discretion.Safety was assessed primarily via adverse event reports. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption.Twenty-six patients were enrolled. Treatment-emergent adverse events were generally mild or moderate; the most common (> or = 15% of patients in either study phase) study drug-related (i.e., ziconotide/morphine combination [or ziconotide monotherapy in the extension phase only]) events were confusion, dizziness, abnormal gait, hallucinations, and anxiety. The mean percentage improvement in visual analog scale of pain intensity scores was 14.5% (95% confidence interval: -9.4% to 38.5%) from baseline to week 5 and varied during the extension phase (range: -0.4% to 42.8%). Mean percentage change from baseline in systemic opioid consumption was -14.3% at week 5 and varied considerably during the extension phase.Ziconotide, combined with stable intrathecal morphine, may reduce pain and decrease systemic opioid use in patients with pain inadequately controlled by intrathecal morphine alone.

  View details for DOI 10.1111/j.1526-4637.2007.00355.x

  View details for Web of Science ID 000254385600002

  View details for PubMedID 18366507

• A novel needle-free powder lidocaine delivery system for rapid local analgesia JOURNAL OF PEDIATRICS Zempsky, W. T., Robbins, B., Richards, P. T., Leong, M. S., Schechter, N. L. 2008; 152 (3): 405-411

  Abstract

  To determine the analgesic effect and tolerability of a novel needle-free powder lidocaine delivery system in children undergoing venipuncture.In this double-blind, placebo-controlled, single-center trial, 306 children age 3 to 18 years were randomized to receive a needle-free powder lidocaine delivery system or matching sham placebo at the back of the hand 2 to 3 minutes before venipuncture. Venipuncture pain was self-reported using the Wong-Baker FACES scale (in 3- to 12-year-olds) and a 100-mm visual analog scale (in 8- to 18-year-olds). Safety was assessed by adverse events, investigator skin site assessments, and children's self-report of the administration comfort of study treatments. Effect sizes were compared by 2-sample t test and Glass's Delta approach.Subjects receiving the needle-free powder lidocaine delivery system exhibited mean pain reductions (effect size) of 33% to 46% relative to sham placebo. Pain reductions were statistically significant for all ages combined and also for the youngest and oldest age strata. Self-reported administration comfort levels were similar in the active system and sham placebo groups. Incidences of adverse events and dermal reactions were low; the most common dermal reaction was mild erythema.The needle-free powder lidocaine delivery system was well tolerated and provided effective local analgesia when administered 2 to 3 minutes before venipuncture.

  View details for DOI 10.1016/j.jpeds.2007.07.018

  View details for Web of Science ID 000253599800023

  View details for PubMedID 18280850

• Dose-finding, safety, and tolerability study of botulinum toxin type B for the treatment of hyperfunctional glabellar lines DERMATOLOGIC SURGERY Carruthers, A., Carruthers, J., Flynn, T. C., Leong, M. S. 2007; 33: S60-S68

  Abstract

  Previous open-label studies have demonstrated that botulinum toxin type B (BTX-B, Myobloc, Solstice Neurosciences) in doses of up to 3,000 U is safe and effective in the treatment of glabellar wrinkles.This double-blind, randomized, placebo-controlled, sequential-dose-escalation study evaluated the safety and tolerability of seven BTX-B doses ranging from 250 to 3,000 U in the treatment of subjects with hyperfunctional glabellar lines.Participants received a single intramuscular treatment of either BTX-B or placebo at five facial sites with a 12-week follow-up period. Primary efficacy outcome measure was the Investigator Global Scale score of subject's glabellar lines at rest and at full frown. Safety was evaluated primarily on the occurrence of adverse events (AEs).The investigator scores demonstrated a statistically significant increasing dose-response trend in the percentage of subjects with no lines or mild lines at rest from Weeks 1 to 12 (p=.0420) and at full frown from Weeks 1 to 8 (p<.0001). Fifty-one subjects (36.7%) experienced AEs; the most common AE was headache not otherwise specified, experienced by 19 subjects (13.7%).BTX-B at doses up to 3,000 U was safe and well tolerated in the treatment of hyperfunctional glabellar lines. Treatment with BTX-B reduced hyperfunctional glabellar lines in subjects, and the duration of action appeared to be related to the dose administered. Further studies using higher doses of BTX-B for treatment of glabellar wrinkles are planned.

  View details for DOI 10.1111/j.1524-4725.2006.32333.x

  View details for Web of Science ID 000253377900010

  View details for PubMedID 17241416

• A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain JOURNAL OF PAIN AND SYMPTOM MANAGEMENT Rauck, R. L., Wallace, M. S., Leong, M. S., MineHart, M., Webster, L. R., Charapata, S. G., Abraham, J. E., Buffington, D. E., Ellis, D., Kartzinel, R. 2006; 31 (5): 393-406

  Abstract

  Safety and efficacy data from a study of slow intrathecal (IT) ziconotide titration for the management of severe chronic pain are presented. Patients randomized to ziconotide (n = 112) or placebo (n = 108) started IT infusion at 0.1 microg/hour (2.4 microg/day), increasing gradually (0.05-0.1 microg/hour increments) over 3 weeks. The ziconotide mean dose at termination was 0.29 microg/hour (6.96 microg/day). Patients' baseline Visual Analogue Scale of Pain Intensity (VASPI) score was 80.7 (SD 15). Statistical significance was noted for VASPI mean percentage improvement, baseline to Week 3 (ziconotide [14.7%] vs. placebo [7.2%; P = 0.036]) and many of the secondary efficacy outcomes measures. Significant adverse events (AEs) reported in the ziconotide group were dizziness, confusion, ataxia, abnormal gait, and memory impairment. Discontinuation rates for AEs and serious AEs were comparable for both groups. Slow titration of ziconotide, a nonopioid analgesic, to a low maximum dose resulted in significant improvement in pain and was better tolerated than in two previous controlled trials that used a faster titration to a higher mean dose.

  View details for DOI 10.1016/j.jpainsymman.2005.10.003

  View details for Web of Science ID 000238207700010

  View details for PubMedID 16716870

• Pump battery assessment: Cold, old, or dead! NEUROMODULATION Leong, M. S., Carpentier, B. W. 2001; 4 (3): 117-119

  Abstract

  Intraspinal drug delivery systems are becoming increasingly utilized for the management of patients with pain or spasticity. Numerous potential complications associated with the use of this technology have previously been described in the literature. We have had experience with a new complication of the internal alarm being triggered by the instillation of cold solution into the pump resevoir. This new finding could have implications for patients with respect to unnecessary reevaluations of the pump, or possible premature scheduling of pump replacement surgery.

  View details for Web of Science ID 000169693100005

  View details for PubMedID 22151656