karen simpson - Academia.edu (original) (raw)

Papers by karen simpson

Research paper thumbnail of Bolus Intrathecal Injection of Ziconotide (Prialt®) to Evaluate the Option of Continuous Administration via an Implanted Intrathecal Drug Delivery (ITDD) System: A Pilot Study

Neuromodulation: Technology at the Neural Interface, 2013

This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai Limited, He... more This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai Limited, Hertfordshire, UK) to assess the option of continuous administration of this drug via an implanted intrathecal drug delivery system. Twenty adults with severe chronic pain who were under consideration for intrathecal (IT) therapy were enrolled in this open label, nonrandomized, pilot study. Informed consent was obtained. Demographics, medical/pain history, pain scores, and concomitant medications were recorded. A physical examination was performed. Creatine kinase was measured. Initial visual analog scale (VAS), blood pressure, heart rate, and respiratory rate were recorded. All patients received an initial bolus dose of 2.5 mcg ziconotide; the dose in the subsequent visits was modified according to response. Subsequent doses were 2.5 mcg, 1.2 mcg, or 3.75 mcg as per protocol. A good response (≥30% reduction in baseline pain VAS) with no side-effects on two occasions was considered a successful trial. Data were analyzed using a generalized estimating equations model, with pain VAS as the outcome and time (seven time points; preinjection and one to six hours postinjection) as the predictor. Generalized estimating equations analysis of summary measures showed a mean reduction of pain VAS of approximately 25% at the group level; of 11 responders, seven underwent pump implantation procedure, two withdrew because of adverse effects, one refused an implant, and one could not have an implant (lack of funding from the Primary Care Trust). Our data demonstrated that mean VAS was reduced by approximately 25% at the group level after IT ziconotide bolus. Treatment efficacy did not vary with sex, center, age, or pain etiology. Ziconotide bolus was generally well tolerated. Larger studies are needed to determine if bolus dosing with ziconotide is a good predictor of response to continuous IT ziconotide via an intrathecal drug delivery system.

Research paper thumbnail of Intrathecal Therapy: What Has Changed With the Introduction of Ziconotide

Pain Practice, 2009

Administering drugs into the intrathecal space is becoming more popular in the treatment of patie... more Administering drugs into the intrathecal space is becoming more popular in the treatment of patients with intractable pain or intolerable side effects of systemic analgesic treatments. Although morphine and ziconotide are the only intrathecal analgesics currently approved by regulatory authorities in the U.S. (Food and Drug Administration) and Europe (national-level approval by individual countries for morphine and European Agency for the Evaluation of Medicinal Products approval for ziconotide), a wide variety of opioid and non-opioid drugs are being used in this way. There is no official guidance concerning the selection of these drugs or their use in combinations and a paucity of efficacy and safety data from randomized controlled trials. The polyanalgesic initiative aims to summarize the current knowledge and to facilitate rational choices of intrathecal drug and drug combinations for the management of chronic pain. The most recent polyanalgesic consensus recommendations were published in 2007. In this review, we shall examine these recommendations, which are tailored toward those practicing intrathecal analgesia in the U.S., and discuss how they should be implemented in Europe, where the healthcare systems and regulations of the medical authorities are different.

Research paper thumbnail of Targinact: targets opioid-induced constipation

Research paper thumbnail of The use of drugs beyond licence in palliative care and pain management

Palliative Medicine, 2002

Research paper thumbnail of A randomized, double-blind, crossover study of the use of transcutaneous spinal electroanalgesia in patients with pain from chronic critical limb ischemia

Journal of Pain and Symptom Management, 2004

Transcutaneous spinal electroanalgesia (TSE) uses two electrodes placed over the skin of the dors... more Transcutaneous spinal electroanalgesia (TSE) uses two electrodes placed over the skin of the dorsal spine to deliver pulses of short wavelength, high frequency, and relatively high voltage to the spinal cord without causing paresthesia. TSE has been used to treat pain and may improve limb blood flow. This randomized, double-blind, crossover study assessed the effect of TSE on microcirculation, pain, and activity in 8 patients (3 men, 5 women, median age 66.5 years, range 62-76 years) with chronic critical limb ischemia (CLI). After a one-week baseline period, patients used an active or inactive TSE machine for one hour daily for one week. Following a week of no stimulation, patients repeated the week of treatment with an identical matched machine. Daily use of TSE for one week did not improve microcirculatory perfusion (transcutaneous oxygenation), pain (verbal rating scale, McGill Pain Questionnaire), physical function (Functional Limitations Profile), mood (Beck Depression Inventory, Beck Anxiety Inventory), or sleep. There was no patient preference for the active TSE machines. This study showed that TSE administered daily for one week did not improve microcirculation, pain, or activity in patients with chronic CLI.

Research paper thumbnail of Validation of the PAC‐SYM questionnaire for opioid‐induced constipation in patients with chronic low back pain

European Journal of Pain, 2006

Background The Patient Assessment of Constipation Symptoms (PAC‐SYM) questionnaire is a 12‐item s... more Background The Patient Assessment of Constipation Symptoms (PAC‐SYM) questionnaire is a 12‐item self‐report instrument divided into abdominal, rectal and stool domains.Aims This study aimed to (1) evaluate the psychometric properties of PAC‐SYM in assessing the symptoms and severity of opioid‐induced constipation; (2) test for differences in opioid‐induced constipation between Durogesic® fentanyl transdermal reservoir (TDF) and oral sustained‐release morphine (SRM) in patients with chronic low back pain (CLBP).Methods In a 13‐month, open‐label, parallel‐group study, 680 patients were randomised to receive either TDF (n = 338) or SRM (n = 342) for CLBP. Assessments were recorded at Visit 1 (baseline), Visit 5 (Day 29) and Visit 17 (Month 13). Concurrent validity, clinical validity and responsiveness of PAC‐SYM were determined based on patients' confirmation of constipation (CC) scores. Differences in PAC‐SYM scores between treatment groups were also evaluated.Results The study in...

Research paper thumbnail of A Cochrane Systematic Review of Transcutaneous Electrical Nerve Stimulation for Cancer Pain

Journal of Pain and Symptom Management, Apr 30, 2009

Cancer-related pain is complex and multi-dimensional; yet, the mainstay of cancer pain management... more Cancer-related pain is complex and multi-dimensional; yet, the mainstay of cancer pain management has been the biomedical approach. There is a need for nonpharmacological and innovative pain management strategies. Transcutaneous electrical nerve stimulation (TENS) may have a role. The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED, and PEDro databases were searched for randomized controlled trials (RCTs) investigating the use of TENS for the management of cancer-related pain in adults. Once relevant studies were identified, two pairs of reviewers assessed eligibility for inclusion in the review based on a study eligibility form and using the 5-point Oxford Quality Scale. Two RCTs met the study eligibility criteria (these involved 64 patients). These studies were heterogeneous with respect to study population, methodology, and outcome measures. This prevented meta-analysis. In one RCT, there were no significant differences between TENS and placebo in women with chronic pain secondary to breast cancer treatment. In the other RCT, there were no significant differences between acupuncture-like TENS (AL-TENS) and sham in palliative care patients; this study was significantly underpowered. There is insufficient available evidence to determine the effectiveness of TENS in treating cancer-related pain. Further research is needed to help guide clinical practice, and large multi-center RCTs are required to assess the value of TENS in the management of cancerrelated pain in adults.

Research paper thumbnail of Bolus Intrathecal Injection of Ziconotide (Prialt®) to Evaluate the Option of Continuous Administration via an Implanted Intrathecal Drug Delivery (ITDD) System: A Pilot Study

Neuromodulation: Technology at the Neural Interface, 2013

Objectives: This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai... more Objectives: This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai Limited, Hertfordshire, UK) to assess the option of continuous administration of this drug via an implanted intrathecal drug delivery system.

Research paper thumbnail of Managing musculoskeletal pain in palliative care

Research paper thumbnail of New Formulation of Sustained Release Naloxone Can Reverse Opioid Induced Constipation Without Compromising the Desired Opioid Effects

Pain medicine (Malden, Mass.), Jan 24, 2015

An international double-blind randomized placebo controlled study evaluated the safety and effica... more An international double-blind randomized placebo controlled study evaluated the safety and efficacy of four doses of a new sustained release naloxone capsule to treat Opioid Induced Constipation (OIC). Forty patients taking opioids for noncancer related pain, and experiencing OIC, were randomized into 4 cohorts of 10 patients. A multiple ascending dose design was used to evaluate the safety and efficacy of 2.5 mg, 5 mg, 10 mg, and 20 mg naloxone sustained release (NSR) capsules vs placebo. Drug was given once-daily for 3 weeks followed by twice daily (bid) dosing between weeks 4 and 6. The incidence of treatment emergent adverse events was highest in the placebo group. The incidence of adverse events among the four active treatment groups were similar. There were no serious adverse events. The number of severe events was low overall but highest in the placebo group. Significant improvements were seen in Spontaneous Bowel Movements with 5 mg, 10 mg, and 20 mg NSR capsules. Mean chang...

Research paper thumbnail of Interventional techniques for pain management in palliative care

Medicine, 2011

about 10% of patients have pain that is difficult and they may benefit from interventions such as... more about 10% of patients have pain that is difficult and they may benefit from interventions such as nerve blocks, intrathecal drug delivery (iTDD) or percutaneous cordotomy. early referral for specialist pain management is needed if interventional techniques are being considered. it is important to manage pain with the simplest methods possible and to consider all available alternatives to an invasive technique. simple nerve blocks may be easy to organise and readily accepted by the patient. more complex nerve blocks may need hospital admission and coordinated aftercare. iTDD is a demanding technique that requires an experienced multidisciplinary pain team and good care in the community; this must be arranged before any intervention is considered. cordotomy requires specialist expertise and it is probably best provided by a few centres who can maintain adequate patients numbers to retain the necessary skills. Keywords cancer; intrathecal drug delivery; nerve blocks; pain; palliative care About 10% of patients have pain that is difficult to manage using conventional analgesics and co-analgesics (following the WHO analgesic ladder; page 68) and they may benefit from interventions such as nerve blocks, intrathecal drug delivery (ITDD) or percutaneous cordotomy. 1

Research paper thumbnail of Can chronic neuropathic pain following thoracic surgery be predicted during the postoperative period?

Interactive cardiovascular and thoracic surgery, 2009

Chronic pain following thoracic surgery is common and associated with neuropathic symptoms, howev... more Chronic pain following thoracic surgery is common and associated with neuropathic symptoms, however, the proportion of patients with neuropathic pain in the immediate postoperative period is unknown. We aimed to determine the proportion of patients who have neuropathic symptoms and signs immediately after, and at three months following thoracic surgery. The study was designed as a prospective observational cohort study. We identified patients with pain of predominantly neuropathic origin using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score in the immediate postoperative period and the self-report LANSS (S-LANSS) version three months after surgery. One hundred patients undergoing video assisted thoracic surgery (VATS) or thoracotomy completed LANSS scores preoperatively and in the immediate postoperative period. Eighty-seven percent completed three months S-LANSS follow-up scores. Eight percent of patients had positive LANSS scores in the immediate postoperative...

Research paper thumbnail of Radiation safety for anaesthetists

Continuing Education in Anaesthesia Critical Care & Pain, 2012

Anaesthetists are increasingly exposed to ionizing radiation while facilitating diagnosis and tre... more Anaesthetists are increasingly exposed to ionizing radiation while facilitating diagnosis and treatment in many settings. This can be as interventional practitioners, commonly in pain medicine, intensive care, and during vascular access procedures. A logical drive towards minimally invasive and safer interventions has led to an expansion in the use of fluoroscopy by a greater number of specialities including anaesthesia. In addition, better access to radiological services has increased to the point where X-rays can be performed in most clinical areas and CT scanning/fluoroscopyguided interventions occur 24 h a day. Unfortunately, this increase in exposure has not been paralleled by an increase in education about the safe use of ionizing radiation. It is important that anaesthetists do not rely on allied medical professionals to protect themselves and their patients from harm. When utilizing fluoroscopy, the anaesthetist should be aware of, and comply with the regulations surrounding the use of ionizing radiation and make the most effective use of the equipment to ensure exposure is kept as low as reasonably practicable (ALARP).

Research paper thumbnail of Fixed ratio (2:1) prolonged-release oxycodone/naloxone combination improves bowel function in patients with moderate-to-severe pain and opioid-induced constipation refractory to at least two classes of laxatives

Current medical research and opinion, 2014

The effects of combined oxycodone/naloxone prolonged release tablets (OXN PR) were investigated i... more The effects of combined oxycodone/naloxone prolonged release tablets (OXN PR) were investigated in patients with moderate-to-severe chronic cancer-related or non-cancer pain. All patients had opioid-induced constipation (OIC) which persisted despite substantial laxative therapy. This pooled analysis included 75 patients with OIC at study entry that was refractory to at least two laxatives with different modes of action. Patients completed randomized, double-blind treatment with OXN PR 20-120 mg/day for either 12 weeks (OXN 9001: non-cancer pain study) or 4 weeks (OXN 2001: cancer-related pain study). Analgesia and bowel function were assessed using the Brief Pain Inventory Short Form and Bowel Function Index (BFI), respectively. Use of laxative medication and safety were assessed throughout the studies. NCT00513656, EudraCT 2005-002398-57, EudraCT 2005-003510-15. Statistically and clinically significant improvements in bowel function were observed following double-blind treatment wi...

Research paper thumbnail of Microvascular Free-Tissue Transfers in Elderly Patients: The Leeds Experience

Plastic and Reconstructive Surgery, 1996

Research paper thumbnail of A Cochrane Systematic Review of Transcutaneous Electrical Nerve Stimulation for Cancer Pain

Journal of Pain and Symptom Management, 2009

Cancer-related pain is complex and multi-dimensional; yet, the mainstay of cancer pain management... more Cancer-related pain is complex and multi-dimensional; yet, the mainstay of cancer pain management has been the biomedical approach. There is a need for nonpharmacological and innovative pain management strategies. Transcutaneous electrical nerve stimulation (TENS) may have a role. The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED, and PEDro databases were searched for randomized controlled trials (RCTs) investigating the use of TENS for the management of cancer-related pain in adults. Once relevant studies were identified, two pairs of reviewers assessed eligibility for inclusion in the review based on a study eligibility form and using the 5-point Oxford Quality Scale. Two RCTs met the study eligibility criteria (these involved 64 patients). These studies were heterogeneous with respect to study population, methodology, and outcome measures. This prevented meta-analysis. In one RCT, there were no significant differences between TENS and placebo in women with chronic pain secondary to breast cancer treatment. In the other RCT, there were no significant differences between acupuncture-like TENS (AL-TENS) and sham in palliative care patients; this study was significantly underpowered. There is insufficient available evidence to determine the effectiveness of TENS in treating cancer-related pain. Further research is needed to help guide clinical practice, and large multi-center RCTs are required to assess the value of TENS in the management of cancerrelated pain in adults.

Research paper thumbnail of Stimulation-produced analgesia: acupuncture, TENS and related techniques

Anaesthesia & Intensive Care Medicine, 2008

Stimulation-produced analgesia (SPa) is a term that describes many techniques, both non-invasive ... more Stimulation-produced analgesia (SPa) is a term that describes many techniques, both non-invasive and invasive. These techniques relieve pain via both peripheral and central mechanisms. Simple antidromic conduction of non-painful stimuli (electrical or physical) and gate control of noxious impulses typically produce rapid analgesia of short duration. Longer-term effects are dependent on production of endogenous opioids at spinal cord and brain level and activation of non-opioid transmitter systems in the limbic system and at the spinal gate. There is no scientific evidence that metaphysical (without form or substance) energy pathways play any role in SPa. Methods of producing analgesia by nerve stimulation include non-invasive or minimally invasive techniques such as acupuncture, transcutaneous electrical nerve stimulation (TEnS) and acupressure. Good evidence indicates that they are useful as a sole or supplementary analgesic technique for many painful conditions, both acute and chronic. Electronic stimulators may also be permanently implanted at peripheral nerves, into the epidural space or into the brain. These invasive techniques are useful for refractory pain conditions, mostly of neuropathic origin. Keywords acupuncture; analgesia; electrical stimulation therapy; opioid peptides; pain Relieving pain by stimulation of nerves is not a new concept; 'rubbing a pain better' is instinctive. The use of needling is another well-established analgesic technique; the first textbook on acupuncture by the Yellow Emperor was written before 100 BC. 1 Electrical analgesia was documented even earlier by Aristotle who described the use of electric fish as a treatment for the pain of gout. 2 Neurophysiology of stimulation-produced analgesia (Figure 1) It is likely that analgesia after stimulation of nerves is produced via multiple mechanisms at peripheral and central sites. Although

Research paper thumbnail of Management of pain in the terminally ill

Anaesthesia & Intensive Care Medicine, 2013

Pain is common in terminal illness. It is a multi-dimensional experience and requires an integrat... more Pain is common in terminal illness. It is a multi-dimensional experience and requires an integrated approach for its management to be successful. Pharmacological treatment follows the World Health Organization pain ladder, with early use of strong opioid analgesia in moderate to severe cancer pain. A variety of opioids are now available and choice will be tailored to the individual needs of the patient. Complex pain states, such as neuropathic and cancer induced bone pain, often require multimodal treatment with adjuvant analgesia and interventional techniques. In the final days of life, drugs will be administered by continuous parenteral infusion, and titrated until symptom control is achieved.

Research paper thumbnail of Bolus Intrathecal Injection of Ziconotide (Prialt®) to Evaluate the Option of Continuous Administration via an Implanted Intrathecal Drug Delivery (ITDD) System: A Pilot Study

Neuromodulation: Technology at the Neural Interface, 2013

This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai Limited, He... more This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai Limited, Hertfordshire, UK) to assess the option of continuous administration of this drug via an implanted intrathecal drug delivery system. Twenty adults with severe chronic pain who were under consideration for intrathecal (IT) therapy were enrolled in this open label, nonrandomized, pilot study. Informed consent was obtained. Demographics, medical/pain history, pain scores, and concomitant medications were recorded. A physical examination was performed. Creatine kinase was measured. Initial visual analog scale (VAS), blood pressure, heart rate, and respiratory rate were recorded. All patients received an initial bolus dose of 2.5 mcg ziconotide; the dose in the subsequent visits was modified according to response. Subsequent doses were 2.5 mcg, 1.2 mcg, or 3.75 mcg as per protocol. A good response (≥30% reduction in baseline pain VAS) with no side-effects on two occasions was considered a successful trial. Data were analyzed using a generalized estimating equations model, with pain VAS as the outcome and time (seven time points; preinjection and one to six hours postinjection) as the predictor. Generalized estimating equations analysis of summary measures showed a mean reduction of pain VAS of approximately 25% at the group level; of 11 responders, seven underwent pump implantation procedure, two withdrew because of adverse effects, one refused an implant, and one could not have an implant (lack of funding from the Primary Care Trust). Our data demonstrated that mean VAS was reduced by approximately 25% at the group level after IT ziconotide bolus. Treatment efficacy did not vary with sex, center, age, or pain etiology. Ziconotide bolus was generally well tolerated. Larger studies are needed to determine if bolus dosing with ziconotide is a good predictor of response to continuous IT ziconotide via an intrathecal drug delivery system.

Research paper thumbnail of Intrathecal Therapy: What Has Changed With the Introduction of Ziconotide

Pain Practice, 2009

Administering drugs into the intrathecal space is becoming more popular in the treatment of patie... more Administering drugs into the intrathecal space is becoming more popular in the treatment of patients with intractable pain or intolerable side effects of systemic analgesic treatments. Although morphine and ziconotide are the only intrathecal analgesics currently approved by regulatory authorities in the U.S. (Food and Drug Administration) and Europe (national-level approval by individual countries for morphine and European Agency for the Evaluation of Medicinal Products approval for ziconotide), a wide variety of opioid and non-opioid drugs are being used in this way. There is no official guidance concerning the selection of these drugs or their use in combinations and a paucity of efficacy and safety data from randomized controlled trials. The polyanalgesic initiative aims to summarize the current knowledge and to facilitate rational choices of intrathecal drug and drug combinations for the management of chronic pain. The most recent polyanalgesic consensus recommendations were published in 2007. In this review, we shall examine these recommendations, which are tailored toward those practicing intrathecal analgesia in the U.S., and discuss how they should be implemented in Europe, where the healthcare systems and regulations of the medical authorities are different.

Research paper thumbnail of Targinact: targets opioid-induced constipation

Research paper thumbnail of The use of drugs beyond licence in palliative care and pain management

Palliative Medicine, 2002

Research paper thumbnail of A randomized, double-blind, crossover study of the use of transcutaneous spinal electroanalgesia in patients with pain from chronic critical limb ischemia

Journal of Pain and Symptom Management, 2004

Transcutaneous spinal electroanalgesia (TSE) uses two electrodes placed over the skin of the dors... more Transcutaneous spinal electroanalgesia (TSE) uses two electrodes placed over the skin of the dorsal spine to deliver pulses of short wavelength, high frequency, and relatively high voltage to the spinal cord without causing paresthesia. TSE has been used to treat pain and may improve limb blood flow. This randomized, double-blind, crossover study assessed the effect of TSE on microcirculation, pain, and activity in 8 patients (3 men, 5 women, median age 66.5 years, range 62-76 years) with chronic critical limb ischemia (CLI). After a one-week baseline period, patients used an active or inactive TSE machine for one hour daily for one week. Following a week of no stimulation, patients repeated the week of treatment with an identical matched machine. Daily use of TSE for one week did not improve microcirculatory perfusion (transcutaneous oxygenation), pain (verbal rating scale, McGill Pain Questionnaire), physical function (Functional Limitations Profile), mood (Beck Depression Inventory, Beck Anxiety Inventory), or sleep. There was no patient preference for the active TSE machines. This study showed that TSE administered daily for one week did not improve microcirculation, pain, or activity in patients with chronic CLI.

Research paper thumbnail of Validation of the PAC‐SYM questionnaire for opioid‐induced constipation in patients with chronic low back pain

European Journal of Pain, 2006

Background The Patient Assessment of Constipation Symptoms (PAC‐SYM) questionnaire is a 12‐item s... more Background The Patient Assessment of Constipation Symptoms (PAC‐SYM) questionnaire is a 12‐item self‐report instrument divided into abdominal, rectal and stool domains.Aims This study aimed to (1) evaluate the psychometric properties of PAC‐SYM in assessing the symptoms and severity of opioid‐induced constipation; (2) test for differences in opioid‐induced constipation between Durogesic® fentanyl transdermal reservoir (TDF) and oral sustained‐release morphine (SRM) in patients with chronic low back pain (CLBP).Methods In a 13‐month, open‐label, parallel‐group study, 680 patients were randomised to receive either TDF (n = 338) or SRM (n = 342) for CLBP. Assessments were recorded at Visit 1 (baseline), Visit 5 (Day 29) and Visit 17 (Month 13). Concurrent validity, clinical validity and responsiveness of PAC‐SYM were determined based on patients' confirmation of constipation (CC) scores. Differences in PAC‐SYM scores between treatment groups were also evaluated.Results The study in...

Research paper thumbnail of A Cochrane Systematic Review of Transcutaneous Electrical Nerve Stimulation for Cancer Pain

Journal of Pain and Symptom Management, Apr 30, 2009

Cancer-related pain is complex and multi-dimensional; yet, the mainstay of cancer pain management... more Cancer-related pain is complex and multi-dimensional; yet, the mainstay of cancer pain management has been the biomedical approach. There is a need for nonpharmacological and innovative pain management strategies. Transcutaneous electrical nerve stimulation (TENS) may have a role. The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED, and PEDro databases were searched for randomized controlled trials (RCTs) investigating the use of TENS for the management of cancer-related pain in adults. Once relevant studies were identified, two pairs of reviewers assessed eligibility for inclusion in the review based on a study eligibility form and using the 5-point Oxford Quality Scale. Two RCTs met the study eligibility criteria (these involved 64 patients). These studies were heterogeneous with respect to study population, methodology, and outcome measures. This prevented meta-analysis. In one RCT, there were no significant differences between TENS and placebo in women with chronic pain secondary to breast cancer treatment. In the other RCT, there were no significant differences between acupuncture-like TENS (AL-TENS) and sham in palliative care patients; this study was significantly underpowered. There is insufficient available evidence to determine the effectiveness of TENS in treating cancer-related pain. Further research is needed to help guide clinical practice, and large multi-center RCTs are required to assess the value of TENS in the management of cancerrelated pain in adults.

Research paper thumbnail of Bolus Intrathecal Injection of Ziconotide (Prialt®) to Evaluate the Option of Continuous Administration via an Implanted Intrathecal Drug Delivery (ITDD) System: A Pilot Study

Neuromodulation: Technology at the Neural Interface, 2013

Objectives: This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai... more Objectives: This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai Limited, Hertfordshire, UK) to assess the option of continuous administration of this drug via an implanted intrathecal drug delivery system.

Research paper thumbnail of Managing musculoskeletal pain in palliative care

Research paper thumbnail of New Formulation of Sustained Release Naloxone Can Reverse Opioid Induced Constipation Without Compromising the Desired Opioid Effects

Pain medicine (Malden, Mass.), Jan 24, 2015

An international double-blind randomized placebo controlled study evaluated the safety and effica... more An international double-blind randomized placebo controlled study evaluated the safety and efficacy of four doses of a new sustained release naloxone capsule to treat Opioid Induced Constipation (OIC). Forty patients taking opioids for noncancer related pain, and experiencing OIC, were randomized into 4 cohorts of 10 patients. A multiple ascending dose design was used to evaluate the safety and efficacy of 2.5 mg, 5 mg, 10 mg, and 20 mg naloxone sustained release (NSR) capsules vs placebo. Drug was given once-daily for 3 weeks followed by twice daily (bid) dosing between weeks 4 and 6. The incidence of treatment emergent adverse events was highest in the placebo group. The incidence of adverse events among the four active treatment groups were similar. There were no serious adverse events. The number of severe events was low overall but highest in the placebo group. Significant improvements were seen in Spontaneous Bowel Movements with 5 mg, 10 mg, and 20 mg NSR capsules. Mean chang...

Research paper thumbnail of Interventional techniques for pain management in palliative care

Medicine, 2011

about 10% of patients have pain that is difficult and they may benefit from interventions such as... more about 10% of patients have pain that is difficult and they may benefit from interventions such as nerve blocks, intrathecal drug delivery (iTDD) or percutaneous cordotomy. early referral for specialist pain management is needed if interventional techniques are being considered. it is important to manage pain with the simplest methods possible and to consider all available alternatives to an invasive technique. simple nerve blocks may be easy to organise and readily accepted by the patient. more complex nerve blocks may need hospital admission and coordinated aftercare. iTDD is a demanding technique that requires an experienced multidisciplinary pain team and good care in the community; this must be arranged before any intervention is considered. cordotomy requires specialist expertise and it is probably best provided by a few centres who can maintain adequate patients numbers to retain the necessary skills. Keywords cancer; intrathecal drug delivery; nerve blocks; pain; palliative care About 10% of patients have pain that is difficult to manage using conventional analgesics and co-analgesics (following the WHO analgesic ladder; page 68) and they may benefit from interventions such as nerve blocks, intrathecal drug delivery (ITDD) or percutaneous cordotomy. 1

Research paper thumbnail of Can chronic neuropathic pain following thoracic surgery be predicted during the postoperative period?

Interactive cardiovascular and thoracic surgery, 2009

Chronic pain following thoracic surgery is common and associated with neuropathic symptoms, howev... more Chronic pain following thoracic surgery is common and associated with neuropathic symptoms, however, the proportion of patients with neuropathic pain in the immediate postoperative period is unknown. We aimed to determine the proportion of patients who have neuropathic symptoms and signs immediately after, and at three months following thoracic surgery. The study was designed as a prospective observational cohort study. We identified patients with pain of predominantly neuropathic origin using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score in the immediate postoperative period and the self-report LANSS (S-LANSS) version three months after surgery. One hundred patients undergoing video assisted thoracic surgery (VATS) or thoracotomy completed LANSS scores preoperatively and in the immediate postoperative period. Eighty-seven percent completed three months S-LANSS follow-up scores. Eight percent of patients had positive LANSS scores in the immediate postoperative...

Research paper thumbnail of Radiation safety for anaesthetists

Continuing Education in Anaesthesia Critical Care & Pain, 2012

Anaesthetists are increasingly exposed to ionizing radiation while facilitating diagnosis and tre... more Anaesthetists are increasingly exposed to ionizing radiation while facilitating diagnosis and treatment in many settings. This can be as interventional practitioners, commonly in pain medicine, intensive care, and during vascular access procedures. A logical drive towards minimally invasive and safer interventions has led to an expansion in the use of fluoroscopy by a greater number of specialities including anaesthesia. In addition, better access to radiological services has increased to the point where X-rays can be performed in most clinical areas and CT scanning/fluoroscopyguided interventions occur 24 h a day. Unfortunately, this increase in exposure has not been paralleled by an increase in education about the safe use of ionizing radiation. It is important that anaesthetists do not rely on allied medical professionals to protect themselves and their patients from harm. When utilizing fluoroscopy, the anaesthetist should be aware of, and comply with the regulations surrounding the use of ionizing radiation and make the most effective use of the equipment to ensure exposure is kept as low as reasonably practicable (ALARP).

Research paper thumbnail of Fixed ratio (2:1) prolonged-release oxycodone/naloxone combination improves bowel function in patients with moderate-to-severe pain and opioid-induced constipation refractory to at least two classes of laxatives

Current medical research and opinion, 2014

The effects of combined oxycodone/naloxone prolonged release tablets (OXN PR) were investigated i... more The effects of combined oxycodone/naloxone prolonged release tablets (OXN PR) were investigated in patients with moderate-to-severe chronic cancer-related or non-cancer pain. All patients had opioid-induced constipation (OIC) which persisted despite substantial laxative therapy. This pooled analysis included 75 patients with OIC at study entry that was refractory to at least two laxatives with different modes of action. Patients completed randomized, double-blind treatment with OXN PR 20-120 mg/day for either 12 weeks (OXN 9001: non-cancer pain study) or 4 weeks (OXN 2001: cancer-related pain study). Analgesia and bowel function were assessed using the Brief Pain Inventory Short Form and Bowel Function Index (BFI), respectively. Use of laxative medication and safety were assessed throughout the studies. NCT00513656, EudraCT 2005-002398-57, EudraCT 2005-003510-15. Statistically and clinically significant improvements in bowel function were observed following double-blind treatment wi...

Research paper thumbnail of Microvascular Free-Tissue Transfers in Elderly Patients: The Leeds Experience

Plastic and Reconstructive Surgery, 1996

Research paper thumbnail of A Cochrane Systematic Review of Transcutaneous Electrical Nerve Stimulation for Cancer Pain

Journal of Pain and Symptom Management, 2009

Cancer-related pain is complex and multi-dimensional; yet, the mainstay of cancer pain management... more Cancer-related pain is complex and multi-dimensional; yet, the mainstay of cancer pain management has been the biomedical approach. There is a need for nonpharmacological and innovative pain management strategies. Transcutaneous electrical nerve stimulation (TENS) may have a role. The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED, and PEDro databases were searched for randomized controlled trials (RCTs) investigating the use of TENS for the management of cancer-related pain in adults. Once relevant studies were identified, two pairs of reviewers assessed eligibility for inclusion in the review based on a study eligibility form and using the 5-point Oxford Quality Scale. Two RCTs met the study eligibility criteria (these involved 64 patients). These studies were heterogeneous with respect to study population, methodology, and outcome measures. This prevented meta-analysis. In one RCT, there were no significant differences between TENS and placebo in women with chronic pain secondary to breast cancer treatment. In the other RCT, there were no significant differences between acupuncture-like TENS (AL-TENS) and sham in palliative care patients; this study was significantly underpowered. There is insufficient available evidence to determine the effectiveness of TENS in treating cancer-related pain. Further research is needed to help guide clinical practice, and large multi-center RCTs are required to assess the value of TENS in the management of cancerrelated pain in adults.

Research paper thumbnail of Stimulation-produced analgesia: acupuncture, TENS and related techniques

Anaesthesia & Intensive Care Medicine, 2008

Stimulation-produced analgesia (SPa) is a term that describes many techniques, both non-invasive ... more Stimulation-produced analgesia (SPa) is a term that describes many techniques, both non-invasive and invasive. These techniques relieve pain via both peripheral and central mechanisms. Simple antidromic conduction of non-painful stimuli (electrical or physical) and gate control of noxious impulses typically produce rapid analgesia of short duration. Longer-term effects are dependent on production of endogenous opioids at spinal cord and brain level and activation of non-opioid transmitter systems in the limbic system and at the spinal gate. There is no scientific evidence that metaphysical (without form or substance) energy pathways play any role in SPa. Methods of producing analgesia by nerve stimulation include non-invasive or minimally invasive techniques such as acupuncture, transcutaneous electrical nerve stimulation (TEnS) and acupressure. Good evidence indicates that they are useful as a sole or supplementary analgesic technique for many painful conditions, both acute and chronic. Electronic stimulators may also be permanently implanted at peripheral nerves, into the epidural space or into the brain. These invasive techniques are useful for refractory pain conditions, mostly of neuropathic origin. Keywords acupuncture; analgesia; electrical stimulation therapy; opioid peptides; pain Relieving pain by stimulation of nerves is not a new concept; 'rubbing a pain better' is instinctive. The use of needling is another well-established analgesic technique; the first textbook on acupuncture by the Yellow Emperor was written before 100 BC. 1 Electrical analgesia was documented even earlier by Aristotle who described the use of electric fish as a treatment for the pain of gout. 2 Neurophysiology of stimulation-produced analgesia (Figure 1) It is likely that analgesia after stimulation of nerves is produced via multiple mechanisms at peripheral and central sites. Although

Research paper thumbnail of Management of pain in the terminally ill

Anaesthesia & Intensive Care Medicine, 2013

Pain is common in terminal illness. It is a multi-dimensional experience and requires an integrat... more Pain is common in terminal illness. It is a multi-dimensional experience and requires an integrated approach for its management to be successful. Pharmacological treatment follows the World Health Organization pain ladder, with early use of strong opioid analgesia in moderate to severe cancer pain. A variety of opioids are now available and choice will be tailored to the individual needs of the patient. Complex pain states, such as neuropathic and cancer induced bone pain, often require multimodal treatment with adjuvant analgesia and interventional techniques. In the final days of life, drugs will be administered by continuous parenteral infusion, and titrated until symptom control is achieved.