Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder.

OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. METHODS: In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. RESULTS: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. CONCLUSIONS: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.

An Interactive Pain Application (MServ) Improves Postoperative Pain Management.

Background: Most patients have moderate or severe pain after surgery. Opioids are the cornerstone of treating severe pain after surgery but cause problems when continued long after discharge. We investigated the efficacy of multifunction pain management software (MServ) in improving postoperative pain control and reducing opioid prescription at discharge. Methods: We recruited 234 patients to a prospective cohort study into sequential groups in a nonrandomised manner, one day after major thoracic or urological surgery. Group 1 received standard care (SC, n = 102), group 2 were given a multifunctional device that fed back to the nursing staff alone (DN, n = 66), and group 3 were given the same device that fed back to both the nursing staff and the acute pain team (DNPT, n = 66). Patient-reported pain scores at 24 and 48 hours and patient-reported time in severe pain, medications, and satisfaction were recorded on trial discharge. Findings. Odds of having poor pain control (>1 on 0-4 pain scale) were calculated between standard care (SC) and device groups (DN and DNPT). Patients with a device were significantly less likely to have poor pain control at 24 hours (OR 0.45, 95% CI 0.25, 0.81) and to report time in severe pain at 48 hours (OR 0.62, 95% CI 0.47-0.80). Patients with a device were three times less likely to be prescribed strong opioids on discharge (OR 0.35, 95% CI 0.13 to 0.95). Interpretation. Using an mHealth device designed for pain management, rather than standard care, reduced the incidence of poor pain control in the postoperative period and reduced opioid prescription on discharge from hospital.

Feasibility of palliating recurrent gynecological tumors with MRGHIFU: comparison of symptom, quality-of-life, and imaging response in intra and extra-pelvic disease.

OBJECTIVE: To document longitudinal symptom, quality-of-life and imaging response in patients with recurrent gynecological tumors treated with magnetic resonance guided high intensity focused ultrasound (MRgHIFU), and compare changes in patients with intra- versus extra-pelvic lesions. METHODS: Eleven symptomatic patients with painful recurrent gynecological tumors were treated with MRgHIFU (Profound Sonalleve) in a prospective single center study (NCT02714621). Pain scores, analgesic intake and quality-of-life metrics, whole tumor volume, and perfused tumor volume from Gadolinium-enhanced T1W imaging documented before and up to 90 days after treatment were compared between patients with intra- and extra-pelvic tumors. RESULTS: Two of five patients with intra-pelvic and three of six patients with extra-pelvic tumors were classified as responders (>2 point reduction in NRS pain score without analgesia increase or a > 25% reduction in analgesic use). Cohort reductions in worst pain scores were not significant for either group. Emotional functioning for the whole cohort improved, although physical functioning did not. Ablative thermal temperatures were achieved in three patients with extra-pelvic tumors, but in none whose tumors were intra-pelvic. Pain response did not correlate with thermal dose. Tumor volume increased by 18% immediately post-treatment in the extra-pelvic but not in the intra-pelvic group. Ratio of perfused to whole lesion volume decreased by >20% by day 30 in extra-pelvic, but not intra-pelvic tumors although at day 30 both extra-pelvic and intra-pelvic tumors increased in volume. CONCLUSION: MRgHIFU treatments can be delivered safely to patients with recurrent gynecological tumors. Extra-pelvic tumors responded better than intra-pelvic tumors and showed immediate swelling and reduction in perfused volume by day 30.

Recent advances in understanding chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common cause of pain and poor quality of life for those undergoing treatment for cancer and those surviving cancer. Many advances have been made in the pre-clinical science; despite this, these findings have not been translated into novel preventative measures and treatments for CIPN. This review aims to give an update on the pre-clinical science, preventative measures, assessment and treatment of CIPN.

Bleeding from peristomal varices: a complication of portal hypertension.

Peristomal varices are a recognised complication of stomas in the presence of portal hypertension. There has been a progression of treatment options described in the literature, including the transjugular intrahepatic portosystemic shunt (TIPS). The use of TIPS, a percutaneous procedure allowing connection between the portal and systemic circulations within the liver, is a well-recognised method of treating the complications of portal hypertension. This report presents a case of peristomal varices successfully treated with TIPS and subsequently reviews the literature relating to its management.

Central neuronal mechanisms in cancer-induced bone pain.

PURPOSE OF REVIEW: To consider distinct neuropharmacological substrates that underlie transmission of impulses from the periphery to the central nervous system in cancer pain. RECENT FINDINGS: Advances reveal that plasticity, the ability of the nervous system to alter in response to external events, leads to changes throughout the pathways involved in the perception of pain. Exploitation of pharmacological, functional, molecular and genomic techniques is a basis for new insights into the molecular and cellular mechanisms that contribute to the pain that follows pathophysiology. Characteristic changes experienced with chronic or persistent pain from various causes include expanded receptive fields, allodynia and spontaneous pain in the absence of external stimuli. In addition there are the affective and emotional responses that have to be considered along with these sensory aspects of pain. SUMMARY: It is clear that although the sensory and psychological aspects of pain are separable, the neural pathways that contribute to these aspects of pain are interlinked. Furthermore, at both peripheral and central sites, there are mechanisms that amplify and prolong the painful stimulus--this can result in severe pain in the presence of relatively minor peripheral pathology. This review considers these signalling systems and changes therein in the context of pain in cancer.

Efficacy of chronic morphine in a rat model of cancer-induced bone pain: behavior and in dorsal horn pathophysiology.

UNLABELLED: Morphine is one of the main analgesics in cancer-induced bone pain (CIBP). To investigate the efficacy of morphine in CIBP and alteration in dorsal horn pathophysiology, systemic morphine was administered (3 mg/kg) bi-daily between days 11 and 15 after MRMT-1 carcinoma cell injections (compared with a single injection (3 mg/kg) of morphine on day 15, and acute spinal morphine (0.1, 1, 10 microg/50 microL). The chronic systemic morphine schedule significantly attenuated pain behavior (von Frey 15 g; P < .01) to a greater extent than acute systemic morphine (von Frey 15 g; P < .05). In vivo electrophysiology (day 15 chronic systemic morphine) showed an attenuation of hyperexcitable wide dynamic range (WDR) neurons, but the abnormal raised WDR to nociceptive specific neuronal ratio remained. Acute spinal morphine attenuated electrical and natural WDR neuronal response in shams at a lower dose (1 microg) compared with cancer (10 microg). Chronic morphine is more effective at attenuating pain-related behaviors than single doses, although the dorsal horn retains a pathophysiologic characterization. PERSPECTIVE: This study confirms the resemblance of the rat model to human CIBP with respect to the efficacy of morphine and further suggests that adjuvant therapy is required to reverse the dorsal horn pathophysiology.