Ketamine-facilitated behavioral treatment for cannabis use disorder: A proof of concept study.

BACKGROUND: Sub-anesthetic ketamine infusions may benefit a range of psychiatric conditions, including alcohol and cocaine use disorders. Currently, there are no effective pharmacological treatments for cannabis use disorder. OBJECTIVES: The objective of this uncontrolled proof of concept trial was to test the feasibility, tolerability, and potential therapeutic effects of integrating ketamine infusions with a behavioral platform of motivational enhancement therapy and mindfulness-based relapse prevention in treating cannabis use disorder (CUD). METHODS: Eight cannabis-dependent individuals (four female, four male) receiving motivational enhancement therapy and mindfulness-based relapse prevention behavioral treatments completed this single-blind outpatient 6-week study. Participants received either one or two infusions of ketamine (0.71 mg/kg [infusion 1]; 1.41 mg/kg [infusion 2] for non-responders) during the study. Participants self-reported cannabis use (Timeline Follow-Back) and underwent an assessment of confidence in abstaining from using cannabis (Drug-Taking Confidence Questionnaire) at predetermined time points throughout the study. RESULTS: Ketamine infusions were well-tolerated and there were no adverse events. Frequency of cannabis use decreased significantly from baseline (B = 5.1, s.e = 0.7) to the week following the first infusion (B = 0.8, s.e = 0.412), and remained reduced at the end of the study (B = 0.5, s.e = 0.3). Participants' confidence in their ability to abstain from cannabis in potentially triggering situations increased significantly from baseline to the end of study. CONCLUSIONS: These findings suggest that combining ketamine with behavioral therapy is feasible,tolerable, and potentially helpful, in treating cannabis-dependent individuals.

Guanfacine extended-release for cannabis use disorder: a pilot feasibility trial.

Background: Currently, there are no established pharmacotherapies for cannabis use disorders (CUDs). As a long-acting alpha-2-adrenergic receptor agonist, guanfacine extended-release (G-XR) could be useful in the treatment of CUDs by mitigating withdrawal and improving behavioral control.Objectives: To evaluate the feasibility and tolerability of G-XR as a treatment for CUDs.Methods: In an eight-week open-label outpatient pilot trial, we evaluated the safety and tolerability of G-XR in 22 cannabis dependent individuals. Using 2 different titration schedules, G-XR was gradually titrated to a dose of 4 mg or the highest dose tolerated. All participants received standard medication management.Results: Retention at week eight was 41%. Average daily amount of cannabis use (in grams: F1,86 = 8.74, p = .004; in dollars: F1,86 = 16.67, p < .0001) and cannabis using days (F1,86 = 7.67, p = .007) significantly reduced over the course of study participation. There were no significant differences between the titration schedules on emergence of side effects (Fisher exact test, p = .378) or retention (Log-Rank Test X21 = 0.021, p = .886). A total of 3 participants achieved 3 weeks or greater of total abstinence.Conclusions: G-XR is a feasible treatment for CUDs, and should be evaluated further in an efficacy trial.

New Directions in Medication-Facilitated Behavioral Treatment for Substance Use Disorders.

A promising approach to addressing substance use disorders is to integrate pharmacotherapy with a behavioral treatment with which synergy is possible. In this review, we focus on recent research suggesting that this approach may be effective for cocaine and cannabis use disorders, both of which currently lack efficacious medications. We summarize potential targets of pharmacotherapy of particular relevance to combined medication-behavioral treatment and examine preliminary evidence of clinical efficacy. Common to these promising medications is a hypothesized mechanism of action predicated on reversing drug-related neural adaptations, such as high reactivity to stress or drug cues, that might undermine fruitful engagement with behavioral treatment. We also review emerging medications, such as certain glutamatergic and serotonergic agents, which may be feasibly integrated with existing treatments. We conclude with an outline of future directions for research.

Complications and neurological deficits following minimally invasive anterior column release for adult spinal deformity: a retrospective study.

BACKGROUND: Minimally invasive techniques have become increasing popular and are expanding into deformity surgery. The lateral retroperitoneal transpsoas anterior column release (ACR) is a newer minimally invasive alternative to posterior osteotomy techniques for correcting and promoting global spinal alignment. This procedure attempts to avoid the potential complications associated with conventional osteotomies, but has its own subset of unique complications to be discussed in depth. METHODS: A retrospective review was performed in all patients who underwent the minimally invasive (MIS) ACR procedure from 2010 to present at our institution. All perioperative and postoperative complications were recorded by an independent reviewer. Demographics, spinopelvic parameters, and operative data were collected. The primary etiologic diagnosis was adult spinal deformity. Spinopelvic parameters were measured based on standing 36-inch scoliosis films. RESULTS: Thirty-one patients underwent a total of 47 MIS-ACRs. The mean age of the cohort was 62. Mean follow up was 12 months (range 3-38 months). The average change from in lumbar lordosis (LL) was 17.6°, in pelvic tilt was 4.3°, coronal Cobb was 13.9 and in SVA was 3.8 cm. Of the 47 MIS-ACR procedures, there were 9 (9/47, 19 %) major complications related to the ACR. Iliopsoas weakness was seen in eight patients and retrograde ejaculation in one patient. Only one patient remained with mild motor deficit at the most recent follow-up. No revision surgeries were required for the anterolateral approach. There was no vascular, visceral, or infectious complications associated with the MIS-ACR. CONCLUSION: The MIS-ACR is one of the most technically demanding procedures performed from the lateral transpsoas approach. This procedure has the advantage of maintaining and improving spinal global alignment while minimizing blood loss and excessive tissue dissection. It comes with its own unique set of potentially catastrophic complications and should only be performed by surgeons proficient in both deformity correction and the lateral approach.

Occipitocervical fusion via occipital condylar fixation: a clinical case series.

STUDY DESIGN: Retrospective review/case series. OBJECTIVE: This study aims to present the clinical feasibility of condylar fixation in occipitocervical (OC) fusion. Here, we present the largest clinical series to date of patients who underwent OC fusion via cervicocondylar fixation using a polyaxial screw/rod construct. SUMMARY OF BACKGROUND DATA: The novel technique using the occipital condyles as the sole cranial fixation point has been described. Both cadaveric and biomechanical studies, in recent literature, have shown technical feasibility and surgical safety of condylar fixation. METHODS: We retrospectively reviewed a prospectively acquired database of all patients treated with OC fusion via cervicocondylar fixation at our institution between 2007 and 2011. All patients were scheduled for follow-up postoperatively at weeks 2, 6, 12, 24, and annually thereafter. Outcome measures included estimated blood loss, operative time, complications, integrity of the construct, and fusion rates. Exclusion criteria included condylar fracture, previous cervical fusion, or vertebral artery injury. Enrolled patients subsequently underwent posterior OC fixation using occipital condyle, C1 lateral mass, and/or C2 pars interarticularis screw fixation. Subaxial cervical fixation consisted of lateral mass screw placement. Intraoperative fluoroscopy and hypoglossal monitoring were used. RESULTS: We identified 12 consecutive patients who underwent OC fusion using the occipital condyle as the cranial fixation point using polyaxial screws. The mean operative time was 283 minutes (192-416). The mean total blood loss was 229 mL (100-400). Mean follow-up was 21.4 months (4-39). One patient suffered from a superficial wound infection. There were no neural or vascular complications. Radiographic evidence of OC fusion was noted for all patients with >6-month follow-up. CONCLUSIONS: OC fusion using occipital condylar screws is a feasible alternative to current occipital plate fixation. Condylar screw fixation can be performed safely with successful arthrodesis as a treatment for OC instability in patients.

Individual mindfulness-based psychotherapy for cannabis or cocaine dependence: a pilot feasibility trial.

BACKGROUND: Mindfulness-based approaches may be effective treatments for substance use disorders (SUDs), but they have only been investigated for SUDs in the group setting. METHODS: A novel 10-week individual mindfulness-based psychotherapy was provided weekly to participants. Tolerability and therapeutic feasibility were assessed by retention rates, incidence of adverse events or clinical worsening, and abstinence rates at the end of the protocol. RESULTS: Twenty-five patients were enrolled overall, and 19 completed (74% overall retention rate). Of the 14 cannabis dependent patients enrolled in the study, 11 completed (79%), and 8 achieved abstinence (57% by intent-to-treat analysis) at 10 weeks. Of the 11 cocaine dependent patients, 8 completed (73%), and 6 achieved abstinence (55% by ITT) at 10 weeks. Abstinence rates were substantially greater than those of historical comparison groups. CONCLUSIONS: These findings indicate that mindfulness training can be tolerably and feasibly extended to the individual psychotherapy setting for the treatment of cocaine or cannabis dependence.

Does Amicar affect blood loss in patients with adolescent idiopathic scoliosis treated with pedicle screws and Ponte osteotomies?

Amicar may affect estimated blood loss (EBL) and blood transfusion in patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF) with pedicle screws and Ponte osteotomies. We performed a retrospective analysis of a prospectively collected, single-center database of 33 patients with main thoracic AIS treated with greater than 80% pedicle screws. Patients were divided into two groups based on whether they received Amicar (Yes), or did not receive any antifibrinolytics and Ponte osteotomies (No). Demographic, radiographic, and intraoperative data were compared between the two groups. Seventeen patients were treated with Amicar (Yes) (10 of whom had Ponte osteotomies) and 16 patients had neither antifibrinolytics nor Ponte osteotomies (No). The two groups had similar preoperative main Cobb angles, major curve flexibility, and gender. Despite longer operating times and a majority of patients receiving Ponte osteotomies, the Amicar group had a significantly lower EBL and homologous blood transfusion rate. Autologous transfusion volume was less in the Amicar group and trended toward significance. There were no differences in mean arterial pressure during surgery. There were no complications in either group. Amicar reduces EBL and homologous transfusion requirements in patients with main thoracic AIS undergoing PSF with pedicle screws and Ponte osteotomies.

The role of non-ordinary states of consciousness occasioned by mind-body practices in mental health illness.

BACKGROUND: Research with hallucinogens suggests that non-ordinary states of consciousness (NOSCs), particularly mystical-type experiences, predict improvements in various affective disorders and substance use disorders (SUDs). Little is known, however, about the therapeutic potential of NOSCs induced by mind-body practices such as meditation, yoga and breathwork. METHODS: We conducted a literature review in online databases (PubMed, Scopus, Google Scholar) and preprint databases (SSRN, bioRxiv) to identify studies of NOSCs induced by mind-body practices and their effects in affective disorders and SUDs. RESULTS: A wide variety of mind-body practices involving physical movement (i.e., shamanic drumming, yoga) and deliberate immersive experiences (i.e., meditation, breathwork) have been reported in the literature. Preliminary evidence, mostly from qualitative studies and open label studies, suggest that mind-body practices produce NOSCs. These experiences have also been correlated with short-term reductions in anxiety and depression, with increased motivation to change addictive behaviors, and with enhanced self-awareness and well-being. LIMITATIONS: Findings are limited by the scarcity of literature in this field. Further rigorous and methodologically sound empirical research is needed, including comparative studies of NOSCs occasioned by different methods. CONCLUSIONS: Mind-body practices may represent a promising approach for treating mental health disorders. The NOSCs induced by such practices may lead to beneficial shifts in perceptions, values, beliefs, and behaviors. Given the challenges with hallucinogen-based therapies, mind-body practices may represent a more accessible and acceptable way of eliciting potentially helpful NOSCs in clinical practice.

The effect of the retroperitoneal transpsoas minimally invasive lateral interbody fusion on segmental and regional lumbar lordosis.

BACKGROUND: The minimally invasive lateral interbody fusion (MIS LIF) in the lumbar spine can correct coronal Cobb angles, but the effect on sagittal plane correction is unclear. METHODS: A retrospective review of thirty-five patients with lumbar degenerative disease who underwent MIS LIF without supplemental posterior instrumentation was undertaken to study the radiographic effect on the restoration of segmental and regional lumbar lordosis using the Cobb angles on pre- and postoperative radiographs. Mean disc height changes were also measured. RESULTS: The mean follow-up period was 13.3 months. Fifty total levels were fused with a mean of 1.42 levels fused per patient. Mean segmental Cobb angle increased from 11.10° to 13.61° (P < 0.001) or 22.6%. L2-3 had the greatest proportional increase in segmental lordosis. Mean regional Cobb angle increased from 52.47° to 53.45° (P = 0.392). Mean disc height increased from 6.50 mm to 10.04 mm (P < 0.001) or 54.5%. CONCLUSIONS: The MIS LIF improves segmental lordosis and disc height in the lumbar spine but not regional lumbar lordosis. Anterior longitudinal ligament sectioning and/or the addition of a more lordotic implant may be necessary in cases where significant increases in regional lumbar lordosis are desired.

Early outcomes of minimally invasive anterior longitudinal ligament release for correction of sagittal imbalance in patients with adult spinal deformity.

The object of this study was to evaluate a novel surgical technique in the treatment of adult degenerative scoliosis and present our early experience with the minimally invasive lateral approach for anterior longitudinal ligament release to provide lumbar lordosis and examine its impact on sagittal balance. Methods. All patients with adult spinal deformity (ASD) treated with the minimally invasive lateral retroperitoneal transpsoas interbody fusion (MIS LIF) for release of the anterior longitudinal ligament were examined. Patient demographics, clinical data, spinopelvic parameters, and outcome measures were recorded. Results. Seven patients underwent release of the anterior longitudinal ligament (ALR) to improve sagittal imbalance. All cases were split into anterior and posterior stages, with mean estimated blood loss of 125 cc and 530 cc, respectively. Average hospital stay was 8.3 days, and mean follow-up time was 9.1 months. Comparing pre- and postoperative 36'' standing X-rays, the authors discovered a mean increase in global lumbar lordosis of 24 degrees, increase in segmental lumbar lordosis of 17 degrees per level of ALL released, decrease in pelvic tilt of 7 degrees, and decrease in sagittal vertical axis of 4.9 cm. At the last followup, there was a mean improvement in VAS and ODI scores of 26.2% and 18.3%. Conclusions. In the authors' early experience, release of the anterior longitudinal ligament using the minimally invasive lateral retroperitoneal transpsoas approach may be a feasible alternative in correcting sagittal deformity.

A comparison of independent depression and substance-induced depression in cannabis-, cocaine-, and opioid-dependent treatment seekers.

Depressive symptoms often coexist with substance use disorders (SUDs). The DSM-IV has identified two distinct categories for depression coexisting with SUDs-independent depression and substance-induced depression. While this distinction has important therapeutic and prognostic implications, it remains difficult to make in clinical practice; the differentiation is often guided by chronological and symptom severity criteria that patients may be unable to precisely provide. Furthermore, it is unclear whether the various substances commonly abused-cannabis, cocaine, and opioids-are equally associated with the two types of depression. Predictors, associations, and other markers may be helpful in guiding the diagnostic process. We, therefore, examined the differences between cannabis-, cocaine-, and opioid-dependent individuals contending with independent depression and those contending with substance-induced depression in regard to several variables, hypothesizing that independent depression is more commonly found in females, and that it is associated with higher symptom severity and psychiatric comorbidity. Cocaine-, cannabis-, and/or opioid-dependent, treatment-seeking individuals underwent a structured clinical interview for DSM-IV-TR disorders after providing consent at our clinical research site; those with co-existing primary depression or substance-induced depression diagnoses were provided with further questionnaires and were entered into this analysis (n= 242). Pair-wise comparisons were conducted between the groups classified as independent versus substance-induced depression with 2-by-2 tables and chi-square tests for dichotomous independent variables, and t-tests for continuous variables. Binomial logistic regression was performed in order to ascertain which of the variables were significant predictors. Women were more likely than men to have independent depression (p< .005). Cannabis dependence was highly associated with independent depression (p< .001), while cocaine dependence was highly associated with substance-induced depression (p< .05). Independent depression was associated with higher Hamilton depression scale scores (16 vs. 10, p< .005), and was more highly associated with the comorbid diagnosis of posttraumatic stress disorder (p< .05). Cannabis dependence (p< .001) and female gender (p< .05) were highly significant predictors of major depression specifically. Gender, cannabis dependence, psychiatric severity, and psychiatric comorbidity have variable, statistically significant associations with independent and substance-induced depression, and may be helpful in guiding the diagnostic process.

Comparison of polymethylmethacrylate versus expandable cage in anterior vertebral column reconstruction after posterior extracavitary corpectomy in lumbar and thoraco-lumbar metastatic spine tumors.

Single-stage posterior corpectomy for the management of spinal tumors has been well described. Anterior column reconstruction has been accomplished using polymethylmethacrylate (PMMA) or expandable cages (EC). The aim of this retrospective study was to compare PMMA versus ECs in anterior vertebral column reconstruction after posterior corpectomy for tumors in the lumbar and thoracolumbar spine. Between 2006 and 2009 we identified 32 patients that underwent a single-stage posterior extracavitary tumor resection and anterior reconstruction, 16 with PMMA and 16 with EC. There were no baseline differences in regards to age (mean: 58.2 years) or performance status. Differences between groups in terms of survival, estimated blood loss (EBL), kyphosis reduction (decrease in Cobb's angle), pain, functional outcomes, and performance status were evaluated. Mean overall survival and EBL were 17 months and 1165 ml, respectively. No differences were noted between the study groups in regards to survival (p = 0.5) or EBL (p = 0.8). There was a trend for better Kyphosis reduction in favor of the EC group (10.04 vs. 5.45, p = 0.16). No difference in performance status or VAS improvements was observed (p > 0.05). Seven patients had complications that led to reoperation (5 infections). PMMA or ECs are viable options for reconstruction of the anterior vertebral column following tumor resection and corpectomy. Both approaches allow for correction of the kyphotic deformity, and stabilization of the anterior vertebral column with similar functional and performance status outcomes in the lumbar and thoracolumbar area.

Abdominal wall paresis as a complication of minimally invasive lateral transpsoas interbody fusion.

OBJECT: The minimally invasive lateral transpsoas approach for interbody fusion has been increasingly employed to treat various spinal pathological entities. Gaining access to the retroperitoneal space and traversing the abdominal wall poses a risk of injury to the major nervous structures. Nerve injury of the abdominal wall can potentially lead to paresis of the abdominal musculature and bulging of the abdominal wall. Abdominal wall nerve injury resulting from the minimally invasive lateral retroperitoneal transpsoas approach has not been previously reported. The authors describe a case series of patients presenting with paresis and bulging of the abdominal wall after undergoing a minimally invasive lateral retroperitoneal approach. METHODS: The authors retrospectively reviewed all patients who underwent a minimally invasive lateral transpsoas approach for interbody fusion and in whom development of abdominal paresis developed; the patients were treated at 4 institutions between 2006 and 2010. All data were recorded including demographics, diagnosis, operative procedure, positioning, hospital course, follow-up, and complications. The onset, as well as resolution of the abdominal paresis, was reviewed. RESULTS: The authors identified 10 consecutive patients in whom abdominal paresis developed after minimally invasive lateral transpsoas spine surgery out of a total of 568 patients. Twenty-nine interbody levels were fused (range 1-4 levels/patient). There were 4 men and 6 women whose mean age was 54.1 years (range 37-66 years). All patients presented with abdominal paresis 2-6 weeks postoperatively. In 8 of the 10 patients, abdominal wall paresis had resolved by the 6-month follow-up visit. Two patients only had 1 and 4 months of follow-up. No long-term sequelae were identified. CONCLUSIONS: Abdominal wall paresis is a rare but known potential complication of abdominal surgery. The authors report the first case series associated with the minimally invasive lateral transpsoas approach.

Mindfulness impairments in individuals seeking treatment for substance use disorders.

BACKGROUND: Mindfulness training may be an effective treatment for substance use disorders (SUDs). Little research has been done, however, on baseline levels of mindfulness in the substance using population. OBJECTIVES/METHODS: We investigated mindfulness levels using the Mindful Attention Awareness Scale (MAAS) in individuals presenting for substance use treatment, and compared polydrug vs. monodrug users, as well as investigated for differences between groups based on substance used, predicting that group means would fall below the mean obtained from a large national adult sample, that the different drug groups would have comparable scores, and that the polydrug users would have a significantly lower score than do monodrug users. RESULTS: We found that the means of most drug groups were below the national mean, and that the polydrug users had a lower score on the MAAS than did monodrug users (4 vs. 3.6, p = 0.04). We were also surprised to find that opiate users had a significantly higher score (4.31) than did users of other substances (p = 0.02). CONCLUSION/SIGNIFICANCE: These results suggest that mindfulness deficits may be common in the substance using population, that there may be sub-groups in which these deficits are more pronounced, and that they may be a suitable focus of SUD treatment. These findings lend support to the ongoing development of mindfulness-based treatments for SUDs, and suggest that particular sub-groups may benefit more than others. Future research can aim at clarifying these deficits, and at elucidating their clinical relevance.

Mystical-type experiences occasioned by ketamine mediate its impact on at-risk drinking: Results from a randomized, controlled trial.

BACKGROUND: Sub-anesthetic ketamine administration may be helpful for substance use disorders. Converging evidence suggests that the efficacy of ketamine for certain conditions may implicate a subset of its psychoactive effects. AIMS: The aim of this analysis is to evaluate whether the mystical-type effects of ketamine are critical for clinical efficacy in alcohol-dependent individuals. In this secondary analysis, we determine if a subset of the psychoactive effects of ketamine, the so-called mystical-type experience, mediates the effect of ketamine, when combined with motivational enhancement therapy, on at-risk drinking behavior in alcohol-dependent individuals interested in treatment. METHODS: Forty alcohol dependent adults were randomized to either a 52-minute infusion of ketamine or midazolam, which they received on a designated quit-day during the second week of a five-week motivational enhancement therapy regimen. Psychoactive effects were assessed following the infusion, and alcohol use was monitored for the subsequent 3 weeks at each twice-weekly visit. RESULTS: We found that ketamine leads to significantly greater mystical-type effects (by Hood Mysticism Scale) and dissociation (by Clinician Administered Dissociative States Scale) compared to the active control. Ketamine also led to significant reduction in at-risk drinking. The Hood Mysticism Scale, but not Clinician Administered Dissociative States Scale score, was found to mediate the effect of ketamine on drinking behavior. CONCLUSIONS: This trial adds evidence to the literature on the importance of mystical-type experiences in addiction treatment. Future research should continue to investigate the relationship between the psychoactive effects of psychedelic therapeutics and clinical outcomes for other substance use and mental health disorders.

Early outcomes and safety of the minimally invasive, lateral retroperitoneal transpsoas approach for adult degenerative scoliosis.

OBJECT: The object of this study was to evaluate an alternative surgical approach to degenerative thoracolumbar deformity in adults. The authors present their early experience with the minimally invasive, lateral retroperitoneal transpsoas approach for placing interbody grafts and providing anterior column support for adult degenerative deformity. METHODS: The authors retrospectively reviewed a prospectively acquired database of all patients with adult thoracolumbar degenerative deformity treated with the minimally invasive, lateral retroperitoneal transpsoas approach at our institution. All patient data were recorded including demographics, preoperative evaluation, procedure used, postoperative follow-up, operative time, blood loss, length of hospital stay, and complications. The Oswestry Disability Index and visual analog scale (for pain) were also administered pre- and postoperatively as early outcome measures. All patients were scheduled for follow-up postoperatively at weeks 2, 6, 12, and 24, and at 1 year. RESULTS: The authors identified 25 patients with adult degenerative deformity who were treated using the minimally invasive, lateral retroperitoneal transpsoas approach. All patients underwent discectomy and lateral interbody graft placement for anterior column support and interbody fusion. The mean total blood loss was 53 ml per level. The average length of stay in the hospital was 6.2 days. Mean follow-up was 11 months (range 3-20 months). A mean improvement of 5.7 points on visual analog scale scores and 23.7% on the Oswestry Disability Index was observed. Perioperative complications include 1 patient with rhabdomyolysis requiring temporary hemodialysis, 1 patient with subsidence, and 1 patient with hardware failure. Three patients (12%) experienced transient postoperative anterior thigh numbness, ipsilateral to the side of approach. In this series, 20 patients (80%) were identified who had more than 6 months of follow-up and radiographic evidence of fusion. The minimally invasive, lateral retroperitoneal transpsoas approach, without the use of osteotomies, did not correct the sagittal balance in approximately one-third of the patients. CONCLUSIONS: Degenerative scoliosis of the adult spine is secondary to asymmetrical degeneration of the discs. Surgical decompression and correction of the deformity can be performed from an anterior, posterior, or combined approach. These procedures are often associated with long operative times and a high incidence of complications. The authors' experience with the minimally invasive, lateral retroperitoneal transpsoas approach for placement of a large interbody graft for anterior column support, restoration of disc height, arthrodesis, and realignment is a feasible alternative to these procedures.

A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial.

OBJECTIVE: Pharmacotherapy and behavioral treatments for alcohol use disorder are limited in their effectiveness, and new treatments with innovative mechanisms would be valuable. In this pilot study, the authors tested whether a single subanesthetic infusion of ketamine administered to adults with alcohol dependence and engaged in motivational enhancement therapy affects drinking outcomes. METHODS: Participants were randomly assigned to a 52-minute intravenous administration of ketamine (0.71 mg/kg, N=17) or the active control midazolam (0.025 mg/kg, N=23), provided during the second week of a 5-week outpatient regimen of motivational enhancement therapy. Alcohol use following the infusion was assessed with timeline followback method, with abstinence confirmed by urine ethyl glucuronide testing. A longitudinal logistic mixed-effects model was used to model daily abstinence from alcohol over the 21 days after ketamine infusion. RESULTS: Participants (N=40) were mostly middle-aged (mean age=53 years [SD=9.8]), predominantly white (70.3%), and largely employed (71.8%) and consumed an average of five drinks per day prior to entering the study. Ketamine significantly increased the likelihood of abstinence, delayed the time to relapse, and reduced the likelihood of heavy drinking days compared with midazolam. Infusions were well tolerated, with no participants removed from the study as a result of adverse events. CONCLUSIONS: A single ketamine infusion was found to improve measures of drinking in persons with alcohol dependence engaged in motivational enhancement therapy. These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder. Further research is needed to replicate these promising results in a larger sample.

Extended release mixed amphetamine salts and topiramate for cocaine dependence: A randomized clinical replication trial with frequent users.

BACKGROUND: Cocaine use disorder (CUD) remains a substantial public health problem with no clearly effective pharmacotherapy available. In a prior trial, combined amphetamine and topiramate treatment significantly reduced cocaine use among individuals demonstrating the most frequent use at baseline. This trial targeted such frequent users. METHODS: A double-blind, randomized placebo-controlled trial, testing the combination of mixed amphetamine salts extended-release (MAS-ER) and topiramate or placebo over a 12-week medication phase was conducted. The two-site outpatient trial included 127 adults (96 males) with CUD using at least 9 days in the prior month. MAS-ER was titrated to a maximum dose of 60 mg/day and topiramate to a maximum dose of 100 mg twice/day. The primary outcome was the proportion of individuals who achieved three consecutive abstinent weeks at the end of the study (EOS) as measured by urine toxicology and self-report. RESULTS: The proportion of participants achieving three abstinent weeks at the EOS was significantly (P = .03) larger in the treatment (14.1%) compared to the placebo group (0.0%), while controlling for baseline cocaine use, sex, current alcohol use disorder, and site. Of note, due to conservative cardiac safety-parameters a considerable number of individuals in the treatment group were discontinued from study medication (20.3%). CONCLUSIONS: While these findings provide further evidence that the combination of MAS-ER and topiramate is efficacious in promoting abstinence in CUD adults with frequent use it remains possible that the combination treatment is no more effective than either treatment alone. Despite this, the study provides a valuable "proof of concept."

Management of delayed esophageal perforations after anterior cervical spinal surgery.

OBJECT: Delayed esophageal perforation is an uncommon but well-known complication after anterior cervical spine surgery. To the authors' knowledge there is no consensus to the optimal management of these patients in the literature. METHODS: The authors performed a retrospective review of 5 cases involving patients who were referred to their institution for the management of delayed esophageal perforations after undergoing anterior cervical spine surgery for a variety of reasons. RESULTS: The primary presenting symptom in all 5 patients was dysphagia. All patients initially underwent primary closure of the perforation with a sternocleidomastoid muscle flap. One patient required multiple surgeries to correct the perforation and ultimately required a free flap. CONCLUSIONS: The authors recommend a multidisciplinary approach that involves otolaryngological surgeons as well as spine surgeons. They recommend removal of all anterior hardware and believe that it is essential to the treatment of esophageal perforations. If the patient does not have evidence of fusion at the time of presentation, then posterior cervical instrumentation is a viable alternative.