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Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial

Levin, Frances R; Mariani, John J; Pavlicova, Martina; Brooks, Daniel; Glass, Andrew; Mahony, Amy; Nunes, Edward V; Bisaga, Adam; Dakwar, Elias; Carpenter, Kenneth M; Sullivan, Maria A; Choi, Jean C
BACKGROUND: Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. METHODS: One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. RESULTS: There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. CONCLUSIONS: Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder.
PMCID:4729291
PMID: 26711160
ISSN: 1879-0046
CID: 2042242

Naltrexone-facilitated buprenorphine discontinuation: a feasibility trial

Dakwar, Elias; Kleber, Herbert D
RATIONALE: Buprenorphine is an effective and popular treatment for opioid dependence. It remains unclear, however, when or how to transition stable buprenorphine-maintained individuals to complete abstinence. This trial investigates the feasibility of using naltrexone to facilitate buprenorphine discontinuation in stable individuals who had tolerated a taper to 2mg or less but were unable to terminate entirely due to withdrawal-related distress. METHODS: The sample consisted of 6 buprenorphine-maintained individuals in sustained full remission, and who had tolerated a taper but were unable to discontinue altogether. A rapid induction procedure was performed, which included supervised buprenorphine discontinuation, oral naltrexone titration with a starting dose of 6.25mg, and administration of long-acting injectable naltrexone. Participants were followed weekly for 5weeks after the injection, with telephone follow-up occurring at 6months. RESULTS: The rapid induction procedure was well tolerated. There was no observed or reported clinical worsening over the course of study participation. Notably, no participants experienced an increase in Subjective Opioid Withdrawal Scale (SOWS) scores after the first oral dose of NTX as compared to day 1 (24hours after last dose of buprenorphine); instead, SOWS scores decreased between days 1 and 7 (p=0.043). All participants were able to discontinue buprenorphine and to remain opioid free during the trial and at follow-up. CONCLUSIONS: This preliminary trial represented for all participants the first successful attempt at buprenorphine discontinuation. Further research is needed to better understand if naltrexone is effective at facilitating buprenorphine discontinuation, as well as the feasibility of a sequential approach (buprenorphine stabilization to naltrexone) for opioid use disorders.
PMID: 25819700
ISSN: 1873-6483
CID: 1519142

Sagittal Spinopelvic Parameters in Scheuermann's Kyphosis: A Preliminary Study

Cahill, Patrick J; Steiner, Craig D; Dakwar, Elias; Trobisch, Per D; Lonner, Baron S; Newton, Peter O; Shah, Suken A; Sponseller, Paul D; Shufflebarger, Harry L; Samdani, Amer F
STUDY DESIGN: Retrospective, controlled, clinical study. OBJECTIVES: To define the average values for sagittal spinopelvic parameters including pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) in Scheuermann's kyphosis (SK); evaluate the differences in spinopelvic parameters among patients with SK and unaffected normal controls; and evaluate the correlation of various sagittal spinopelvic parameters to each other in SK and normal controls. METHODS: Prospectively collected radiographic data from a study on SK were compared with those from previously published series of unaffected patients. Measures were made according to standard, defined measurement methods. Parameters measured included PT, PI, SS, thoracic kyphosis, lumbar lordosis, and radiographic sagittal alignment. Values were compared using independent-samples t test. Pearson correlation coefficient was used to analyze relationships between variables. RESULTS: A total of 47 patients with SK and 50 control patients, mean age 16.1 and 13.5 years, respectively, were included. In SK, average PI was 42 degrees , average PT was 7 degrees , and average SS was 35 degrees . These values were not different from those of normal controls (PI, 46 degrees [p = .084]; PT, 8 degrees [p = .476]; SS, 37 degrees [p = .162]). Pelvic incidence directly correlated with lordosis in both groups (p < .005). T5-12 kyphosis correlated with lordosis in normal controls (p
PMID: 27927469
ISSN: 2212-1358
CID: 2468822

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

Murray, Gisela; Beckman, Joshua; Bach, Konrad; Smith, Donald A; Dakwar, Elias; Uribe, Juan S
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 degrees , in pelvic tilt was 4.3 degrees , 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.
PMID: 25850388
ISSN: 1432-0932
CID: 1528462

First Treatment Contact for ADHD: Predictors of and Gender Differences in Treatment Seeking

Dakwar, Elias; Levin, Frances R; Olfson, Mark; Wang, Shuai; Kerridge, Bradley; Blanco, Carlos
Objective: For attention-deficit hyperactivity disorder (ADHD), treatment seeking is a critical first step in treatment initiation and remains insufficiently understood. The aims of this study were to estimate ADHD treatment-seeking probabilities over the lifetime and to identify predictors of treatment seeking for ADHD separately for males and females. Methods: Data were drawn from 2001 to 2005 as part of the National Epidemiologic Survey on Alcohol and Related Conditions, a two-wave face-to-face survey conducted by the National Institute on Alcohol Abuse and Alcoholism (N=34,653). Results: The lifetime cumulative probability of ADHD treatment seeking was estimated at 55%. Males identifying as African American, with less than 12 years of education, or paranoid personality disorder or in an older cohort (>30 years old) at the time of interview were more likely to experience delays, whereas males with comorbid alcohol dependence, dysthymic disorder, borderline personality disorder, or histrionic personality disorder were less likely. Among females, older age (>44 years) was the only predictor of a delay to first treatment seeking, whereas bipolar disorder was associated with more rapid treatment seeking. Age of onset had opposite effects on treatment-seeking delays by gender; males but not females with early-onset ADHD were more likely to experience treatment-seeking delays. Conclusions: A large proportion of persons with ADHD do not seek treatment. Furthermore, treatment seeking by males was affected by a greater number of identifiable characteristics, suggesting that males might be more responsive to efforts directed toward expediting treatment entry. Future research should explore how to facilitate early access to treatment for individuals with ADHD.
PMCID:4312741
PMID: 25081894
ISSN: 1075-2730
CID: 1090372

The Effects of Subanesthetic Ketamine Infusions on Motivation to Quit and Cue-Induced Craving in Cocaine-Dependent Research Volunteers

Dakwar, Elias; Levin, Frances; Foltin, Richard W; Nunes, Edward V; Hart, Carl L
BACKGROUND: Cocaine dependence involves problematic neuroadaptations that might be responsive to modulation of glutamatergic circuits. This investigation examined the effects of subanesthetic ketamine infusions on motivation for quitting cocaine and on cue-induced craving in cocaine-dependent participants, 24 hours postinfusion. METHODS: Eight volunteers with active DSM-IV cocaine dependence not seeking treatment or abstinence were entered into this crossover, double-blind trial. Three 52-min intravenous infusions were administered: ketamine (.41 mg/kg or .71 mg/kg) or lorazepam 2 mg, counterbalanced into three orderings in which ketamine .41 mg/kg always preceded the .71 mg/kg dose. Infusions were separated by 48 hours, and assessments occurred at baseline and at 24 hours postinfusion. Outcomes were change between postinfusion and preinfusion values for: 1) motivation to quit cocaine scores with the University of Rhode Island Change Assessment; and 2) sums of visual analogue scale craving ratings administered during cue exposure. RESULTS: Compared with the active control lorazepam, a single ketamine infusion (.41 mg/kg) led to a mean 3.9-point gain in University of Rhode Island Change Assessment (p = .012), which corresponds to an approximately 60% increase over preceding values. There was a reduction of comparable magnitude in cue-induced craving (p = .012). A subsequent ketamine infusion (.71 mg/kg) led to further reductions in cue-induced craving compared with the control. Infusions were well-tolerated. CONCLUSIONS: Subanesthetic ketamine demonstrated promising effects on motivation to quit cocaine and on cue-induced craving, 24 hours postinfusion. Research is needed to expand on these preliminary results and to evaluate the efficacy of this intervention in clinical settings.
PMCID:4105157
PMID: 24035344
ISSN: 0006-3223
CID: 896922

Occipitocervical fusion via occipital condylar fixation: a clinical case series

Ahmadian, Amir; Dakwar, Elias; Vale, Fernando L; Uribe, Juan S
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.
PMID: 24866907
ISSN: 1536-0652
CID: 1018672

Therapeutic infusions of ketamine: Do the psychoactive effects matter?

Dakwar, E; Anerella, C; Hart, C L; Levin, F R; Mathew, S J; Nunes, E V
BACKGROUND: Sub-anesthetic ketamine infusions may benefit a variety of psychiatric disorders, including addiction. Though ketamine engenders transient alterations in consciousness, it is not known whether these alterations influence efficacy. This analysis evaluates the mystical-type effects of ketamine, which may have therapeutic potential according to prior research, and assesses whether these effects mediate improvements in dependence-related deficits, 24h postinfusion. METHODS: Eight cocaine dependent individuals completed this double-blind, randomized, inpatient study. Three counter-balanced infusions separated by 48h were received: lorazepam (2mg) and two doses of ketamine (0.41mg/kg and 0.71mg/kg, with the former dose always preceding the latter). Infusions were followed within 15min by measures of dissociation (Clinician Administered Dissociative Symptoms Scale: CADSS) and mystical-type effects (adapted from Hood's Mysticism Scale: HMS). At baseline and 24h postinfusion, participants underwent assessments of motivation to stop cocaine (University of Rhode Island Change Assessment) and cue-induced craving (by visual analogue scale for cocaine craving during cue exposure). RESULTS: Ketamine led to significantly greater acute mystical-type effects (by HMS) relative to the active control lorazepam; ketamine 0.71mg/kg was associated with significantly higher HMS scores than was the 0.41mg/kg dose. HMS score, but not CADSS score, was found to mediate the effect of ketamine on motivation to quit cocaine 24h postinfusion. CONCLUSIONS: These findings suggest that psychological mechanisms may be involved in some of the anti-addiction benefits resulting from ketamine. Future research can evaluate whether the psychoactive effects of ketamine influence improvements in larger samples.
PMCID:4091719
PMID: 24480515
ISSN: 0376-8716
CID: 811092

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

Dakwar, Elias; Levin, Frances R
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.
PMCID:4076045
PMID: 24131158
ISSN: 1055-0496
CID: 896932

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

Iorio, Justin; Bennett, James T; Orlando, Giuseppe; Singla, Anuj; Dakwar, Elias; Bonet, Harry; Samdani, Amer F
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.
PMID: 23975447
ISSN: 1090-3941
CID: 896912