Buprenorphine-naloxone Versus Buprenorphine for Treatment of Opioid Use Disorder in Pregnancy.

OBJECTIVES: Data regarding treatment outcomes with the use of buprenorphine-naloxone (BUP-NX) in pregnancy are scarce. The objective of this study is to examine the outcomes in a cohort of pregnancies treated with BUP-NX versus buprenorphine (BUP). METHODS: This single-center, retrospective cohort study examined birthing person-infant dyads treated with BUP-NX versus BUP. The primary birthing person outcome was return to opioid use in pregnancy. The primary neonatal outcome was the need for pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). RESULTS: The BUP-NX and the BUP treatment groups included 33 and 73 dyads, respectively. Except for psychiatric medication use, all demographics were similar between groups. In the final regression models, neither the birthing person nor the neonatal outcomes differed. The adjusted odds ratio for return to use during pregnancy for the BUP-NX versus BUP groups was 1.93 (95% confidence interval, 0.78-4.76). The adjusted odds ratio for pharmacologic treatment of NOWS for the BUP-NX versus BUP groups was 0.65 (95% confidence interval, 0.27-1.54). Among a subgroup of persons who transitioned from BUP to BUP-NX mid-pregnancy, there was no proximate return to use or need for dose increase. CONCLUSIONS: Compared with BUP, the use of BUP-NX in pregnancy is not associated with a higher risk of return to opioid use or a higher need for pharmacological treatment for NOWS.

Association of Peripheral Serum MicroRNAs With Persistent Phantom Limb Pain in Individuals With Amputation.

OBJECTIVE: Individuals with major limb amputation(s) frequently experience phantom limb sensations, which are described as vivid impressions of either parts or entire missing limb(s). Despite the high incidence and prevalence of phantom limb pain, the underlying pathophysiology of phantom limb pain remains poorly understood. The objective of this study was to evaluate a possible role of microRNAs in the pathophysiology of phantom limb pain. DESIGN: Adults with acquired limb amputation and varying degrees of phantom limb pain consented to provide clinical data and blood samples. One hundred forty participants with single or multiple limb amputation(s) were enrolled. The Visual analog scale and neuropathic pain symptom inventory were administered to evaluate the pain. Serum samples were analyzed for microRNA expression and bioinformatic analysis was performed. RESULTS: Sixty-seven participants did not experience phantom limb pain, whereas 73 participants experienced varying severities of phantom limb pain measured on a pain scale. Linear regression analysis suggested that the time since amputation is inversely related to severity of the pain. A significantly increased expression of 16 microRNAs was observed in participants experiencing phantom limb pain. Bioinformatic analysis shows a possible role of these microRNAs in regulating genes expressed in peripheral neuropathy. CONCLUSIONS: This study provides the first evidence of association of microRNA in phantom limb pain.

Characteristics of phantom limb pain in U.S. civilians and service members.

OBJECTIVES: The population of Americans with limb loss is on the rise, with a different profile than in previous generations (e.g., greater incidence of amputation due to diabetes). This study aimed to identify the key characteristics of phantom limb sensation (PLS) and pain (PLP) in a current sample of Americans with limb loss. METHODS: This cross-sectional study is the first large-scale (n=649) study on PLP in the current population of Americans with limb loss. A convenience sample of military and civilian persons missing one or more major limbs was surveyed regarding their health history and experience with phantom limb phenomena. RESULTS: Of the participants surveyed, 87% experienced PLS and 82% experienced PLP. PLS and PLP typically first occurred immediately after amputation (47% of cases), but for a small percentage (3-4%) onset did not occur until over a year after amputation. Recent PLP severity decreased over time (ß=0.028, 95% CI: -0.05-0.11), but most participants reported PLP even 10 years after amputation. Higher levels of recent PLP were associated with telescoping (ß=0.123, 95% CI: 0.04-0.21) and higher levels of pre-amputation pain (ß=0.104, 95% CI: 0.03-0.18). Those with congenitally missing limbs experienced lower levels of recent PLP (t (37.93)=3.93, p<0.01) but there were no consistent differences in PLP between other amputation etiologies. CONCLUSIONS: Phantom limb phenomena are common and enduring. Telescoping and pre-amputation pain are associated with higher PLP. Persons with congenitally missing limbs experience lower levels of PLP than those with amputation(s), yet PLP is common even in this subpopulation.

Clinical evaluation of the revolutionizing prosthetics modular prosthetic limb system for upper extremity amputees.

Individuals with upper extremity (UE) amputation abandon prostheses due to challenges with significant device weight-particularly among myoelectric prostheses-and limited device dexterity, durability, and reliability among both myoelectric and body-powered prostheses. The Modular Prosthetic Limb (MPL) system couples an advanced UE prosthesis with a pattern recognition paradigm for intuitive, non-invasive prosthetic control. Pattern recognition accuracy and functional assessment-Box & Blocks (BB), Jebsen-Taylor Hand Function Test (JHFT), and Assessment of Capacity for Myoelectric Control (ACMC)-scores comprised the main outcomes. 10 participants were included in analyses, including seven individuals with traumatic amputation, two individuals with congenital limb absence, and one with amputation secondary to malignancy. The average (SD) time since limb loss, excluding congenital participants, was 85.9 (59.5) months. Participants controlled an average of eight motion classes compared to three with their conventional prostheses. All participants made continuous improvements in motion classifier accuracy, pathway completion efficiency, and MPL manipulation. BB and JHFT improvements were not statistically significant. ACMC performance improved for all participants, with mean (SD) scores of 162.6 (105.3), 213.4 (196.2), and 383.2 (154.3), p = 0.02 between the baseline, midpoint, and exit assessments, respectively. Feedback included lengthening the training period to further improve motion classifier accuracy and MPL control. The MPL has potential to restore functionality to individuals with acquired or congenital UE loss.

Virtual Integration Environment as an Advanced Prosthetic Limb Training Platform.

Background: Despite advances in prosthetic development and neurorehabilitation, individuals with upper extremity (UE) loss continue to face functional and psychosocial challenges following amputation. Recent advanced myoelectric prostheses offer intuitive control over multiple, simultaneous degrees of motion and promise sensory feedback integration, but require complex training to effectively manipulate. We explored whether a virtual reality simulator could be used to teach dexterous prosthetic control paradigms to individuals with UE loss. Methods: Thirteen active-duty military personnel with UE loss (14 limbs) completed twenty, 30-min passive motor training sessions over 1-2 months. Participants were asked to follow the motions of a virtual avatar using residual and phantom limbs, and electrical activity from the residual limb was recorded using surface electromyography. Eight participants (nine limbs), also completed twenty, 30-min active motor training sessions. Participants controlled a virtual avatar through three motion sets of increasing complexity (Basic, Advanced, and Digit) and were scored on how accurately they performed requested motions. Score trajectory was assessed as a function of time using longitudinal mixed effects linear regression. Results: Mean classification accuracy for passive motor training was 43.8 ± 10.7% (14 limbs, 277 passive sessions). In active motor sessions, >95% classification accuracy (which we used as the threshold for prosthetic acceptance) was achieved by all participants for Basic sets and by 50% of participants in Advanced and Digit sets. Significant improvement in active motor scores over time was observed in Basic and Advanced sets (per additional session: ß-coefficient 0.125, p = 0.022; ß-coefficient 0.45, p = 0.001, respectively), and trended toward significance for Digit sets (ß-coefficient 0.594, p = 0.077). Conclusions: These results offer robust evidence that a virtual reality training platform can be used to quickly and efficiently train individuals with UE loss to operate advanced prosthetic control paradigms. Participants can be trained to generate muscle contraction patterns in residual limbs that are interpreted with high accuracy by computer software as distinct active motion commands. These results support the potential viability of advanced myoelectric prostheses relying on pattern recognition feedback or similar controls systems.

Clinical Trial of the Virtual Integration Environment to Treat Phantom Limb Pain With Upper Extremity Amputation.

Background: Phantom limb pain (PLP) is commonly seen following upper extremity (UE) amputation. Use of both mirror therapy, which utilizes limb reflection in a mirror, and virtual reality therapy, which utilizes computer limb simulation, has been used to relieve PLP. We explored whether the Virtual Integration Environment (VIE), a virtual reality UE simulator, could be used as a therapy device to effectively treat PLP in individuals with UE amputation. Methods: Participants with UE amputation and PLP were recruited at Walter Reed National Military Medical Center (WRNMMC) and instructed to follow the limb movements of a virtual avatar within the VIE system across a series of study sessions. At the end of each session, participants drove virtual avatar limb movements during a period of "free-play" utilizing surface electromyography recordings collected from their residual limbs. PLP and phantom limb sensations were assessed at baseline and following each session using the Visual Analog Scale (VAS) and Short Form McGill Pain Questionnaire (SF-MPQ), respectively. In addition, both measures were used to assess residual limb pain (RLP) at baseline and at each study session. In total, 14 male, active duty military personnel were recruited for the study. Results: Of the 14 individuals recruited to the study, nine reported PLP at the time of screening. Eight of these individuals completed the study, while one withdrew after three sessions and thus is not included in the final analysis. Five of these eight individuals noted RLP at baseline. Participants completed an average of 18, 30-min sessions with the VIE leading to a significant reduction in PLP in seven of the eight (88%) affected limbs and a reduction in RLP in four of the five (80%) affected limbs. The same user reported an increase in PLP and RLP across sessions. All participants who denied RLP at baseline (n = 3) continued to deny RLP at each study session. Conclusions: Success with the VIE system confirms its application as a non-invasive and low-cost therapy option for PLP and phantom limb symptoms for individuals with upper limb loss.

Initial Clinical Evaluation of the Modular Prosthetic Limb.

The Modular Prosthetic Limb (MPL) was examined for its feasibility and usability as an advanced, dexterous upper extremity prosthesis with surface electromyography (sEMG) control in with two individuals with below-elbow amputations. Compared to currently marketed prostheses, the MPL has a greater number of sequential and simultaneous degrees of motion, as well as wrist modularity, haptic feedback, and individual digit control. The MPL was successfully fit to a 33-year-old with a trans-radial amputation (TR01) and a 30-year-old with a wrist disarticulation amputation (TR02). To preserve anatomical limb length, we adjusted the powered degrees of freedom of wrist motion between users. Motor training began with practicing sEMG and pattern recognition control within the virtual integration environment (VIE). Prosthetic training sessions then allowed participants to complete a variety of activities of daily living with the MPL. Training and Motion Control Accuracy scores quantified their ability to consistently train and execute unique muscle-to-motion contraction patterns. Each user also completed one prosthetic functional metric-the Southampton Hand Assessment Procedure (SHAP) for TR01 and the Jebsen-Taylor Hand Function Test (JHFT) for TR02. Haptic feedback capabilities were integrated for TR01. TR01 achieved 95% accuracy at 84% of his VIE sessions. He demonstrated improved scores over a year of prosthetic training sessions, ultimately achieving simultaneous control of 13 of the 17 (76%) attempted motions. His performance on the SHAP improved from baseline to final assessment with an increase in number of tasks achieved. TR01 also used vibrotactile sensors to successfully discriminate between hard and soft objects being grasped by the MPL hand. TR02 demonstrated 95% accuracy at 79% of his VIE sessions. He demonstrated improved scores over months of prosthetic training sessions, however there was a significant drop in scores initially following a mid-study pause in testing. He ultimately achieved simultaneous control of all 13 attempted powered motions, and both attempted passive motions. He completed 5 of the 7 (71%) JHFT tasks within the testing time limit. These case studies confirm that it is possible to use non-invasive motor control to increase functional outcomes with individuals with below-elbow amputation and will help to guide future myoelectric prosthetic studies.

Effect of concussion and blast exposure on symptoms after military deployment.

OBJECTIVE: To examine whether blast exposure alone and blast-associated concussion result in similar neurologic and mental health symptoms. METHODS: A 14-item questionnaire was administered to male US Marines on their return from deployment in Iraq and/or Afghanistan. RESULTS: A total of 2,612 Marines (median age 22 years) completed the survey. Of those, 2,320 (88.9%) reported exposure to ≥1 blast during their current and/or prior deployments. In addition, 1,022 (39.1%) reported ≥1 concussion during the current deployment, and 731 (28.0%) had experienced at least 1 prior lifetime concussion. Marines were more likely to have sustained a concussion during the current deployment if they had a history of 1 (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-2.0) or ≥1 (OR 2.3, 95% CI 1.7-3.0) prior concussion. The most common symptoms were trouble sleeping (38.4%), irritability (37.9%), tinnitus (33.8%), and headaches (33.3%). Compared to those experiencing blast exposure without injury, Marines either experiencing a concussion during the current deployment or being moved or injured by a blast had an increased risk of postinjury symptoms. CONCLUSIONS: There appears to be a continuum of increasing total symptoms from no exposure to blast exposure plus both current deployment concussion and past concussion. Concussion had a greater influence than blast exposure alone on the presence of postdeployment symptoms. A high blast injury score can be used to triage those exposed to explosive blasts for evaluation.

A Randomized, Controlled Trial of Mirror Therapy for Upper Extremity Phantom Limb Pain in Male Amputees.

OBJECTIVE: Phantom limb pain (PLP) is prevalent in patients post-amputation and is difficult to treat. We assessed the efficacy of mirror therapy in relieving PLP in unilateral, upper extremity male amputees. METHODS: Fifteen participants from Walter Reed and Brooke Army Medical Centers were randomly assigned to one of two groups: mirror therapy (n = 9) or control (n = 6, covered mirror or mental visualization therapy). Participants were asked to perform 15 min of their assigned therapy daily for 5 days/week for 4 weeks. The primary outcome was pain as measured using a 100-mm Visual Analog Scale. RESULTS: Subjects in the mirror therapy group had a significant decrease in pain scores, from a mean of 44.1 (SD = 17.0) to 27.5 (SD = 17.2) mm (p = 0.002). In addition, there was a significant decrease in daily time experiencing pain, from a mean of 1,022 (SD = 673) to 448 (SD = 565) minutes (p = 0.003). By contrast, the control group had neither diminished pain (p = 0.65) nor decreased overall time experiencing pain (p = 0.49). A pain decrement response seen by the 10th treatment session was predictive of final efficacy. CONCLUSION: These results confirm that mirror therapy is an effective therapy for PLP in unilateral, upper extremity male amputees, reducing both severity and duration of daily episodes. REGISTRATION: NCT0030144 ClinicalTrials.gov.

Residual Limb Hyperhidrosis and RimabotulinumtoxinB: A Randomized Placebo-Controlled Study.

OBJECTIVE: To investigate the use of rimabotulinumtoxinB (BoNT/B [Myobloc]) compared with placebo in treating hyperhidrosis in the residual limbs of individuals with amputation. DESIGN: Randomized, double-blind, placebo-controlled pilot study. SETTING: Military medical center. PARTICIPANTS: Male participants (N=9) with 11 major amputations of the lower limbs and who complained of excessive sweating in their residual limbs were enrolled in the study between September 24, 2008 to October 28, 2011. Participants' lower limbs were randomly assigned to receive injections of either BoNT/B (n=7) or placebo (n=4). INTERVENTION: BoNT/B. MAIN OUTCOME MEASURES: The primary efficacy variable was a minimum of 50% reduction in sweat production 4 weeks after the injection as measured via gravimetric sweat analysis after 10 minutes of physical exertion. Secondary analyses were performed on prosthetic function and pain. RESULTS: All volunteers (100%; 7) in the BoNT/B group achieved a minimum of 50% reduction in sweat production as compared with only 50% (2) in the placebo group. The percent reduction was significantly greater for the BoNT/B group than for the placebo group (-72.7%±15.7% vs -32.7%±39.2%; P<.05). Although both groups subjectively self-reported significant sweat reduction and improved prosthetic function (P<.05 for both), objective gravimetric sweat analyses significantly decreased only for the BoNT/B group (2.3±2.3g vs 0.7±1.1g; P<.05). Neither group reported a change in phantom limb pain or residual limb pain (P>.05 for both). CONCLUSIONS: BoNT/B successfully reduces sweat production in individuals with residual limb hyperhidrosis, but does not affect pain. No differences were found in perceived effect on prosthetic use between BoNT/B and placebo groups.

Recent advances in bioelectric prostheses.

Worldwide prevalence of amputation has created an increasing demand for improved upper and lower extremity prostheses. Current prosthetics are often uncomfortable and difficult to control and provide limited functional restoration. Moreover, the inability to normalize anthropomorphic biomechanics with a prosthesis increases one's risk of developing long-term health risks such as arthritis, skin breakdown, and pain. Recent advances in bionic prosthetic development hold great promise for rehabilitation and improving quality of life with limb loss. This brief review discusses the current state of advanced prostheses, the integration of robotics in the care of individuals with major limb amputation, and some innovative surgical techniques that are being explored for clinical feasibility.