Expanding the Boundaries of RNA Sequencing as a Diagnostic Tool for Rare Mendelian Disease.

Gene-panel and whole-exome analyses are now standard methodologies for mutation detection in Mendelian disease. However, the diagnostic yield achieved is at best 50%, leaving the genetic basis for disease unsolved in many individuals. New approaches are thus needed to narrow the diagnostic gap. Whole-genome sequencing is one potential strategy, but it currently has variant-interpretation challenges, particularly for non-coding changes. In this study we focus on transcriptome analysis, specifically total RNA sequencing (RNA-seq), by using monogenetic neuromuscular disorders as proof of principle. We examined a cohort of 25 exome and/or panel "negative" cases and provided genetic resolution in 36% (9/25). Causative mutations were identified in coding and non-coding exons, as well as in intronic regions, and the mutational pathomechanisms included transcriptional repression, exon skipping, and intron inclusion. We address a key barrier of transcriptome-based diagnostics: the need for source material with disease-representative expression patterns. We establish that blood-based RNA-seq is not adequate for neuromuscular diagnostics, whereas myotubes generated by transdifferentiation from an individual's fibroblasts accurately reflect the muscle transcriptome and faithfully reveal disease-causing mutations. Our work confirms that RNA-seq can greatly improve diagnostic yield in genetically unresolved cases of Mendelian disease, defines strengths and challenges of the technology, and demonstrates the suitability of cell models for RNA-based diagnostics. Our data set the stage for development of RNA-seq as a powerful clinical diagnostic tool that can be applied to the large population of individuals with undiagnosed, rare diseases and provide a framework for establishing minimally invasive strategies for doing so.

Clinical supervision in frontline health care: A survey of social workers in Ontario, Canada.

Researchers have documented diminishing staff supervision in health care settings, while noting the complexity and dynamic nature of health care systems. A secondary data analysis of a survey of the Ontario Association of Social Workers (N=666) explored the contemporary receipt of different types of supervision in frontline health care. Most social worker participants were involved in supervision, receiving administrative and supportive supervision. Only 52% engaged in clinical supervision, even though most spent over 50% of work time with clients with complex needs. Factors related to the receipt of clinical supervision included setting, experience, gender, and availability of clinical practice leaders.

A Multicenter Matched Cohort Study of Processed Nerve Allograft and Conduit in Digital Nerve Reconstruction.

PURPOSE: Biomaterials used to restore digital nerve continuity after injury associated with a defect may influence ultimate outcomes. An evaluation of matched cohorts undergoing digital nerve gap reconstruction was conducted to compare processed nerve allograft (PNA) and conduits. Based on scientific evidence and historical controls, we hypothesized that outcomes of PNA would be better than for conduit reconstruction. METHODS: We identified matched cohorts based on patient characteristics, medical history, mechanism of injury, and time to repair for digital nerve injuries with gaps up to 25 mm. Data were stratified into 2 gap length groups: short gaps of 14 mm or less and long gaps of 15 to 25 mm. Meaningful sensory recovery was defined as a Medical Research Council scale of S3 or greater. Comparisons of meaningful recovery were made by repair method between and across the gap length groups. RESULTS: Eight institutions contributed matched data sets for 110 subjects with 162 injuries. Outcomes data were available in 113 PNA and 49 conduit repairs. Meaningful recovery was reported in 61% of the conduit group, compared with 88% in the PNA group. In the group with a 14-mm or less gap, conduit and PNA outcomes were 67% and 92% meaningful recovery, respectively. In the 15- to 25-mm gap length group, conduit and PNA outcomes were 45% and 85% meaningful recovery, respectively. There were no reported adverse events in either treatment group. CONCLUSIONS: Outcomes of digital nerve reconstruction in this study using PNA were consistent and significantly better than those of conduits across all groups. As gap lengths increased, the proportion of patients in the conduit group with meaningful recovery decreased. This study supports the use of PNA for nerve gap reconstruction in digital nerve reconstructions up to 25 mm. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Peripheral nerve repair throughout the body with processed nerve allografts: Results from a large multicenter study.

BACKGROUND: Peripheral nerve damage resulting in pain, loss of sensation, or motor function may necessitate a reconstruction with a bridging material. The RANGER® Registry was designed to evaluate outcomes following nerve repair with processed nerve allograft (Avance® Nerve Graft; Axogen; Alachua, FL). Here we report on the results from the largest peripheral nerve registry to-date. METHODS: This multicenter IRB-approved registry study collected data from patients repaired with processed nerve allograft (PNA). Sites followed their own standard of care for patient treatment and follow-up. Data were assessed for meaningful recovery, defined as ≥S3/M3 to remain consistent with previously published results, and comparisons were made to reference literature. RESULTS: The study included 385 subjects and 624 nerve repairs. Overall, 82% meaningful recovery (MR) was achieved across sensory, mixed, and motor nerve repairs up to gaps of 70 mm. No related adverse events were reported. There were no significant differences in MR across the nerve type, age, time-to-repair, and smoking status subgroups in the upper extremity (p > .05). Significant differences were noted by the mechanism of injury subgroups between complex injures (74%) as compared to lacerations (85%) or neuroma resections (94%) (p = .03) and by gap length between the <15 mm and 50-70 mm gap subgroups, 91 and 69% MR, respectively (p = .01). Results were comparable to historical literature for nerve autograft and exceed that of conduit. CONCLUSIONS: These findings provide clinical evidence to support the continued use of PNA up to 70 mm in sensory, mixed and motor nerve repair throughout the body and across a broad patient population.

Vascularized Composite Allotransplantation of the Elbow Joint: A Cadaveric Study.

BACKGROUND: Surgical options for the unreconstructable elbow are limited to arthrodesis, total arthroplasty, or osteoarticular allograft reconstruction. Each of these options is limited by severe functional impairment and/or high complication rates. Vascularized allotransplantation of the elbow joint has the potential to mitigate these complications. In this study, we describe our technique for harvesting the elbow for vascularized joint transplantation and demonstrate the flap's vascularity using contrast angiography. METHODS: Anatomical studies were used to design and harvest a vascularized elbow joint flap pedicled on the brachial vessels in 10 cadaveric arms. Diaphyseal blood supply is provided by 3 nutrient arteries, and periarticular supply arises from the various collateral arteries of the arm and recurrent arteries of the forearm. The brachialis and supinator, and their respective nerves, were included as functional muscles because of their intimate association with critical vasculature. Tendinous insertions of the biceps and triceps, as well as the flexor/pronator and extensor origins, were preserved for repair in the transplant recipient. Both lateral arm and radial forearm flaps were preserved to aid in soft tissue inset as well as vascular/immunologic monitoring. Contrast angiography of each dissected specimen was performed to assess the location of the nutrient vessels and assess flap vascularity, as indicated by filling of the critical extraosseous and endosteal vessels. RESULTS: Angiographic imaging of 10 specimens demonstrated that this flap dissection preserves the nutrient endosteal supply to the humeral, radial, and ulnar diaphysis, in addition to the critical extraosseous arterial structures perfusing the elbow joint and periarticular tissues. From proximal to distal, these arteries are the musculoperiosteal radial, posterior branch of the radial collateral, inferior ulnar collateral, recurrent interosseous, radial recurrent, and the anterior and the posterior ulnar recurrent. CONCLUSIONS: Vascularized composite allotransplantation of the elbow joint holds promise as a motion and function preserving option for young, high-demand patients with a sensate and functional hand, who would otherwise be limited by the restrictions of total elbow arthroplasty or fusion. In this study, we propose a flap design and technique for harvest and also offered vascular imaging-based evidence that this flap is adequately vascularized.

Development of the policy indicator checklist: a tool to identify and measure policies for calorie-dense foods and sugar-sweetened beverages across multiple settings.

OBJECTIVES: We developed the policy indicator checklist (PIC) to identify and measure policies for calorie-dense foods and sugar-sweetened beverages to determine how policies are clustered across multiple settings. METHODS: In 2012 and 2013 we used existing literature, policy documents, government recommendations, and instruments to identify key policies. We then developed the PIC to examine the policy environments across 3 settings (communities, schools, and early care and education centers) in 8 communities participating in the Childhood Obesity Research Demonstration Project. RESULTS: Principal components analysis revealed 5 components related to calorie-dense food policies and 4 components related to sugar-sweetened beverage policies. Communities with higher youth and racial/ethnic minority populations tended to have fewer and weaker policy environments concerning calorie-dense foods and healthy foods and beverages. CONCLUSIONS: The PIC was a helpful tool to identify policies that promote healthy food environments across multiple settings and to measure and compare the overall policy environments across communities. There is need for improved coordination across settings, particularly in areas with greater concentration of youths and racial/ethnic minority populations. Policies to support healthy eating are not equally distributed across communities, and disparities continue to exist in nutrition policies.

Peripheral neuropathy: surgical approaches simplified for the imagers.

Peripheral nerves traverse through different soft tissue compartments in the upper and lower extremities via specific anatomical tunnels, where they are susceptible to entrapment. Common sites in the upper extremity include carpal tunnel, cubital tunnel and radial tunnel. Common sites in the lower extremity include piriformis, fibular neck, and tarsal tunnel. Compressive peripheral neuropathy can develop in these sites, and are amenable for surgical decompression.

Sarcomatoid carcinoma in head and neck: a review of 30 years of experience--clinical outcomes and reconstructive results.

PROBLEM PRESENTED: Sarcomatoid carcinoma (SaCa) is a rare variant of squamous cell carcinoma (SCC) with sarcomatoid features. This study investigated the clinical presentation and outcomes of head and neck SaCa. In addition, reconstructive outcome for a subset of patients was also evaluated. STUDIES UNDERTAKEN: Seventy-eight SaCa cases including 72 men and 6 women were identified from 13,777 head and neck SCC cases. Clinical outcomes were evaluated based on locoregional control, distant metastases, and multivariate analyses. Reconstructive outcome was evaluated by flap survival rate. RESULT: Of the 78 cases, 71% (55) of cases were located in the oral mucosa; 64% (50) of patients were classified as T3 or T4 at the time of diagnosis. The 5-year survival was only 16%. Multivariate analysis revealed better outcomes only when the patient had a history of previous SCC. Forty-five patients underwent flap reconstruction, with 98% flap survival rate but the functional result varied because of the inevitable adjuvant radiotherapy and advanced stage of tumor. CONCLUSIONS: Sarcomatoid carcinoma is a different entity from the conventional SCC of the head and neck. Sarcomatoid carcinoma carries a poorer prognosis despite aggressive surgical intervention and concurrent adjuvant therapies. It remains a great challenge for clinical oncologists, and the optimal treatment strategy requires further studies. Free flap is still preferred for defect reconstruction but the design should be simplified to avoid complications.

Force-amplifying implant to improve key pinch strength in tendon transfer surgery: Cadaver model proof-of-concept.

The brachioradialis (BR) to flexor pollicis longus (FPL) tendon transfer surgery is a common procedure used to restore key pinch grip for incomplete spinal cord injury patients. However, the procedure only restores 22% of the physiological grip strength, which is important for successfully grasping objects and minimizing fatigue. The purpose of this study was to evaluate the efficacy of using a novel force-amplifying pulley implant to modify the standard BR to FPL tendon transfer surgery to improve key pinch grip strength in a human cadaver forearm model. A total of eight cadaveric specimens were mounted onto a custom testbed where a torque-controlled motor actuated the BR tendon to produce key pinch grip. In each cadaver, two experimental groups were examined: a standard and an implant-modified BR to FPL tendon transfer surgery. A force sensor mounted to the thumb recorded isometric key pinch grip forces over a range of input BR forces (2 N-25 N) applied in a ramp-and-hold protocol. Across the range of input BR forces, the average improvement in key pinch grip strength in the implant-modified surgery compared to the standard surgery was 58 ± 7.1% (ranging from 41% to 64% improvement). Throughout the experiments, we observed that the implant did not hinder the movement of the BR or FPL tendons. These results suggest that a BR to FPL tendon transfer surgery utilizing a force-amplifying pulley implant to augment force transmission can provide additional functional strength restoration over the standard procedure that directly sutures two tendons together.

Targeted muscle reinnervation and regenerative peripheral nerve interfaces for pain prophylaxis and treatment: A systematic review.

OBJECTIVE: Nerve pain frequently develops following amputations and peripheral nerve injuries. Two innovative surgical techniques, targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI), are rapidly gaining popularity as alternatives to traditional nerve management, but their effectiveness is unclear. LITERATURE SURVEY: A review of literature pertaining to TMR and RPNI pain results was conducted. PubMed and MEDLINE electronic databases were queried. METHODOLOGY: Studies were included if pain outcomes were assessed after TMR or RPNI in the upper or lower extremity, both for prophylaxis performed at the time of amputation and for treatment of postamputation pain. Data were extracted for evaluation. SYNTHESIS: Seventeen studies were included, with 14 evaluating TMR (366 patients) and three evaluating RPNI (75 patients). Of these, one study was a randomized controlled trial. Nine studies had a mean follow-up time of at least 1 year (range 4-27.6 months). For pain treatment, TMR and RPNI improved neuroma pain in 75%-100% of patients and phantom limb pain in 45%-80% of patients, averaging a 2.4-6.2-point reduction in pain scores on the numeric rating scale postoperatively. When TMR or RPNI was performed prophylactically, many patients reported no neuroma pain (48%-100%) or phantom limb pain (45%-87%) at time of follow-up. Six TMR studies reported Patient-Reported Outcomes Measurement Information System (PROMIS) scores assessing pain intensity, behavior, and interference, which consistently showed a benefit for all measures. Complication rates ranged from 13% to 31%, most frequently delayed wound healing. CONCLUSIONS: Both TMR and RPNI may be beneficial for preventing and treating pain originating from peripheral nerve dysfunction compared to traditional techniques. Randomized trials with longer term follow-up are needed to directly compare the effectiveness of TMR and RPNI with traditional nerve management techniques.

Surgical Technique for Concurrent Endoscopic Carpal Tunnel Release and Distal Radius Fracture Fixation Using the Flexor Carpi Radialis Approach: A Case Series.

Purpose: Multiple prior studies have assessed the results of open approaches for concurrent carpal tunnel release with distal radius fracture fixation; however, less is known regarding the feasibility of endoscopic techniques, especially in the setting of high-energy trauma. In this study, we assessed the feasibility and results of concurrent endoscopic carpal tunnel release and distal radius fracture fixation using the flexor carpi radialis approach after high- and low-energy trauma. Methods: We performed a retrospective, single-surgeon study of 17 consecutive adult patients (aged >18 years) who underwent open reduction internal fixation of an acute distal radius fracture with concurrent endoscopic carpal tunnel release at a level 1 trauma center between April 2017 and October 2020. Recovery from median nerve dysfunction was assessed from patient charts at routinely scheduled postoperative follow-up visits (at 2 weeks, 4 weeks, 6 weeks, and 12 weeks). Results: The transverse carpal ligament could be visualized and released in all patients. All patients had a return of light touch sensibility with or without intermittent paresthesia by 12 weeks after surgery (the median time from surgery to recovery was 19 days [range, 12-82 days]). There were no patient reports or clinical examination evidence of palmar cutaneous branch, recurrent motor branch, or the third common digital nerve injury. Time to recovery was significantly different in the setting of high- versus low-energy trauma (26 days vs 18 days, respectively; P = .02). Conclusions: In this study, we demonstrated that concurrent endoscopic carpal tunnel release using the flexor carpi radialis approach for distal radius fracture fixation in the settings of high- and low-energy trauma is safe from major complications and effective at releasing the transverse carpal ligament. Type of study/level of evidence: Therapeutic IV.

Oral Health Service Access in Racial/Ethnic Minority Neighborhoods: A Geospatial Analysis in Washington, DC, USA.

Previous studies on individual-level variables have improved our knowledge base of oral health service use. However, environmental or contextual variables are also important in understanding oral health disparities in racial and ethnic neighborhoods. Based on Bronfenbrenner's ecological framework, this study examines the geographic availability of oral health providers in Washing-ton DC, U.S.A. Census tract-level data were drawn from the American Community Survey, joined with tract-level shapefiles, and overlaid with the geographic location of dental services throughout the city. Visual maps, descriptive statistics, and spatial lag regression models showed that census tracts with higher concentrations of African Americans were significantly farther from their nearest oral health providers (r = 0.19, p < 0.001), after controlling for neighborhood poverty rate, median age, and gender. Such findings confirm that in urban areas with highly di-verse populations such as Washington DC, racial disparities in oral health care access are signifi-cant. The study highlights that identifying neighborhoods with limited oral health care providers should be a priority in diminishing racial disparities in oral health service access. Improving access to racial/ethnic minority communities, especially African American neighborhoods, will require changes in health policies and programs, workforce development, resource allocation, community outreach, and educational programs.

Using GIS to Analyze Inequality in Access to Dental Care in the District of Columbia.

BACKGROUND: Access to dental care in mixed-race and predominantly African American wards in the District of Columbia (DC) was investigated in relation to community development. METHODS: This study used high-resolution geographic information system (GIS) tools to map all general dentistry and periodontal practice locations in DC wards. The spatial analysis contextualized each ward's land use and demographic data obtained from DC government reports. FINDINGS: The analysis revealed inter-ward inequity in dental care access, which was measured by proximity to and number of dental clinics in each DC ward. Residents in affluent wards had access to many dental practices and superior amenities. Residents in wards poorly served by public transportation and with few resources had few, if any, dental clinics. CONCLUSIONS: Dental practices are inequitably distributed across DC wards. DC policy should prioritize community development-specifically, resource allocation and community outreach-to promote health equity and improve access to and quality of dental care among residents of color.

Management of Artery-Only Digit Replantation: A Systematic Review of the Literature.

BACKGROUND: Artery-only replantation may be necessary in circumstances when venous repair cannot be performed due to their size or vessel injury. Venous congestion of the replanted part is inevitable. A systematic review was performed to identify techniques for mitigating congestion and analyze the outcomes of those techniques. METHODS: A comprehensive literature search was performed to identify relevant articles related to artery-only replantation. An initial query identified 1286 unique articles. A total of 55 articles were included in the final review. Included studies were categorized by decongestive technique. Data from each article included the number of patients treated, level of amputation, graft use, anticoagulation or antiplatelet therapy, replant viability, and follow-up duration. Weighted averages were determined from studies that reported five or more digits. RESULTS: A total of 1498 individual digital replantations were described. Very rarely did studies report artery-only replantation proximal to the distal interphalangeal joint. An overall survival rate of 78.5 percent was found irrespective of technique but was variable based on each particular study. Studies utilizing medicinal leech therapy were more likely to report use of intravenous anticoagulation, whereas surface bleeding techniques were more likely to report use of topical or local anticoagulant. CONCLUSIONS: Lack of a vein for anastomosis should not be regarded as a contraindication to replantation. These digits instead require a method to establish reliable drainage sufficient to allow for low resistance inflow and maintain a physiologic pressure gradient across capillary beds. The surgeon should select a decongestive technique that best suits the patient and their specific injury.

Osteoplastic Thumb Reconstruction in the Immediate Setting: A Case Series.

Background: Traumatic thumb amputation can have devastating effects on residual hand function. When replantation is not possible, thumb reconstruction is often performed in a delayed manner and may require multiple stages. Furthermore, reconstruction techniques often require microsurgical skills and equipment, which are not readily available at all institutions. This case series illustrates our technique for immediate osteoplastic thumb reconstruction following traumatic amputation. Methods: This is a case series involving all patients who sustained unreplantable thumb amputations and underwent immediate osteoplastic thumb reconstruction with bone autograft and pedicled groin flap by the senior author from September 2016 through August 2018. Results: Five patients underwent immediate osteoplastic thumb reconstruction during the study period. Total operative time for the initial osteoplastic reconstruction averaged 158 minutes (range 96-290 minutes). In addition to flap division surgery, patients underwent an average of 1.2 revision procedures (range 0-2), primarily for debulking and hardware removal. Patients achieved an average gain in length of 3.3 cm compared with the maximum anticipated length with revision amputation at the time of injury, and had stable clinical outcomes for a minimum of 12 months. Conclusions: Osteoplastic thumb reconstruction is a useful technique for thumb reconstruction for select patients following traumatic thumb amputation. Advantages of this approach include shorter overall operative times and hospital length of stay, minimal donor site morbidity, and a straightforward, reproducible technique.

Surface Electromyography-Driven Therapeutic Gaming for Rehabilitation of Upper Extremity Weakness: A Pilot Study.

SUMMARY: In patients with severe upper extremity weakness that may result from peripheral nerve injuries, stroke, and spinal cord injuries, standard therapy in the earliest stages of recovery consists primarily of passive rather than active exercises. Adherence to prescribed therapy may be poor, which may contribute to suboptimal functional outcomes. The authors have developed and integrated a custom surface electromyography device with a video game to create an interactive, biofeedback-based therapeutic gaming platform. Sensitivity of the authors' custom surface electromyography device was evaluated with simultaneous needle electromyography recordings. Testing of this therapeutic gaming platform was conducted with a single 30-minute gameplay session in 19 patients with a history of peripheral nerve injury, stroke, spinal cord injury, and direct upper extremity trauma, including 11 patients who had undergone nerve and/or tendon transfers. The device was highly sensitive in detecting low levels of voluntary muscle activation and was used with 10 distinct muscles of the arm, forearm, and hand. Nerve and tendon transfer patients successfully activated the donor nerve/muscle and elicited the desired movement to engage in gameplay. On surveys of acceptability and usability, patients felt the system was enjoyable, motivating, fun, and easy to use, and their hand therapists expressed similar enthusiasm. Surface electromyography-based therapeutic gaming is a promising approach to rehabilitation that warrants further development and investigation to examine its potential efficacy, not only for building muscle strength and endurance but also for facilitating motor relearning after nerve and tendon transfer surgical procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Antipsychotic medication for early episode schizophrenia.

BACKGROUND: Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. OBJECTIVES: To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. SELECTION CRITERIA: Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. DATA COLLECTION AND ANALYSIS: Working independently, we critically appraised records from 681studies, of which five studies met inclusion criteria. John Rathbone from the Schizophrenia Group supported us with the data extraction. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. MAIN RESULTS: Five studies with a combined N = 998 met inclusion criteria. Four studies (N = 724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs N = 353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT N = 240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT N = 236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT N = 94, RR 0.96 CI 0.3 to 3.6). Two studies (Cole 1964; May 1976) contributed data to assessment of side effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications compared to placebo. Rappaport 1978 suggested a higher rehospitalisation rate for those receiving chlorpromazine compared to placebo (N = 80, RR 2.29 CI 1.3 to 4.0, NNH 2.9). However, a higher attrition in the placebo group is likely to have introduced a survivor bias into this comparison, as this difference becomes non-significant in a sensitivity analysis on intent-to-treat participants (N = 127, RR 1.69 CI 0.9 to 3.0). One study (May 1976) contributes data to a comparison of trifluoperazine to psychotherapy on long-term health in favour of the trifluoperazine group (N = 92, MD 5.8 CI 1.6 to 0.0); however, data from this study are also likely to contain biases due to selection and attrition. One study (Mosher 1995) contributes data to a comparison of typical antipsychotic medication to psychosocial treatment on six-week outcome measures of global psychopathology (N = 89, MD 0.01 CI -0.6 to 0.6) and global improvement (N = 89, MD -0.03 CI -0.5 to 0.4), indicating no between-group differences. On the whole, there is very little useable data in the few studies meeting inclusion criteria. AUTHORS' CONCLUSIONS: With only a few studies meeting inclusion criteria, and with limited useable data in these studies, it is not possible to arrive at definitive conclusions. The preliminary pattern of evidence suggests that people with early episode schizophrenia treated with typical antipsychotic medications are less likely to leave the study early, but more likely to experience medication-related side effects. Data are too sparse to assess the effects of antipsychotic medication on outcomes in early episode schizophrenia.

Nonsurgical Approaches to Neuroma Management.

Symptomatic neuromas and chronic neuropathic pain are significant problems affecting patients' quality of life and independence that are challenging to treat. These symptoms are due to structural and functional changes that occur peripherally within neuromas, as well as alterations that occur centrally within the brain and spinal cord. A multimodal approach is most effective, with goals to minimize opioid use, to capitalize on the synergistic effects of nonopioid medications and to explore potential benefits of novel adjunctive treatments.

Targeted Peripheral Nerve Interface: Case Report with Literature Review.

Nerve transection injuries can result in painful neuromas that adversely affect patient recovery. This is especially significant following amputation surgeries in the setting of prosthetic wear and function. Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interface (RPNI) are 2 modern surgical techniques that provide neuromuscular targets for these transected nerve endings to reinnervate. These strategies have been previously shown to reduce phantom limb pain, residual limb pain, and neuroma-related pain.1,2,7,11 Two recent articles described technical adaptations of combining targeted muscle reinnervation and RPNI to create a hybrid procedure.3,12 In this article, we propose a different modification of targeted muscle reinnervation and RPNI, where the transected nerve stump is coapted to a recipient unit consisting of an intact distal nerve branch with its associated muscle graft. We called this recipient unit a targeted peripheral nerve interface because it contains a distal nerve branch for nerve coaptation and can guide axonal regeneration from the donor nerve to its target muscle graft. We theorize that targeted peripheral nerve interface may lead to more even distribution of regenerating axons with potentially less pain and stronger signals for prosthetic control when compared with standard RPNI.