Drug delivery device for the inner ear: ultra-sharp fully metallic microneedles.

Drug delivery into the inner ear is a significant challenge due to its inaccessibility as a fluid-filled cavity within the temporal bone of the skull. The round window membrane (RWM) is the only delivery portal from the middle ear to the inner ear that does not require perforation of bone. Recent advances in microneedle fabrication enable the RWM to be perforated safely with polymeric microneedles as a means to enhance the rate of drug delivery from the middle ear to the inner ear. However, the polymeric material is not biocompatible and also lacks the strength of other materials. Herein we describe the design and development of gold-coated metallic microneedles suitable for RWM perforation. When developing microneedle technology for drug delivery, we considered three important general attributes: (1) high strength and ductility material, (2) high accuracy and precision of fabrication, and (3) broad design freedom. We developed a hybrid additive manufacturing method using two-photon lithography and electrochemical deposition to fabricate ultra-sharp gold-coated copper microneedles with these attributes. We refer to the microneedle fabrication methodology as two-photon templated electrodeposition (2PTE). We demonstrate the use of these microneedles by inducing a perforation with a minimal degree of trauma in a guinea pig RWM while the microneedle itself remains undamaged. Thus, this microneedle has the potential literally of opening the RWM for enhanced drug delivery into the inner ear. Finally, the 2PTE methodology can be applied to many different classes of microneedles for other drug delivery purposes as well the fabrication of small scale structures and devices for non-medical applications. Graphical Abstract Fully metallic ultra-sharp microneedle mounted at end of a 24-gauge stainless steel blunt syringe needle tip: (left) Size of microneedle shown relative to date stamp on U.S. one-cent coin; (right) Perforation through guinea pig round window membrane introduced with microneedle.

Adhering to Radiographic Clinical Practice Guidelines for Distal Radial Fracture Management Is Associated with Improved Outcomes and Lower Costs.

BACKGROUND: The American Academy of Orthopaedic Surgeons Clinical Practice Guideline on the Treatment of Distal Radius Fractures has not been evaluated in clinical practice. We hypothesized that adhering to the distal radial fracture radiographic clinical practice guideline (CPG) improves outcomes and reduces costs. METHODS: We reviewed 266 patients with distal radial fractures treated at 1 institution. Based on CPG radiographic parameters (Recommendation 3), care was rated as "appropriate" or "inappropriate." QuickDASH (an abbreviated version of the Disabilities of the Arm, Shoulder and Hand [DASH] questionnaire) scores were collected. The direct costs of distal radial fracture care were determined. Descriptive statistics and nonparametric tests were used to evaluate demographic characteristics and outcomes across groups. QuickDASH scores, grouped by postoperative time interval, were analyzed using linear mixed effect models to predict outcome trends. RESULTS: In this study, 145 patients in the operative treatment group and 121 patients in the nonoperative treatment group were included. Of the 145 patients in the operative treatment group, 6 underwent an inappropriate surgical procedure, limiting any analyses of that group. Of the 121 patients in the nonoperative treatment group, 68 were treated inappropriately. For the patients in the nonoperative treatment group, appropriate care provided a significant outcome benefit by 1 year; the median QuickDASH score was 10.1 points for the appropriate treatment group and 19.5 points for the inappropriate treatment group (p = 0.05). The total direct costs for inappropriate nonoperative treatment were, on average, 60% higher than appropriate nonoperative treatment. In predictive models, patients with appropriate care in the operative treatment group and the nonoperative treatment group had better outcomes than patients with inappropriate nonoperative treatment at all time points after 29 days. CONCLUSIONS: When nonoperative distal radial fracture management was aligned with radiographic CPG criteria, patients in our cohort had improved patient-reported outcomes with lower costs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Outcomes and indications for early hand therapy after multiple concomitant elective hand procedures.

STUDY DESIGN: Retrospective comparative study. INTRODUCTION: Trigger finger and carpal tunnel surgery are common, but not without complications including pain and edema, which are treated with hand therapy (HT). There are limited data for the outcomes of multiple trigger finger releases (MTFRs) or combined trigger finger and carpal tunnel surgery and the subsequent need for HT. PURPOSE OF THE STUDY: Based on our hypothesis that patients with more than 1 procedure may benefit from an early HT visit, we performed this study to compare the frequency of HT orders after single trigger finger releases (STFRs) and MTFRs and determine the reasoning for variation in the rate of HT orders after releases. METHODS: Subjects receiving either an STFR or an MTFR were identified. Patient-reported outcomes were recorded preoperatively and 2 weeks postoperatively. RESULTS: One hundred fifty-nine eligible subjects were identified; 33 MTFRs and 126 STFRs. MTFR subjects were prescribed postoperation HT at a higher rate compared with STFR subjects (66.7% vs 34.1%; P < .001). Of the HT subjects, MTFR subjects received prescriptions for edema management at a significantly higher rate compared with STFR subjects (P = .02). DISCUSSION: Patients with soft tissue dissection, edema, and stiffness would most likely benefit from HT services. It is important to identify these at-risk subpopulations to potentially alter their postoperative trajectories and improve outcomes. CONCLUSIONS: Higher rates of referral to HT occur when there are multiple concomitant hand procedures. This suggests surgeons triage HT services based on need. Policies that disallow postoperative therapy will have a greater impact on patients with these indications.

Comparison of Direct Perioperative Costs in Treatment of Unstable Distal Radial Fractures: Open Reduction and Internal Fixation Versus Closed Reduction and Percutaneous Pinning.

BACKGROUND: As the United States transitions to value-based insurance, bundled payments, and capitated models, it is paramount to understand health-care costs and resource utilization. The financial implications of open reduction and internal fixation (ORIF) with a volar locking plate for management of unstable distal radial fractures have not been established. We aimed to elucidate cost differences between ORIF and closed reduction and percutaneous pinning (CRPP). Our hypothesis was that ORIF has greater direct perioperative costs than CRPP but that the costs equilibrate over time. METHODS: We reviewed financial data for 40 patients prospectively enrolled and randomized to undergo CRPP or ORIF for treatment of a closed, displaced, unstable distal radial fracture. Clinical and functional outcomes, hospital-associated direct perioperative costs, postoperative care and therapy costs, and costs for additional procedures were compared. Cost data were stratified into perioperative, 90-day, and 1-year periods, and were reported utilizing cost ratios (CRs) relative to the CRPP cohort. Statistical analysis was performed with chi-square and independent-samples t tests with an alpha level of <0.05. RESULTS: Seventeen patients underwent CRPP and 23 underwent ORIF with a volar plate. Patients who underwent ORIF incurred greater 90-day (CR = 2.03/1.0, p < 0.001) and 1-year (CR = 1.60/1.0, p < 0.001) direct costs than those who underwent CRPP. The differential was greatest in the immediate perioperative period and gradually decreased over time. Operating room fees (CR = 1.7/1.0, p < 0.001), operating room implants, anesthesia (CR = 1.8/1.0, p < 0.001), and total perioperative costs (CR = 2.7/1.0, p < 0.001) were significantly greater in the ORIF cohort. Rehabilitation and cast technician costs were comparable (CR = 0.9/1.0 [ORIF/CRPP], p = 0.69). At 1 year, the CR for all costs of decreased to 1.6/1.0 (ORIF/CRPP, p < 0.001). Compared with the CRPP cohort, the ORIF cohort demonstrated significantly better functional outcomes at 6, 9, and 12 weeks and similar outcomes at 1 year. CONCLUSIONS: ORIF for a displaced, unstable distal radial fracture incurred greater direct costs than CRPP. Although implant costs for ORIF provided the greatest cost differential, additional procedures and higher clinic costs in the CRPP cohort narrowed the 90-day and 1-year cost gaps. LEVEL OF EVIDENCE: Economic Level II. See Instructions for Authors for a complete description of levels of evidence.

Bone Material Strength Index as Measured by Impact Microindentation in Postmenopausal Women With Distal Radius and Hip Fractures.

We tested whether cortical bone tissue properties assessed by in vivo impact microindentation would distinguish postmenopausal women with recent distal radius (DRF) or hip fracture (HF) from nonfracture controls (CONT). We enrolled postmenopausal women with recent DRF (n = 57), HF (n = 41), or CONT (n = 93), and used impact microindentation to assess bone material strength index (BMSi) at the anterior surface of the mid-tibia diaphysis. Areal bone mineral density (aBMD) (g/cm2 ) of the femoral neck (FN), total hip (TH), and lumbar spine (LS) were measured by dual-energy X-ray absorptiometry (DXA). HF and DRF subjects had significantly lower BMD than CONT at all sites (-5.6% to -8.2%, p < 0.001 for all). BMSi was 4% lower in DRF compared to CONT (74.36 ± 8.77 versus 77.41 ± 8.79, p = 0.04). BMSi was similarly lower in HF versus CONT, but the difference did not reach statistical significance (74.62 ± 8.47 versus 77.41 ± 8.79, p = 0.09). Lower BMSi was associated with increased risk of DRF (unadjusted OR, 1.43; 95% CI, 1.02 to 2.00, per SD decrease, p = 0.04), and remained statistically significant after adjustment for age, age and BMI, and age, BMI, and FN BMD (OR = 1.48 to 1.55). Lower BMSi tended to be associated with HF, but only reached borderline significance (unadjusted OR = 1.39; 95% CI, 0.96 to 2.01, p = 0.08). These results provide strong rationale for future investigations aimed at assessing whether BMSi can predict fracture in prospective studies and improve identification of women at risk for fragility fractures. © 2017 American Society for Bone and Mineral Research.