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Abstract Background Pedicle screw loosening and breakage are common causes of revision surgery after lumbar fusion. Thus, there remains a continued need for supplemental fixation options that offer immediate stability without the associated failure modes. This finite element analysis compared the biomechanical properties of a novel cortico-pedicular posterior fixation (CPPF) device with those of a conventional pedicle screw system (PSS). Methods The CPPF device is a polyetheretherketone strap providing circumferential cortical fixation for lumbar fusion procedures via an arcuate tunnel. Using a validated finite element model, we compared the stability and load transfer characteristics of CPPF to intact conditions under a 415 N follower load and PSS conditions under a 222 N preload. Depending on the instrumented levels, two different interbody devices were used: a lateral lumbar interbody device at L4–5 or an anterior lumbar interbody device at L5-S1. Primary outcomes included range of motion of the functional spinal units and anterior load transfer, defined as the total load through the disk and interbody device after functional motion and follower load application. Results Across all combinations of interbody devices and lumbar levels evaluated, CPPF consistently demonstrated significant reductions in flexion (ranging from 90 to 98%), extension (ranging from 88 to 94%), lateral bending (ranging from 75 to 80%), and torsion (ranging from 77 to 86%) compared to the intact spine. Stability provided by the CPPF device was comparable to PSS in all simulations (range of motion within 0.5 degrees for flexion–extension, 0.6 degrees for lateral bending, and 0.5 degrees for torsion). The total anterior load transfer was higher with CPPF versus PSS, with differences across all tested conditions ranging from 128 to 258 N during flexion, 89–323 N during extension, 135–377 N during lateral bending, 95–258 N during torsion, and 82–250 N during standing. Conclusion Under the modeled conditions, cortico-pedicular fixation for supplementing anterior or lateral interbody devices between L4 and S1 resulted in comparable stability based on range of motion measures and less anterior column stress shielding based on total anterior load transfer measures compared to PSS. Clinical studies are needed to confirm these finite element analysis findings.

Carmen Cuffari,1 David Pierce,2 Bartosz Korczowski,3 Krzysztof Fyderek,4 Heather Van Heusen,5 Stuart Hossack,6 Hong Wan,5 Alena YZ Edwards,7 Patrick Martin5 1Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Shire, Basingstoke, UK; 3Medical College, University of Rzeszów, Rzeszów, Poland; 4University Children’s Hospital of Cracow, Cracow, Poland; 5Shire, Wayne, PA, USA; 6Covance Clinical Research Unit Limited, Leeds, UK; 7ICON Early Phase Services, Marlow, Buckinghamshire, UK Background: Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC).Aim: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC.Methods: Participants (5–17 years of age; 18–82 kg, stratified by weight) with UC received multimatrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model.Results: Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%–45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified.Conclusion: Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844. Keywords: ulcerative colitis, mesalamine, pharmacology

Lumbar spinal stenosis has been shown to negatively impact health-related quality of life. Interspinous process decompression (IPD) is a minimally invasive procedure that utilizes a stand-alone spacer to serve as a joint extension blocker to relieve neural compression in patients with spinal stenosis. Using the 5-year results from an FDA randomized controlled trial of IPD, the quality of life in 189 patients treated with the Superion® spacer was evaluated with the SF-12. Physical and mental component summary (PCS, MCS) scores were computed preoperatively and at annual intervals. For the PCS, mean scores improved from 29.4 ± 8.1 preoperatively to 41.2 ± 12.4 at 2 years (40%) and to 43.8 ± 11.6 at 5 years (49%) (p0.10 for both comparisons). These results demonstrate that the significant impairment in physical well-being found in patients with lumbar spinal stenosis can be ameliorated, in large part, by IPD treatment.

David Pierce,1 Mary Corcoran,2 Maria Velinova,3 Stuart Hossack,4 Mieke Hoppenbrouwers,5 Patrick Martin,21Shire, Basingstoke, UK; 2Shire, Wayne, PA, USA; 3PRA International, Zuidlaren, the Netherlands; 4Covance, Leeds, UK; 5Shire-Movetis NV, Turnhout, BelgiumBackground: About 30% of patients with gastroesophageal reflux disease continue to experience symptoms despite treatment with proton pump inhibitors. The 5-hydroxytryptamine 4 receptor agonist revexepride (SSP-002358) is a novel prokinetic that stimulates gastrointestinal motility, which has been suggested as a continued cause of symptoms in these patients. The aim of this study was to assess whether revexepride pharmacokinetics were affected by co-administration of omeprazole, in preparation for a proof-of-concept evaluation of revexepride added to proton pump inhibitor treatment.Methods: In this phase 1, open-label, randomized, two-period crossover study, healthy adults aged 18–55 years were given a single dose of revexepride 1 mg or revexepride 1 mg + omeprazole 40 mg. Pharmacokinetic parameters were assessed for up to 48 hours after administration of the investigational product. Adverse events, clinical chemistry and hematology parameters, electrocardiograms, and vital signs were monitored.Results: In total, 42 participants were enrolled and 40 completed the study. The median age was 24 years (18–54 years), 55% were women and 93% were white. The pharmacokinetic parameters of revexepride were similar without or with omeprazole co-administration. The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) was 23.3 ng · h/mL (standard deviation [SD]: 6.33 ng · h/mL) versus 24.6 ng · h/mL (SD: 6.31 ng · h/mL), and maximum plasma concentrations (Cmax) were 3.89 ng/mL (SD: 1.30 ng/mL) and 4.12 ng/mL (SD: 1.29 ng/mL) in participants without and with omeprazole, respectively. For AUC0–∞ and Cmax, the 90% confidence intervals for the ratios of geometric least-squares means (with:without omeprazole) were fully contained within the pre-defined equivalence limits of 0.80–1.25. Mean apparent terminal phase half-life was 9.95 hours (SD: 2.06 hours) without omeprazole, and 11.0 hours (SD: 3.25 hours) with omeprazole.Conclusion: Co-administration of the 5-hydroxytryptamine receptor 4 agonist revexepride with omeprazole did not affect the pharmacokinetics of revexepride in healthy adults.Keywords: revexepride, omeprazole, pharmacokinetics, gastroesophageal reflux disease

David Pierce,1 Mary Corcoran,2 Patrick Martin,2 Karen Barrett,1 Susi Inglis,1 Peter Preston,2 Thomas N Thompson,3 Sandra K Willsie3 1Shire, Basingstoke, UK; 2Shire, Wayne, PA, USA; 3PRA International, Lenexa, KS, USA Background: MMX® mesalamine is a once daily oral 5-aminosalicylic acid formulation, effective in induction and maintenance of ulcerative colitis remission. Patients on long-term mesalamine maintenance may occasionally require concomitant antibiotic treatment for unrelated infections. Aim: To evaluate the potential for pharmacokinetic interactions between MMX mesalamine and amoxicillin, ciprofloxacin extended release (XR), metronidazole, or sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period crossover studies. Methods: In all four studies, healthy adults received placebo once daily or MMX mesalamine 4.8 g once daily on days 1–4 in one of two treatment sequences. In studies 1 and 2, subjects also received a single dose of amoxicillin 500 mg (N=62) or ciprofloxacin XR 500 mg (N=30) on day 4. In studies 3 and 4, subjects received metronidazole 750 mg twice daily on days 1–3 and once on day 4 (N=30); or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on days 1–3 and once on day 4 (N=44). Results: MMX mesalamine had no significant effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the 90% confidence intervals (CIs) around the geometric mean ratios (antibiotic + MMX mesalamine: antibiotic + placebo) for maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) fell within the predefined equivalence range (0.80–1.25). Sulfamethoxazole exposure increased by a statistically significant amount when coadministered with MMX mesalamine; however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at steady state) was not considered clinically significant, as the 90% CIs for each point estimate fell entirely within the predefined equivalence range. Adverse events in all studies were generally mild. Conclusion: MMX mesalamine may be coadministered with amoxicillin, ciprofloxacin, metronidazole, or sulfamethoxazole, without affecting pharmacokinetics or safety of these antibiotics. ClinicalTrials.gov identifiers: NCT01442688, NCT01402947, NCT01418365, and NCT01469637. Keywords: ulcerative colitis, pharmacokinetics, safety

Background: The traditional open midline posterior cervical spine fusion procedure has several shortcomings. It can cause soft tissue damage, muscle atrophy, compromise of the lateral masses and painful prominent posterior cervical instrumentation or spinous process if there is dehiscence of the fascia. Additionally, patients frequently experience the rapid development of adjacent segment disease, which can result in the reemergence of debilitating pain and functional impairment. Clinical relevance: Tissue-sparing posterior cervical fusion is an alternative method for treating patients with symptomatic cervical degenerative disc disease. However, widespread clinical adoption has been challenged by ambiguity, misunderstandings and misinterpretations regarding appropriate procedural reimbursement coding. Technological advancement: The tissue-sparing posterior cervical fusion procedure was approved by the US Food and Drug Administration (FDA) in 2018 (CORUS™ Spinal System and CAVUX® Facet Fixation System (CORUS/CAVUX); Providence™ Medical Technology). This technique addresses the concerns with traditional spine fusion methods by achieving the stability and outcomes of posterior cervical fusion without the morbidity associated with significant muscle stripping in the traditional approach. This technology uses specialized implants and instrumentation to perform all of the steps required to facilitate bone fusion and provide stability while minimizing tissue disruption. The technique involves extensive bone preparation for fusion and placement of specialized stabilization implants that span the facet joint, promoting natural bone growth and fusion while reducing the need for extensive exposure. This procedure provides an effective, less invasive solution for patients with cervical degenerative disc disease. Reimbursement and coding clarity: The article provides a comprehensive rationale for appropriate reimbursement coding for tissue-sparing posterior cervical fusion. This is a critical aspect for the adoption and accessibility of medical technologies. This information is crucial for practitioners and healthcare administrators, ensuring that innovative procedures are accurately coded and reimbursed. Procedural details and clinical evidence: By detailing the procedural steps, instruments used and the physiological basis for the procedure, this article serves as a valuable educational resource for spine surgeons and payers to appropriately code for this procedure. Conclusions: The description of work for CORUS/CAVUX is equivalent to the current surgical standard of lateral mass screw fixation with decortication and onlay posterior grafting to facilitate posterior fusion. Thus, it is recommended that CPT codes 22600/22840 be used, as they best reflect the surgical approach, instrumentation, decortication, posterior cervical fusion and bone grafting procedures. [ABSTRACT FROM AUTHOR]

A new CO |$^+$| fluorescence emission model for analysing cometary spectra is presented herein. Accurate line lists are produced using the PGOPHER software for all transitions between the three electronic states (X |$^2\Sigma$|⁠ , A |$^2\Pi$|⁠ , B |$^2\Sigma$|⁠) with vibrational states up to |$v_\textrm {max} = 9, 8, 6$|⁠ , respectively, and maximum rotational states with rotational quantum numbers |$N\le 20$|⁠. As a result of improved molecular constants and theoretical transition rates, an expansion of the utilized solar spectrum into the infrared, and the substantial expansion of the included rovibronic states, the model provides an update of the fluorescence efficiencies of the CO |$^+$| cation. The dependencies on heliocentric velocity and distance are explicitly included. We report, for the first time, quantification of the fluorescence efficiencies for the ground state rovibrational transitions of CO |$^+$| and predict the positions and relative intensities of CO |$^+$| lines in windows accessible to both ground- and space-based observatories. The computed fluorescence efficiencies show excellent agreement with UV/optical observations of both C/2016 R2 (PanSTARRS) and 29P/Schwassmann-Wachmann 1. The updated fluorescence efficiencies allow for revised N |$_2$| /CO abundances for comets 1P/Halley, C/1987 P1 (Bradfield), and C/2016 R2 (PanSTARRS), which can change by up to 30 per cent when accounting for recent improvements to CO |$^+$| and N |$_2^+$| fluorescence efficiencies. The model code, input files, and fluorescence efficiencies are publicly available and distributed on permanent archives for future uses in cometary analyses. [ABSTRACT FROM AUTHOR]

Pedicle screw fixation is a commonly utilized adjunct for lumbar interbody fusion, yet risks include screw malposition, pullout, loosening, neurovascular injury, and stress transfers leading to adjacent segment degeneration. This report describes the preclinical and initial clinical results of a minimally invasive, metal-free cortico-pedicular fixation device used for supplemental posterior fixation in lumbar interbody fusion. Safety of arcuate tunnel creation was evaluated in cadaveric lumbar (L1–S1) specimens. A finite element analysis study evaluated clinical stability of the device to pedicular screw-rod fixation at L4–L5. Preliminary clinical results were assessed by analysis of Manufacturer and User Facility Device Experience database complications, and 6-month outcomes in 13 patients treated with the device. Among 35 curved drill holes in 5 lumbar specimens, no breaches of the anterior cortex were identified. The mean minimum distance from the anterior surface of the hole to the spinal canal ranged from 5.1 mm at L1–L2 to 9.8 mm at L5–S1. In the finite element analysis study, the polyetheretherketone strap provided comparable clinical stability and reduced anterior stress shielding compared to the conventional screw-rod construct. The Manufacturer and User Facility Device Experience database identified 1 device fracture with no clinical sequelae among 227 procedures. Initial clinical experience showed a 53% decrease in pain severity (P = 0.009), a 50% decrease in Oswestry Disability Index (P < 0.001), and no device-related complications. Cortico-pedicular fixation is a safe and reproducible procedure that may address limitations of pedicle screw fixation. Longer term clinical data in large clinical studies are recommended to confirm these promising early results. [ABSTRACT FROM AUTHOR]