A randomised, double-blind comparison of 20 units of onabotulinumtoxinA with 30 units of incobotulinumtoxinA for glabellar lines.

BACKGROUND: Biological activity data indicate that the units of incobotulinumtoxinA are not equivalent to those of onabotulinumtoxinA. OBJECTIVE: This study compared 20 units of onabotulinumtoxinA with 30 units of incobotulinumtoxinA in the treatment of glabellar lines. METHODS AND MATERIALS: In this multicenter, randomised, double-blind study, subjects with moderate or severe glabellar lines received a single treatment with 20 units of onabotulinumtoxinA (n = 112), or 30 units of incobotulinumtoxinA (n = 112). The primary endpoint was the percentage of subjects with a reduction of ≥ 1 point on the Facial Wrinkle Scale at maximum contraction as rated by injectors on day 28 post injection. The same variable was evaluated on days 84, 98, and 112. RESULTS: At the primary endpoint, 20 units of onabotulinumtoxinA was as effective as 30 units of incobotulinumtoxinA (96% vs. 95% responders, respectively; difference in proportion of responders = 0.02, 95% confidence interval [CI] - 0.04, 0.07). At subsequent time points, a trend towards a higher percentage of responders was observed in the group treated with 20 units of onabotulinumtoxinA. Given that the 95% CI surpassed the upper equivalence margin at these time points, equivalence was not established. CONCLUSION: These data support the non-interchangeability of units of onabotulinumtoxinA and incobotulinumtoxinA, and the absence of a fixed dose ratio in clinical practice.

Medical Affairs Transformation in Specialty Pharma: Next-Level Collaboration at the Core.

Pharmaceutical companies with a medical mindset and an empowered Medical Affairs function are well equipped to meet the needs and expectations of patients and society. Yet, as capacity to understand and serve those needs accelerates, so too do expectations. Evidence-based practice, without delay, is expected throughout the development and delivery of medicine, healthcare, and information, and potential sources of evidence are legion. To keep pace and go beyond, to innovate, requires efficiencies. Not the disguised cutbacks of political language, but the collaborative constructive efficiencies of shared learning, forming new evidence bases for further progress. Here, we describe the first year of a medical transformation process at a global mid-sized pharmaceutical company. Beginning with a broad review designed to leverage collective intelligence and focus on meaningful outcomes for patients, this process examined and reshaped the structure, culture, and tools of the medical organization and its interactions within and outside the company. We report the findings of the diagnostic phase, outline the solutions implemented to date, and anticipate the next steps in this dynamic evolving journey.

Non-specific effects of rabies vaccine on the incidence of self-reported common infectious disease episodes: A randomized controlled trial.

Vaccines may affect recipients' immune systems in ways that change morbidity or mortality rates to unrelated infections in vaccinated populations. It has been proposed that these non-specific effects differ by type of vaccine and by sex, with non-live vaccines enhancing susceptibility of females to unrelated infections, and live vaccines enhancing resistance in both sexes. Rabies vaccine-a non-live vaccine-has been associated with protection against unrelated central nervous system infections. Data from randomized controlled trials are needed to assess this effect against other illnesses. This phase IV, single-site, participant-blinded, randomized, placebo-controlled trial in a population of veterinary students on the rabies-free island of St. Kitts assessed the effect of a primary course of rabies vaccine on the incidence rate of weekly self-reported new episodes of common infectious disease (CID) syndromes, defined as a new episode of any one of the following syndromes in a particular week: upper respiratory illness (URI), influenza-like illness (ILI), diarrheal illness (DIA) or undifferentiated febrile illness (UFI). As a secondary objective, we tested for modification of the effect of rabies vaccine on study outcomes by sex. 546 participants were randomized (274 to rabies vaccine and 272 to placebo). No statistically significant differences between groups were observed for any study outcomes: CID incidence rate ratio (IRR) 0.95 (95% CI 0.77-1.18); URI IRR 1.15 (95% CI 0.86-1.54); ILI IRR 0.83 (95% CI 0.54-1.27); DIA IRR 0.93 (95% CI 0.70-1.24) and UFI IRR 1.09 (95% CI 0.48-2.44). In a secondary analysis, there was little evidence that sex modified the effect of vaccination on any of the evaluated outcomes, although the power to detect this was low. In conclusion, rabies vaccine did not provide protection against mild self-reported illness among a young and healthy group of adults attending veterinary school. Clinical trial registration. ClinicalTrials.gov: NCT03656198.

Double-blind, randomised, parallel group pilot study comparing two botulinum toxin type A products for the treatment of blepharospasm.

Botulinum neurotoxins (BoNTs) are the primary treatment for focal dystonias such as blepharospasm. Several different BoNT products are available in various countries. Given the variability in manufacturing, formulation, and unit doses of BoNTs, it is important to compare the profiles of products from different manufacturers. This double-blind, randomised, parallel-group pilot study compared the efficacy and safety of the BoNT type A product Xeomin® from Merz to BOTOX® from Allergan. Subjects (n = 65) were randomly assigned to receive one or the other BoNTA in a 1:1 proportion at a dose equal to that of their most recent treatment (≥20 U/eye). Symptoms were assessed on the Blepharospasm Disability Index (BSDI), Jankovic Rating Scale (JRS), and Patient Global Assessment (PGA) scale at 4 and 8 weeks. Both BoNTA products reduced scores on the BSDI and JRS (no statistically significant difference, tendency toward greater improvements with BOTOX® than Xeomin® at 4 and 8 weeks). A post hoc analysis showed a significantly greater number of BOTOX® treated patients reaching a responder threshold of 4 points on the total BSDI score and 0.67 points on the BSDI mean item score. No significant differences between products were noted in PGA and adverse events at the doses used in this study.

OnabotulinumtoxinA Improves Pain in Patients With Post-Stroke Spasticity: Findings From a Randomized, Double-Blind, Placebo-Controlled Trial.

CONTEXT: Patients with post-stroke spasticity (PSS) commonly experience pain in affected limbs, which may impact quality of life. OBJECTIVES: To assess onabotulinumtoxinA for pain in patients with PSS from the BOTOX(®) Economic Spasticity Trial, a multicenter, randomized, double-blind, placebo-controlled trial. METHODS: Patients with PSS (N = 273) were randomized to 22- to 34-week double-blind treatment with onabotulinumtoxinA + standard care (SC) or placebo injection + SC and were eligible to receive open-label onabotulinumtoxinA up to 52 weeks. Assessments included change from baseline on the 11-point pain numeric rating scale, proportion of patients with baseline pain ≥4 achieving ≥30% and ≥50% improvement in pain, and pain interference with work at Week 12, end of double-blind treatment, and Week 52. RESULTS: At baseline, most patients (74.3%) experienced pain and 47.4% had pain ≥4 (pain subgroup). Mean pain reduction from baseline at Week 12 was significantly greater with onabotulinumtoxinA + SC (-0.77, 95% CI -1.14 to -0.40) than placebo + SC (-0.13, 95% CI -0.51 to 0.24; P < 0.05). Higher proportions of patients in the pain subgroup achieved ≥30% and ≥50% reductions in pain at Week 12 with onabotulinumtoxinA + SC (53.7% and 37.0%, respectively) compared with placebo (28.8% and 18.6%, respectively; P < 0.05). Reductions in pain were sustained through Week 52. Compared with placebo + SC, onabotulinumtoxinA consistently reduced pain interference with work. CONCLUSION: This is the first randomized, placebo-controlled trial demonstrating statistically significant and clinically meaningful reductions in pain and pain interference with work with onabotulinumtoxinA in patients with PSS.

Evaluation of the performance of the OneTouch Select Plus blood glucose test system against ISO 15197:2013.

OBJECTIVES: Assess laboratory and in-clinic performance of the OneTouch Select(®) Plus test system against ISO 15197:2013 standard for measurement of blood glucose. METHODS: System performance assessed in laboratory against key patient, environmental and pharmacologic factors. User performance was assessed in clinic by system-naïve lay-users. Healthcare professionals assessed system accuracy on diabetes subjects in clinic. RESULTS: The system demonstrated high levels of performance, meeting ISO 15197:2013 requirements in laboratory testing (precision, linearity, hematocrit, temperature, humidity and altitude). System performance was tested against 28 interferents, with an adverse interfering effect only being recorded for pralidoxime iodide. Clinic user performance results fulfilled ISO 15197:2013 accuracy criteria. Subjects agreed that the color range indicator clearly showed if they were low, in-range or high and helped them better understand glucose results. CONCLUSION: The system evaluated is accurate and meets all ISO 15197:2013 requirements as per the tests described. The color range indicator helped subjects understand glucose results and supports patients in following healthcare professional recommendations on glucose targets.

Functional goal achievement in post-stroke spasticity patients: the BOTOX® Economic Spasticity Trial (BEST).

OBJECTIVE: Evaluate changes in active and passive function with onabotulinumtoxinA + standard of care within goal-oriented rehabilitation programmes in adults with focal post-stroke spasticity. METHODS: Prospective, 24-week double-blind study with an open-label extension. Subjects were randomized to onabotulinumtoxinA + standard of care or placebo + standard of care, at baseline and at 12 weeks, if judged appropriate, with follow-up to 52 weeks. The primary endpoint was the number of patients achieving their principal active functional goal at 24 weeks (or 10 weeks after an optional second injection). Secondary endpoints included achievement of a different active or a passive goal at this timepoint. RESULTS: The intent-to-treat population comprised 273 patients. The proportion of patients achieving their principal active functional goal and secondary active functional goal with onabotulinumtoxinA + standard of care was not statistically different from placebo + standard of care. Significantly more patients achieved their secondary passive goal with onabotulinumtoxinA + standard of care (60.0%) vs. placebo + standard of care (38.6%) (odds ratio, 2.46; 95% confidence interval, 1.18-5.14) as well as higher Goal Attainment Scaling levels for upper limb and ankle flexor subgroups. CONCLUSIONS: Addition of onabotulinumtoxinA to standard of care as part of goal-oriented rehabilitation in post-stroke spasticity patients significantly increased passive goal achievement and was associated with higher levels of active function.

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD.

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion.

Retrieval study of tibial baseplate fracture after total knee arthroplasty.

Twenty-five cases of fractured metal tibial baseplates were reviewed from retrieved knee arthroplasty. A total of 74 cases have been reported, including the 25 in this series. Baseplate fracture is an avoidable problem with careful choice of prosthesis, attention to surgical detail, and satisfactory postoperative follow-up. There is a relatively short duration of symptoms before fracture, (mean, 10.8 months; range, 1-36 months). Patients should also be advised to self-report if there is sudden onset of pain or any symptoms of instability or mechanical failure, such as squeaks, clicks, or swelling. Early revision should be considered if there is concern about potential baseplate fracture as delay may compromise the ultimate result. A classification for these baseplate fractures is proposed, and the multifactorial etiology is discussed.