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Objectives and Methods: OSVaLD (Observational Study in patients suffering from recurrent peripheral vestibular Vertigo to Assess the effect of betahistine 48 mg/day on quality of Life and Dizziness symptoms) is a 3-month, open-label, multi-national post-marketing surveillance study of betahistine 48 mg/day in the management of patients with vertigo of less than 5 years in duration. The aim of the study is to examine the burden of disease associated with vertigo, as determined by scores on the Dizziness Handicap Inventory (DHI), Short Form-36 (SF-36) questionnaire and the Hospital Anxiety and Depression Scale (HADS). Changes in DHI, SF-36 and HADS scores between baseline and 3 months are used to assess the therapeutic effects of betahistine.Results: Participants (n = 2037) have been recruited from 13 countries in four continents (North and South America, Asia and Europe), representing a wide range of cultural and linguistic traditions. Approximately two-thirds of the patients are women. Sixty per cent of patients have diagnoses of peripheral vestibular vertigo of unknown pathology or benign paroxysmal positional vertigo; 13% have a diagnosis of Ménière's disease. All three of the instruments used characterize this as a population with extensive vertigo-attributable morbidity at baseline. The mean DHI score of the population is 63.7 +/- 15.7 (DHI scale: 0 = no handicap; 100 = major self-perceived handicap), SF-36 scores in all domains are below the population average for the USA and the HADS indicated that > 50% of patients exhibit symptoms of anxiety or depression or both, including 9% who have severe manifestations of either or both conditions.Conclusions: This report describes the design and implementation of OSVaLD and presents baseline demographic and clinical features of the patients. Full results of the study, anticipated in 2007, will provide more details about the manifestations of vertigo in routine practice and the response to betahistine. [ABSTRACT FROM AUTHOR]

Background: Immunosuppressive regimens are imperative for improving patient and graft survival following kidney transplantation in patients with kidney failure. However, real-world evidence regarding treatments and outcomes in these patients is scarce. We sought to describe the treatment switches (assessed by line of treatment [LOT]), patterns, and outcomes in patients who underwent kidney transplantation in the United States., Methods: This retrospective cohort study used claims data from the Optum Research Database in the United States. Adult and pediatric patients undergoing a kidney transplantation between January 1, 2000, and June 30, 2019, who had ≥1 year of baseline and follow-up visits and continuous enrollment in the Optum Research Database, were included., Results: Data from 7159 patients (6833, adult; 326, pediatric) were included. The mean age for adult and pediatric patients was 51.4 ± 12.8 years and 10.4 ± 5.1 years, respectively. The mean number of LOTs in patients with ≥1 LOT (n = 7004) was 4.1 ± 2.6 LOTs. Tacrolimus, antiproliferative agents, and prednisone were the most frequently prescribed immunosuppressants. No strong correlations were identified between switching from LOT1 to LOT2 and potential predictors of treatment switches. The proportion of patients who did not experience graft loss gradually decreased between month 3 and month 120 (72%-36%), driven by return to dialysis (66%-18%). A slower decrease was observed for graft rejection (98%-84%), retransplantation (98%-93%), and graft removal (98%-92%)., Conclusions: We described treatment switches, patterns, and outcomes in patients who underwent kidney transplantation in the United States. Future analytical studies are needed to test hypotheses derived from these observations., Competing Interests: Declaration of competing interest YG is an employee and shareholder at Novartis Pharma AG, Basel, Switzerland. JCJ is an employee of Optum, which received funding from Novartis Pharma AG for the conduct of the study. HG is an employee at Novartis Pharma AG, Basel, Switzerland. EA is an employee and shareholder at Novartis Pharma AG, Basel, Switzerland. DK is an employee at Novartis Pharma AG, Basel, Switzerland. JMS is an employee of Optum, which received funding from Novartis Pharma AG for the conduct of the study. GB is a former employee at Novartis Pharma AG, Basel, Switzerland. LP is an employee and shareholder at Novartis Pharma AG, Basel, Switzerland., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Dryness, fatigue and joint/muscle pain are typically assessed in Sjögren's trials using European Alliance of Associations for Rheumatology Sjögren's Syndrome Patient Reported Index (ESSPRI). A Patient Acceptable Symptom State of <5 and a Minimal Clinically Important Improvement (MCII)/responder definition (RD) of ≥1 point or 15% on ESSPRI have previously been defined. This study explored alternative RDs to better discriminate between active treatment and placebo in trials., Methods: Anchor-based and distribution-based methods were used to derive RD thresholds in blinded phase IIb trial data (N=190) and confirm these in blinded data pooled from three early phase II trials (N=126). The populations consisted of individuals with moderate-to-severe systemic primary Sjögren's. Anchors were prioritised by ESSPRI correlations and used in similar conditions. Triangulated estimates were discussed with experts (N=3). The revised RD was compared with the original using unblinded data to assess placebo and treatment responder rates., Results: Patients were predominantly female (>90%), white (90%), with mean age of 50 years. Receiver operating characteristic estimates supported an MCII threshold of 1.5-1.6 in the phase II data, whereas correlation-weighted mean change estimates supported a low/minimal symptom severity threshold of ≥2. A low/minimal symptom severity of ≤3 showed the greatest sensitivity/specificity balance. Analyses in the pooled data supported these thresholds (MCII: 1.5-2.1; low/minimal symptom severity: 2.7-3.7). Unblinded analyses confirmed the revised RD reduced placebo rates., Conclusions: Completing a trial with an improvement of ≥1.5 points compared with baseline and an ESSPRI score of ≤3 points is a relevant RD for moderate-to-severe systemic Sjögren's and reduces placebo rates., Competing Interests: Competing interests: Authors on this manuscript are either employees of or consultants to Novartis, a pharmaceutical company developing products for patients with Sjogren’s. SB has consulted in the field of Sjogren’s in the past 3 years for AbbVie, AstraZeneca, BMS, Galapagos, Novartis and Resolve Pharmaceuticals., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Voriconazole is well established as standard treatment for invasive aspergillosis (IA). In 2017, isavuconazole, a new antifungal from the azole class, with a broader pathogen spectrum, was introduced in Sweden. A model has therefore been developed to compare the cost-effectiveness of isavuconazole and voriconazole in the treatment of possible IA in adults in Sweden., Methods: The cost-effectiveness of isavuconazole versus voriconazole was evaluated using a decision-tree model. Patients with possible IA entered the model, with 6% assumed to actually have mucormycosis. It was also assumed that pathogen information would become available during the course of treatment for only 50% of patients, with differential diagnosis unavailable for the remainder. Patients who were considered unresponsive to first-line treatment were switched to second-line treatment with liposomal amphotericin-B. Data and clinical definitions included in the model were taken from the published randomised clinical trial comparing isavuconazole with voriconazole for the treatment of IA and other filamentous fungi (SECURE) and the single-arm, open-label trial and case-control analysis of isavuconazole for the treatment of mucormycosis (VITAL). A probabilistic sensitivity analysis was used to estimate the combined parameter uncertainty, and a deterministic sensitivity analysis and a scenario analysis were performed to test the robustness of the model assumptions. The model followed a Swedish healthcare payer perspective, therefore only considering direct medical costs., Results: The base case analysis showed that isavuconazole resulted in an incremental cost-effectiveness ratio (ICER) of 174,890 Swedish krona (SEK) per additional quality adjusted life-year (QALY) gained. This was mainly due to the efficacy of isavuconazole against IA and mucormycosis, as opposed to voriconazole, which is only effective against IA. Sensitivity and scenario analyses of the data showed that the average ICER consistently fell below the willingness to pay (WTP) threshold of 1,000,000 SEK. The probability of isavuconazole being cost-effective at a WTP of 170,000 SEK per QALY gained was 50% and at a WTP of 500,000 SEK per QALY gained was 100%., Conclusions: This model suggests that the treatment of possible IA with isavuconazole is cost-effective compared with treatment with voriconazole from a Swedish healthcare payer perspective.

Objectives: Voriconazole, amphotericin B (AmB) formulations, and isavuconazole are all included in guideline recommendations for treatment of patients with invasive aspergillosis (IA) but the relative efficacy of isavuconazole versus AmB formulations has not been directly compared. We aimed to estimate the relative efficacy of isavuconazole compared with AmB deoxycholate (AmB-D), liposomal AmB (L-AmB), and voriconazole for the treatment of patients with proven/probable IA., Methods: Nine literature databases were screened for randomized controlled trials comparing treatments with any of voriconazole, AmB-D, L-AmB and isavuconazole for treatment of proven/probable IA. Articles meeting the criteria were included in a meta-analysis to determine the efficacy of AmB-D, L-AmB and voriconazole relative to isavuconazole based on all-cause mortality (ACM) and overall response using a fixed-effects model., Results: Four articles were identified that compared L-AmB with AmB-D (Study 1), standard-dose L-AmB (3-5 mg/kg/day) with high-dose L-AmB (10 mg/kg/day; Study 2), voriconazole with AmB-D (Study 3), and isavuconazole with voriconazole (Study 4). In the network meta-analysis, isavuconazole was statistically superior to AmB-D on both ACM (odds ratio [95% credible intervals] shown as natural log, 1.00 [0.26, 1.74]) and overall response (-1.39 [-2.21, -0.63]). Differences between isavuconazole, and standard-dose L-AmB, high-dose L-AmB and voriconazole were not statistically significant for either ACM (0.18 [-1.17, 1.53], 0.50 [-1.11, 2.13] and 0.32 [-0.19, 0.84], respectively) or overall response (-0.99 [-2.21, 0.29], -0.89 [-2.41, 0.65] and 0.06 [-0.43, 0.57], respectively)., Conclusions: This data suggests that the efficacy of isavuconazole for treatment of IA is superior to AmB-D and comparable with both L-AmB and voriconazole.

Aim: Invasive mold diseases (IMDs) are associated with significant morbidity and mortality. Approved treatments include voriconazole (VORI), liposomal amphotericin B (L-AMB), posaconazole (POSA) and isavuconazole (ISAV). A UK-based economic model was developed to explore the cost of treating IMDs with ISAV versus L-AMB followed by POSA., Materials & Methods: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration & monitoring, and hospitalization costs were evaluated from the healthcare system perspective., Results: Per-patient costs were UK£14,842 with ISAV versus UK£18,612 with L-AMB followed by POSA. Savings were driven by drug acquisition, and administration & monitoring costs., Conclusion: ISAV has the potential to reduce IMD treatment costs relative to L-AMB followed by POSA.

Aim: Mucormycosis is a fungal infection associated with high mortality. Until recently, the only licensed treatments were amphotericin B (AMB) formulations. Isavuconazole (ISAV) is a new mucormycosis treatment. A UK-based economic model explored treatment costs with ISAV versus liposomal AMB followed by posaconazole., Materials & Methods: As a matched case-control analysis showed similar efficacy for ISAV and AMB, a cost-minimization approach was taken. Direct costs - drug acquisition, monitoring and administration, and hospitalization costs - were estimated from the National Health Service perspective., Results: Per-patient costs for ISAV and liposomal AMB + posaconazole were UK£26,810 and UK£41,855, respectively, with savings primarily driven by drug acquisition and hospitalization costs., Conclusion: ISAV may reduce costs compared with standard mucormycosis therapy.

Objective: Despite the high prevalence of vertigo globally and an acknowledged, but under-reported, effect on an individual's wellbeing, few studies have evaluated the burden on healthcare systems and society. This study was aimed to quantitatively determine the impact of vertigo on healthcare resource use and work productivity., Methods: The economic burden of vertigo was assessed through a multi-country, non-interventional, observational registry of vertigo patients: the Registry to Evaluate the Burden of Disease in Vertigo. Patients included were those with a new diagnosis of Meniere's disease, benign paroxysmal positional vertigo, other vertigo of peripheral vestibular origin, or peripheral vestibular vertigo of unknown origin., Results: A total of 4,294 patients at 618 centers in 13 countries were included during the registry. Of the 4,105 patients analyzed, only half were in employment. Among this working patient population, 69.8% had reduced their workload, 63.3% had lost working days, and 4.6% had changed and 5.7% had quit their jobs, due to vertigo symptoms. Use of healthcare services among patients was high. In the 3 months preceding Visit 1, patients used emergency services 0.4 ± 0.9 times, primary care consultations 1.6 ± 1.8 times, and specialist consultations 1.4 ± 2.0 times (all mean ± SD). A mean of 2.0 ± 5.4 days/patient was also spent in hospital due to vertigo., Conclusion: In addition to the negative impact on the patient from a humanistic perspective, vertigo has considerable impact on work productivity and healthcare resource use.

Implementation of guidelines can improve clinical practice. The aim in this study was to investigate whether neurologists in Germany adhered to the national Parkinson's disease guideline. Data were obtained from a cross-sectional survey of 60 neurologists. Analyses were performed on 320 patients with idiopathic Parkinson's disease with either low grades of functional impairment (Hoehn and Yahr stage I) or higher grades of functional impairment (stage II-V) but without motor complications. The sample was divided into four groups depending on age and grade of functional impairment. For each group, a biometric parameter on the use of dopamine agonists and L-dopa was defined based on the guideline. In patients aged <70 years, the recommendation to use dopamine agonists without L-dopa (parameter 1) was observed in 53% of patients with lower grades of functional impairment, whilst recommended use of dopamine agonists in more functionally impaired patients (parameter 2) was followed to a greater extent (84%). In patients aged ≥70 years, recommendations to use L-dopa without dopamine agonists were adhered to in only 50% of less functionally impaired (parameter 3) and 52% of more functionally impaired (parameter 4) patients. In conclusion, our results indicated there was moderate but not full adherence to the guideline.