A systematic review and economic evaluation of adalimumab and dexamethasone for treating non-infectious intermediate, posterior or panuveitis in adults

Background: Non-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic corticosteroids, immunosuppressants and biologic drugs. Objectives: To evaluate clinical and cost-effectiveness of subcutaneous adalimumab and dexamethasone intravitreal implant in adults with non-infectious intermediate, posterior or panuveitis. Methods: Nine electronic databases were searched to June 2016. A Markov model was developed to assess cost-effectiveness of dexamethasone and adalimumab, each compared with current practice, from an NHS and PSS perspective over a lifetime horizon, parameterised with published evidence. Costs and benefits were discounted at 3.5%. Substantial sensitivity analyses were undertaken. Results: Two studies (VISUAL I, active uveitis; and VISUAL II, inactive uveitis) compared adalimumab against placebo, plus limited standard care in both arms. Time to treatment failure (reduced visual acuity, intraocular inflammation, new vascular lesions) was longer for adalimumab than placebo, with hazard ratio 0.50 (95% CI 0.36 to 0.70, p<0.001) in VISUAL I and 0.57 (0.39 to 0.84, p=0.004) in VISUAL II. Adalimumab provided significantly greater improvement in VFQ-25 composite score in VISUAL I (mean difference, 4.20; p=0.010) but not VISUAL II (mean difference, 2.12; p=0.16). Some systemic adverse effects occurred more frequently with adalimumab than placebo. One study (HURON, active uveitis) compared single 0.7mg dexamethasone implant against sham, plus limited standard care in both arms. Dexamethasone provided significant benefits over sham at 8 and 26 weeks in percentage of patients with vitreous haze score zero (p<0.014); mean BCVA improvement (p≤0.002); and percentage of patients with ≥5-point improvement in VFQ-25 (p<0.05). Raised intraocular pressure and cataracts occurred more frequently with dexamethasone than sham. The incremental cost-effectiveness ratio (ICER) of one dexamethasone implant in one eye for a combination of patients with unilateral and bilateral uveitis, compared with limited current practice as per the HURON trial, is estimated as £19,509 per quality-adjusted life year (QALY) gained. The ICER of adalimumab for patients with mainly bilateral uveitis, compared with limited current practice as per the VISUAL trials, is estimated as £94,523 and £317,547 per QALY gained in active and inactive uveitis respectively. Sensitivity analyses suggest rate of blindness has the biggest impact upon model results. The interventions may be more cost-effective in populations where there is a greater risk of blindness. Limitations: The clinical trials did not fully reflect clinical practice. Thirteen studies of clinically-relevant comparator treatments were identified; however, network meta-analysis was not feasible. The model results are highly uncertain due to the limited evidence base. Conclusions: Two RCTs of systemic adalimumab and one RCT of unilateral, single dexamethasone implant showed significant benefits over placebo or sham. The ICERs for adalimumab are estimated to be above generally accepted thresholds for cost-effectiveness. The cost-effectiveness of dexamethasone is estimated to fall below standard thresholds. However there is substantial uncertainty around the model assumptions. Future work: Primary research should compare dexamethasone and adalimumab with current treatments over the long term, and in important subgroups, and consider how short-term improvements relate to long-term effects on vision. Study registration: PROSPERO CRD42016041799 Funding details: NIHR HTA Programm

Does the serum uric acid level have any relation to arterial stiffness or blood pressure in adults with congenital renal agenesis and/or hypoplasia?

Background: The relationship between serum uric acid and arterial stiffness or blood pressure is not clear. The serum uric acid level and its association with cardiovascular risk is not well known in patients with reduced renal mass. We aimed to investigate the relation between serum uric acid levels and arterial stiffness and also blood pressure in patients with congenital renal agenesis and/or hypoplasia. Material and Methods: In this single center, cross-sectional study, a total of 55 patients (39 (% 70.9) with unilateral small kidney and 16 (%29.1) with renal agenesis) were included. The median age was 35 (21–50) years. The study population was divided into tertiles of serum uric acid (according to 2.40–3.96, 3.97–5.10, and 5.11–9.80 mg/dl cut-off values of serum uric acid levels). Official and 24-h ambulatory non-invasive blood pressures of all patients were measured. The arterial stiffness was assessed by pulse wave velocity (PWV). Results: PWV values were increased from first to third tertile (5.5 ± 0.6, 5.7 ± 0.8, 6.1 ± 0.7, respectively), but this gradual increase between tertiles did not reach significance. Linear regression analyses showed a positive correlation between serum uric acid levels and PWV (β = 0.40, p = 0.010), but no correlation was found between uric acid and daytime systolic blood pressure (β = 0.24, p = 0.345). Conclusion: In congenital renal agenesis/hypoplasia, the serum uric acid level was positively correlated with arterial stiffness, but there was no correlation with blood pressure

Reconstruction of Coup de Sabre Deformity (Linear Localized Scleroderma) by Using Galeal Frontalis Muscle Flap and Demineralized Bone Matrix Combination

WOS: 000286195600060PubMed: 21233742In this clinical report, we are presenting the combination of demineralized bone matrix combined with bilateral galea frontalis flaps. Based on our 6-month results, this seems to be a reasonable combination to accomplish long-lasting restoration of forehead defects related to en coup de sabre linear localized scleroderma

A survey of applications of artificial intelligence and machine learning in future mobile networks-enabled systems

Different fields have been thriving with the advents in mobile communication systems in recent years. These fields reap benefits of data collected by Internet of Things (IoT) in next generation (5G and 5BG) mobile networks. The IoT concept transforms different fields by providing large amount of data to be used in their operations. This is achieved by massively utilized sensors and mobile devices that acquire data from internet connected devices to keep track of physical systems. Hence, different use cases benefit from the data generated thanks to future mobile network systems. Intelligent Transportation Systems, Smart Energy, Digital Twins, Unmanned Aerial Vehicles (UAVs), Smart Health, Cyber Security are of significant use cases that big data plays an important role for them. Large amount of data entails more intelligent systems with respect to conventional methods, and it also entails highly reduced response time for use cases. Artificial intelligence and machine learning models are adept in satisfying the requirements of this big data situations for different use cases. In this sense, this paper provides a survey of machine learning and artificial intelligence applications for different use cases enabled by future mobile communication systems. An overview of machine learning types and artificial intelligence is presented to provide insights into the intelligent method concepts. Available studies are extensively summarized, and they are also grouped to provide a complete overview of the study. Discussions on the reviewed papers based on artificial intelligence and machine learning concepts are made, and some descriptive figures about the results of the discussions are also given in the paper. Finally, research challenges for artificial intelligence and machine learning applications in the use cases are introduced, future research directions and concluding remarks are presented accordingly