IntroductionJuvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ.MethodsJoint inflammation was initiated by injecting two doses of complete Freund’s adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague–Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 mg of P-DEX intra-articularly (n = 9), (2) 15 mg of P-DEX into the tail vein (n = 7), or (3) nothing in addition to CFA (n = 8). The rats were killed 28 days later and measured by radiography for ramus height (condylar superior to gonion inferior [CsGoInf]), by micro-computed tomography for condylar width (CW) and bone volume/standardized condylar volume (BV/CV), and by histology for retrodiscal inflammatory cells. Inflammation targeting of systemic P-DEX was confirmed by IVIS infrared dye imaging. Inflammation and bone growth were compared between groups using analysis of variance and Pearson’s correlations.ResultsCFA caused a significant reduction in CsGoInf (p < 0.05), but neither route of P-DEX administration had an effect on CsGoInf or CW at CFA injection sites. BV/CV was significantly reduced in both inflamed and control condyles as a result of either steroid application (p < 0.05). The inflammatory infiltrate was overwhelmingly lymphocytic, comprising 16.4 ± 1.3 % of the field in CFA alone vs. <0.01 % lymphocytes in contralateral controls (p < 0.0001). Both P-DEX TMJ (10.1 ± 1.2 %) and systemic P-DEX (8.9 ± 1.7 %) reduced lymphocytes (p < 0.002). The total area of inflammatory infiltrate was significantly less in the systemic injection group than in the group that received CFA injections alone (2.6 ± 1.5 mm2 vs. 8.0 ± 1.3 mm2; p = 0.009), but not in the group that received intra-articular P-DEX (8.8 ± 1.2 mm2).ConclusionsHigh-dose systemic administration of inflammation-targeting P-DEX is more effective than an intra-articular injection in reducing TMJ inflammation, but both routes may affect TMJ bone density.

A343infant in comparison to no-screening strategy. Transferred to the entire birth cohort newborn screening is able to reduce total costs by 14 million € from the Austrian health care systems perspective each year. ConClusions: Funding the new-born screening saves money and is cost-effective for the Austrian health care system.

Objectives: Two SGLT-2 inhibitors, CANA and DAPA, are recommended in the UK for combination therapy in T2DM. Through an insulin-independent mechanism of action, SGLT-2 inhibitors improve glucose levels, blood pressure, and weight with a low inherent risk of hypoglycaemia. The cost-effectiveness of using CANA or DAPA in combination with MET was evaluated in patients inadequately controlled with MET monotherapy, from the perspective of the UK NHS. MethOds: The ECHO-T2DM model was used to estimate 40-year outcomes and costs associated with using CANA (100mg or 300mg) versus DAPA 10mg in dual therapy. HbA1c efficacy estimates were obtained from a Network Meta-Analysis (NMA). Analyses of pooled data from trials investigating CANA dual therapy (with MET) were used for parameters unavailable in the NMA (i. e., SBP, LDL, HDL and AEs). A broad set of sensitivity analyses were performed. Results: Both doses of CANA were associated with more QALYs (0.01,0. 03 for 100mg and 300mg, respectively) and higher costs (£101, £594, respectively). The associated incremental cost-effectiveness ratios (ICERs) were £7,423 and £17,734, respectively; both below the willingness-to-pay for QALY threshold in the UK. The key driver of the result for CANA 300mg was the greater HbA1c efficacy versus DAPA 10mg, and for CANA 100mg, a lower need for insulin rescue since CANA (but not DAPA) can be used in persons with moderate renal impairment. The ICERs were robust under all scenarios tested. Only use of UK-specific and not clinical trial patient characteristics substantively impacted the results; none reversed the interpretation of CANA as cost-effective versus DAPA. cOnclusiOns: SGLT-2 inhibitors reduce HbA1C, body weight, and blood pressure, and thus the risk of micro-and macrovascular complications. Economic simulations suggest that both doses of CANA are cost-effective versus DAPA in dual therapy treatment of T2DM (with MET) in the UK.

No abstract

No abstract