Epidemiology of Distal Renal Tubular Acidosis: A Study Using Linked UK Primary Care and Hospital Data

Introduction: Distal renal tubular acidosis (dRTA), or RTA type 1, a rare inherited or acquired disease, is a disorder of the distal tubule caused by impaired urinary acid secretion. Due to associated conditions and nonspecific symptoms, dRTA may go undetected. This analysis aims to estimate the prevalence of dRTA in the UK Clinical Practice Research Datalink (CPRD) databases and extrapolate it to European Union Five (EU5) populations. Methods: A retrospective analysis was conducted using the CPRD GOLD database and linked Hospital Episode Statistics (HES) data to identify diagnosed and potentially undiagnosed or miscoded patients (suspected patients). Patients’ records with at least one diagnosis code for dRTA, RTA, specific autoimmune diseases, or renal disorders recorded between January 1987 and November 2017 were obtained and analyzed. An algorithm was developed to detect potentially undiagnosed/miscoded dRTA, based on associated conditions and prescriptions. Results: A total of 216 patients with diagnosis of RTA or dRTA were identified (with 98 linked to hospital data), and 447 patients were identified as having suspected dRTA. dRTA prevalence for 2017 was estimated between 0.46 (recorded cases, of which 22.1% were considered primary) and 1.60 when including suspected cases (7.6% primary) per 10,000 people. Prescription and clinical records of diagnosed patients revealed a wide range of comorbidities and a need for pharmacological treatment to manage associated symptoms. Conclusion: The study provides new estimates of dRTA prevalence in Europe and suggests that patients may often be unreported or miscoded, potentially confounding appropriate disease management

Additive energy forward curves in a Heath-Jarrow-Morton framework

One of the peculiarities of power and gas markets is the delivery mechanism of forward contracts. The seller of a futures contract commits to deliver, say, power, over a certain period, while the classical forward is a financial agreement settled on a maturity date. Our purpose is to design a Heath-Jarrow-Morton framework for an additive, mean-reverting, multicommodity market consisting of forward contracts of any delivery period. The main assumption is that forward prices can be represented as affine functions of a universal source of randomness. This allows us to completely characterize the models which prevent arbitrage opportunities: this boils down to finding a density between a risk-neutral measure $\mathbb{Q}$, such that the prices of traded assets like forward contracts are true $\mathbb{Q}$-martingales, and the real world probability measure $\mathbb{P}$, under which forward prices are mean-reverting. The Girsanov kernel for such a transformation turns out to be stochastic and unbounded in the diffusion part, while in the jump part the Girsanov kernel must be deterministic and bounded: thus, in this respect, we prove two results on the martingale property of stochastic exponentials. The first allows to validate measure changes made of two components: an Esscher-type density and a Girsanov transform with stochastic and unbounded kernel. The second uses a different approach and works for the case of continuous density. We apply this framework to two models: a generalized Lucia-Schwartz model and a cross-commodity cointegrated market.Comment: 28 page

Cost-Effectiveness Of Everolimus Plus Reduced Tacrolimus In De Novo Liver-Recipients In The Italian Setting.

Objectives: Prolonged exposure to CNI-based immunosuppressant therapy (IS) in liver transplant (LTx) recipients is associated with long-term complications. In the global registration trial H2304, patients receiving everolimus + reduced tacrolimus (EVR + reduced TAC) demonstrated non-inferior efficacy and supe- rior renal function at Month 12 that was sustained at 36 months compared to tacrolimus alone (TAC). A peer-reviewed Markov model has been adapted to the Italian setting to explore the cost-effectiveness of EVR + reduced TAC compared to TAC, in de novo liver-recipients. MethOds: The model estimates long-term out- comes associated with IS following LTx along two independent pathways: 1. liver- related (acute rejection, hepatocellular carcinoma, hepatitis C [HCV] recurrence, graft loss); 2. kidney-related (chronic kidney disease, dialysis, renal transplanta- tion) and death. All patients, stratified by liver diagnosis, entered the model at time of LTx and followed both pathways, allowing for multiple combinations of liver and kidney health states. The lifetime model used an annual cycle length except for the 1styear post LTx (quarterly). Efficacy and safety of IS strategies were assessed through the risk of acute rejection, change in renal function, HCV fibrosis progression and frequency of adverse events. Utilities and costs were assigned to each renal and liver state. Subgroup and sensitivity analyses were performed. Results: With a mean life expectancy of 18 years, the model predicts patients treated with EVR + reduced TAC gain on average 1.84 years of life and 1.55 QALYs vs. TAC. The risk of acute rejection was reduced by 20%. The incremental cost of EVR + TAC was €38,884 per life year gained and €46,103 per QALY gained vs. TAC. cOnclusiOns: This model shows a strategy of EVR + reduced TAC post- LTx improves survival and quality of life. Higher treatment costs are offset by slower progression of renal deterioration predicted in the first 10 years and fewer lifetime liver complications

Abaloparatide for risk reduction of non-vertebral fractures in postmenopausal women with osteoporosis: an updated network meta-analysis.

peer reviewedSummary: This network meta-analysis assessed the efficacy of abaloparatide versus other treatment options to reduce the risk of fractures in women with postmenopausal osteoporosis. The analysis indicates that abaloparatide reduces the risk of fractures in women with postmenopausal osteoporosis versus placebo and compared with other treatment options. Introduction: This network meta-analysis (NMA) assessed the relative efficacy of abaloparatide versus other treatments to reduce the risk of fractures in women with postmenopausal osteoporosis (PMO). Methods: PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published before December 20, 2017, that included women with PMO who were eligible to receive interventions for primary or secondary fracture prevention. The NMA was conducted by fracture site (vertebral [VF], nonvertebral [NVF], and wrist), with the relative risk (RR) of fracture versus placebo the main clinical endpoint. The NMA used fixed-effects and random-effects approaches. Results: A total of 4978 articles were screened, of which 22 were included in the analysis. Compared with other treatments, abaloparatide demonstrated the greatest treatment effect relative to placebo in the VF network (RR = 0.13; 95% credible interval [CrI] 0.04–0.34), the NVF network (RR = 0.50; 95% CrI 0.28–0.85), and the wrist fracture network (RR = 0.39; CrI 0.15–0.90). Treatment ranking showed that abaloparatide had the highest estimated probability of preventing fractures in each of the networks (79% for VF, 70% for NVF, and 53% for wrist fracture) compared with other treatments. Individual networks demonstrated a good level of agreement with direct trial evidence and direct pair-wise comparisons. Conclusions: This NMA indicates that abaloparatide reduces the RR of VF, NVF, and wrist fracture in women with PMO with or without prior fracture versus placebo, compared with other treatment options. Limitations include that adverse events and drug costs were not considered, and that generalizability is limited to the trial populations and endpoints included in the NMA. © 2019, The Author(s)