吡啶类与苯胺类缓蚀剂的生产及应用

以氯化苄和吡啶为原料,合成物经与其它物料复配而生产出吡啶类缓蚀剂;以苯胺和环己酮为原料,反应物经与其它物料复配而生产出苯胺类缓蚀剂。经复配后的性能评价表明:吡啶与氯化苄的反应物和甲醇1:5稀释,复配2%甲醛、3%的丙炔醇,腐蚀速度可以降到2g/m2·h以下,苯胺与环己酮的反应物和甲醇1:6稀释,复配2%左右的丙炔醇、2%左右的碘化钾,腐蚀速度可以降到7g/m2·h以下。在室内试验的基础上,通过对两类缓蚀剂进行了工业化的生产与应用,取得了良好的效果。     

Cost-effectiveness of dipeptidyl peptidase-4 inhibitor monotherapy versus sulfonylurea monotherapy for people with type 2 diabetes and chronic kidney disease in Thailand

Objective: With a high prevalence of chronic kidney disease (CKD) in type 2 diabetes (T2DM) in Thailand, the appropriate treatment for the patients has become a major concern. This study aimed to evaluate long-term cost-effective of dipeptidyl peptidase-4 (DPP-4) inhibitor monothearpy vs sulfonylurea (SFU) monotherapy in people with T2DM and CKD.

Methods: A validated IMS CORE Diabetes Model was used to estimate the long-term costs and outcomes. The efficacy parameters were identified and synthesized using a systematic review and meta-analysis. Baseline characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. Costs were expressed in 2014?US Dollars. Outcomes were presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty.

Results: From a societal perspective, treatment with DPP-4 inhibitors yielded more quality-adjusted life years (QALYs) (0.024) at a higher cost (>66,000 Thai baht (THB) or >1,829.27 USD) per person than SFU, resulting in the ICER of >2.7 million THB/QALY (>74,833.70 USD/QALY). The cost-effectiveness results were mainly driven by differences in HbA1c reduction, hypoglycemic events, and drug acquisition cost of DPP-4 inhibitors. At the ceiling ratio of 160,000 THB/QALY (4,434.59 USD/QALY), the probability that DPP-4 inhibitors are cost-effective compared to SFU was less than 10%.

Conclusions: Compared to SFU, DPP-4 inhibitor monotherapy is not a cost-effective treatment for people with T2DM and CKD in Thailand.     

Disease-specific cost savings of treating nighttime versus daytime gastroesophageal reflux disease in an employed population

Summary

Objective: The extent to which proton pump inhibitors (PPIs) can offset direct medical costs by reducing symptoms related to gastroesophageal reflux disease (GERD) in order to improve work productivity is not well understood. This study aimed to evaluate the economic impact of treating GERD with PPIs versus no treatment, from an employer's perspective.

Study design: An economic model was developed to simulate symptom reduction and breakthrough symptoms as well as associated costs over 1 year among a population of 100,000 with a 20% GERD prevalence rate. Medical costs, including GERD-related office visits, hospitalisations and procedures, were delineated by symptom severity. Indirect costs represented the monetised work productivity loss. PPI treatment costs $2/day (standard dose).

Results: The GERD burden was substantial ($62,500,000). Treatment yielded $32,600,000 in savings ($1,630 saved/patient/year), mostly from reducing indirect costs. Treatment produced greater savings among nighttime GERD patients throughout the PPI cost range ($1–$5/day). Savings dropped if the price of standard doses of PPI exceeded $3.92/day for the treatment of daytime GERD patients.     

Large-scale participatory co-shaping of technological developments: First experiments with PARDIZIPP

A future-oriented participatory procedure on the basis of the Delphi method was developed and empirically tested a first time with the goal to improve the shaping of technological developments. The technology under study here was micro-electronics or rather their relationship with labor and the test took place in NorthRhine-Westphalia.Today problems exist in all walks of life. There is a lot of talk about today's problems as if they were new, though one has heard similar arguments throughout history. How do we assess if we are really in danger of bringing the world to an end? Although this danger appears real, it would not be the first time in history that people have thought and felt like this--However, one thing that is new are the consequences of modern sciences and technology, which are not suited to given social and environmental requirements. They have given rise to questions concerning the quality of the decision-makers. The questioning of many of these decisions has increased for some time and is now getting more and more specific, with a demand for quality and information rather than managerial skills and competitiveness from the decision-makers. The term ‘decision-maker’ describes those who determine the application of technology, science and technical equipment which has either existed for a long time already or has recently been developed.--It is not easy to change the structures and processes of decision-making so that new structures and processes will be more suited to social and environmental requirements. We have tested our ideas as to how this could be done, in an empirical project. Although we called it ‘Project NRW-2000’, it would probably be better described as an experiment.--We persuaded 90 ordinary people to participate in this project as ‘experts on daily life and work’. This group was asked to work in six regional sub-groups and discuss, with reference to three given normative societal scenarios for the year 2020, the relationship between microelectronics and labour markets of the year 2020, on the basis of a participatory Delphi procedure. Before we elaborate on the concept of our project in Section 3, we would like to outline it in terms of the mainstream of the sociology of technology as well as with research on ‘acceptance’ in Section 1. In Section 2 we will briefly illustrate the framework of the research programme ‘Socially Oriented Shaping of Technology’ of the state of Northrhine-Westphalia, which funded our research project. Section 4 particularly deals with the participatory elements of our project, while Section 5 is devoted to the development of the scenarios. Section 6 sums up the results of the ‘scenario-construction’. Regarding specific elements, we restrict ourselves to topics concerning technology, labour, and the relationship between women workers/employees and technology. As a final outlook we deal with the political implications of our approach. All that is left is to remind our readers that we regard this project as a first application or experiment within our overall approach.     

Pediatric gastroesophageal reflux disease and acid-related conditions: trends in incidence of diagnosis and acid suppression therapy

Abstract

Objective: To describe the incidence of diagnosis of gastroesophageal reflux disease and acid-related conditions (GERD/ARC) throughout childhood and characterize patterns of diagnosis and treatment with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H₂RAs).

Methods: Cohorts of GERD/ARC children (age 0–18 years) were identified from a large US administrative claims database covering 1999–2005 using ICD-9 codes. Incidence, healthcare utilization (HCU), costs, therapy discontinuation and switching rates were compared between various age and patient groups.

Results: Between 2000 and 2005 annual incidence of GERD/ARC diagnosis among infants (age ≤1 year) more than tripled (from 3.4 to 12.3%) and increased by 30% to 50% in other age groups. Patients diagnosed by GI specialists (9.2%) were more likely to be treated with PPIs compared to patients diagnosed by primary care physician (PCP). PPI-initiated patients doubled (from 31.5% in 1999 to 62.6% in 2005) and, when compared with H₂RA-initiated patients, were associated with 30% less discontinuation and 90% less therapy switching in the first month, and with higher comorbidity burden and pre-treatment total HCU and costs when diagnosed by GI specialists.

Limitations: The use of an exploratory definition for GERD/ARC, administrative claims data and potential coding errors in diagnosis codes used in selection process may limit the generalizability of the results.

Conclusions: GERD/ARC incidence increased for children of all ages between 2000 and 2005. PCPs made the majority of diagnoses. PPI initiations have now surpassed H₂RA initiations.     

Cost analysis of plasma-derived factor VIII/von Willebrand factor versus recombinant factor VIII for treatment of previously untreated patients with severe hemophilia A in the United States

Background: Inhibitor development to factor VIII (FVIII) hemophilia therapy results in increased complications and substantial economic costs. The SIPPET study, the first randomized controlled trial to compare the immunogenicity of plasma-derived FVIII (pdFVIII)/von Willebrand factor (VWF) and recombinant-DNA-derived FVIII (rFVIII), demonstrated higher inhibitor rates in previously untreated patients (PUPs) treated with rFVIII than in PUPs treated with pdFVIII/VWF.

Objective: To quantify the economic impact of treating PUPs with pdFVIII/VWF vs rFVIII.

Methods: An Excel-based clinical and economic model was developed from a US healthcare payer perspective and run over a 5-year period. The analysis utilized a cohort approach to model patient treatment and outcomes over a monthly cycle to quantify differences in costs of FVIII, bypassing agents, and hospitalizations for serious bleeds. Rates of high-titer inhibitor development were obtained from the SIPPET study. Patients developing high-titer inhibitors were treated with immune tolerance induction (ITI). Patients who developed low-titer inhibitors and those who did not develop inhibitors continued their usual FVIII treatment. Patients who were successfully treated with ITI returned to FVIII treatment, while unsuccessfully treated patients received bypassing agents. Total costs per treated patient were estimated and a one-way sensitivity analysis was conducted to quantify the impact of parameter uncertainty on the model outcomes.

Results: Total cumulative costs per patient over 5 years were $834,621 for pdFVIII/VWF patients and $1,237,163 for rFVIII patients, representing a total saving of $402,542 per patient over the 5-year period, for an average annual saving of $80,508 per patient.

Conclusions: Based on data from the SIPPET study, this analysis found that initiating FVIII treatment in severe hemophilia A PUPs with pdFVIII/VWF has the potential to offer substantial cost savings to healthcare payers, amounting to a one-third reduction in costs.     

Budget impact analysis of niraparib and olaparib for maintenance treatment of platinum-sensitive,recurrent ovarian cancer in the US

Aims: This study aimed to evaluate the budget impact of niraparib and olaparib in patients with platinum-sensitive, recurrent ovarian cancer from a US third party payer perspective.

Materials and methods: A budget impact model was constructed to assess the additional per member per month (PMPM) costs associated with the introduction of niraparib and olaparib, two poly ADP-ribose polymerase ribose polymerase (PARP) inhibitors recently approved to be used in platinum-sensitive, recurrent ovarian cancer patients with and without a gBRCA mutation. The model assessed both pharmacy costs and medical costs. Pharmacy costs included adjusted drug costs, coinsurance, and dispensing fees. Medical costs included costs associated with disease monitoring and management of adverse events from the treatment. Epidemiological data from the literature were used to estimate the target population size. The analysis used 1-year time frame, and patients were assumed on treatment until disease progression or death. All costs were computed in 2017 USD. One-way sensitivity analyses were conducted to evaluate the model robustness.

Results: In a hypothetical plan of 1,000,000 members, 206 patients were estimated to be potential candidates for niraparib or olaparib maintenance treatment after applying all epidemiological parameters. At listed 30-day supply WAC prices of $14,750 for niraparib and $13,482 for olaparib, budget impacts of these two drugs were $0.169 PMPM and $0.156 PMPM, respectively, most of which were contributed by pharmacy costs. Sensitivity analyses suggested that assumptions around market share, platinum-sensitive rate after first treatment, and WAC prices affected results the most.

Limitations: In this model, it was assumed that adopting niraparib and olaparib would not affect utilization of existing medications. Also, the estimated clinical parameters from clinical trials could differ from real-world data.     

Outcomes of tumor necrosis factor inhibitor cycling versus switching to a disease-modifying anti-rheumatic drug with a new mechanism of action among patients with rheumatoid arthritis

Objectives: To examine treatment patterns, treatment effectiveness, and treatment costs for 1 year after patients with rheumatoid arthritis switched from a tumor necrosis factor inhibitor (TNFi) (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab), either cycling to another TNFi (“TNFi cyclers”) or switching to a new mechanism of action (abatacept, tocilizumab, or tofacitinib) (“new MOA switchers”).

Methods: This retrospective cohort study used administrative claims data for a national insurer. Treatment persistence (without switching again, restarting, or discontinuing), treatment effectiveness (defined below), and costs were assessed for the 12-month post-switch period. Patients were “effectively treated” if they satisfied all six criteria for a treatment effectiveness algorithm (high adherence, no dose increase, no new conventional synthetic disease-modifying anti-rheumatic drug, no subsequent switch in therapy, no new/increased oral glucocorticoids, and <2 glucocorticoid injections). Multivariable logistic models were used to adjust for baseline factors.

Results: The database included 581 new MOA switchers and 935 TNFi cyclers. New MOA switchers were 39% more likely than TNFi cyclers to persist after the switch (odds ratio [OR]?=?1.39; 95% confidence interval [CI]?=?1.12–1.74; p?=?.003) and 36% less likely to switch therapy again (OR?=?0.64; 95% CI?=?0.51–0.81; p?p?=?.006). New MOA switchers had 16% lower drug costs than TNFi cyclers (cost ratio?=?0.84; 95% CI?=?0.79–0.88; p?p?Limitations: Claims payments may not reflect rebates or other cost offsets. Medical and pharmacy claims do not include clinical end-points or reasons that lead to new MOA switching vs TNFi cycling.

Conclusions: These results support switching to a new MOA after a patient fails treatment with a TNFi, which is consistent with recent guidelines for the pharmacologic management of established rheumatoid arthritis.     

中国松嫩平原盐碱土固碳潜力过程及机理研究

目的 通过2019—2021年对松嫩平原盐碱地土壤呼吸的监测,探究盐碱土是否存在净碳吸收过程,明确盐碱土碳吸收在区域碳循环中的作用和地位。方法 文章基于纯盐碱地原位土壤呼吸的3年连续监测,探究盐碱地土壤CO₂通量动态变化及其环境响应。结果 （1）松嫩平原盐碱地除碳释放外存在阶段性碳吸收,不同年份盐碱土发生碳吸收的时间和强度不一致。（2）2019年和2021年土壤碳吸收主要发生在夜间,两次间歇性碳吸收分别发生于生长季初期和末期,其强度与土壤温、湿度显著相关,是由水分参与下的NaCO₃转化为NaHCO₃的化学性吸碳。（3）松嫩平原盐碱土在水淹期间存在连续性碳吸收,水淹状态下的吸碳来源于温度梯度驱动的大气CO₂形成水合二氧化碳的物理性吸碳。结论 （1）生长季的不同时期,松嫩平原盐碱土有着不同的碳吸收模式和强度。（2）土壤水分是影响盐碱土夜间间歇性吸碳的关键因素,温差是影响水淹吸碳的重要驱动力,随着温差加大,土壤碳吸收加强。（3）2019年和2021年夜间土壤碳吸收的最大值分别为-0.31 μmol CO₂ m^-2 s^-1和-0.75 μmol CO₂ m^-2 s^-1;2020年和2021年淹水期间碳吸收最大强度为-1.51 μmol CO₂ m^-2 s^-1和-1.27 μmol CO₂ m^-2 s^-1。（4）松嫩平原盐碱土的规律性固碳可为生态系统年净碳吸收贡献15%。不考虑土壤碳吸收的空间异质性,其每年的碳吸收潜力预计可达0.37 Tg C a^-1。