Do PPIs cause CKD and progression of CKD? PRO

Abstract Objective The developer and sponsor of new combination products in US needs to forecast which classification and designation to the regulatory scheme of drug, biological product, or device would be required for the new products by the Food and Drug Administration (FDA). To improve the predictability and acceptability of the designation of new combination products for innovators, developers, and sponsors, and to encourage the development and early access of new combination products, we proposed new visualization models of the designation pathway and group categorization. Method We searched the website of the FDA on 15 November, 2020 to identify the regulatory scheme of the FDA’s 129 capsular decision cases of device–drug and device–biologics combination products and other publicly available cases the FDA designated to the drug/biologic or device regulatory scheme. Results By introducing a new definition for primary intended use (PIU) by developers and sponsors extracted from the classification factors of primary mode of action (PMOA), we developed new visualization models of the designation pathway and two-dimensional group categorization. And applying these models to the cases the FDA designated, we proposed a new group categorization of combination products while focusing on the device component function. Conclusions The new visualization models with PIU and PMOA and the new group categorization focusing on the device component function proposed in this study may increase predictability and acceptability of the classification of newly developed combination products into the regulatory scheme of drug, biological product, and device, for innovators, developers, and sponsors.

Download Full-text

124P Talazoparib in locally advanced or metastatic breast cancer patients: Experience from an early access program in Turkey

Annals of Oncology ◽

10.1016/j.annonc.2021.03.138 ◽

2021 ◽

Vol 32 ◽

pp. S74

Author(s):

M.A.N. Sendur ◽

B. Cakar ◽

M. Hızal ◽

E. Eraslan ◽

S. Aksoy ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Locally Advanced ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Early Access ◽

Patients Experience ◽

Access Program

Download Full-text

Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920980558 ◽

2021 ◽

Vol 13 ◽

pp. 175883592098055 ◽

Cited By ~ 1

Author(s):

Nikolaj Frost ◽

Petros Christopoulos ◽

Diego Kauffmann-Guerrero ◽

Jan Stratmann ◽

Richard Riedel ◽

...

Keyword(s):

Treatment Failure ◽

Survival Rates ◽

Real Life ◽

Progression Free Survival ◽

Leptomeningeal Carcinomatosis ◽

Resistance Mutations ◽

Duration Of Treatment ◽

Tp53 Mutations ◽

Early Access ◽

Access Program

Introduction: We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib. Patients and Methods: Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed. Results: In total, 52 patients were included [median age 57 years (range 32–81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively. G1202R and G2032R resistance mutations prior to treatment with lorlatinib were observed in 10 of 26 evaluable patients (39%), 11 of 39 patients showed TP53 mutations (28%). Thirty-six patients (69%) had active brain metastases (BM) and nine (17%) leptomeningeal carcinomatosis when entering the EAP. Median number of prior specific TKIs was 3 (range 1–4). Median duration of treatment, progression-free survival (PFS), response rate and time to treatment failure were 10.4 months, 8.0 months, 54% and 13.0 months. Calculated 12-, 18- and 24-months survival rates were 65, 54 and 47%, overall survival since primary diagnosis (OS2) reached 79.6 months. TP53 mutations were associated with a substantially reduced PFS (3.7 versus 10.8 month, HR 3.3, p = 0.003) and were also identified as a strong prognostic biomarker (HR for OS2 3.0 p = 0.02). Neither prior treatments with second-generation TKIs nor BM had a significant influence on PFS and OS. Conclusions: Our data from real-life practice demonstrate the efficacy of lorlatinib in mostly heavily pretreated patients, providing a clinically meaningful option for patients with resistance mutations not covered by other targeted therapies and those with BM or leptomeningeal carcinomatosis.

Download Full-text

741 Manipulation and Reduction of Paediatric Forearm Fractures in The Emergency Department Using Intranasal Diamorphine and Entonox

British Journal of Surgery ◽

10.1093/bjs/znab134.481 ◽

2021 ◽

Vol 108 (Supplement_2) ◽

Author(s):

S Kapoor ◽

A Valand ◽

J Dartnell

Keyword(s):

Emergency Department ◽

Patient Discharge ◽

General Anaesthetic ◽

Forearm Fractures ◽

Distal Radial Fractures ◽

Access To Treatment ◽

Early Access ◽

The Mean ◽

Salter Harris

Abstract Background Paediatric forearm fractures are commonly encountered in Trauma and Orthopaedics. Currently most forearm fractures are manipulated in theatre the following day, increasing resource burden and delays in management. The aim of this project was to introduce guidelines to reduce fractures in the Emergency Department (ED) using intranasal Diamorphine and Entonox. Method 197 cases were identified over a 6-month period in 2018 and 2019. 74 distal radial fractures and 123 mid shaft forearm fractures were analysed. Fractures with an intact periosteal hinge or a Salter Harris type 2 were reduced in ED. The pre manipulation and post manipulation radiographs were compared with particular attention to the post reduction angles. Results 67% of fractures were reduced in the correct setting. A number of fractures reduced in ED required re-manipulation or internal fixation. Overall, there was a 56% reduction in patients undergoing general anaesthetic. There was a reduction in the mean length of stay from 36 hours to 3.5 hours. Conclusions Intranasal Diamorphine and Entonox offer a safe method for managing paediatric forearm fractures in ED. Implementation of this method facilitates early access to treatment and early patient discharge. Manipulation in ED offers significant financial savings and reduces demands on the Trauma Theatres.

Download Full-text

Bonding Social Capital, Afghan Refugees, and Early Access to Employment

International Migration Review ◽

10.1177/01979183211000282 ◽

2021 ◽

pp. 019791832110002

Author(s):

Matteo Vergani ◽

Ihsan Yilmaz ◽

Greg Barton ◽

James Barry ◽

Galib Bashirov ◽

...

Keyword(s):

Social Capital ◽

Migration Policy ◽

Research Note ◽

Bonding Social Capital ◽

Afghan Refugees ◽

Employment Success ◽

The Third ◽

Early Access ◽

Second Year ◽

The Impact

This IMR Research Note examines the impact of the level of bonding social capital on access to employment among newly arrived Afghan refugees in Victoria (Australia). Based on a mixed-methods analysis of biographical interviews with 80 Afghan refugees, it examines their use of social capital, year by year, during the first three years after their arrival. Our analysis shows that higher levels of bonding social capital are associated with greater success in finding employment during the first and second year of settlement. In the third year, however, bonding social capital for Afghan refugees in Victoria is no longer a significant predictor of employment. This Research Note helps clarify inconsistent findings in the literature on the effects of social capital on obtaining employment by suggesting that bonding social capital’s impact on refugee employment success changes significantly across the first three years after arrival. This finding has important implications for migration policy and the prioritization of resources toward services for newly arrived refugees.

Download Full-text

A Bibliometric Evaluation of the Top 100 Cited Dimethyl Fumarate Articles

Molecules ◽

10.3390/molecules26041085 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1085

Author(s):

Francisco Javier García-Fernández ◽

Alba Estela García-Fernández ◽

Ichiro Ikuta ◽

Eduardo Nava ◽

Julian Solis García del Pozo ◽

...

Keyword(s):

Dimethyl Fumarate ◽

Original Research ◽

H Index ◽

Early Access ◽

Research Areas ◽

Electronic Search ◽

Time Period ◽

The Usa ◽

Immunomodulatory Drug ◽

Number Of Citations

Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple sclerosis. We performed a bibliometric study examining the characteristics and trends of the top 100 cited articles that include dimethyl fumarate in the title. On 21 September 2020 we carried out an electronic search in the Web of Science (WOS), seeking articles that include the following terms within the title: dimethyl fumarate, BG-12, or Tecfidera. To focus our investigation on original research, we refined the search to include only articles, early access, others, case report, and clinical trials. We obtained a total of 1115 items, which were cited 7169 times, had a citation density of 6.43 citations/item, and an h-index of 40. Around 2010, there was a jump in the number of published articles per year, rising from 5 articles/year up to 12 articles/year. We sorted all the items by the number of citations and selected the top 100 most cited (T100). The T100 had 4164 citations, with a density of 37 citations/year and contained 16 classic research articles. They were published between 1961 and 2018; the years 2010–2018 amassed nearly 80% of the T100. We noted 17 research areas with articles in the T100. Of these, the number one ranking went to neurosciences/neurology with 39 articles, and chemistry ranked second on the T100 list with 14 items. We noticed that the percentage of articles belonging to different journals changed depending on the time period. Chemistry held the highest number of papers during 1961–2000, while pharmacology andneurosciences/neurology led the 2001–2018 interval. A total of 478 authors from 145 institutions and 25 countries were included in the T100 ranking. The paper by Gold R et al. was the most successful with 14 articles, 1.823 citations and a density of 140.23 citations/year. The biotechnological company Biogen led the T100 list with 20 articles. With 59 published articles, the USA was the leading country in publications. We concluded that this study analyzed the use of and research on dimethyl fumarate from a different perspective, which will allow the readership (expert or not) to understand the relevance of classic and recent literature on this topic.

Download Full-text