scholarly journals Evaluation of Real-Life Investigational Use of Enoximone in Asthma, the Third Step in Drug Repurposing: A Preliminary Report

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jan Beute ◽  
Pieter Boermans ◽  
Alex KleinJan
Keyword(s):  
Oral Treatment ◽  
Real Life ◽  
Drug Repurposing ◽  
Chronic Asthma ◽  
Duration Of Treatment ◽  
Off Label ◽  
The Third ◽  
Asthma Symptoms ◽  
Asthma Patients ◽  
Pde3 Inhibitor

Background. The population of uncontrolled asthma patients represents a large therapeutic burden. The PDE3-inhibitor enoximone is a strong and quick bronchodilator and is known to successfully treat life-threatening bronchial asthma (status asthmaticus). Translational mice models showed anti-inflammatory effects when PDE3 was targeted. Methods. Here, we investigated the effectiveness of PDE3-inhibitor enoximone as oral treatment for chronic asthma in a real-life off-label setting. Investigational use of PDE3-inhibitor enoximone: 51 outpatients (age 18–77) with chronic asthma were followed using off-label personalized low doses of the PDE3-inhibitor enoximone. Duration of treatment was 2–8 years. Results. Four groups could be distinguished as follows: The first group includes patients who use enoximone as an add-on, because it helps them in maintaining a better general wellbeing; they still use their traditional medication (n = 5). The second group consists of patients who use enoximone and were able to phase down their traditional medication without deterioration of their asthma symptoms (n = 11). The third group comprises patients who were able to discontinue their traditional medication and use only enoximone without deterioration of their asthma symptoms (n = 24). The last one has patients who, after having used enoximone for some time, saw their symptoms disappear and now use no medication at all, not even enoximone (n = 11). All patients reported improvement or at least alleviation of their asthma symptoms. All patients reported a better quality of life and greater drug compliance. Conclusion. The evaluation shows that PDE3-inhibitor enoximone is a viable alternative for or addition to current asthma therapeutics, as both add-on and stand-alone, considerably reducing the use of LABAs/SABAs/ICS, with no or negligible side effects. Additional studies are advisable.

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

2021 ◽  
Vol 13 ◽  
pp. 175883592098055 ◽  
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.

scholarly journals Rivaroxaban versus warfarin for the management of left ventricle thrombus

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Monirah A. Albabtain ◽  
Yahya Alhebaishi ◽  
Ola Al-Yafi ◽  
Hatim Kheirallah ◽  
Adel Othman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Retrospective Study ◽  
Left Ventricle ◽  
Surface Area ◽  
Median Time ◽  
Randomized Clinical Trials ◽  
Off Label Use ◽  
Duration Of Treatment ◽  
Off Label ◽  
Warfarin Group

Abstract Background Rivaroxaban has been recently introduced for the management of non-valvular intra-cardiac thrombosis with variable results. We aimed to compare the results of the off-label use of rivaroxaban versus warfarin in the management of patients with left ventricle (LV) thrombus. This research is a retrospective study conducted on 63 patients who had LV thrombus from January to December 2016. We compared patients treated with warfarin (n=35) to patients who had rivaroxaban (n=28), and study outcomes were time to thrombus resolution, bleeding, stroke, and mortality. Results The median duration of treatment was 9.5 (25th-75th percentiles: 6-32.5) months for rivaroxaban and 14 (3-41) months for warfarin. Thrombus resolution occurred in 24 patients in the warfarin group (68.6%) and 20 patients in the rivaroxaban group (71.4%). The median time to resolution in the warfarin group was 9 (4-20) months and 3 (2-11.5) months in the rivaroxaban group. Thrombus resolution was significantly faster in patients on rivaroxaban (p= 0.019). Predictors of thrombus resolution were thrombus surface area (HR: 1.21; CI 95% (1.0-1.46); p= .048) and the use of rivaroxaban (HR: 1.92; CI 95% (1.01-3.65); p= 0.048). There was no difference in stroke, bleeding, and mortality between both groups. Conclusion Rivaroxaban was as effective and safe as warfarin in managing patients with left ventricle thrombus. Larger randomized clinical trials are recommended to confirm our findings.

scholarly journals PENANGANAN PERIOPERATIF PADA ASMA

2013 ◽  
Vol 5 (1) ◽  
Author(s):  
Christina Suhartono ◽  
Harold F Tambajong ◽  
Diana Ch. Lalenoh
Keyword(s):  
Perioperative Management ◽  
Smooth Muscles ◽  
Special Treatment ◽  
Asthma Symptoms ◽  
Asthma Attack ◽  
Asthma Patients ◽  
Post Operation ◽  
Laboratory Examinations ◽  
Keywords Asthma ◽  
Selection Of

Abstract: The management of a patient with asthma during surgery requires a special treatment based on thorough clinical and laboratory examinations to reduce complications during surgery and the post-operative state. Asthma is characterized by a difficulty in breathing due to spastic contractions of bronchiolar smooth muscles, which partially block the bronchioles’ airways. The evaluation of asthma patients before anesthesia and surgical procedures is essential to prevent or control the occurence of asthma attacks during intra-operation and post-operation. Patients with histories of chronic asthma or frequent exacerbations of asthma have to be treated to achieve an optimal condition or a condition in which asthma symptoms are minimal. Patients with frequent bronchospasms should be treated. The selection of drugs and anesthetic procedures should be considered meticulously to avoid a stimulation of  bronchospasm or an asthma attack. Keywords: asthma, perioperative management, patient.   Abstrak: Pengelolaan pasien dengan penyakit asma selama pembedahan membutuhkan penanganan khusus berdasarkan pemeriksaan klinis dan laboratorium yang saksama untuk mengurangi komplikasi selama dan pasca pembedahan. Asma adalah kesukaran bernapas yang ditandai dengan kontraksi spastik otot polos bronkiolus, yang menyumbat bronkiolus secara parsial. Evaluasi pasien asma sebelum tindakan anestesia dan pembedahan sangat penting untuk mencegah atau mengendalikan kejadian serangan asma, baik selama pembedahan maupun pasca pembedahan. Pasien dengan riwayat asma berulang atau kronis memerlukan pengobatan hingga tercapai kondisi yang optimal untuk dilakukan operasi atau kondisi dimana gejala-gejala asma sudah minimal. Pasien dengan  bronkospasme berulang harus diobati terlebih dahulu. Pemilihan obat-obatan dan tindakan anestesia perlu dipertimbangkan dengan cermat untuk menghindari terjadinya bronkospasme atau serangan asma. Kata kunci: asma, penanganan perioperatif, pasien.

scholarly journals Off-Label Medication: From a Simple Concept to Complex Practical Aspects

2021 ◽  
Vol 18 (19) ◽  
pp. 10447
Author(s):  
Carmen-Maria Rusz ◽  
Bianca-Eugenia Ősz ◽  
George Jîtcă ◽  
Amalia Miklos ◽  
Mădălina-Georgiana Bătrînu ◽  
...  
Keyword(s):  
Rare Diseases ◽  
Drug Repurposing ◽  
Regulatory Agencies ◽  
Systematic Research ◽  
Clinical Practices ◽  
Safe Practice ◽  
Safety Issues ◽  
Off Label ◽  
Simple Concept ◽  
Approved Drugs

Off-label use of drugs is widely known as unapproved use of approved drugs, and it can be perceived as a relatively simple concept. Even though it has been in existence for many years, prescribing and dispensing of drugs in an off-label regimen is still a current issue, triggered especially by unmet clinical needs. Several therapeutic areas require off-label approaches; therefore, this practice is challenging for prescribing physicians. Meanwhile, the regulatory agencies are making efforts in order to ensure a safe practice. The present paper defines the off-label concept, and it describes its regulation, together with several complex aspects associated with clinical practices regarding rare diseases, oncology, pediatrics, psychiatry therapeutic areas, and the safety issues that arise. A systematic research of the literature was performed, using terms, such as “off-label”, ”prevalence”, ”rare diseases”, ”oncology”, ”psychiatry”, ”pediatrics”, and ”drug repurposing”. There are several reasons for which off-label practice remains indispensable in the present; therefore, efforts are made worldwide, by the regulatory agencies and governmental bodies, to raise awareness and to ensure safe practice, while also encouraging further research.

scholarly journals Sources of anthroponyms in P. Kulish’s novel “Chorna Rada”

2020 ◽  
pp. 53-60
Author(s):  
Oles Fedoruk
Keyword(s):  
Real Life ◽  
Close Friend ◽  
The Novel ◽  
The Third ◽  
Russian Novel ◽  
Different Sources

The paper analyzes different sources of anthroponyms in the original and final texts of P. Kulish’s novel “Chorna Rada: Khronika 1663 Roku” (“The Black Council: A Chronicle of the Year 1663”). Three types of sources have been identified: the historical prototypes, names and surnames of Kulish’s friends, and archival (documentary) records. In addition, numerous notes in the early editions of the Russian novel contain references to the works of various people (M. Markevych, D. Bantysh-Kamenskyi, V. Kokhovskyi, etc.). The last group of anthroponyms stands outside of the plot, and the paper does not focus on it. The historical and autobiographical sources of anthroponyms are generally known. Among the first are prototypes of two hetmans — Yakym Somko and Ivan Briukhovetskyi, military secretary M. Vukhaievych, regimental osaul M. Hvyntovka. The second group comprises the occasional characters Hordii Kostomara (a historian M. Kostomarov), Ivan Yusko (a teacher I. Yuskevych-Kraskovskyi), Hulak (M. Hulak, the founder of The Brotherhood of Saints Cyril and Methodius), Bilozerets (Kulish’s brother-in-law V. Bilozerskyi), Petro Serdiuk (Kulish’s close friend Petro Serdiukov), Oleksa Senchylo (teacher Oleksa Senchylo-Stefanovskyi). In the novel, Kulish drew the love line as a projection of his relationship with Oleksandra Bilozerska and her mother Motrona. The characters of Petro Shramenko, Lesia Cherevanivna and her mother Melaniia have an autobiographical basis. Accordingly, Lesia’s name was also taken from real life. The third group of sources supplying the anthroponyms is archival records. The paper analуzes Kulish’s extracts from the roster of Cossack regiments of the Hetmanate (1741). This source wasn’t used previously. It contains the anthroponyms Vasyl Nevolnyk (‘Slave’), Puhach, Petro Serdiuk, Taranukha, Chepurnyi, Cherevan, Tur, Shramko and Shramchenko, Shkoda, which the author used in various editions of the novel.

scholarly journals “Regulatory Sandboxes” in Russia: New Horizons and Challenges

2020 ◽  
Vol 1 (2) ◽  
pp. 17-27
Author(s):  
Damir R. Salikhov
Keyword(s):  
Artificial Intelligence ◽  
Real Life ◽  
Federal Law ◽  
Digital Innovation ◽  
New Horizons ◽  
The Third ◽  
Special Mechanism ◽  
Life Model ◽  
The Government ◽  
Universal Mechanism

“Regulatory sandboxes” are regarded as a special mechanism for setting up experimental regulation in the area of digital innovation (especially in financial technologies), creating a special regime for a limited number of participants and for a limited time.Russiahas its own method of experimental regulation, which is not typical but may be helpful for other jurisdictions. There are three approaches to legal experiments (including digital innovations) inRussia. The first approach is accepting special regulation on different issues. There are recent examples of special laws (e.g. Federal Law on the experiment with artificial intelligence technologies inMoscow). An alternative to this option is establishing experimental regulation by an act of the Government if legislation does not prohibit it (e.g. labeling with means of identification). The second approach deals only with Fintech innovations and provides a special mechanism to pilot models of innovative financial technologies. The participants of such a “sandbox” may create a close-to-life model in order to estimate the effects and risks. If the model works fine, the regulation may be amended. The third approach works with creating a universal mechanism of real-life experiments in the sphere of digital innovations based on the special Federal Law and the specific decision of the Government of theRussian Federationor the Bank of Russia in the financial sphere. The author compares the three approaches and their implementation within the framework of Russian legislation and practice and concludes that this experience may be used by developing countries with inflexible regulation, in order to facilitate the development of digital innovations.

Home Nebuliser Use in Children with Asthma in Two Scottish Health Board Areas

1995 ◽  
Vol 40 (5) ◽  
pp. 141-143 ◽  
Author(s):  
P.J. Madge ◽  
L. Nisbet ◽  
J.H. McColl ◽  
A. Vallance ◽  
J.Y. Paton ◽  
...  
Keyword(s):  
Symptom Control ◽  
Postal Questionnaire ◽  
Standards Of Care ◽  
Health Board ◽  
Chronic Asthma ◽  
Drug Usage ◽  
Bronchodilator Therapy ◽  
Asthma Symptoms ◽  
Children With Asthma ◽  
Acute Attacks

Objective: To audit the use of home nebulisers in children with asthma. Design: Postal questionnaire. Setting: Two Health Board Areas in Central Scotland-one large industrialised city, one mixed urban and rural. Subjects: 297 children with asthma. Measures evaluated: Initial supply and technical support for the compressor. Education: Pattern of drug usage. Symptom control: Monitoring and treatment of acute attacks. Results: The full burden of the home nebulised therapy is not being met by the NHS. Supply and servicing arrangements for home nebuliser therapy were poorly organised. Chronic asthma symptoms did not appear to be optimally controlled on present medication, with 61% reporting sleep disturbance in the previous three months. About 20% of parents admitted that they would give nebulised bronchodilator therapy more frequently than the recommended 3 to 4 hourly. Conclusion: Re-organisation of resources and arrangements could improve the service and bring it in line with recognised standards of care.

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