Medicine (Baltimore). 2022 Mar 11;101(10):e25578. doi: 10.1097/MD.0000000000025578.

ABSTRACT

Natural killer/T-cell lymphoma (NK/TL) is a chemotherapy-sensitive disease, and asparaginase-based chemotherapy has become the standard primary treatment for patients with this malignancy recently. The objective of this study was to evaluate the adverse reactions on blood coagulation of the administered pegylated Escherichia coli (E coli) asparaginase (PEG-ASP) to the NK/TL patients. Clinical data of 71 NK/TL patients (range 13-73 years), who received 239 cycles of chemotherapy treatment containing PEG-ASP in the Hematology Department of Shanxi Province Cancer Hospital of China from January 2016 to December 2019 were analyzed retrospectively. Data of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FBG), and antithrombinIII (ATIII) were obtained at the time points routinely and statistically analyzed. There were statistical differences between the monitored parameters of baseline day0 (the day before use of PEG-ASP, named day0) and those of day3 (the 3rd day after treatment) to day6, and data showed all of the indicators could recover within 21 days. The events included PT prolonged in 33 patients (46.5%), APPT prolonged in 41 patients (57.7%, 20 patients with APTT >60 seconds), FBG decreased in 49 patients (69.0%, 12 patients with FBG <1 g/L), and ATIII decreased in 52 patients (73.2%). The patients' average number of cycles received was 2.3 for PT (>14 seconds), 2.5 for APTT (>35 seconds), 2.7 for FBG (<2 g/L), and 2.6 for D-dimer (>550 ng/mL). Compared with those at day0, PT and APTT prolonged sharply at day3 (P < .05), reached the peak at day12, maintained the prolonged level from day3 to day15, and gradually recovered at day 21. FBG and ATIII significantly decreased at day6 and day3 respectively (P < .05), both of them fell to the minimum at day12, and then returned the normal. The D-dimer levels were no significantly change during the whole treatment course. The APTT >60 seconds or FBG <1 g/L side effects were improved by symptomatic treatment of supplementation of fresh frozen plasma or cryoprecipitate infusion, no concomitant bleeding or thrombotic events emerging. Our data suggested although chemotherapy including PEG-ASP impacted moderately on the coagulation function of NK/TL patients, clinically monitored regularly were necessary and most NK/TL patients can complete the chemotherapy cycles successfully.

PMID:35451376 | PMC:PMC8913082 | DOI:10.1097/MD.0000000000025578

MMW Fortschr Med. 2022 Apr;164(8):12-14. doi: 10.1007/s15006-022-1069-7.

NO ABSTRACT

PMID:35449255 | DOI:10.1007/s15006-022-1069-7

Brief Bioinform. 2022 Apr 23:bbac140. doi: 10.1093/bib/bbac140. Online ahead of print.

ABSTRACT

Drug-drug interactions (DDIs) are known as the main cause of life-threatening adverse events, and their identification is a key task in drug development. Existing computational algorithms mainly solve this problem by using advanced representation learning techniques. Though effective, few of them are capable of performing their tasks on biomedical knowledge graphs (KGs) that provide more detailed information about drug attributes and drug-related triple facts. In this work, an attention-based KG representation learning framework, namely DDKG, is proposed to fully utilize the information of KGs for improved performance of DDI prediction. In particular, DDKG first initializes the representations of drugs with their embeddings derived from drug attributes with an encoder-decoder layer, and then learns the representations of drugs by recursively propagating and aggregating first-order neighboring information along top-ranked network paths determined by neighboring node embeddings and triple facts. Last, DDKG estimates the probability of being interacting for pairwise drugs with their representations in an end-to-end manner. To evaluate the effectiveness of DDKG, extensive experiments have been conducted on two practical datasets with different sizes, and the results demonstrate that DDKG is superior to state-of-the-art algorithms on the DDI prediction task in terms of different evaluation metrics across all datasets.

PMID:35453147 | DOI:10.1093/bib/bbac140

BMJ Evid Based Med. 2022 Apr 21:bmjebm-2022-111914. doi: 10.1136/bmjebm-2022-111914. Online ahead of print.

ABSTRACT

Accelerating Food and Drug Administration (FDA) product approval to market based on surrogate markers in the absence of proven efficacy creates a risk of adverse outcomes for affected patients, even in response to a life-threatening condition, such as in this case, Alzheimer's disease. FDA's recent unexpected approval of aducanumab, despite the unified opposition of its own highly respected advisory committee after the early termination of two efficacy trials, creates the potential risk of adverse effects and lack of clinical efficacy at very high costs. In view of these concerns, a thorough review of the issues and pressures that led to this decision is worth the careful consideration of the clinical and scientific communities with regard to whether this approval represents a calculated and balanced compassionate decision versus a disturbing precedent.

PMID:35450946 | DOI:10.1136/bmjebm-2022-111914

Drug Ther Bull. 2022 Apr 21:dtb-2022-000023. doi: 10.1136/dtb.2022.000023. Online ahead of print.

ABSTRACT

Overview of: Unintentional paracetamol overdose in adult inpatients with low bodyweight. Independent report by the Healthcare Safety Investigation Branch (I2020/027).

PMID:35450926 | DOI:10.1136/dtb.2022.000023

Cureus. 2022 Mar 17;14(3):e23272. doi: 10.7759/cureus.23272. eCollection 2022 Mar.

ABSTRACT

The combination of immune checkpoint inhibitors (ICIs) and other anticancer agents is the standard of care for various cancers. Bevacizumab, an anti-angiogenesis inhibitor, causes serious adverse events such as pulmonary hemorrhage (PH). Here, we present a case of drug-induced diffuse alveolar hemorrhage (DAH), an adverse event, in a patient with hepatocellular carcinoma who was treated with a combination of ICIs and anti-angiogenesis inhibitors after long-term use of lenvatinib, which inhibits vascular endothelial growth factor (VEGF). An 85-year-old man with hepatocellular carcinoma initially received lenvatinib, a multi-kinase inhibitor, but the drug was later switched to bevacizumab-atezolizumab combination therapy owing to disease progression. After five cycles, he developed dyspnea and diffuse ground-glass opacities, which improved with discontinuation of the combination therapy and initiation of steroid pulse therapy. Our case findings indicate that both ICIs and anti-angiogenesis inhibitors cause drug-induced DAH, and their combination may increase the severity of DAH. Moreover, long-term VEGF inhibition may induce the development of DAH. Clinicians need to be aware that long-term VEGF inhibition may be associated with DAH and should consider the risk management of such adverse events while using this combination therapy.

PMID:35449623 | PMC:PMC9012575 | DOI:10.7759/cureus.23272

BMJ Case Rep. 2022 Apr 20;15(4):e249177. doi: 10.1136/bcr-2022-249177.

ABSTRACT

Over the past decade, the treatment of ovarian cancer has been revolutionised by poly(ADP-ribose polymerase (PARP)) inhibitors. Based on the results from clinical trials, olaparib, a PARP inhibitor, is indicated for use in the first-line treatment for patients with BRCA gene mutations, and as a maintenance treatment in platinum-sensitive relapsed ovarian cancer after a complete or partial response to platinum-based chemotherapy. Although PARP inhibitors have been shown to be well tolerated, adverse side effects can affect the quality of life of patients and lead to the discontinuation of therapy. Here, we report a case of dermatosis of the left dorsal hand as a rare adverse side effect of olaparib. Dermatological adverse side effects may become the crux of a clinical problem that requires the cooperation of professionals in many fields.

PMID:35444023 | DOI:10.1136/bcr-2022-249177

NPJ Syst Biol Appl. 2022 Apr 20;8(1):12. doi: 10.1038/s41540-022-00221-0.

ABSTRACT

Despite advances in modern medicine that led to improvements in cardiovascular outcomes, cardiovascular disease (CVD) remains the leading cause of mortality and morbidity globally. Thus, there is an urgent need for new approaches to improve CVD drug treatments. As the development time and cost of drug discovery to clinical application are excessive, alternate strategies for drug development are warranted. Among these are included computational approaches based on omics data for drug repositioning, which have attracted increasing attention. In this work, we developed an adjusted similarity measure implemented by the algorithm SAveRUNNER to reposition drugs for cardiovascular diseases while, at the same time, considering the side effects of drug candidates. We analyzed nine cardiovascular disorders and two side effects. We formulated both disease disorders and side effects as network modules in the human interactome, and considered those drug candidates that are proximal to disease modules but far from side-effects modules as ideal. Our method provides a list of drug candidates for cardiovascular diseases that are unlikely to produce common, adverse side-effects. This approach incorporating side effects is applicable to other diseases, as well.

PMID:35443763 | DOI:10.1038/s41540-022-00221-0

Biosci Trends. 2022 Apr 20. doi: 10.5582/bst.2022.01115. Online ahead of print.

ABSTRACT

Whether there are differences in the time to onset of drug-induced parkinsonism (DIP) depending on the type of drugs causing DIP remains uncertain, so that question was investigated here using a large real-world database. Fourteen DIP-related drug categories were defined to perform a disproportionality analysis using a large Japanese pharmacovigilance database containing more than 600,000 self-reported adverse events (AEs) recorded between April 2004 and September 2021 to identify AEs indicating "parkinsonism" in association with the defined drug categories. The time from drug administration to the onset of DIP was comparatively analyzed. Results indicated that the median time to onset was shorter than 1 month in more than half of the cases of DIP; it was shortest with peripheral dopamine antagonists (median: 0.1 weeks), followed by benzodiazepine (median: 0.5 weeks), butyrophenone (median: 0.7 weeks), novel antidepressants (median: 2.5 weeks), atypical antipsychotics (median: 3.3 weeks), other antidepressants (e.g., lithium, median: 3.7 weeks), and benzamide (median: 4.5 weeks). In contrast, anti-dementia drugs, tricyclic antidepressants, and antiepileptic drugs resulted in a relatively longer time to onset (median: 9.9, 17.2, and 28.4 weeks, respectively). In addition, a maximum delay of even longer than 2 years was reported for benzamide (846 weeks), anti-Parkinsonism drugs (382 weeks), phenothiazine (232 weeks), atypical antipsychotics (167 weeks), anti-dementia drugs (161 weeks), and benzodiazepines (120 weeks). The current results suggested that the characteristics of the time to onset of DIP may substantially differ depending on the type of drug causing that DIP. This finding may help when diagnosing patients with parkinsonism.

PMID:35444114 | DOI:10.5582/bst.2022.01115

Drug Ther Bull. 2022 Apr 20:dtb-2022-000025. doi: 10.1136/dtb.2022.000025. Online ahead of print.

ABSTRACT

Overview of: O'Fee K, Deych E, Ciani O, et al Assessment of nonfatal myocardial infarction as a surrogate for all-cause and cardiovascular mortality in treatment or prevention of coronary artery disease: a meta-analysis of randomised clinical trials. JAMA Intern Med 2021;181:1575-87.

PMID:35444003 | DOI:10.1136/dtb.2022.000025

J Assoc Physicians India. 2022 Apr;70(4):11-12.

ABSTRACT

DOTS under National Tuberculosis elimination Program have shown to be highly effective, but poor compliance remains a challenge to the TB programs and is a major threat to development of drug resistant tuberculosis. Objective of this study was to describe the factors determining compliance to treatment and timing of treatment interruption.

MATERIAL: Information was collected from TB register and treatment cards of drug sensitive tuberculosis patients registering for treatment at DOTS center during study period at -Mandya institute of medical sciences, Mandya. Patients completed treatment during the year January 2018 to January 2020 were interviewed during there last visit to DOTS centre or during there follow up visit to elicit the reason for non compliance using a structured proforma.

OBSERVATION: A total of 162 patients were enrolled, 95 male, 66 female and 1 transgender, 157 new TB patients and 5 were previously treated Drug sensitive TB patients were included (131 of pulmonary tuberculosis, 31 of extra-pulmonary tuberculosis). Out of 166, 89 were compliant, 63 were non compliant, 10 patients died during the treatment. Of 63 non compliant, 12 were lost to follow up (called defaulters previously) and 51 interrupted treatment for more than one day but less than one month. More than one reason was often reported for discontinuation of treatment and most interruptions occurred in early part of continuation phase. Among factors determining compliance, interruption was more common in males(58.6%) than females(40.7%). Early improvement (30.05%) and addictive habits 16.39%)were found to be the two most common reasons, followed by unaware long duration of treatment, long distance to travel, drug related side effects and forget fullness are the causes leading to treatment interruption. whereas effective counseling by doctor and proper instructions by health care workers were the most common reasons for maintaining compliance.

CONCLUSION: compliance still remains the major factor in treatment of tuberculosis, doctors and health care workers can play a major role in this by doing effective counseling and providing proper instructions to the patients about treatment of TB. Particularly during the time when patient feels he is becoming better and no longer needs treatment. Also addressing the addictive habits is important in preventing treatment interruption.

PMID:35443461

J Assoc Physicians India. 2022 Apr;70(4):11-12.

ABSTRACT

Remogliflozin Etabonate (RE) &amp; Vildagliptin are twice-daily medications that are individually approved and widely used in India for the treatment of diabetes. A single pill fixed dose combination of RE &amp; Vildagliptin was formulated as potential pharmaco-therapeutic agent that would not only offer beneficial pharmacologic effects, but also reduces the pill burden, leading to a simplified treatment regimen with better treatment compliance. The fixed dose combination (FDC) of Remogliflozin + Vildagliptin added on to Metformin has been evaluated in this pivotal phase III study.

MATERIAL: This 16 week, multi-centric, prospective, double blind, double dummy, parallel group, randomized controlled study compared efficacy and safety of FDC of RE 100mg + Vildagliptin 50mg (RV) given twice daily with active comparator of Empagliflozin 25mg +Linagliptin 5mg (EL) given once daily. Adult T2DM patients with HbA1c 8-11% on Metformin stable dose of ≥1500mg for ≥8 weeks before screening were randomized to either of treatment arms. The study endpoints were mean changes from baseline (CFB) in HbA1c (primary), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), body weight (BW) and blood pressure (BP) for efficacy and adverse events (AE) monitoring for safety assessments.

OBSERVATION: Of 400 eligible subjects (200 in each arm), 357 (89.3%) subjects completed the study. The baseline demographic characteristics were well balanced between 2 treatment arms. In the mITT population, the least squares (LS) mean (SE) change from baseline in HbA1c levels at week 16 was -1.46% (0.098) in the RV arm and -1.38% (0.100) in the EL arm (p &lt; 0.001 for within group change from baseline). The mean difference of -0.08% (95%CI: -0.28, 0.13) in HbA1c demonstrated non-inferiority (NI) of RV compared to EL (p&lt;0.001 for NI test). Similarly, significant reduction was observed in FPG, PPG, BW and BP which was found to be comparable between the two treatment arms. Drug related AEs were observed in 5.5% and 4.5% subjects of EL and RV arm respectively, with low incidence of hypoglycemia, genital and urinary tract infections (0.5-3%).

CONCLUSION: Overall, FDC of Remogliflozin Etabonate + Vildagliptin added on to Metformin was found to be efficacious and well tolerated in the treatment of patients with T2DM, and demonstrated non-inferiority to Empagliflozin 25mg + Linagliptin 5mg treatment added on to Metformin.

PMID:35443373

Eur Rev Med Pharmacol Sci. 2022 Apr;26(7):2373-2387. doi: 10.26355/eurrev_202204_28467.

ABSTRACT

OBJECTIVE: Drug-related problems (DRPs) could affect patient care and lead to deleterious manifestations, therefore, this investigation aimed to review the recently published studies concerning DRPs to improve their availability to clinical pharmacists, hoping that this information will be supportive and relevant to their practice settings. MATERIALS AND METHODS: A search of Elsevier, Sage, Springer/Nature, and Wiley online libraries on Egyptian Knowledge Bank (EKB) was limited to the cumulative period from 1/1/2015 to 20/10/2020. The abstracts of 156 articles were critically reviewed and 50 articles were included based on relevance while excluding books. The selected articles reported DRPs and different strategies to reduce them. Moreover, drug-drug interactions (DDIs) in various patient populations were confirmed by many articles. Additionally, potential drug-drug interactions (pDDIs) predisposing factors were reported by others. RESULTS: 24 articles (48%) illustrated DDIs, 5 articles (10%) demonstrated ADRs, 4 articles (8%) showed medication errors (MEs), and 25 articles (50%) revealed efforts to reduce DRPs. The psychiatric population is at the utmost risk of pDDIs. Polypharmacy was the furthest recurrently reported risk factor related to DDIs. Adverse drug events (ADEs) increased healthcare costs. Different strategies to avoid DRPs were published through the stated period. CONCLUSIONS: Our findings can be supportive to healthcare professionals in enhancing their patients' quality of care by reducing the exposure to ADEs.

GRAPHICAL ABSTRACT: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-Abstract-11328.png.

PMID:35442491 | DOI:10.26355/eurrev_202204_28467

JAMA Netw Open. 2022 Apr 1;5(4):e228224. doi: 10.1001/jamanetworkopen.2022.8224.

NO ABSTRACT

PMID:35442456 | DOI:10.1001/jamanetworkopen.2022.8224

Arq Gastroenterol. 2022 Jan-Mar;59(1):89-96. doi: 10.1590/S0004-2803.202200001-16.

ABSTRACT

BACKGROUND: Variceal hemorrhage (VH) is a medical emergency. Prompt endoscopic variceal ligation (EVL) is therapeutic. Terlipressin is used in VH and continued for 2-5 days even after EVL. As hemostasis is primarily achieved by EVL, the benefit of continuing trelipressin after EVL is unknown.

OBJECTIVE: To evaluate the efficacy of continuing terlipressin after EVL to prevent re-bleed and mortality.

METHODS: In this pilot study, after EVL 74 patients of VH were randomized into two treatment groups TG2 & TG5, received terlipressin (1 mg IV bolus q 4 hourly) for 2 days and 5 days respectively and one control group (TG0), received 0.9% normal saline (10 mL IV bolus q 4 hourly) and followed up for 8 weeks.

RESULTS: A total of 9 (12.6%) patients had re-bleed with maximum 4 (5.6%) patients in TG5 group followed by 3 (4.2%) in TG2 and 2 (2.8%) in TG0 groups (P=0.670). The overall mortality was 15 (21.1%) patients, 6 (8.5%) patients in TG0 group, followed by 5 (7.0%) in TG5 and 4 (5.6%) in TG2 group (P=0.691). Adverse drug reactions were significantly higher in treatment groups with maximum 18 (24.32%) patients in TG5, followed by 8 (10.8%) in TG2 and 2 (2.7%) in TG0 groups (P=0.00). Duration of hospital stay was also significantly higher in treatment group, 6.63 (±0.65) days in TG5 followed by 3.64 (±0.57) in TG2 and 2.40 (±0.50) days in TG0 groups (P=0.00).

CONCLUSION: The rational for continuing terlipressin after EVL is doubtful as it didn't have any benefit for the prevention of re-bleed or mortality; rather it increased the risk of adverse drug reactions and duration of hospital stay. Further randomized clinical trials are encouraged to generate more evidence in support or against continuing terlipressin after EVL.

PMID:35442343 | DOI:10.1590/S0004-2803.202200001-16

CMAJ. 2022 Apr 19;194(15):E565-E568. doi: 10.1503/cmaj.211083-f.

NO ABSTRACT

PMID:35440509 | DOI:10.1503/cmaj.211083-f

CMAJ. 2022 Apr 19;194(15):E554. doi: 10.1503/cmaj.210703.

NO ABSTRACT

PMID:35440504 | DOI:10.1503/cmaj.210703

Ann Med. 2022 Dec;54(1):1014-1035. doi: 10.1080/07853890.2022.2063375.

ABSTRACT

Sarcoidosis is a heterogeneous disease, which can affect virtually every body organ, even though lungs and intra thoracic lymph nodes are almost universally affected. The presence of noncaseating granulomas is the histopathological hallmark of the disease, and clinical picture depends on the organs affected. Data about interaction between sarcoidosis and comorbidities, such as cardiovascular and pulmonary diseases, autoimmune disorders, malignancy and drug-related adverse events are limited. Several lung conditions can be associated with sarcoidosis, such as pulmonary hypertension and fibrosis, making it difficult sometimes the differentiation between complications and distinctive pathologies. Their coexistence may complicate the diagnosis of sarcoidosis and contribute to the highly variable and unpredictable natural history, particularly if several diseases are recognised. A thorough assessment of specific disorders that can be associated with sarcoidosis should always be carried out, and future studies will need to evaluate sarcoidosis not only as a single disorder, but also in the light of possible concomitant conditions.Key messagesComorbidities in sarcoidosis are common, especially cardiovascular and pulmonary diseases.In the diagnostic workup, a distinction must be made between sarcoidosis-related complaints and complaints caused by other separate disorders. It can be very difficult to distinguish between complications of sarcoidosis and other concomitant conditions.The coexistence of multiple conditions may complicate the diagnosis of sarcoidosis, affect its natural course and response to treatment.

PMID:35441568 | DOI:10.1080/07853890.2022.2063375

JAMA Netw Open. 2022 Apr 1;5(4):e227970. doi: 10.1001/jamanetworkopen.2022.7970.

ABSTRACT

IMPORTANCE: During the COVID-19 pandemic, urgent clinical management of patients has mainly included drugs currently administered for other diseases, referred to as repositioned drugs. As a result, some of these drugs have proved to be not only ineffective but also harmful because of adverse events associated with drug-drug interactions (DDIs).

OBJECTIVE: To identify DDIs that led to adverse clinical outcomes and/or adverse drug reactions in patients with COVID-19 by systematically reviewing the literature and assessing the value of drug interaction checkers in identifying such events.

EVIDENCE REVIEW: After identification of the drugs used during the COVID-19 pandemic, the drug interaction checkers Drugs.com, COVID-19 Drug Interactions, LexiComp, Medscape, and WebMD were consulted to analyze theoretical DDI-associated adverse events in patients with COVID-19 from March 1, 2020, through February 28, 2022. A systematic literature review was performed by searching the databases PubMed, Scopus, and Cochrane for articles published from March 1, 2020, through February 28, 2022, to retrieve articles describing actual adverse events associated with DDIs. The drug interaction checkers were consulted again to evaluate their potential to assess such events.

FINDINGS: The DDIs identified in the reviewed articles involved 46 different drugs. In total, 575 DDIs for 58 drug pairs (305 associated with at least 1 adverse drug reaction) were reported. The drugs most involved in DDIs were lopinavir and ritonavir. Of the 6917 identified studies, 20 met the inclusion criteria. These studies, which enrolled 1297 patients overall, reported 115 DDI-related adverse events: 15 (26%) were identifiable by all tools analyzed, 29 (50%) were identifiable by at least 1 of them, and 14 (24%) remained nonidentifiable.

CONCLUSIONS AND RELEVANCE: The main finding of this systematic review is that the use of drug interaction checkers could have identified several DDI-associated adverse drug reactions, including severe and life-threatening events. Both the interactions between the drugs used to treat COVID-19 and between the COVID-19 drugs and those already used by the patients should be evaluated.

PMID:35438752 | DOI:10.1001/jamanetworkopen.2022.7970

J Assoc Physicians India. 2022 Feb;70(2):11-12.

ABSTRACT

COVID-19 vaccines have been rolled out recently in several parts of the world. Little is known about the post-vaccination experience outside of clinical trial conditions. The aim of this study was to investigate the adverse effects and infection rate of vaccinated people in a community scenario. It will help to educate the public, dispel misinformation and reduce vaccine hesitancy.

AIM AND OBJECTIVES: Assessing total beneficiaries of COVID-19 vaccination and finding among them COVID-19 infection and AEFI after vaccination.

SUBJECT AND METHODS: Cross sectional Study at COVID-19 Vaccination centre at DCH in Mumbai, since 1st February2021-31st July 2021, Data was collected by calling telephonically the registered beneficiaries in Vaccination Centre, data was collected and analysed in MS-excel sheet and SPSS using CHI-square test.

RESULTS: 49.68% of the beneficiaries were from the age group of 45-60 years followed by &gt;60 years age group (34.70%). 97.08% beneficiaries were from Mumbai. 3593(43.59%) had taken both the doses of COVID-19 vaccine while 4650(56.41%) had taken only first dose of COVID -19 vaccine. 36(0.44%) had contracted COVID-19 infection after vaccination. 88.71% had no AEFI after taking vaccine. 1.65% had mild AEFI 9.63% had moderate AEFI.

CONCLUSION: Very few had contracted COVID-19 infection after vaccination. Out of all AEFI maximum were mild to moderate.

PMID:35436817