J Infect Public Health. 2023 Mar 15;16(5):799-807. doi: 10.1016/j.jiph.2023.03.007. Online ahead of print.

ABSTRACT

Monkeypox virus (MPXV) was confirmed in May 2022 and designated a global health emergency by WHO in July 2022. MPX virions are big, enclosed, brick-shaped, and contain a linear, double-stranded DNA genome as well as enzymes. MPXV particles bind to the host cell membrane via a variety of viral-host protein interactions. As a result, the wrapped structure is a potential therapeutic target. DeepRepurpose, an artificial intelligence-based compound-viral proteins interaction framework, was used via a transfer learning setting to prioritize a set of FDA approved and investigational drugs which can potentially inhibit MPXV viral proteins. To filter and narrow down the lead compounds from curated collections of pharmaceutical compounds, we used a rigorous computational framework that included homology modeling, molecular docking, dynamic simulations, binding free energy calculations, and binding pose metadynamics. We identified Elvitegravir as a potential inhibitor of MPXV virus using our comprehensive pipeline.

PMID:36966703 | DOI:10.1016/j.jiph.2023.03.007

Inflammopharmacology. 2023 Mar 25. doi: 10.1007/s10787-023-01193-1. Online ahead of print.

ABSTRACT

The "Thalidomide tragedy" is a landmark in the history of the pharmaceutical industry. Despite limited clinical trials, there is a continuous effort to investigate thalidomide as a drug for cancer and inflammatory diseases such as rheumatoid arthritis, lepromatous leprosy, and COVID-19. This review focuses on the possibilities of targeting inflammation by repurposing thalidomide for the treatment of idiopathic pulmonary fibrosis (IPF). Articles were searched from the Scopus database, sorted, and selected articles were reviewed. The content includes the proven mechanisms of action of thalidomide relevant to IPF. Inflammation, oxidative stress, and epigenetic mechanisms are major pathogenic factors in IPF. Transforming growth factor-β (TGF-β) is the major biomarker of IPF. Thalidomide is an effective anti-inflammatory drug in inhibiting TGF-β, interleukins (IL-6 and IL-1β), and tumour necrosis factor-α (TNF-α). Thalidomide binds cereblon, a process that is involved in the proposed mechanism in specific cancers such as breast cancer, colon cancer, multiple myeloma, and lung cancer. Cereblon is involved in activating AMP-activated protein kinase (AMPK)-TGF-β/Smad signalling, thereby attenuating fibrosis. The past few years have witnessed an improvement in the identification of biomarkers and diagnostic technologies in respiratory diseases, partly because of the COVID-19 pandemic. Hence, investment in clinical trials with a systematic plan can help repurpose thalidomide for pulmonary fibrosis.

PMID:36966238 | DOI:10.1007/s10787-023-01193-1

Indian J Pharmacol. 2023 Jan-Feb;55(1):53-58. doi: 10.4103/ijp.ijp_700_22.

ABSTRACT

Novel SARS-CoV-2 (COVID-19) is affecting worldwide as declared pandemic by the WHO. Various repositioning and novel therapeutic agents are being evaluated under different clinical setups; however, there is no promising therapeutic agent reported to date. Small molecules like peptides have their popularity as their specificity, delivery, and synthesizability as promising therapeutic agents. In this study, we have reviewed the published literature describing peptide designing, in silico binding mode, antiviral activity, preventive measures, and in vivo assessments. Here, we reported all the results which are promising against SARS-CoV-2 as therapeutic and preventive (vaccine candidates), and their status in the drug development process.

PMID:36960521 | DOI:10.4103/ijp.ijp_700_22

Biochem Biophys Res Commun. 2023 Mar 20;656:131-138. doi: 10.1016/j.bbrc.2023.03.048. Online ahead of print.

ABSTRACT

Drug repurposing holds abundant opportunity in the development of novel anticancer drugs. Chloroquine (CQ), a FDA approved anti-malarial drug, is demonstrated to enhance anticancer efficacy of standard anticancer drugs including doxorubicin (DOX) in several types of cancer cells. Here, we aimed to exploit the chemosensitizing effects of CQ against DOX in human cervical cancer (HeLa) cells that remains to be investigated yet. We show that a combination of DOX (40 nM) and CQ (40 μM) resulted in a synergistic cytotoxicity (combination index; CI < 1) in HeLa cells compared to the DOX or CQ alone. Synergistic effect of the combination (DOX + CQ) was associated with the impaired autophagic flux and enhanced apoptosis. Following treatment with the combination (DOX + CQ), the level of p62/SQSTM and LC-3II proteins was increased, while a decrease was noted in the expression of LAMP-2, Syntaxin17, Rab 5, and Rab 7 proteins that play critical roles in the fusion of autophagosomes to lysosomes. Autophagy inhibition by combination (DOX + CQ) enhanced the apoptotic cell death synergistically by increasing the cleavage of procaspase-3 and PARP1. Further, a prior incubation of HeLa cells with Z-VAD-FMK (a pan-caspase inhibitor) for 4 h, suppressed the combination (DOX + CQ)-induced cell death. Our data suggest that a combination of DOX + CQ had a better anti-cancer efficacy in HeLa cells than either of the drugs alone. Thus, CQ, as a repurposed drug, may hold the potential to synergize anticancer effects of DOX in cervical cancer cells.

PMID:36963349 | DOI:10.1016/j.bbrc.2023.03.048

J Gastroenterol. 2023 Mar 24. doi: 10.1007/s00535-023-01983-y. Online ahead of print.

NO ABSTRACT

PMID:36961556 | DOI:10.1007/s00535-023-01983-y

Appl Biochem Biotechnol. 2023 Mar 24. doi: 10.1007/s12010-023-04439-4. Online ahead of print.

ABSTRACT

COVID-19 infection is a new disease and our knowledge is limited; day in and day out more and more interesting yet diverse observations are reported by the different research groups from different corners of the world. So, there is an urgent requirement of the invention of some effective and efficient drugs that can carry out the end of the deadly viral infection. Throughout the world, there have been many efforts carried out in different labs to invent such a drug and also identifying any pre-existing drugs which can carry out the killing of the virus. In this review, an effort has been made to understand the potential drugs which can be used against the SARS-CoV-2 viral infection. Again, the strategies on the current and the future drug discovery mechanisms against the SARS-CoV-2 are also mentioned. The different drugs made and the drugs re-used and also the drugs which are in the making process in different research laboratories across the world are also mentioned. To combat this unexpected crisis, we still need some more efforts from the different scientific communities around the world for finding a cure against this viral infection and this is needed to be done for the prevention of more loss of human life.

PMID:36961509 | DOI:10.1007/s12010-023-04439-4

J Biomol Struct Dyn. 2023 Mar 24:1-24. doi: 10.1080/07391102.2023.2193994. Online ahead of print.

ABSTRACT

The outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused an unprecedented global pandemic, and new cases are still on the rise due to the absence of effective medicines. However, developing new drugs within a short time is extremely difficult. Repurposing the existing drugs provides a fast and effective strategy to identify promising inhibitors. Here we focus on the screening of drugs database for discovering potential covalent inhibitors that target 3-chymotrypsin-like protease (3CLpro), an essential enzyme mediating viral replication and transcription. Firstly, we constructed a receptor-ligand pharmacophore model and verified it through decoy set. The importance of pharmacophore features was evaluated by combining molecular dynamics simulation with interaction analyses. Then, covalent docking was used to perform further screening. According to docking score and Prime/Molecular Mechanics Generalized Born Surface Area (MM-GBSA) score, total ten compounds obtained good scores and successfully established covalent bonds with the catalytic Cys145 residue. They also formed favorable interactions with key residues in active sites and closely integrated with 3CLpro with binding modes similar to known 3CLpro inhibitor. Finally, the top four hits DB08732, DB04653, DB01871 and DB07299 were further subjected to 100 ns molecular dynamics (MD) simulation and MM-GBSA binding free energy calculations. The results suggest that the four candidates show good binding affinities for 3CLpro, which warrants further evaluation for their in-vitro/in-vivo activities. Overall, our research methods provide a valuable reference for discovering promising inhibitors against SARS-CoV-2 and help to fight against the epidemic.Communicated by Ramaswamy H. Sarma.

PMID:36961210 | DOI:10.1080/07391102.2023.2193994

Mult Scler Relat Disord. 2023 Mar 16;73:104622. doi: 10.1016/j.msard.2023.104622. Online ahead of print.

ABSTRACT

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease affecting numerous people worldwide. While the relapsing subtypes of MS are to some extent treatable, the disease remains incurable leading to progressive disability. Limited efficacy of current small molecule drugs necessitates development of efficient and safe MS medications. Accordingly, drug repurposing is an invaluable strategy that recognizes new targets for known drugs especially in the field of poorly addressed therapeutic areas. Drug discovery largely depends on the identification of potential binding molecules to the intended biomolecular target(s). In this regard, current study was devoted to in silico repurposing of 263 small molecule CNS drugs to achieve superior binders to some MS-related targets. On the basis of molecular docking scores, thioxanthene and benzisothiazole-based antipsychotics could be identified as potential binders to sphingosine-1-phosphate lyase (S1PL) and cyclophilin D (CypD). Tightest interaction modes were observed for zuclopenthixol-S1PL (ΔGb -7.96 kcal/mol) and lurasidone-CypD (ΔGb -8.84 kcal/mol) complexes. Molecular dynamics (MD) simulations proved the appropriate and stable accommodation of top-ranked drugs inside enzyme binding sites during 100 ns. Hydroxyethyl piperazine of zuclopenthixol and benzisothiazole of lurasidone flipped inside the binding pocket to interact with adjacent polar and apolar residues. Solvent accessible surface area (SASA) fluctuations confirmed the results of binding trajectory analysis and showed that non-polar hydrophobic interactions played significant roles in acquired stabilities. Our results on lurasidone binding pattern were interestingly in accordance with previous reports on X-ray structures of other norbornane maleimide derivatives as CypD inhibitors. According to this, Asn144, Phe102 and Phe155 served as important residues in providing stable binding pose of lurasidone through both exo and endo conformations. Although experimental results are necessary to be achieved, the outcomes of this study proposed the potentiality of some thioxanthene and benzisothiazole-based antipsychotics for binding to S1PL and CypD, respectively, as MS-related targets.

PMID:36958175 | DOI:10.1016/j.msard.2023.104622

Clin Exp Metastasis. 2023 Mar 23. doi: 10.1007/s10585-023-10202-0. Online ahead of print.

ABSTRACT

Brain metastasis is the main cause of treatment failure and melanoma-related death. Inadequate concentrations of therapeutic drugs in the brain due to the blood-brain barrier (BBB) pose a major challenge in the treatment of brain metastasis. Antipsychotics can cross the BBB to reach the brain. Fluphenazine (FPZ) inhibits the survival of melanoma cells in vitro. However, its efficacy in suppressing the metastasis of melanoma, especially brain metastasis, remains unknown. Therefore, we explored whether fluphenazine (FPZ) can be repurposed for treating melanoma metastasis. A subcutaneous tumor model, and experimental metastasis models that simulate the outgrowth of melanoma cells in the brain, lung, and bone were established to verify the inhibitory effect of FPZ on melanoma cells. FPZ showed potential inhibitory effects against melanoma both in vivo and in vitro. It induced G0/G1 phase arrest and-mitochondrion-mediated intrinsic apoptosis, and inhibited autophagic flux in melanoma cells in vitro. In vivo, subcutaneous tumor, brain, lung, and bone models of metastatic melanoma were established. Intraperitoneal injection of FPZ (8 mg/kg) significantly inhibited melanoma growth in the subcutaneous and experimental metastasis models. In a lung metastasis model, FPZ reduced the proportion of M2 macrophages and increased the proportion of CD8+ T cells and NK cells in vivo, thereby promoting an anticancer immune response. The findings of this study indicate that FPZ is a potential drug candidate for treating metastatic melanoma.

PMID:36952079 | DOI:10.1007/s10585-023-10202-0

Emerg Microbes Infect. 2023 Mar 23:2195020. doi: 10.1080/22221751.2023.2195020. Online ahead of print.

ABSTRACT

SARS-CoV-2, the causative virus of COVID-19, continues to threaten global public health. COVID-19 is a multi-organ disease, causing not only respiratory distress, but also extrapulmonary manifestations, including gastrointestinal symptoms with SARS-CoV-2 RNA shedding in stool long after respiratory clearance. Despite global vaccination and existing antiviral treatments, variants of concern are still emerging and circulating. Of note, new Omicron BA.5 sublineages both increasingly evade neutralizing antibodies and demonstrate an increased preference for entry via the endocytic entry route. Alternative to direct-acting antivirals, host-directed therapies interfere with host mechanisms hijacked by viruses, and enhance cell-mediated resistance with a reduced likelihood of drug resistance development. Here, we demonstrate that the autophagy-blocking therapeutic berbamine dihydrochloride robustly prevents SARS-CoV-2 acquisition by human intestinal epithelial cells via an autophagy-mediated BNIP3 mechanism. Strikingly, berbamine dihydrochloride exhibited pan-antiviral activity against Omicron subvariants BA.2 and BA.5 at nanomolar potency, providing a proof of concept for the potential for targeting autophagy machinery to thwart infection of current circulating SARS-CoV-2 subvariants. Furthermore, we show that autophagy-blocking therapies limited virus-induced damage to intestinal barrier function, affirming the therapeutic relevance of autophagy manipulation to avert the intestinal permeability associated with acute COVID-19 and post-COVID-19 syndrome. Our findings underscore that SARS-CoV-2 exploits host autophagy machinery for intestinal dissemination and indicate that repurposed autophagy-based antivirals represent a pertinent therapeutic option to boost protection and ameliorate disease pathogenesis against current and future SARS-CoV-2 variants of concern.

PMID:36951188 | DOI:10.1080/22221751.2023.2195020

Sci Rep. 2023 Mar 22;13(1):4685. doi: 10.1038/s41598-023-31276-6.

ABSTRACT

Some recent studies showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and idiopathic pulmonary fibrosis (IPF) disease might stimulate each other through the shared genes. Therefore, in this study, an attempt was made to explore common genomic biomarkers for SARS-CoV-2 infections and IPF disease highlighting their functions, pathways, regulators and associated drug molecules. At first, we identified 32 statistically significant common differentially expressed genes (cDEGs) between disease (SARS-CoV-2 and IPF) and control samples of RNA-Seq profiles by using a statistical r-package (edgeR). Then we detected 10 cDEGs (CXCR4, TNFAIP3, VCAM1, NLRP3, TNFAIP6, SELE, MX2, IRF4, UBD and CH25H) out of 32 as the common hub genes (cHubGs) by the protein-protein interaction (PPI) network analysis. The cHubGs regulatory network analysis detected few key TFs-proteins and miRNAs as the transcriptional and post-transcriptional regulators of cHubGs. The cDEGs-set enrichment analysis identified some crucial SARS-CoV-2 and IPF causing common molecular mechanisms including biological processes, molecular functions, cellular components and signaling pathways. Then, we suggested the cHubGs-guided top-ranked 10 candidate drug molecules (Tegobuvir, Nilotinib, Digoxin, Proscillaridin, Simeprevir, Sorafenib, Torin 2, Rapamycin, Vancomycin and Hesperidin) for the treatment against SARS-CoV-2 infections with IFP diseases as comorbidity. Finally, we investigated the resistance performance of our proposed drug molecules compare to the already published molecules, against the state-of-the-art alternatives publicly available top-ranked independent receptors by molecular docking analysis. Molecular docking results suggested that our proposed drug molecules would be more effective compare to the already published drug molecules. Thus, the findings of this study might be played a vital role for diagnosis and therapies of SARS-CoV-2 infections with IPF disease as comorbidity risk.

PMID:36949176 | DOI:10.1038/s41598-023-31276-6

ACS Med Chem Lett. 2023 Mar 22;14(4):386-395. doi: 10.1021/acsmedchemlett.3c00015. eCollection 2023 Apr 13.

ABSTRACT

Gene expression and cell morphology data are high-dimensional biological readouts of much recent interest for drug discovery. They are able to describe biological systems in different states (e.g., healthy and diseased), as well as biological systems before and after compound treatment, and they are hence useful for matching both spaces (e.g., for drug repurposing) as well as for characterizing compounds with respect to efficacy and safety endpoints. This Microperspective describes recent advances in this direction with a focus on applied drug discovery and drug repurposing, as well as outlining what else is needed to advance further, with a particular focus on better understanding the applicability domain of readouts and their relevance for decision making, which is currently often still unclear.

PMID:37077392 | PMC:PMC10107910 | DOI:10.1021/acsmedchemlett.3c00015

Biol Pharm Bull. 2023 Mar 21. doi: 10.1248/bpb.b22-00674. Online ahead of print.

ABSTRACT

Myelosuppression, a side effect of anticancer drugs, makes people more susceptible to infectious diseases by compromising the immune system. When a cancer patient develops a contagious disease, treatment with an anticancer drug is suspended or postponed to treat the infectious disease. If there were a drug that suppresses the growth of cancer cells among antibacterial agents, it would be possible to treat both infectious diseases and cancer. Therefore, this study investigated the effect of antibacterial agents on cancer cell development. Vancomycin (VAN) had little effect on cell proliferation against the breast cancer cell, MCF-7, prostate cancer cell, PC-3, and gallbladder cancer cell, NOZ C-1. Alternatively, Teicoplanin (TEIC) and Daptomycin (DAP) promoted the growth of some cancer cells. In contrast, Linezolid (LZD) suppressed the proliferation of MCF-7, PC-3, and NOZ C-1 cells. Therefore, we found a drug that affects the growth of cancer cells among antibacterial agents. Next, when we examined the effects of the combined use of existing anticancer and antibacterial agents, we found VAN did not affect the growth suppression by anticancer agents. However, TEIC and DAP attenuated the growth suppression of anticancer agents. In contrast, LZD additively enhanced the growth suppression by Docetaxel in PC-3 cells. Furthermore, we showed that LZD inhibits cancer cell growth by mechanisms that involve PI3K/Akt pathway suppression. Therefore, LZD might simultaneously treat cancer and infectious diseases.

PMID:36948634 | DOI:10.1248/bpb.b22-00674

Eur J Med Chem. 2023 Feb 10;251:115179. doi: 10.1016/j.ejmech.2023.115179. Online ahead of print.

ABSTRACT

Schistosomiasis is an infectious disease caused by blood flukes of the genus Schistosoma and affects approximately 200 million people worldwide. Since Praziquantel (PZQ) is the only drug for schistosomiasis, alternatives are needed. By a biochemical approach, we identified a tegumentally expressed aldehyde dehydrogenase (ALDH) of S. mansoni, SmALDH_312. Molecular analyses of adult parasites showed Smaldh_312 transcripts in both genders and different tissues. Physiological and cell-biological experiments exhibited detrimental effects of the drug disulfiram (DSF), a known ALDH inhibitor, on larval and adult schistosomes in vitro. DSF also reduced stem-cell proliferation and caused severe tegument damage in treated worms. In silico-modelling of SmALDH_312 and docking analyses predicted DSF binding, which we finally confirmed by enzyme assays with recombinant SmALDH_312. Furthermore, we identified compounds of the Medicine for Malaria Venture (MMV) pathogen box inhibiting SmALDH_312 activity. Our findings represent a promising starting point for further development towards new drugs for schistosomiasis.

PMID:36948075 | DOI:10.1016/j.ejmech.2023.115179

J Clin Psychiatry. 2023 Mar 20;84(3):22r14494. doi: 10.4088/JCP.22r14494.

ABSTRACT

Importance: "Psychotropic" drugs have widespread reach and impact throughout the brain and body. Thus, many of these drugs could be repurposed for non-psychiatric indications of high public health impact.

Observations: The selective serotonin reuptake inhibitor (SSRI) fluvoxamine was shown efficacious as a COVID-19 treatment based on randomized controlled trials (RCTs), and a benefit of other antidepressants has been posited based on observational and preclinical studies. In this review, we illuminate features of SSRIs and other psychiatric drugs that make them candidates to repurpose for non-psychiatric indications. We summarize research that led to fluvoxamine's use in COVID-19 and provide guidance on how to use it safely. We summarize studies suggestive of benefit of other antidepressants versus COVID-19 and long COVID. We also describe putative mechanisms of psychiatric drugs in treating long COVID, Alzheimer's disease, cancer, and other conditions.

Conclusion and Relevance: There is a potentially great clinical and public health impact of psychotropic drug repurposing. Challenges exist to such repurposing efforts, but solutions exist for researchers, regulators, and funders that overcome these challenges.

PMID:36946597 | DOI:10.4088/JCP.22r14494

J Med Virol. 2023 Mar 22. doi: 10.1002/jmv.28693. Online ahead of print.

ABSTRACT

Cancer management is major concern of health organizations and viral cancers account for approximately 15.4% of all known human cancers. Due to large number of patients, efficient treatments for viral cancers are needed. De novo drug discovery is time consuming and expensive process with high failure rate in clinical stages. To address this problem and provide treatments to patients suffering from viral cancers faster, drug repurposing emerges as an effective alternative which aims to find the other indications of the FDA approved drugs. Applied to viral cancers, drug repurposing studies following the niche have tried to find if already existing drugs could be used to treat viral cancers. Multiple drug repurposing approaches till date have been introduced with successful results in viral cancers and many drugs have been successfully repurposed various viral cancers. Here in this study, a critical review of viral cancer related databases, tools, and different machine learning, deep learning and virtual screening-based drug repurposing studies focusing on viral cancers is provided. Additionally, the mechanism of viral cancers is presented along with drug repurposing case study specific to each viral cancer. Finally, the limitations and challenges of various approaches along with possible solutions are provided. This article is protected by copyright. All rights reserved.

PMID:36946499 | DOI:10.1002/jmv.28693

J Cell Biochem. 2023 Mar 22. doi: 10.1002/jcb.30397. Online ahead of print.

ABSTRACT

Mpox (formerly Monkeypox), a zoonotic illness caused by the Mpox virus, belongs to the Orthopoxvirus genus in the family Poxviridae. To design and develop effective antiviral therapeutics against DNA viruses, the DNA-dependent RNA polymerase (DdRp) of poxviruses has emerged as a promising drug target. In the present study, we modeled the three-dimensional (3D) structure of DdRp using a template-based homology approach. After modeling, virtual screening was performed to probe the molecular interactions between 1755 Food and Drug Administration-approved small molecule drugs (≤500 molecular weight) and the DdRp of Mpox. Based on the binding affinity and molecular interaction patterns, five drugs, lumacaftor (-11.7 kcal/mol), conivaptan (-11.7 kcal/mol), betulinic acid (-11.6 kcal/mol), fluspirilene (-11.3 kcal/mol), and imatinib (-11.2 kcal/mol), have been ranked as the top drug compounds interacting with Mpox DdRp. Complexes of these shortlisted drugs with DdRp were further evaluated using state-of-the-art all-atoms molecular dynamics (MD) simulations on 200 nanoseconds followed by principal component analysis (PCA). MD simulations and PCA results revealed highly stable interactions of these small drugs with DdRp. After due validation in wet-lab using available in vitro and in vivo experiments, these repurposed drugs can be further utilized for the treatment of contagious Mpox virus. The outcome of this study may establish a solid foundation to screen repurposed and natural compounds as potential antiviral therapeutics against different highly pathogenic viruses.

PMID:36946432 | DOI:10.1002/jcb.30397

Expert Rev Clin Pharmacol. 2023 Mar 21:1-4. doi: 10.1080/17512433.2023.2193683. Online ahead of print.

NO ABSTRACT

PMID:36945753 | DOI:10.1080/17512433.2023.2193683

Funct Integr Genomics. 2023 Mar 21;23(2):94. doi: 10.1007/s10142-023-01007-1.

ABSTRACT

Breast cancer is one of the leading causes of death in women worldwide. Initially, it develops in the epithelium of the ducts or lobules of the breast glandular tissues with limited growth and the potential to metastasize. It is a highly heterogeneous malignancy; however, the common molecular mechanisms could help identify new targeted drugs for treating its subtypes. This study uses computational drug repositioning approaches to explore fresh drug candidates for breast cancer treatment. We also implemented reversal gene expression and gene expression-based signatures to explore novel drug candidates computationally. The drug activity profiles and related gene expression changes were acquired from the DrugBank, PubChem, and LINCS databases, and then in silico drug screening, molecular dynamics (MD) simulation, replica exchange MD simulations, and simulated annealing molecular dynamics (SAMD) simulations were conducted to discover and verify the valid drug candidates. We have found that compounds like furosemide, gold, and dopamine showed significant outcomes. Furthermore, the expression of genes related to breast cancer was observed to be reversed by these shortlisted drugs. Therefore, we postulate that combining furosemide, gold, and dopamine would be a potential combination therapy measurement for breast cancer patients.

PMID:36943579 | DOI:10.1007/s10142-023-01007-1

Matern Child Health J. 2023 Mar 20. doi: 10.1007/s10995-023-03621-8. Online ahead of print.

ABSTRACT

OBJECTIVES: We sought to identify the most common diagnostic categories linked to dispensed opioid prescriptions among children 1-36 months old and changes in patterns over the years 2000 to 2017.

METHODS: This study used South Carolina's Medicaid claims data of pediatric dispensed outpatient opioid prescriptions between 2000 and 2017. The major opioid-related diagnostic category (indication) for each prescription was identified using visit primary diagnoses and the Clinical Classification System (AHRQ-CCS) software. The variables of interest were the rate of opioid prescriptions per 1,000 visits for each diagnostic category and the relative percentage of opioid prescriptions assigned to each category compared to all categories.

RESULTS: Six major diagnostic categories were identified; Diseases of the respiratory system (RESP), Congenital anomalies (CONG), Injury (INJURY), Diseases of the nervous system and sense organs (NEURO), Diseases of the digestive system (GI), and Diseases of the genitourinary system (GU). The overall rate of dispensed opioid prescriptions per category declined significantly for four diagnostic categories throughout the study period, RESP by 15.13, INJURY by 8.49, NEURO by 7.33, and GI by 5.93. Two categories increased during the same time, CONG (by 9.47) and GU (by 6.98). RESP was the most prevalent category linked to a dispensed opioid prescription within 2010-2012 (almost 25%) but CONG was the most prevalent by 2014 (17.77%).

CONCLUSIONS FOR PRACTICE: Among Medicaid children 1-36 months old, annual dispensed opioid prescription rates declined for most major diagnostic categories (RESP, INJURY, NEURO, and GI). Future studies should explore alternatives to current opioid dispensing practices for GU and CONG cases.

PMID:36939951 | DOI:10.1007/s10995-023-03621-8