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  1. Article ; Online: Sensitivity and specificity of the posterolateral rotatory drawer test in the diagnosis of lateral collateral ligament insufficiency of the elbow.

    Stone, Andrew / Venkatakrishnan, Shruti / Phadnis, Joideep

    Journal of shoulder and elbow surgery

    2023  Volume 32, Issue 11, Page(s) 2346–2354

    Abstract: Background: Numerous clinical tests are described for the diagnosis of chronic lateral collateral ligament (LCL) insufficiency of the elbow; however, none of these tests have been adequately assessed for sensitivity, with at most 8 patients included in ... ...

    Abstract Background: Numerous clinical tests are described for the diagnosis of chronic lateral collateral ligament (LCL) insufficiency of the elbow; however, none of these tests have been adequately assessed for sensitivity, with at most 8 patients included in previous studies. Furthermore, no test has had specificity assessed. The posterolateral rotatory drawer (PLRD) test is thought to have improved diagnostic accuracy over other tests in the awake patient. The aim of this study is to formally assess this test using reference standards in a large cohort of patients.
    Methods: A total of 106 eligible patients were identified for inclusion from a single-surgeon database of operative procedures. Examination under anesthetic (EUA) and arthroscopy were chosen as the reference standards to compare the PLRD test against. Only patients with a clearly documented PLRD test finding performed preoperatively in the clinic, and a clearly documented EUA and/or arthroscopic findings from surgery were included. A total of 102 patients underwent EUA, 74 of whom also underwent arthroscopy. Twenty-eight patients had EUA, and then an open procedure without arthroscopy. Four patients had arthroscopy without a clearly documented EUA. Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were calculated with 95% confidence intervals.
    Results: Thirty-seven patients had a positive PLRD test, and 69 had a negative test. Compared to the reference standard of EUA (n = 102), the PLRD test had a sensitivity of 97.3% (85.8%-99.9%) and a specificity of 98.5% (91.7%-100%) (PPV = 0.973, NPV = 0.985). Compared to the reference standard of arthroscopy (n = 78), the PLRD test had a sensitivity of 87.5% (61.7%-98.5%) and a specificity of 98.4% (91.3%-100%) (PPV = 0.933, NPV = 0.968). Compared to either reference standard (n = 106), the PLRD test has a sensitivity of 94.7% (82.3%-99.4%) and a specificity of 98.5% (92.1%-100%) (PPV = 0.973, NPV = 0.971).
    Conclusion: The PLRD test demonstrated an overall sensitivity of 94.7% and specificity of 98.5% with high positive and negative predictive values. This test is recommended as the primary diagnostic tool for LCL insufficiency in the awake patient and should be widely incorporated into surgical training.
    Language English
    Publishing date 2023-07-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1170782-3
    ISSN 1532-6500 ; 1058-2746
    ISSN (online) 1532-6500
    ISSN 1058-2746
    DOI 10.1016/j.jse.2023.05.032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Customized esthetic wrought wire retainer in distal extension interim prosthesis: An alternate technique.

    Keerthivasan, M S / Venkatakrishnan, C J / Fathima, T Sumaiya

    Journal of Indian Prosthodontic Society

    2023  Volume 23, Issue 3, Page(s) 301–302

    MeSH term(s) Esthetics, Dental ; Denture, Partial, Removable ; Orthodontic Retainers
    Language English
    Publishing date 2023-10-20
    Publishing country India
    Document type Journal Article
    ISSN 1998-4057
    ISSN (online) 1998-4057
    DOI 10.4103/jips.jips_90_23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Why did Rubens add a parrot to Titian's The Fall of Man? A pictorial manipulation of joint attention.

    Alexander, Robert G / Venkatakrishnan, Ashwin / Chanovas, Jordi / Ferguson, Sophie / Macknik, Stephen L / Martinez-Conde, Susana

    Journal of vision

    2024  Volume 24, Issue 4, Page(s) 1

    Abstract: Almost 400 years ago, Rubens copied Titian's The Fall of Man, albeit with important changes. Rubens altered Titian's original composition in numerous ways, including by changing the gaze directions of the depicted characters and adding a striking red ... ...

    Abstract Almost 400 years ago, Rubens copied Titian's The Fall of Man, albeit with important changes. Rubens altered Titian's original composition in numerous ways, including by changing the gaze directions of the depicted characters and adding a striking red parrot to the painting. Here, we quantify the impact of Rubens's choices on the viewer's gaze behavior. We displayed digital copies of Rubens's and Titian's artworks-as well as a version of Rubens's painting with the parrot digitally removed-on a computer screen while recording the eye movements produced by observers during free visual exploration of each image. To assess the effects of Rubens's changes to Titian's composition, we directly compared multiple gaze parameters across the different images. We found that participants gazed at Eve's face more frequently in Rubens's painting than in Titian's. In addition, gaze positions were more tightly focused for the former than for the latter, consistent with different allocations of viewer interest. We also investigated how gaze fixation on Eve's face affected the perceptual visibility of the parrot in Rubens's composition and how the parrot's presence versus its absence impacted gaze dynamics. Taken together, our results demonstrate that Rubens's critical deviations from Titian's painting have powerful effects on viewers' oculomotor behavior.
    MeSH term(s) Male ; Animals ; Humans ; Parrots ; Eye Movements ; Attention ; Fixation, Ocular ; Paintings
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2106064-2
    ISSN 1534-7362 ; 1534-7362
    ISSN (online) 1534-7362
    ISSN 1534-7362
    DOI 10.1167/jov.24.4.1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Diversity and Inclusion in Drug Development: Rethinking Intrinsic and Extrinsic Factors with Patient Centricity.

    Venkatakrishnan, Karthik / Benincosa, Lisa J

    Clinical pharmacology and therapeutics

    2021  Volume 112, Issue 2, Page(s) 204–207

    MeSH term(s) Cultural Diversity ; Humans
    Language English
    Publishing date 2021-09-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.2416
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Uncovering the Genetic Basis of Congenital Heart Disease: Recent Advancements and Implications for Clinical Management.

    Chhatwal, Karanjot / Smith, Jacob J / Bola, Harroop / Zahid, Abeer / Venkatakrishnan, Ashwin / Brand, Thomas

    CJC pediatric and congenital heart disease

    2023  Volume 2, Issue 6Part B, Page(s) 464–480

    Abstract: Congenital heart disease (CHD) is the most prevalent hereditary disorder, affecting approximately 1% of all live births. A reduction in morbidity and mortality has been achieved with advancements in surgical intervention, yet challenges in managing ... ...

    Abstract Congenital heart disease (CHD) is the most prevalent hereditary disorder, affecting approximately 1% of all live births. A reduction in morbidity and mortality has been achieved with advancements in surgical intervention, yet challenges in managing complications, extracardiac abnormalities, and comorbidities still exist. To address these, a more comprehensive understanding of the genetic basis underlying CHD is required to establish how certain variants are associated with the clinical outcomes. This will enable clinicians to provide personalized treatments by predicting the risk and prognosis, which might improve the therapeutic results and the patient's quality of life. We review how advancements in genome sequencing are changing our understanding of the genetic basis of CHD, discuss experimental approaches to determine the significance of novel variants, and identify barriers to use this knowledge in the clinics. Next-generation sequencing technologies are unravelling the role of oligogenic inheritance, epigenetic modification, genetic mosaicism, and noncoding variants in controlling the expression of candidate CHD-associated genes. However, clinical risk prediction based on these factors remains challenging. Therefore, studies involving human-induced pluripotent stem cells and single-cell sequencing help create preclinical frameworks for determining the significance of novel genetic variants. Clinicians should be aware of the benefits and implications of the responsible use of genomics. To facilitate and accelerate the clinical integration of these novel technologies, clinicians should actively engage in the latest scientific and technical developments to provide better, more personalized management plans for patients.
    Language English
    Publishing date 2023-10-19
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2772-8129
    ISSN (online) 2772-8129
    DOI 10.1016/j.cjcpc.2023.10.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Pharmacometrics Golems: Exposure-Response Models in Oncology.

    Khandelwal, Akash / Grisic, Ana-Marija / French, Jonathan / Venkatakrishnan, Karthik

    Clinical pharmacology and therapeutics

    2022  Volume 112, Issue 5, Page(s) 941–945

    MeSH term(s) Humans ; Medical Oncology ; Models, Biological
    Language English
    Publishing date 2022-03-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.2564
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Variable or variate? A conundrum in pharmacometrics exposure-response models.

    Grisic, Ana-Marija / Venkatakrishnan, Karthik / French, Jonathan / Khandelwal, Akash

    CPT: pharmacometrics & systems pharmacology

    2022  Volume 12, Issue 2, Page(s) 144–147

    Abstract: Key elements of scientific writing-consistency and clarity-can be compromised in case of inaccurate use of methodological terms, especially in complex and multidisciplinary scientific fields. Such is the case in reports of pharmacometrics exposure- ... ...

    Abstract Key elements of scientific writing-consistency and clarity-can be compromised in case of inaccurate use of methodological terms, especially in complex and multidisciplinary scientific fields. Such is the case in reports of pharmacometrics exposure-response analyses with the use of the terms univariate/multivariate and univariable/multivariable. This perspective outlines the issues in the use of these terms, clarifies their definitions, provides examples, and makes recommendations for authors, reviewers, and journals in the fields of clinical pharmacology and pharmacometrics.
    MeSH term(s) Humans ; Pharmacology, Clinical ; Writing
    Language English
    Publishing date 2022-12-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2697010-7
    ISSN 2163-8306 ; 2163-8306
    ISSN (online) 2163-8306
    ISSN 2163-8306
    DOI 10.1002/psp4.12905
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Web3-based storage solutions for biomedical research and clinical data exchange.

    Tugaoen, Julian / Becker, Alana / Guo, Chenmeinian / Parasidis, Efthimios / Venkatakrishnan, Shaileshh Bojja / Otero, José Javier

    Journal of the American Medical Informatics Association : JAMIA

    2023  Volume 31, Issue 3, Page(s) 790–793

    MeSH term(s) Biomedical Research ; Database Management Systems
    Language English
    Publishing date 2023-12-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 1205156-1
    ISSN 1527-974X ; 1067-5027
    ISSN (online) 1527-974X
    ISSN 1067-5027
    DOI 10.1093/jamia/ocad227
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Evaluation of the drug-drug interaction potential of brigatinib using a physiologically-based pharmacokinetic modeling approach.

    Hanley, Michael J / Yeo, Karen Rowland / Tugnait, Meera / Iwasaki, Shinji / Narasimhan, Narayana / Zhang, Pingkuan / Venkatakrishnan, Karthik / Gupta, Neeraj

    CPT: pharmacometrics & systems pharmacology

    2024  Volume 13, Issue 4, Page(s) 624–637

    Abstract: Brigatinib is an oral anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive metastatic non-small cell lung cancer. In vitro studies indicated that brigatinib is primarily metabolized by CYP2C8 and CYP3A4 and inhibits P-gp, ...

    Abstract Brigatinib is an oral anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive metastatic non-small cell lung cancer. In vitro studies indicated that brigatinib is primarily metabolized by CYP2C8 and CYP3A4 and inhibits P-gp, BCRP, OCT1, MATE1, and MATE2K. Clinical drug-drug interaction (DDI) studies with the strong CYP3A inhibitor itraconazole or the strong CYP3A inducer rifampin demonstrated that CYP3A-mediated metabolism was the primary contributor to overall brigatinib clearance in humans. A physiologically-based pharmacokinetic (PBPK) model for brigatinib was developed to predict potential DDIs, including the effect of moderate CYP3A inhibitors or inducers on brigatinib pharmacokinetics (PK) and the effect of brigatinib on the PK of transporter substrates. The developed model was able to predict clinical DDIs with itraconazole (area under the plasma concentration-time curve from time 0 to infinity [AUC
    MeSH term(s) Humans ; Rifampin/pharmacokinetics ; Cytochrome P-450 CYP3A Inhibitors/pharmacology ; Itraconazole/pharmacology ; Cytochrome P-450 CYP3A/metabolism ; Carcinoma, Non-Small-Cell Lung ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Lung Neoplasms ; Neoplasm Proteins/metabolism ; Cytochrome P-450 CYP3A Inducers/pharmacokinetics ; Drug Interactions ; Membrane Transport Proteins ; Receptor Protein-Tyrosine Kinases/metabolism ; Models, Biological ; Organophosphorus Compounds ; Pyrimidines
    Chemical Substances Rifampin (VJT6J7R4TR) ; Cytochrome P-450 CYP3A Inhibitors ; brigatinib (HYW8DB273J) ; Itraconazole (304NUG5GF4) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Neoplasm Proteins ; Cytochrome P-450 CYP3A Inducers ; Membrane Transport Proteins ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Organophosphorus Compounds ; Pyrimidines
    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2697010-7
    ISSN 2163-8306 ; 2163-8306
    ISSN (online) 2163-8306
    ISSN 2163-8306
    DOI 10.1002/psp4.13106
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Clinical Pharmacology of Brigatinib: A Next-Generation Anaplastic Lymphoma Kinase Inhibitor.

    Gupta, Neeraj / Hanley, Michael J / Griffin, Robert J / Zhang, Pingkuan / Venkatakrishnan, Karthik / Sinha, Vikram

    Clinical pharmacokinetics

    2023  Volume 62, Issue 8, Page(s) 1063–1079

    Abstract: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor designed to overcome mechanisms of resistance associated with crizotinib, is approved for the treatment of ALK-positive advanced or metastatic non-small cell lung cancer. After oral ...

    Abstract Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor designed to overcome mechanisms of resistance associated with crizotinib, is approved for the treatment of ALK-positive advanced or metastatic non-small cell lung cancer. After oral administration of single doses of brigatinib 30-240 mg, the median time to reach maximum plasma concentration ranged from 1 to 4 h. In patients with advanced malignancies, brigatinib showed dose linearity over the dose range of 60-240 mg once daily. A high-fat meal had no clinically meaningful effect on systemic exposures of brigatinib (area under the plasma concentration-time curve); thus, brigatinib can be administered with or without food. In a population pharmacokinetic analysis, a three-compartment pharmacokinetic model with transit absorption compartments was found to adequately describe brigatinib pharmacokinetics. In addition, the population pharmacokinetic analyses showed that no dose adjustment is required based on body weight, age, race, sex, total bilirubin (< 1.5× upper limit of normal), and mild-to-moderate renal impairment. Data from dedicated phase I trials have indicated that no dose adjustment is required for patients with mild or moderate hepatic impairment, while a dose reduction of approximately 40% (e.g., from 180 to 120 mg) is recommended for patients with severe hepatic impairment, and a reduction of approximately 50% (e.g., from 180 to 90 mg) is recommended when administering brigatinib to patients with severe renal impairment. Brigatinib is primarily metabolized by cytochrome P450 (CYP) 3A, and results of clinical drug-drug interaction studies and physiologically based pharmacokinetic analyses have demonstrated that coadministration of strong or moderate CYP3A inhibitors or inducers with brigatinib should be avoided. If coadministration with a strong or moderate CYP3A inhibitor cannot be avoided, the dose of brigatinib should be reduced by approximately 50% (strong CYP3A inhibitor) or approximately 40% (moderate CYP3A inhibitor), respectively. Brigatinib is a weak inducer of CYP3A in vivo; data from a phase I drug-drug interaction study showed that coadministration of brigatinib 180 mg once daily reduced the oral midazolam area under the plasma concentration-time curve from time zero to infinity by approximately 26%. Brigatinib did not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6 at clinically relevant concentrations in vitro. Exposure-response analyses based on data from the ALTA (ALK in Lung Cancer Trial of AP26113) and ALTA-1L pivotal trials of brigatinib confirm the favorable benefit versus risk profile of the approved titration dosing regimen of 180 mg once daily (after a 7-day lead-in at 90 mg once daily).
    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Lung Neoplasms/drug therapy ; Anaplastic Lymphoma Kinase ; Cytochrome P-450 CYP3A Inhibitors/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances brigatinib (HYW8DB273J) ; Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; Cytochrome P-450 CYP3A Inhibitors ; Protein Kinase Inhibitors
    Language English
    Publishing date 2023-07-26
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 197627-8
    ISSN 1179-1926 ; 0312-5963
    ISSN (online) 1179-1926
    ISSN 0312-5963
    DOI 10.1007/s40262-023-01284-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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