Author
Alexander A. Vinks
Other affiliations: Boston Children's Hospital, VU University Amsterdam, Hospital Research Foundation ...read more
Bio: Alexander A. Vinks is an academic researcher from Cincinnati Children's Hospital Medical Center. The author has contributed to research in topics: Population & Dosing. The author has an hindex of 46, co-authored 278 publications receiving 8186 citations. Previous affiliations of Alexander A. Vinks include Boston Children's Hospital & VU University Amsterdam.
Papers published on a yearly basis
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TL;DR: The challenges related to patients and pathogens that contribute to inadequate antibiotic dosing are explored and how to implement a process for individualised antibiotic therapy that increases the accuracy of dosing and optimises care for critically ill patients is discussed.
Abstract: Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in suboptimum outcomes. In this Review, we explore the challenges related to patients and pathogens that contribute to inadequate antibiotic dosing and discuss how to implement a process for individualised antibiotic therapy that increases the accuracy of dosing and optimises care for critically ill patients. To improve antibiotic dosing, any physiological changes in patients that could alter antibiotic concentrations should first be established; such changes include altered fluid status, changes in serum albumin concentrations and renal and hepatic function, and microvascular failure. Second, antibiotic susceptibility of pathogens should be confirmed with microbiological techniques. Data for bacterial susceptibility could then be combined with measured data for antibiotic concentrations (when available) in clinical dosing software, which uses pharmacokinetic/pharmacodynamic derived models from critically ill patients to predict accurately the dosing needs for individual patients. Individualisation of dosing could optimise antibiotic exposure and maximise effectiveness.
707 citations
TL;DR: Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies and clinical activity was reported in the majority of the disorders.
Abstract: BACKGROUND AND OBJECTIVES: Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days. METHODS: Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m 2 per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection - related deaths. RESULTS: Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred. CONCLUSIONS: Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.
543 citations
TL;DR: Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation as discussed by the authors, however, individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacromin as compared with those who are CYP 3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations.
Abstract: Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).
418 citations
01 Jul 2015
TL;DR: Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose‐adjusted trough concentrations of tacrolimus as compared with those who are CYP 3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations.
Abstract: Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose‐adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).
352 citations
University of Barcelona1, Erasmus University Rotterdam2, Oslo University Hospital3, Université catholique de Louvain4, Cliniques Universitaires Saint-Luc5, Mayo Clinic6, French Institute of Health and Medical Research7, University of Limoges8, Synlab Group9, University of Cincinnati Academic Health Center10, Cincinnati Children's Hospital Medical Center11, Charité12, Leipzig University13, University of Utah14, Medical University of Warsaw15, St George's Hospital16, Kyushu University17, Christian Medical College & Hospital18, Leiden University Medical Center19, Erasmus University Medical Center20, Heidelberg University21, University of Colorado Denver22
TL;DR: It is concluded that considerable advances in the different fields of tacrolimus monitoring have been achieved during this last decade, and the Expert Committee concludes that Continued efforts should focus on the opportunities to implement in clinical routine the combination of new standardized PK approaches with PG, and valid biomarkers to further personalize tacolimus therapy and to improve long-term outcomes for treated patients.
Abstract: Ten years ago, a consensus report on the optimization of tacrolimus was published in this journal. In 2017, the Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicity (IATDMCT) decided to issue an updated consensus report considering the most relevant advances in tacrolimus pharmacokinetics (PK), pharmacogenetics (PG), pharmacodynamics, and immunologic biomarkers, with the aim to provide analytical and drug-exposure recommendations to assist TDM professionals and clinicians to individualize tacrolimus TDM and treatment. The consensus is based on in-depth literature searches regarding each topic that is addressed in this document. Thirty-seven international experts in the field of TDM of tacrolimus as well as its PG and biomarkers contributed to the drafting of sections most relevant for their expertise. Whenever applicable, the quality of evidence and the strength of recommendations were graded according to a published grading guide. After iterated editing, the final version of the complete document was approved by all authors. For each category of solid organ and stem cell transplantation, the current state of PK monitoring is discussed and the specific targets of tacrolimus trough concentrations (predose sample C0) are presented for subgroups of patients along with the grading of these recommendations. In addition, tacrolimus area under the concentration-time curve determination is proposed as the best TDM option early after transplantation, at the time of immunosuppression minimization, for special populations, and specific clinical situations. For indications other than transplantation, the potentially effective tacrolimus concentrations in systemic treatment are discussed without formal grading. The importance of consistency, calibration, proficiency testing, and the requirement for standardization and need for traceability and reference materials is highlighted. The status for alternative approaches for tacrolimus TDM is presented including dried blood spots, volumetric absorptive microsampling, and the development of intracellular measurements of tacrolimus. The association between CYP3A5 genotype and tacrolimus dose requirement is consistent (Grading A I). So far, pharmacodynamic and immunologic biomarkers have not entered routine monitoring, but determination of residual nuclear factor of activated T cells-regulated gene expression supports the identification of renal transplant recipients at risk of rejection, infections, and malignancy (B II). In addition, monitoring intracellular T-cell IFN-g production can help to identify kidney and liver transplant recipients at high risk of acute rejection (B II) and select good candidates for immunosuppression minimization (B II). Although cell-free DNA seems a promising biomarker of acute donor injury and to assess the minimally effective C0 of tacrolimus, multicenter prospective interventional studies are required to better evaluate its clinical utility in solid organ transplantation. Population PK models including CYP3A5 and CYP3A4 genotypes will be considered to guide initial tacrolimus dosing. Future studies should investigate the clinical benefit of time-to-event models to better evaluate biomarkers as predictive of personal response, the risk of rejection, and graft outcome. The Expert Committee concludes that considerable advances in the different fields of tacrolimus monitoring have been achieved during this last decade. Continued efforts should focus on the opportunities to implement in clinical routine the combination of new standardized PK approaches with PG, and valid biomarkers to further personalize tacrolimus therapy and to improve long-term outcomes for treated patients.
338 citations
Cited by
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St George's Hospital1, New York University2, McMaster University3, Brown University4, Catholic University of the Sacred Heart5, Hebron University6, University of Manitoba7, Emory University Hospital8, Hebrew University of Jerusalem9, Sunnybrook Health Sciences Centre10, University of Pittsburgh11, Saint Thomas - West Hospital12, University College London13, Vanderbilt University Medical Center14, Keio University15, Memorial Hospital of South Bend16, Cooper University Hospital17, University of Mississippi Medical Center18, Rush University Medical Center19, University of Ulsan20, Federal University of São Paulo21, Regions Hospital22, St. Michael's Hospital23, Washington University in St. Louis24, Ottawa Hospital25, University of Sydney26, Mount Sinai Hospital27, University of New South Wales28, Fujita Health University29, Christiana Care Health System30, Stanford University31, King Abdullah University of Science and Technology32, University of Kansas33, Harvard University34, California Pacific Medical Center35, University of Amsterdam36, Houston Methodist Hospital37
TL;DR: Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
Abstract: To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
4,303 citations
TL;DR: Recent progress on drug metabolism activity profiles, interindividual variability and regulation of expression, and the functional and clinical impact of genetic variation in drug metabolizing P450s are reviewed.
2,832 citations
St George’s University Hospitals NHS Foundation Trust1, New York University2, McMaster University3, Brown University4, Catholic University of the Sacred Heart5, Autonomous University of Barcelona6, University of Manitoba7, Emory University8, Hebrew University of Jerusalem9, University of Toronto10, University of Pittsburgh11, St Thomas' Hospital12, University College London13, Vanderbilt University14, Keio University15, Memorial Hospital of South Bend16, Rowan University17, University of Mississippi18, Rush University Medical Center19, University of Ulsan20, Universidade Federal do Rio Grande do Sul21, Federal University of São Paulo22, Regions Hospital23, Washington University in St. Louis24, University of Ottawa25, University of Sydney26, University of New South Wales27, Fujita Health University28, University of Copenhagen29, Sapienza University of Rome30, Christiana Care Health System31, Stanford University32, King Abdullah University of Science and Technology33, University of Kansas34, Harvard University35, California Pacific Medical Center36, University of Amsterdam37, Université libre de Bruxelles38, Houston Methodist Hospital39
TL;DR: A consensus committee of 55 international experts representing 25 international organizations was assembled at key international meetings (forSurviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012 as discussed by the authors ).
Abstract: Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for
2,414 citations
University of Nebraska Medical Center1, University of Connecticut2, Harvard University3, Queen's University4, University of California, San Diego5, Stony Brook University6, University of Michigan7, National Institutes of Health8, Johns Hopkins University9, University of Barcelona10, University at Buffalo11, Summa Health System12, University of Texas Health Science Center at San Antonio13, University of Queensland14, Royal Brisbane and Women's Hospital15, University of Western Australia16, University of Colorado Denver17, McMaster University18
TL;DR: These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia.
Abstract: It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
2,359 citations
Patent•
30 Oct 2007
TL;DR: An analyte monitor includes a sensor, a sensor control unit, and a display unit as discussed by the authors, which is used to display an indication of a level of an analyte, based on the data obtained using the sensor.
Abstract: An analyte monitor includes a sensor, a sensor control unit, and a display unit. The sensor has, for example, a substrate, a recessed channel formed in the substrate, and conductive material disposed in the recessed channel to form a working electrode. The sensor control unit typically has a housing adapted for placement on skin and is adapted to receive a portion of an electrochemical sensor. The sensor control unit also includes two or more conductive contacts disposed on the housing and configured for coupling to two or more contact pads on the sensor. A transmitter is disposed in the housing and coupled to the plurality of conductive contacts for transmitting data obtained using the sensor. The display unit has a receiver for receiving data transmitted by the transmitter of the sensor control unit and a display coupled to the receiver for displaying an indication of a level of an analyte. The analyte monitor may also be part of a drug delivery system to alter the level of the analyte based on the data obtained using the sensor.
1,856 citations