Immunosuppressant quantification in intravenous microdialysate - towards novel quasi-continuous therapeutic drug monitoring in transplanted patients.

OBJECTIVES: Therapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA). METHODS: We analyzed the time course over 8 h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed. RESULTS: Using LC-MS/MS, the free concentrations of CsA (fCsA) and MPA (fMPA) were detectable and the time courses of total and free CsA comparable. fCsA and fMPA and area-under-the-curves (AUCs) in µDs correlated well with those determined in UCs (r≥0.79 and r≥0.88, respectively). Moreover, fCsA in µDs measured with the immunosensor correlated clearly with those determined by LC-MS/MS (r=0.82). CONCLUSIONS: The new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM.

Application of visible/NIR spectroscopy for the estimation of soluble solids, dry matter and flesh firmness in stone fruits.

BACKGROUND: Soluble solids concentration (SSC), dry matter concentration (DMC) and flesh firmness (FF) are important fruit quality parameters in stone fruits. This study investigated the ability of a commercial visible/near-infrared (NIR) spectrometer to determine SSC, DMC and FF in nectarine, peach, apricot and Japanese plum cultivars at harvest. The work was conducted in summer 2019/2020 on 14 stone fruit cultivars at Tatura, Australia. Two sub-samples of 100 fruit each were collected before and after commercial maturity (± 5 days) in order to maximize sample variability. RESULTS: Partial least square (PLS) regression models based on the second derivative of the absorbance in the 729-975 nm spectral region proved accurate for the prediction of SSC and DMC (R2 CV > 0.750). Only the model generated for SSC in 'Golden May' apricot was less precise compared to other cultivars. No visible/NIR models were accurate enough to predict FF in the cultivars under study (R2 CV < 0.750). CONCLUSION: This study demonstrated that the visible/NIR spectrometer was a reliable tool to monitor SSC and DMC in stone fruits at harvest but proved less useful for FF estimation. These results highlight the potential of visible/NIR spectrometry to evaluate stone fruit quality both in situ pre-harvest and in the laboratory after harvest. © 2020 Society of Chemical Industry.

Apoplasmic and simplasmic phloem unloading mechanisms: Do they co-exist in Angeleno plums under demanding environmental conditions?

Biophysical fruit growth depends on a balance among the vascular and transpiration flows entering/exiting the fruit via phloem, xylem and through the epidermis. There is no information on vascular flows of Japanese plums, a species characterized by high-sugar content of its fruit at harvest. Vascular flows of Angeleno plums were monitored by fruit gauges during late fruit development, under the dry environment of the Goulburn Valley, Victoria, Australia. Phloem, xylem flows and skin transpiratory losses were determined, as well as diurnal leaf, stem and fruit pressure potentials. Fruit seasonal development, skin conductance and dry matter accumulation were also monitored. Fruit grew following a double-sigmoid pattern, but fruit size increased only 3.1 g over the last 3 weeks of development. Fruit grew very little in the morning, primarily due to phloem inflows (0.05 g fruit-1hr-1), while water left the fruit via the xylem. Negligible skin transpiration was recorded for vapour pressure deficit (VPD) values below 3 kPa. This growth pattern, in the absence of skin transpiration, suggests apoplastic phloem unloading. However, at VPD values over 3 kPa (e.g. from early afternoon to a peak around 18:00 h), transpiratory losses through the skin (up to 0.25 g fruit-1hr-1) caused fruit to shrink, leading to enhanced phloem and xylem inflows (ca. 0.15 g fruit-1hr-1), a scenario that would correspond to symplastic phloem unloading. Over 24 h the fruit showed a slightly negative total growth, consistent with fruit growth measured in situ during the season at weekly intervals. A few fruit species are known to alter their phloem unloading mechanism, switching from symplastic to apoplastic during the season. Our data support the coexistence in Japanese plum of different phloem unloading strategies within the same day.

Improving access to colorectal cancer screening through medical philanthropy: feasibility of a flexible sigmoidoscopy health fair for uninsured patients.

OBJECTIVES: Only half of eligible patients in the United States undergo colorectal cancer (CRC) screening as recommended. Hypothesizing that the medical philanthropy platform may be effective in improving access to CRC screening, we aimed to demonstrate the feasibility of a flexible sigmoidoscopy (FS)-based CRC screening "health fair" for uninsured patients. METHODS: Uninsured patients older than 50 years who had not undergone CRC screening in the preceding 10 years were recruited through local free clinics and health fairs. A standard medical clinic was transformed into a fully functional endoscopy unit. Medicolegal protection for volunteers was obtained through the Florida Department of Health's Volunteer Health Care Provider Program. Unsedated FS with polypectomy was performed. Those with high-risk endoscopic features were given instructions on obtaining a full colonoscopy. RESULTS: Fifty-two patients without access to any form of CRC screening underwent FS. Ninety-four percent had an adequate bowel preparation, although 40% required on-site enema. Eighteen patients had a total of 22 polyps, 4 of which were adenomatous. There were no complications. The total cost of the fair, excluding donated resources such as endoscopes and processors, was $6,531.47, amounting to $126 per patient screened. CONCLUSIONS: Health fair-style CRC screening for uninsured patients is feasible. With improved efficiency, widespread application of CRC screening using the medical philanthropy platform may represent a viable approach to reducing the underuse of CRC screening among the uninsured.

Practicing effectively in today's health system: teaching systems-based care.

BACKGROUND AND OBJECTIVES: The Institute of Medicine and the new Accreditation Council for Graduate Medical Education General Essentials have focused attention on the Undergraduate Medical Education for the 21st Century (UME-21) core content area of systems-based care. Through teaching systems-based care, medical students can learn how physicians effectively deliver and coordinate care within the health system. While medical students can be introduced to the organization, financing, and delivery of the health care system through lectures, the principles and practice of systems-based care must be reinforced through structured learning experiences during the clinical (ie, third and fourth) years. The purpose of this article is to define the undergraduate clinical content and experiences in systems-based care offered by the eight UME-21 partner schools. METHODS: The eight partner UME-21 schools exposed third- and fourth-year medical students to a variety of clinical experiences outside the traditional teaching hospital in such settings as physician offices, skilled nursing facilities, the patient's home, hospice, and public health departments. They also taught systems-based care skills such as care coordination, performance assessment, and quality improvement. RESULTS: Based on surveys of graduating students, the UME-21 programs were successful in exposing students to the aforementioned topics, though there was variability among schools. DISCUSSION: The experiences of the UME-21 schools in teaching about systems-based care, as discussed in this paper, may be useful to those involved in medical school curricula planning.

A curriculum in systems-based care: experiential learning changes in student knowledge and attitudes.

BACKGROUND: To provide efficient, quality patient care, physicians must have a fundamental understanding of how the health care delivery system functions and how to appropriately use the various components of this system. As part of the Undergraduate Medical Education for the 21st Century (UME-21) initiative, the University of Miami in partnership with AvMed Health Plans, a nonprofit managed care organization (MCO) developed a longitudinal educational program that prepares all students for medical practice in emerging systems of care. METHODS: The program, which spans the 4-year undergraduate curriculum, incorporates didactic sessions and practical experiences to teach about the clinical, managerial, financial, and ethical aspects of systems-based care. During the third year of medical school, students visit the administrative offices of AvMed Health Plans for a day-long series of presentation-discussions and experiential tours through the various administrative departments. There, they experience first-hand all facets of a systems-based approach to care using evidence-based practice guidelines, utilization review, quality measurement and improvement, and chronic disease management. RESULTS: An attitudinal survey, constructed to evaluate general attitudes toward managing care and MCOs, was administered to students at the beginning of their first, second, and third year and immediately before and after their visit to AvMed during their third year. Using factor analysis, there were no significant differences in students' attitudes at the beginning of the first, second, or third year nor immediately before the seminar day at the MCO. However, the day-long seminar at AvMed did have a favorable effect on attitudes toward systems of care and MCOs in general. In addition, students performed well on post-evaluation knowledge assessments addressing fundamental concepts of systems of care and the function of an MCO in managing the care of its members. The visit to the MCOs (AvMed) offices and the day-long curriculum was replicated at another medical school, with similar effects on students' attitudes. CONCLUSIONS: Medical students have neutral-to-negative opinions of systems of care and MCOs. Early educational experiences such as classroom lectures and panels that address managing care issues have minimal effect on these opinions. However, bringing medical students to an MCO's administrative offices, seeing first-hand how systems of care operate, and having an open dialogue with physician administrators does effect a positive change in medical student opinions of a system in which care is managed. In addition, medical students can gain new knowledge about effective systems-based practice.