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Dipeptidyl peptidase-4 inhibitors (DPP4i) are a class of orally available, small molecule inhibitors for the management of Type-II diabetes. A rapid, real-time, functional breath test for DPP4 enzyme activity could help to define DPP4i efficacy in patients that are refractory to treatment. We aimed to develop a selective, non-invasive, stable-isotope 13C-breath test for DPP4. In vitro experiments were performed using high (Caco-2) and low (HeLa) DPP4 expressing cells. DPP gene expression was determined in cell lines by qRT-PCR. A DPP4 selective 13C-tripeptide was added to cells in the presence and absence of the DPP4 inhibitor Sitagliptin. Gas samples were collected from the cell headspace and 13CO2 content quantified by isotope ratio mass spectrometry (IRMS). DPP4 was highly expressed in Caco-2 cells compared to HeLa cells and using the 13C-tripeptide, we detected a high 13CO2 signal from Caco2 cells. Addition of Sitaglitpin to Caco2 cells significantly inhibited this 13CO2 signal. 13C-assay DPP4 activity correlated positively with the enzyme activity detected using a colorimetric substrate. We have developed a selective, non-invasive, 13C-assay for DPP4 that could have broad translational applications in diabetes and gastrointestinal disease.

Dipeptidyl peptidase-4 inhibitors (DPP4i) are a class of orally available, small molecule inhibitors for the management of Type-II diabetes. A rapid, real-time, functional breath test for DPP4 enzyme activity could help to define DPP4i efficacy in patients that are refractory to treatment. We aimed to develop a selective, non-invasive, stable-isotope 13C-breath test for DPP4. In vitro experiments were performed using high (Caco-2) and low (HeLa) DPP4 expressing cells. DPP gene expression was determined in cell lines by qRT-PCR. A DPP4 selective 13C-tripeptide was added to cells in the presence and absence of the DPP4 inhibitor Sitagliptin. Gas samples were collected from the cell headspace and 13CO2 content quantified by isotope ratio mass spectrometry (IRMS). DPP4 was highly expressed in Caco-2 cells compared to HeLa cells and using the 13C-tripeptide, we detected a high 13CO2 signal from Caco2 cells. Addition of Sitaglitpin to Caco2 cells significantly inhibited this 13CO2 signal. 13C-assay DPP4 activity correlated positively with the enzyme activity detected using a colorimetric substrate. We have developed a selective, non-invasive, 13C-assay for DPP4 that could have broad translational applications in diabetes and gastrointestinal disease.

To demonstrate how to use the value-based integrated case management Complexity Assessment Grid to develop a prioritized care plan. To use the developed care plan to assist and support individuals in reversing identified barriers to improvement and stabilizing health. To document clinical, functional, cost, satisfaction, and quality of life outcomes during integrated case management assistance and support. To prepare individuals and their clinicians for return to standard care—graduation. To report consolidated adult and pediatric outcomes for individuals and groups assisted through value-based integrated case management.

To describe the use of an individual value-based integrated case manager guided “dialogue” in performing relationship-based complexity assessments. To summarize the open-ended questions used to complete the guided dialogue. To discuss special question-asking procedures for children/youth and caregivers/parents in completing pediatric complexity assessments. To connect completed integrated case management assessments with multi-domain care plan development and the measurement of clinical, functional, health system, satisfaction, and quality of life outcomes. To explain documentation methodology in prioritizing care plan assistance, communication with clinicians and other care delivery stakeholders, outcome measurement, and case closure.

To describe the three primary goals in health care and the role of value-based integrated case management in achieving them. To describe the difference between the application of current case management models versus the value-based integrated case management model. To describe value-based integrated case management and the value-based integrated case management complexity assessment grid. To describe the use of the care plan and patient-centered integrated case management performance tool in documenting outcomes related to value-based integrated case management.

To develop comfort in talking about health behaviors, cognitive issues, and emotional problems in the context of physical disease and about physical illness in the context of behavioral health issues and disorders. To discuss how to include behavioral health and physical conditions during standard value-based integrated case management assessments. To review general characteristics about how to handle special medical, behavioral health, and pediatric situations as a value-based integrated case management manager. To describe the knowledge and skill base needed to integrate assistance for common physical and behavioral health conditions in value-based integrated case management.

To define “health complexity” and the importance of medical and “behavioral health” information in value-based, integrated case management. To describe the adverse interaction of physical and behavioral health disorders in adults/elderly and children/youth with health complexity. To discuss the difficulty in delivering concurrent and coordinated treatment for physical and behavioral health disorders and their impact on health and cost outcomes. To summarize the potential value of physical and behavioral health service integration and corresponding value-based integrated case management.

To review research on the effectiveness of motivational interviewing. To clarify the importance of strong initial and ongoing training in motivational interviewing. To define motivational interviewing processes and key skills in managing complex individuals.

To illustrate implementation of a value-based integrated case management complexity assessment using adult VP-ICM methodology for Lucinda. To connect complexity assessment findings to the development of a personal care plan. To demonstrate how to document care plan outcomes and to use the patient-centered ICM performance tool for recording participating individual and VB-ICM manager-based outcomes. To walk through the VB-ICM assistance and support process with Lucinda, including her graduation from VB-ICM and return to standard care.

To summarize needed “program” components for outcome-changing VB-ICM. To define value-based integrated case management training/certification for adult and pediatric professionals. To delineate case manager training course requirements—managers, manager assistants, educators/instructors. To describe the curriculum for adult and pediatric training. To provide an understanding about the objectives of value-based integrated case management training/certification.

To provide a high-level view of workplace preparation for delivery of value-based adult and pediatric integrated case management. To describe the personnel and training needed/required for effective delivery of value-based integrated case management. To review value-based integrated case management caseloads and caseload limits, including determination of the number and cost of case managers needed to support effective delivery. To define the interdisciplinary characteristics of value-based integrated case management, program goals, and the ultimate goals of patient stabilization and graduation. To discuss the potential return on investment of value-based integrated case management, if organized correctly.

To illustrate the use of integrated case management assessment and intervention in a child of 13. To highlight unique issues faced in working with children/youth and caregivers/parents in the pediatric setting. To use pediatric value-based integrated case management complexity assessment grid findings to develop a child/youth and family care plan. To document changes in health and function in children/youth on the pediatric care plan and the pediatric patient-centered integrated case management performance tool. To demonstrate how to move a child/youth and his/her caregivers/parents toward case management graduation.

To illustrate the effects of using value-based integrated case management complexity assessments and care plans while working with an individual employed by a large manufacturer. To practice connecting health complexity barriers to a care plan designed to reverse health- and life-related challenges affecting workplace performance. To illustrate the simplicity in documenting of health and life outcomes during performance of value-based integrated case management. To record Robert’s case outcomes in a grouped VB-ICM performance grid, which establishes value for the population served.

To provide a synopsis of the Physician’s Guide, i.e., the treating clinician and case management leadership introduction to value-based integrated case management, including key features, operational aspects, and expected outcomes. To appreciate the difference between Medical Directors of value-based integrated case management programs and treating clinicians with individuals participating in value-based integrated case management. To discuss the important process of working with value-based integrated case management Medical Directors in maximizing participating individual outcomes. To review how to work with treating clinicians of individuals agreeing to assistance and support by value-based integrated case managers. Value-based integrated case management in programs without Medical Directors or treating clinician involvement.

To provide an overview of the adult and pediatric value-based integrated case management-complexity assessment grids. To illustrate the application of complexity assessment grid rules in scoring adult and pediatric risk items as part of value-based integrated case management assessments. To discuss individual item complexity and total grid scores in the development of individualized care plans.

To put into context the role of cross-disciplinary health condition information gathering for use in value-based integrated case management. To illustrate assessment content needed for assistance to comorbid individuals with common behavioral health conditions. To illustrate assessments content needed for assistance to comorbid individuals with common chronic general medical disorders. To discuss utilization of gathered information in the development of clinical goals and actions.

To depict manager activities in value-based adult and pediatric integrated case management from initiation through graduation. To describe the value-based integrated case management team approach and the use of manager “pods” for assistance to individuals with health complexity. To outline needed value-based integrated case management training prior to the delivery of adult and pediatric value-based integrated case management. To summarize value-based integrated case management triage, prioritization, stratification, and enrollment procedures. To walk budding value-based integrated case management managers though the process of delivering outcome-changing assistance to complex individuals.

Oesophageal cancer is a significant cause of cancer related mortality, with increasing incidence worldwide. Ornithine decarboxylase (ODC) is an enzyme involved in polyamine synthesis and cellular proliferation, and ODC expression and activity has been implicated as a prognostic marker of oesophageal cancer. This study aimed to develop and optimise an in vitro (13)C-stable isotope assay for ODC activity as a non-invasive marker of oesophageal cancer. Experiments were performed in triplicate (n = 3/group/cell line) using Caco2, HeLa, Flo-1, OE33, TE7 and OE21 cell lines (colorectal, cervical, oesophageal adenocarcinoma and oesophageal squamous carcinoma respectively). Following addition of 2mM (13)C-ornithine to cells, 10 ml gas samples were collected from the headspace every 20 min for a total of five hours. Gas samples were analysed using isotope ratio mass spectrometry to quantify (13)CO2. Assay specificity was determined using the selective ODC inhibitor, N-(4'-Pyridoxil)-Ornithine(BOC)-OMe (POB). All data is expressed as δ (13)CO2 from baseline. High ODC activity was detected by (13)C-ornithine assay in Caco2 (32.00 ± 1.12 δ (13)CO2) in contrast to HeLa cells (5.44 ± 0.14 δ (13)CO2) cells. POB inhibited activity in Caco2 cells to 12.87 ± 1.10 δ (13)CO2. Differential ODC activity was detected in all oesophageal cancer cells, and 53 h incubation of cell lines with POB reduced activity by 72%, 56%, 64% and 69% in the Flo-1, OE33, OE21 and TE7 cell lines respectively. We have shown that ODC activity can be selectively detected by a non-invasive, stable-isotope (13)C-ornithine assay. ODC activity was detected in all oesophageal cancer cell lines in vitro. Further studies are indicated to quantify ODC activity in oesophageal cancer patients.