Paul E. Knudson

Columbia University's Informatics for Diabetes Education and Telemedicine (IDEATel) Project: rationale and design.

The Columbia University Informatics for Diabetes Education and Telemedicine (IDEATel) Project is a four-year demonstration project funded by the Centers for Medicare and Medicaid Services with the overall goals of evaluating the feasibility, acceptability, effectiveness, and cost-effectiveness of telemedicine in the management of older patients with diabetes. The study is designed as a randomized controlled trial and is being conducted by a state-wide consortium in New York. Eligibility requires that participants have diabetes, are Medicare beneficiaries, and reside in federally designated medically underserved areas. A total of 1,500 participants will be randomized, half in New York City and half in other areas of the state. Intervention participants receive a home telemedicine unit that provides synchronous videoconferencing with a project-based nurse, electronic transmission of home fingerstick glucose and blood pressure data, and Web access to a project Web site. End points include glycosylated hemoglobin, blood pressure, and lipid levels; patient satisfaction; health care service utilization; and costs. The project is intended to provide data to help inform regulatory and reimbursement policies for electronically delivered health care services.

Comparison of palpation-guided versus ultrasound-guided fine-needle aspiration biopsies of thyroid nodules in an outpatient endocrinology practice.

OBJECTIVE To investigate the role of thyroid ultrasonography in our outpatient endocrine practice. METHODS We compared the efficacy of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) of thyroid nodules with that of palpation-guided aspiration (P-FNAB) and determined the malignancy rates of palpable and nonpalpable nodules. All patients referred for assessment of thyroid nodular disease from October 1997 through August 2001 were included in the study. Fine-needle aspirations were performed by palpation guidance until October 1999, after which US-FNAB was exclusively performed. All thyroid examinations, ultrasound imaging, and aspiration biopsies were performed by the same endocrinologist in an office-based setting. Histopathologic and cytologic diagnoses were compared for patients who underwent thyroidectomy. RESULTS A total of 376 nodules in 276 patients were aspirated during a 47-month period. P-FNAB was used on 157 nodules, and US-FNAB was performed on 219 nodules (both procedures were done on 21 nodules). For palpable thyroid nodules that were resected, the cytologic diagnostic accuracy rate was 60.9% and 80% for P-FNAB and US-FNAB, respectively. With use of ultrasound guidance, the sensitivity, positive predictive value, and negative predictive value increased significantly. In addition, the inadequate specimen rate decreased from 11.2% in the P-FNAB group to 7.1% in the US-FNAB group. Among the nodules that were not palpable, the malignancy rate was similar to that for the palpable thyroid nodules (5.1% versus 6.8%). CONCLUSION US-FNAB improved the cytologic diagnostic accuracy, sensitivity, and positive predictive value and reduced the false-negative rate in comparison with P-FNAB. The malignancy rate for nonpalpable thyroid nodules was similar to that for palpable nodules.

Effect of hemoglobin concentration variation on the accuracy and precision of glucose analysis using tissue modulated, noninvasive, in vivo Raman spectroscopy of human blood: a small clinical study

Tissue modulated Raman spectroscopy was used noninvasively to measure blood glucose concentration in people with type I and type II diabetes with HemoCue fingerstick measurements being used as reference. Including all of the 49 measurements, a Clarke error grid analysis of the noninvasive measurements showed that 72% were A range, i.e., clinically accurate, 20% were B range, i.e., clinically benign, with the remaining 8% of measurements being essentially erroneous, i.e., C, D, or E range. Rejection of 11 outliers gave a correlation coefficient of 0.80, a standard deviation of 22 mg/dL with p<0.0001 for N=38 and places all but one of the measurements in the A and B ranges. The distribution of deviations of the noninvasive glucose measurements from the fingerstick glucose measurements is consistent with the suggestion that there are at least two systematic components in addition to the random noise associated with shot noise, charge coupled device spiking, and human factors. One component is consistent with the known variation of fingerstick glucose concentration measurements from laboratory reference measurements made using plasma or whole blood. A weak but significant correlation between the deviations of noninvasive measurements from fingerstick glucose measurements and the test subjects hemoglobin concentration was also observed.

Progress in the noninvasive in-vivo tissue-modulated Raman spectroscopy of human blood

We have recently presented the first Raman spectra of in vivo human blood. A brief review of how to obtain such spectra and normalize them to the appropriate blood volume is given showing how to produce spectra that can be used for noninvasive quantitative analysis of blood in vivo. New clinical data from individuals and groups completely reproduce and extend all the earlier results. These new data reveal how certain small differences between individuals result in some variability in their noninvasive quantitation. We show the origin of this variability and how to obtain quantitative corrections based entirely on the individual measurement and tabulated data.

Medical data on demand with WebMIA

This article focuses on the creation of a system for managing and archiving large-scale medical data. Specifically, this case study demonstrates the new paradigm through the prototype system WebMIA. The system enables storage, maintenance, sharing, updating, and retrieval of medical files based on the existing Internet facilities and the state-of-the-art literature in medical image indexing and multimedia information presentation. It also incorporates our current research in image retrieval and multimodal medical image fusion. It surpasses the existing systems in the commercial and research sectors as it provides convenient, efficient, effective, and flexible online processing, annotation, and multimodal querying capabilities in one forum. The patient confidentiality issue is well addressed when the sharing of the medical information is provided. This technology will assist medical practitioners/researchers by enabling efficient management and sharing of medical files within or across a community, without being subject to geographical restrictions an d without creating the problems of inconsistent and fragmented medical data.

Noninvasive blood analysis by tissue-modulated NIR Raman spectroscopy

We present tissue modulated Raman spectroscopy as a technique for noninvasively measuring the concentration of blood analytes in vivo. We present preliminary data used to determine the best methods for analyzing our data. These experiments provide additional proof that we are indeed able to obtain the spectra of human blood in vivo and noninvasively. We discuss differences between our spectra and spectra of bulk blood in vitro. We also discuss the variations between individuals and the impact of those variations on our noninvasive blood glucose measurements.

Immune Checkpoint Inhibitor-Associated Type 1 Diabetes Mellitus: Case Series, Review of the Literature, and Optimal Management

With the introduction of immune checkpoint inhibitors into clinical practice, various autoimmune toxicities have been described. Antibodies targeting the receptor:ligand pairing of programmed death receptor-1 (PD-1) and its cognate ligand programmed death-ligand 1 (PD-L1) in rare reports have been associated with autoimmune diabetes mellitus. We report 2 cases of rapid-onset, insulin-dependent, type 1 diabetes mellitus in the setting of administration of nivolumab, a fully human monoclonal antibody to PD-1, and atezolizumab, a humanized monoclonal antibody to PD-L1. This appears to be the first report of autoimmune diabetes mellitus associated with atezolizumab. In addition, we provide a brief review of similar cases reported in the literature and a discussion of potential mechanisms for this phenomenon and propose a diagnostic and treatment algorithm.

CENTRAL DIABETES INSIPIDUS DUE TO HERPES SIMPLEX IN A PATIENT IMMUNOSUPPRESSED BY CUSHING'S SYNDROME

OBJECTIVE To describe a patient immunocompromised by Cushings syndrome in whom central diabetes insipidus developed as a complication of herpes simplex involvement of the hypothalamus. METHODS We present a case, including results of laboratory and histopathologic studies, in which herpes simplex was established as the causative agent for central diabetes insipidus. RESULTS A woman with ectopic corticotropin-dependent Cushings syndrome, diabetes mellitus, carcinoid tumor, and a history of thyroid cancer had the precipitous onset of seizure and fever, and hypotonic polyuria and progressive hypernatremia developed. Central diabetes insipidus was diagnosed and successfully treated with desmopressin. Nevertheless, the patients condition deteriorated and she died. Autopsy revealed herpes simplex encephalitis involving the magnicellular neurons of the hypothalamus. CONCLUSION Central diabetes insipidus caused by viral infections has been reported in immunosuppressed patients, such as those with acquired immunodeficiency syndrome (AIDS). To our knowledge, this is the first report of a herpes infection causing diabetes insipidus in a patient immunosuppressed by Cushings syndrome. This case demonstrates that, in patients with Cushings syndrome, diabetes insipidus may develop as a result of herpes simplex infection of the hypothalamus.

Noninvasive in-vivo tissue-modulated Raman spectroscopy of human blood: microcirculation and viscosity effects

We recently presented the first Raman spectra of in vivo human blood. A brief review of how to obtain such spectra and then normalize them to the appropriate blood volume is given showing how to produce spectra that can be used for noninvasive quantitative analysis of blood in vivo. A more careful comparison of tissue modulated spectra with static in vitro and invasive in vivo spectra suggests that there are small microcirculation differences between individuals resulting in some variability in their noninvasive quantitation. This variability is based on the mechanism for blood volume normalization and various means for obtaining necessary corrections are suggested. We present new clinical data from individuals and groups supporting this mechanism and suggesting how such measurements might also be used to quantify various microcirculation abnormalities.

A Device for Noninvasive Assessment of Vascular Impairment Risk in the Lower Extremity

The repeatability and resolution of the clinical gold standard of vascular assessment, the ankle-brachial index (ABI), was compared to that of a new device that dynamically assesses tissue perfusion during external loading utilizing laser Doppler flowmetry. Eight subjects of varying levels of vascular impairment were tested in successive weeks using two different sites on the subjects posterior calf. These new measures included the perfusion decrease as well as the unloading delay during cyclic loading. Some new dynamic tissue perfusion measures demonstrated comparable levels of reproducibility with the ABI (e.g., 10%-20%). Only the unloading delay showed potentially enhanced resolution over ABI measures. The perfusion decrease showed little resolution, and the remaining parameters exhibited too great variability (25%-90%). The unloading delay associated with the reperfusion response during cyclic loading displayed the greatest combination of reproducibility and differentiation between subject groups of varying levels of vascular impairment. The preliminary results of this pilot study were also used to estimate sample sizes necessary to detect possible significant (P<0.05) differences between subject groups for all measured perfusion parameters. From these calculations, at least 30 subjects are needed for future study in each of the five subject groups.