Dynamical phenotyping: using temporal analysis of clinically collected physiologic data to stratify populations.

Using glucose time series data from a well measured population drawn from an electronic health record (EHR) repository, the variation in predictability of glucose values quantified by the time-delayed mutual information (TDMI) was explained using a mechanistic endocrine model and manual and automated review of written patient records. The results suggest that predictability of glucose varies with health state where the relationship (e.g., linear or inverse) depends on the source of the acuity. It was found that on a fine scale in parameter variation, the less insulin required to process glucose, a condition that correlates with good health, the more predictable glucose values were. Nevertheless, the most powerful effect on predictability in the EHR subpopulation was the presence or absence of variation in health state, specifically, in- and out-of-control glucose versus in-control glucose. Both of these results are clinically and scientifically relevant because the magnitude of glucose is the most commonly used indicator of health as opposed to glucose dynamics, thus providing for a connection between a mechanistic endocrine model and direct insight to human health via clinically collected data.

Association between cholesterols, homocysteine and silent brain infarcts.

BACKGROUND: The aim of this study was to assess the relationship between total plasma homocysteine, cholesterol levels, vitamin B(12), folate, thyroid hormones, urea, ferritin, uric acid, C-reactive protein, cardiovascular risk factors and silent brain infarct (SBI) in patients without any neurological disorder. Whether the factors of interest were associated with SBI is investigated. METHODS: One hundred and forty-two subjects with a mean age of 52.1 +/- 13.1 years (21-87 years) without any history of stroke, transient ischaemic attack and neurological abnormality were enrolled in this cross-sectional study. The subjects underwent brain magnetic resonance imaging and blood chemistry determinations. Student's t-test was used to compare differences in means of laboratory results between the groups with and without SBI. The chi(2)-test was used for categorized variables. Multiple logistic regression analysis was used to determine the independent predictors of SBI. RESULTS: The group comprised 56 men and 86 women. SBI were found in 40 patients (28%). The low-density lipoprotein levels were significantly higher in the infarct group (P = 0.019), homocysteine concentrations were significantly higher in the men-infarct group (P = 0,029) and total cholesterol levels were significantly higher in the women-infarct group than the women non-infarct group (P = 0.006). CONCLUSION: Serum low-density lipoprotein, total cholesterol and homocysteine levels were associated with SBI.

Is laparotomy necessary in the diagnosis of fever of unknown origin?

Fever of unknown origin (FUO) is a diagnostic challenge for the practising physician. Detailed medical history, physical examination, non-invasive laboratory tests, and radiologic examinations compose the first level in the diagnostic approach to the FUO. When a diagnosis cannot be established with these procedures, some invasive diagnostic techniques and finally exploratory laparotomy are performed. Although advanced diagnostic measures and imaging-guided less invasive procedures have decreased the need, laparotomy remains as a final diagnostic method for FUO cases. In this study we evaluate the role and importance of laparotomy in the diagnosis of our FUO cases. In 17 out of 126 patients (8 male, 9 female, the median age 35.8 years) hospitalized in our clinic between 1982 and 2002 with the diagnosis of FUO, the diagnosis was established by laparotomy. The diagnosis was made directly in 13 patients, and indirectly (by excluding other diseases) in 2 patients. In several FUO series, the contribution of laparotomy to the diagnosis of FUO was reported as 27-100%. This rate was found to be 88% in the present study. During laparotomy on 17 cases, tissue samples were taken from spleen, liver, intra-abdominal and mesenteric lymph nodes. Pathologic examination of these tissue samples revealed miliary tuberculosis in 4; non-Hodgkin's lymphoma in 3; Hodgkin's lymphoma in 3; liver tumour in 1; hairy cell leukemia in 1; peritonitis carcinomatosis in 1. In the patients with miliary tuberculosis, the liver (3) and/or spleen (2), and/or lymph node (3) revealed caseating granulomas. Laparotomy diagnosed 3 of 5 cases whose abdominal ultrasonography and computerized tomography were normal. In conclusion, although advanced diagnostic methods decreased the need for laparotomy in FUO, if non-invasive and invasive diagnostic measures fail, laparotomy may contribute to the diagnosis. The selection of the patient and the timing are important for laparotomy.

Hamiltonian formalism and the Garrett-Munk spectrum of internal waves in the ocean.

Wave turbulence formalism for long internal waves in a stratified fluid is developed, based on a natural Hamiltonian description. A kinetic equation appropriate for the description of spectral energy transfer is derived, and its anisotropic self-similar stationary solution corresponding to a direct cascade of energy toward the short scales is found. This solution is very close to the high wave-number limit of the Garrett-Munk spectrum of long internal waves in the ocean. In fact, a small modification of the Garrett-Munk formalism includes a spectrum consistent with the one predicted by wave turbulence.

Near-field coherent spectroscopy and microscopy of a quantum dot system.

We combined coherent nonlinear optical spectroscopy with nano-electron volt energy resolution and low-temperature near-field microscopy with subwavelength resolution (

Spectral bifurcations in dispersive wave turbulence.

Dispersive wave turbulence is studied numerically for a class of one-dimensional nonlinear wave equations. Both deterministic and random (white noise in time) forcings are studied. Four distinct stable spectra are observed-the direct and inverse cascades of weak turbulence (WT) theory, thermal equilibrium, and a fourth spectrum (MMT; Majda, McLaughlin, Tabak). Each spectrum can describe long-time behavior, and each can be only metastable (with quite diverse lifetimes)-depending on details of nonlinearity, forcing, and dissipation. Cases of a long-live MMT transient state dcaying to a state with WT spectra, and vice-versa, are displayed. In the case of freely decaying turbulence, without forcing, both cascades of weak turbulence are observed. These WT states constitute the clearest and most striking numerical observations of WT spectra to date-over four decades of energy, and three decades of spatial, scales. Numerical experiments that study details of the composition, coexistence, and transition between spectra are then discussed, including: (i) for deterministic forcing, sharp distinctions between focusing and defocusing nonlinearities, including the role of long wavelength instabilities, localized coherent structures, and chaotic behavior; (ii) the role of energy growth in time to monitor the selection of MMT or WT spectra; (iii) a second manifestation of the MMT spectrum as it describes a self-similar evolution of the wave, without temporal averaging; (iv) coherent structures and the evolution of the direct and inverse cascades; and (v) nonlocality (in k-space) in the transferral process.

Counseling patients about prescribed medication: 12-year trends.

OBJECTIVES: The authors determined patients' report of prescription drug counseling activities after withdrawal of the pilot program to require patient package inserts in 1980 and implementation of Omnibus Budget Reconciliation Act of 1990 counseling requirements in 1993. METHODS: Four cross-sectional national telephone surveys were conducted in the fall of 1982, 1984, 1992, and 1994. Telephone households were chosen by random-digit dialing. Subjects had obtained a new prescription for themselves or for a family member at a retail pharmacy during the previous 4 weeks. Verbal counseling rates at physician offices and pharmacies for five information categories and the distribution of written information at those locations were determined. RESULTS: Spontaneous verbal counseling at the physician's office has increased slightly, with the largest increases focused on the delivery of side effect and precautionary information. Slightly larger increases in pharmacy-delivered information regarding directions for use and precautions have occurred. Patient questioning has remained at single digit levels at both sites. The percentage of patients receiving any written information has increased from 5% to 15% at the physician's office and from 16% to 59% at the pharmacy. CONCLUSIONS: The data indicate small increases in verbal counseling but larger increases in the delivery of written information provided at the pharmacy. In light of Healthy People: 2000 goals for patient counseling and legislation encouraging private-sector initiatives, these data should help to refocus attention on the continuing need for effective patient education interventions.

Characteristics of controlled studies of patient education and counseling for preventive health behaviors.

To determine characteristics of controlled studies (quasi-experimental and randomized) of clinical patient education/counseling for behavior change to prevent disease, we conducted an extensive literature review of published and unpublished studies from 1971 to 1989. Sixty-four studies with 101 intervention groups met specific criteria for relevance and scientific acceptability. We examine these studies in terms of prevention area, subject source, intervention characteristics, and use of educational principles. Findings reveal many controlled clinical studies in smoking cessation, nutrition, and weight control but sparcity in other areas (injury prevention, exercise, stress, drug and alcohol misuse, STD prevention); an emphasis on communication by a single clinical practitioner; and varied use of educational principles. We recommend adhering to educational principles to enhance likelihood of success.

Definition and yield of inclusion criteria for a meta-analysis of patient education studies in clinical preventive services.

Because selection of studies for a literature review influences conclusions, inclusion criteria are of utmost importance. For a meta-analysis of studies testing effects of patient education on preventive behaviors, we present the framework and concepts used for setting inclusion criteria for primary studies. We also present the yield in terms of number and distribution of studies that resulted from the inclusion criteria. Because we were interested in a diverse range of behaviors and a broad definition of patient education, we present a method for grouping behaviors by type of behavior change and describe parameters for subgrouping interventions by orientation and communication channel. Of 5,451 citations located and abstracts screened, 561 citations reporting potentially relevant studies were reviewed. Based on our inclusion criteria, 171 citations contained relevant studies, of which 64 studies (found in 62 citations) also met our acceptability criteria. We examine the effects of alternate inclusion criteria on the yield of primary studies and their distributions across the subgroupings.

Improving disclosure of smoking by pregnant women.

Smoking is a major modifiable risk factor in pregnancy, and low-cost interventions have been developed and tested in diverse populations of pregnant smokers. Successful intervention depends on identification, however, and nondisclosure can be a problem. This randomized study compared rates of disclosure with two response formats--multiple choice, in which the patient is able to describe herself as having "cut down," and the usual history question, "Do you smoke?," in which she is forced to answer simply "yes" or "no". Each format was tested in both oral and written channels with a multiethnic adult prenatal population (n = 1078) entering care in a multispecialty group. Study results indicate that the multiple choice question improved disclosure, regardless of channel (oral versus written), by 40%. This effect was observed across racial and ethnic groups. Biochemical tests of urine samples from reported nonsmokers indicated smoking in only 3%. Eleven percent of the "nonsmokers" in the experimental groups refused consent for the urine test, however, and many of these were probably smokers.

Patterns of counseling techniques used by family practice physicians for smoking, weight, exercise, and stress.

Members of the American Academy of Family Physicians (nonfederal, continental U.S.) were surveyed regarding their involvement in health-habit modification (response rate = 70.4%, n = 903). Frequency and indications for use of specific counseling techniques were assessed in each of four health-habit areas: smoking, exercise, weight control, and stress management. Factor analysis of responses produced clusters of techniques labeled "traditional teaching," "behavioral," "interpersonal with follow-up," and "referral." The dominant style varied by health-habit area. The factors were less clear for stress than for the other three areas. Results indicated no relationships or weak relationships between counseling approaches and physician gender, year of graduation, board status, region, community size, practice type, average visit length, and selected patient characteristics. Study findings suggest that family physician counseling varies with the health habit and that background and practice variables are not associated with counseling approach.

Encouraging patient question-asking: a clinical trial.

Increases in patient participation in medical interactions have been achieved to date using structured waiting-room interviews. In this pilot study, a printed intervention was tested as an inexpensive alternative with potential for wider dissemination. Sixty-seven family medicine patients were assigned randomly to one to two educational conditions just prior to their medical visit: a treatment booklet stressing the importance of recognizing information needs and encouraging patients to ask questions; or a placebo education booklet similar in format but not in content. The patient-physician interactions were audiotaped to determine the number of questions patients asked, and a questionnaire was administered after each encounter to assess patient satisfaction with care. The mean numbers of questions asked in the experimental and control groups were 7.46 and 5.63, respectively; the mean difference of 1.83 questions was statistically non-significant (P greater than 0.05). Question-asking did not correlate with reported satisfaction. Suggestions for modification to this research approach are presented.

Effectiveness of the AHEC concept in Colorado.

The SEARCH program (Colorado's area health education program) is designed to alleviate the maldistribution in health manpower by recruiting new professionals to underserved areas through student/resident rotations and to retain those professionals already there by providing accessible continuing education. Data obtained on SEARCH during the first two years of operation are encouraging. Nearly 75 percent of rural physicians practicing in self-assessed areas of need wanted contact with medical students, and the number of University of Colorado medical graduates taking residencies in Colorado increased dramatically. The retention rate of physicians in Colorado was 97.2 percent during this two-year period for those physicians serving as medical student preceptors, whereas it would have been expected to be 83.5 percent based on 1979 data.