A pragmatic digital health informatics based approach for aiding clinical prioritisation and reducing backlog of care: A study in cohort of 4022 people with diabetes.

BACKGROUND AND AIMS: The backlog of care in resource stretched healthcare systems requires innovative approaches to aid clinical prioritisation. Our aim was to develop an informatics tool to identify and prioritise people with diabetes who are likely to deteriorate whilst awaiting an appointment to optimise clinical outcomes and resources. MATERIALS AND METHODS: Using data from electronic health care records we identified 6 risk-factors that could be addressed in 4022 people (52% male, 30% non-Caucasian) with diabetes attending a large university hospital in London. The risk-factors were new clinical events/data occurring since their last routine clinic visit. To validate and compare data-led prioritisation tool to a traditional 'clinical approach' a sample of 450 patients were evaluated. RESULTS: Of the 4022 people, 549 (13.6%) were identified as having one or more risk events/factors. People with risk were more likely to be non-Caucasian and had greater socio-economic deprivation. Taking clinical prioritisation as the gold standard, informatics tool identified high risk patients with a sensitivity of 83% and lower risk patients with a specificity of 81%. An operational pilot pathway over 3 months using this approach demonstrated in 101 high risk people that 40% received interventions/care optimisation to prevent deterioration in health. CONCLUSION: A pragmatic data-driven method identifies people with diabetes at highest need for clinical prioritisation within restricted resources. Health informatics systems such as our can enhance care and improve operational efficiency and better healthcare delivery for people with diabetes.

Comparison of two types of casting in early-onset scoliosis.

Early-onset scoliosis (EOS) can be a progressive and debilitating condition if left untreated. Different casting techniques have fallen in and out of favor over the years for conservative management. Two types of casting, elongation-derotation-flexion (EDF) and body casting (BC) are employed at our institution. Here we compare the radiographic outcomes between these two types of casting in a cohort of patients diagnosed with EOS. Sixteen children with EOS were treated by EDF serial casting while seventeen children with the same diagnosis were treated by BC. Radiographic measurements included Cobb angle, rib-vertebral-angle difference (RVAD) and vertebral rotation (VR) by Nash-Moe method in casting (IC) or out of casting (OOC), thoracic height (TH) and width (TW). All of the patients had x-ray measurements at pre-casting OOC, 1st IC and final post-casting OOC. Casts were changed every 2-4 months. Independent two sample t-test, Wilcoxon rank-sum test, and Chi-square test were performed. There were no significant differences at the initial treatment for age, classification of EOS, OOC, RVAD, VR, kyphosis, TH, and TW between EDF and BC casting. There were no significant differences of changes for OOC, RVAD, VR, kyphosis, TH and TW from pre-casting to the final post-casting status between two casting techniques (P>0.05). However, children with EDF tended to receive 3 to 4 more castings than those with BC (7.5 vs.4 casts) (P=0.007) and achieved better outcomes in success (25% vs.20%) and improvement (50% vs.10%) (P=0.03). EDF has better outcomes with EOS improvement when there is treatment of longer duration.

A survey of drug-resistant Mycobacterium tuberculosis and its relationship to HIV infection.

OBJECTIVE: To compare the prevalence of drug-resistant tuberculosis disease among patients with and without HIV infection. DESIGN: An historical prospective evaluation of patients with culture-proven tuberculosis reported between January 1988 and December 1995. SETTING: A major metropolitan county public health department. PATIENTS: A total of 802 consecutive culture-positive tuberculosis patients were eligible for inclusion in the study. HIV serologic testing and drug susceptibilities were completed on 741 (92%) eligible patients. Of these patients, 646 tested HIV-negative and 95 (12.8%) tested HIV-positive. Patients not tested for HIV (n = 59) and without drug susceptibilities (n = 2) were excluded from the analyses. Outpatient management was based on a policy of universal directly observed therapy. MAIN OUTCOME MEASURES: Patient HIV status, initial drug resistance and acquired drug resistance. Isolates were characterized for resistance to isoniazid, rifampin, rifabutin, ethambutol, streptomycin, capreomycin, kanamycin and ethionamide. Determination of initial resistance was based on the first available susceptibility study and acquired resistance on subsequent susceptibility studies. RESULTS: Initial drug resistance was found in 55 (8.5%) HIV-negative patients and four (4.2%) HIV-positive patients. Acquired drug resistance occurred in five (0.8%) HIV-negative patients and one (1.1%) HIV-positive patient. These differences were not statistically significant. CONCLUSIONS: HIV infection is not a risk factor for drug-resistant tuberculosis. Increased drug resistance in HIV infected tuberculosis patients reflects a failure of tuberculosis control in the underlying population.

Peripheral blood mononuclear-cell interleukin-2 production, receptor generation and lymphokine-activated cytotoxicity in inflammatory bowel disease.

The interleukin-2 pathway is essential for the normal immune response to antigen stimulation; we have examined the possibility that this may underlie abnormal peripheral blood lymphocyte immunoregulatory function that has been observed in patients with inflammatory bowel disease. We studied 11 patients with Crohn's disease and 5 with ulcerative colitis, all with quiescent disease activity. Peripheral blood mononuclear cells were isolated from these patients and from healthy age- and sex-matched controls. Interleukin-2 production after mitogen and phorbol-myristate acetate stimulation was similar in both groups: 381 +/- 71 (mean +/- SE) U/ml by control cells and 451 +/- 70 by patient cells. Interleukin-2 receptor generation was also measured pre- and poststimulation by labeling with anti-Tac antibody. This was 10.45 +/- 1 and 69.95 +/- 3.85% for control cells and 11.41 +/- 1.38 and 60.9 +/- 4.25% for patients cells. Finally, we examined the response of these cells to interleukin-2 stimulation by generating cells with direct cytotoxicity to 51Cr-labeled Daudi-cell targets. Control cells caused 59.5 +/- 46% 51Cr release, whereas patient cells caused 50.8 +/- 5.18% release. None of the above results achieved statistical significance. We conclude that the peripheral blood interleukin-2 pathway is normal in inactive inflammatory bowel disease.

The Parsons visual acuity test for screening children 18 to 48 months old.

The Parsons visual acuity test (PVAT) uses modified Allen test targets for visual acuity assessment in young children and persons who are difficult to test. Using this method, we were able to obtain a visual acuity threshold in 44% of 18- to 24-month-old children and in 90% of children aged 25 to 36 months. At all ages tested, the mode for visual acuity was 20/30; however, the percentage of those with 20/20 increased with age. The decision whether to refer was correctly made by means of the PVAT criterion 83% of the time.

Suppression of antibody responses to topically applied antigens by ultraviolet light irradiation. Induction of phototolerance.

C3Hf/HeN or BALB/c mice, exposed to acute ultraviolet (UV) irradiation and skin-sensitized through the irradiated skin site with soluble protein antigens, exhibit humoral tolerance to subsequent systemic challenge with antigen. We have termed this phenomenon "phototolerance" (PT). With the doses of UV radiation used, PT induction is restricted to the irradiated skin site and is observed only if sensitization is performed via the cutaneous route. PT is antigen specific and operates at the afferent level of the immune response. While single PT induction regimens result in transient humoral suppression, multiple inductions before each systemic challenge can maintain the response at low levels. The capacity to induce PT to a variety of soluble protein antigens may have potentially important clinical applications.

Noncycloplegic vs cycloplegic retinoscopy in pre-school children.

Refractive errors in 311 children between the ages of 18 and 48 months were assessed utilizing standard cycloplegic retinoscopy and a noncycloplegic near retinoscopy technique as promulgated by Mohindra. Results from this study indicate little agreement between the two objective refraction methods.

Lymphokines in autoimmunity: relationship between interleukin-2 and interferon-gamma production in systemic lupus erythematosus.

Interleukin-2 (IL-2) and interferon (IFN) are potent immunoregulatory factors. Recently, it has been demonstrated that IL-2 production is necessary for IFN-gamma synthesis. Thus, defects in IL-2 production could lead to defects in IFN-gamma production. Indeed, in systemic lupus erythematosus, defects in IFN-gamma and IL-2 production have been noted. To test this hypothesis, IL-2 and IFN-gamma production rates by peripheral blood mononuclear cells PBMC were measured simultaneously after stimulation by concanavalin A (Con A) and phorbol myristic acetate (PMA). IL-2 activity was determined employing HT-2, a cell line with an absolute growth requirement for IL-2. IFN-gamma activity was assessed using a standard viral plaque inhibition assay. IL-2 production in normal controls (n = 6) was 14.7 +/- 9.4 units/ml and in SLE patients (n = 10), 18.0 +/- 10.5 units/ml (P greater than 0.05). IFN-gamma production in controls was 74.7 +/- 43.7 units/ml and in SLE patients, 68.8 +/- 35.4 units/ml (P greater than 0.05). Only one SLE patient, who had moderately active disease, demonstrated defects in IL-2 synthesis (less than 4 units/ml) and IFN-gamma production (16 units/ml). Thus, production of these lymphokines in SLE patients was largely normal in response to Con A-PMA. These results imply that the intrinsic pathways of IFN and IL-2 production are basically normal in most SLE patients although defects in production of these lymphokines can occur. The defects in IL-2 and IFN production in SLE previously reported may be secondary to an impaired cellular response to the selected inducing agent rather than a primary defect in the actual ability to produce these important lymphokines.

Cross-reactive transplantation antigens between UV-irradiated skin and UV-induced tumors.

The fate of ultraviolet (UV) light-induced tumors transplanted into syngeneic hosts bearing skin grafts from UV-irradiated donors was studied. Our results suggest that UV-irradiated skin and UV-induced tumors express common antigens. Further, these results may bear on the question of how subcarcinogenic doses of UV radiation can effect the generation of tumor antigen-specific T suppressor cells prior to the existence of UV-induced tumors. Specifically, normal C3Hf/HeJ mice were grafted with UV-irradiated, or normal skin and subsequently implanted with either regressor, progressor, or conversion type UV-induced tumors. Animals bearing UV skin grafts were: a) effectively immunized against conversion type tumors, b) exhibited no differences against regressor type tumors, and c) allowed progressor type tumors to grow at an accelerated rate.

Impaired natural killer cell function in systemic lupus erythematosus. Relationship to interleukin-2 production.

Immune regulation requires clonal expansion of regulatory T cells which is dependent on the presence of interleukin-2 (IL-2). Previously, both natural killer (NK) cell function and IL-2 production were found to be depressed in systemic lupus erythematosus (SLE). This study was designed to determine the relationship between IL-2 production and NK cell activity in SLE. NK activity as determined by a standard 4-hour 51Cr-release assay was impaired in SLE (11.0 +/- 5.1 lytic units/10(7) cells) compared with controls (25.1 +/- 7.1 lytic units/10(7) cells) (P less than 0.05). IL-2 production was induced with concanavalin A and phorbol ester and quantitated using the IL-2 dependent cell line HT-2. IL-2 production was impaired in only 1 SLE patient, despite concomitant abnormalities in NK function in the SLE group as a whole. Moreover, in patients with impaired NK activity, incubation of lymphocytes with exogenous IL-2 did not restore NK activity to normal levels. These findings demonstrate that impaired NK activity in SLE is independent of IL-2 production and that defects in IL-2 production in SLE may not be as common as previously reported.

The school nurse's role in vision screening for the difficult-to-test student.

This article discusses the importance of providing vision screening services to students who are difficult-to-test and describes strategies for providing such services. Included in the discussion is an overview of various instruments that may be used to assess visual acuity. One of the instruments, the Parsons Visual Acuity Test, is described in detail as a tool for assessing visual acuity of the difficult-to-test. In addition, a discussion is presented which emphasizes the importance of providing follow-up services to those children who are referred for professional eye examinations. The authors delineate the vital role of the school nurse in assisting the difficult-to-test students to gain necessary vision care services through screening, referral, obtaining appropriate treatment and providing follow-up services.

Establishment of a continuous T cell line capable of suppressing anti-tumor immune responses in vivo.

This report describes the induction, phenotypic characteristics, and functional properties of a continuous suppressor T cell line. This cell line, UV1, is capable of suppressing anti-tumor immune responses both in vivo and in vitro. The UV1 cell line was derived from a T cell-enriched (nylon wool nonadherent, Ia-negative panned fraction) spleen cell population from a ultraviolet radiation-(UV) exposed BALB/c Wehi mouse. By using an in vivo functional assay designed to demonstrate tumor-specific UV-induced suppressor T lymphocyte (Ts cell) activity, it was found that UV1 cells were capable of rendering normal syngeneic mice susceptible to the growth of UV-induced regressor tumors. In addition to their suppressive activity in vivo, UV1 cells displayed in vitro suppressive activity by blocking the differentiation of cytotoxic T cells from the draining lymph nodes of UV-tumor immunized animals. By flow cytometric analysis it was determined that UV1 cells expressed a number of T lymphocyte differentiation antigens and did not express any detectable amounts of surface immunoglobulin, I-A or E/C antigens, Fc receptors, or macrophage antigens. These data suggest that the UV1 cell line may be representative of the UV-induced Ts cell population and provide a potential means for studying UV-induced immunoregulatory mechanisms in greater detail.

Ultraviolet light-induced suppression of antigen presentation.

Ultraviolet (UV) light irradiation of animals results in the development of specific T suppressor cells that inhibit antitumor immune responses. It is thought that suppression may arise as a consequence of altered antigen presentation by UV-irradiated epidermal cells. This hypothesis is based on evidence demonstrating that specific lymphoid tissues from UV-irradiated hosts exhibit impaired antigen-presenting function and that animals cannot be contact sensitized when antigens are applied to a UV-irradiated skin site. Langerhans cells of the skin are likely candidates as targets of UV-induced defects in antigen presentation as they bear Fc and C3b receptors, express Ia antigens, are of bone marrow origin, and are capable of presenting antigen in vitro. We speculate on the possible clinical usefulness of UV-induced tolerance to specific antigens such as those encountered in monoclonal antibody therapy and tissue transplantation.

Low dose radiosensitivity of alloimmune cytotoxic T cells.

Low dose radiosensitivity of in vitro generated alloimmune murine cytotoxic T lymphocytes (CTL) was studied. It appears that a subset of CTL exists that can be killed with 10-25 rad of x rays. These radiosensitive CTL are Lyt-1,2+ T lymphocytes. Analyses of cytotoxicity by chromium release assays indicate that the radiosensitive CTL are present in responder spleen cell cultures from all strains of mice tested. The generation of these effector cells is most pronounced in animals of the C57BL background. The mechanism of low dose radiosensitivity appears to be interphase death.