Use of hospital admissions data to quantify the burden of emergency admissions in people with diabetes mellitus.

AIMS: Accurate measurement of emergency diabetes admissions is essential for healthcare delivery and research. This study examines whether current approaches to identifying diabetes-related admissions may underestimate the true burden on hospital care. METHODS: Data spanning the period 1 January 2006 to 31 December 2010 inclusive were extracted from Hospital Episode Statistics data for England. Emergency admissions citing diabetes (E10, E11, E13 or E14) in any diagnosis position in adults (≥ 17 years) were included. E10 and E11 were considered analogous to type 1 and type 2 diabetes mellitus respectively; E13 and E14 were grouped as 'other or unspecified' diabetes mellitus. For admissions citing diabetes multiple times, those with concordant citations were classified as appropriate; discordant citations were assigned to the 'other or unspecified' group. Frequencies of diabetes classifications and complications for each diagnosis position and frequencies of all International Classification of Diseases 10th revision codes for the primary diagnosis field were calculated. RESULTS: In total, 2 443 046 admissions were identified. Diabetes was cited as the primary diagnosis in 6.2% and most commonly cited as the third diagnosis (23.1%). Type 2 diabetes mellitus was the most common (85.0%). The majority of diabetes citations were 'without complication' (2 188 965, 89.6%). The most common primary diagnosis was 'chest pain, unspecified' (R07.4, 99 678, 4.1%). CONCLUSIONS: Reliance on the primary diagnosis field to identify emergency admissions in people with diabetes grossly underestimates the true burden placed on hospital care and leads to underestimates of effect sizes in studies utilizing admission rates as outcome measures. An alternative strategy to identify such admissions is required.

Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis.

AIM: Desmoid tumours (DT) are myofibroblastic proliferations occurring in 15% of patients with familial adenomatous polyposis (FAP). Several small series have analysed the incidence of DT and predisposing risk factors. Using meta-analytical techniques, this study aimed to identify risk factors for DT development in patients with FAP. METHOD: Studies of sporadic DT were excluded. The study end-points were the incidence of DT in FAP and DT development by gender, adenomatous polyposis coli (APC) mutation, family history of DT and previous abdominal surgery. A random effect Mantel-Haenszel model was used to calculate odds ratios for each risk factor and age group. RESULTS: Ten studies of 4625 patients with FAP fulfilled our inclusion criteria. A total of 559 (12%) patients developed DT. Cumulative analysis demonstrated that 80% of DT developed by age 40, the peak incidence rate being in the second and third decades. A positive family history of DT was the most significant risk factor (OR 7.02, 95% CI 4.15-11.9, P < 0.001). An APC mutation 3' to codon 1399 (OR 4.37, 95% CI 2.14-8.91, P < 0.001) and previous abdominal surgery (OR 3.35, 95% CI 1.33-8.41, P = 0.01) were also implicated. Women were more likely to develop DT (OR 1.57, 95% CI 1.13-2.18, P = 0.007). CONCLUSION: There is consistency amongst polyposis registries in documenting the incidence and risk factors for DT development. Having a positive family history for DT is of greater significance than a 3' mutation, suggesting the existence of modifier genes, independent of the APC genotype-phenotype correlation. Few of these risk factors are modifiable. Delaying prophylactic surgery could be appropriate in female patients with a 3' APC mutation and attenuated polyposis.

Highly active antiretroviral therapy results in a decrease in CD8+ T cell activation and preferential reconstitution of the peripheral CD4+ T cell population with memory rather than naive cells.

OBJECTIVE: Highly active antiretroviral therapy (HAART) can produce marked increases in peripheral blood CD4+ T cells and decreases in HIV plasma RNA copy numbers. However, it is not clear whether these absolute changes will be accompanied by a recovery in the known naive CD4+ T cell depletion or a decrease in the marked CD8+ T cell activation. DESIGN: Twenty-nine patients were enrolled in studies of either nucleoside therapy alone or nucleoside therapy combined with a protease inhibitor (zidovudine + lamivudine + indinavir). One hundred and ninety-one examinations were carried out at three baseline time points and during 40 weeks of follow-up to evaluate the effect of HAART on CD4+ memory/naive phenotype and CD8+ T cell activation. METHODS: CD4+ and CD8+ T cell number, CD62L/CD45RA expression on CD4+ T cells and CD38 expression on CD8+ T cells were measured by three-color flow cytometry. RESULTS: Most protease inhibitor treated patients had a significant rise in CD4+ numbers. The marked rise in the CD4+ T cells seen in individuals in this study was not accompanied over a 40-week period by a change in the abnormally low CD4+ naive compartment, and thus was almost completely of memory phenotype. The CD38 expression on CD8+ cells fell during treatment, and decreased to a greater degree than the comparable rise in CD4+ T cell counts. This decrease continued in many patients after the CD4+ T cell rise or viral load decline had plateaued. CONCLUSION: HAART results in changes in activation to a greater extent than absolute changes in CD4+ T cell numbers, but is not accompanied by an increase in naive CD4+ T cells. Measurements of CD4+ T cell numbers alone may not allow appropriate interpretation of immune activation or immune competence in patients receiving those drugs.

Bilateral Kimura's disease of the eyelids.

A case of Kimura's disease affecting the eyelids bilaterally is reported in a 5-year-old boy of Afro-Caribbean extraction who has been followed for 12 years with repeat biopsies. He initially presented at 5 years of age with swelling of the left upper eyelid, left cervical lymphadenopathy, and eosinophilia. One year later he developed swelling of the right upper eyelid. There has been no change in the clinical appearance over the next 12 years. Repeated biopsies of the eyelids showed a diffuse inflammatory infiltrate with many eosinophils and lymphocytes. A lymph node biopsy showed reactive lymphoid hyperplasia. Immunohistochemistry using lymphoid markers showed a polyclonal pattern. Kimura's disease is a rare cause of eyelid swelling, particularly at such a young age and with bilateral involvement. This case demonstrates that bilateral orbital lymphoid lesions with cervical node involvement do not always imply lymphoma, but may have a benign pathogenesis. The unusually long follow up in this case confirms an excellent prognosis for Kimura's disease with conservative management. Accurate diagnosis in small orbital biopsies may spare the patient unnecessary radical surgery.

Manchineel keratoconjunctivitis.

The Manchineel tree is an evergreen widely distributed in tropical regions. The toxic nature of Manchineel has been known since the early sixteenth century. Contact with its milky sap (latex) produces bullous dermatitis and acute keratoconjunctivitis. We identified 19 patients who had ocular injuries caused by Manchineel between 1985 and 1990 and were able to review 12. All of these patients had been treated by lavage, cycloplegia, and topical antibiotics. Of 20 episodes of exposure 14 affected both eyes. The cornea was damaged in 16 episodes, the extent varying from large corneal epithelial defects to superficial punctate keratitis. The epithelial changes had resolved in a mean period of 3.75 days (range 1 to 14 days). Two episodes caused stromal infiltration to appear and in one of these a stromal opacity remained 5 years later. The final visual acuity was 6/9 or better in all eyes except in one patient who had visual impairment because of glaucoma. Our results suggest that despite the severity of the acute reaction, the long term visual prognosis is excellent in Manchineel keratoconjunctivitis. The historical and toxicological literature on Manchineel is reviewed.

Th1/Th2 cytokine responses following HIV-1 immunization in seronegative volunteers. The AIDS Vaccine Evaluation Group.

The Th1/Th2 profile that follows human vaccination may profoundly influence the subsequent course of disease after infection. However, the ability to detect IL-4 has been limited outside trials of live vaccination. By using methods in which memory effector cells are allowed to antigenically expand by short term culture, followed by low-dose mitogenic stimulation, we have been able to follow the Th1/Th2 profile in HIV-1 volunteers enrolled in two phase I studies of HIV immunogens (a recombinant gp120 and a multivalent, octomeric V3 loop peptide). Antigen-specific interferon-gamma (IFN-gamma) could be detected in primary stimulation, but IL-4 was observed only after antigenic expansion and restimulation. In both of these studies the responses after initial immunizations were dominated by IFN-gamma, with IL-4 appearing only after multiple rounds of immunization, and IL-4 was temporally related to antibody production. Concomitant with the IL-4 production, the amount of supernatant IFN-gamma declined. Antigen-specific IL-10 was not detected in either study. Such techniques, which have been shown to correlate with outcomes in immunotherapy, may prove useful as future surrogates of human vaccine response.

Detection of intracellular antigen-specific cytokines in human T cell populations.

Determination of antigen-specific cytokine responses of T lymphocytes after vaccination is made difficult by the low frequency of responder cells. In order to detect these responses, the profile of intracellular cytokines was analyzed using flow cytometry after antigenic expansion. Peripheral blood mononuclear cells were stimulated with antigens for 5 days, further expanded with interleukin (IL)-2, and then restimulated on day 10. Cytokine production was detected by intracellular staining with monoclonal antibodies after saponin-based permeabilization. Influenza expansion resulted in specific interferon-gamma (IFN-gamma) production of 6%-20%, with less IL-4 production (0%-2%). Tetanus toxoid resulted in even greater production. IL-4 and IFN-gamma were produced mainly by memory cells of the CD45RO+ phenotype. IFN-gamma production was contributed by both CD4 and CD8 populations. These methods were then applied to a clinical trial of a candidate human immunodeficiency virus type 1 vaccine. Antigen-specific increases in IFN-gamma were measured, which corresponded to antibody production, lymphoproliferation, and skin testing.