How to limit clinical errors in interpretation of data

We all assume that we can understand and correctly interpret what we read. However, interpretation is a collection of subtle processes that are easily influenced by poor presentation or wording of information. This article examines how evidence-based principles of information design can be applied to medical records to enhance clinical understanding and accuracy in interpretation of the detailed data that they contain.     

The origin, content, and workload of e-mail consultations

CONTEXT: Despite the common use of e-mail, little beyond anecdote or impressions has been published on patient-clinician e-mail consultation. OBJECTIVE: To report our experiences with free-of-charge e-mail consultations. DESIGN: Retrospective review of all e-mail consultation requests received between November 1, 1995, and June 31, 1998. SETTING AND PARTICIPANTS: Consecutive e-mail consultation requests sent to the Division of Pediatric Gastroenterology at the Children's Medical Center of the University of Virginia in Charlottesville. MAIN OUTCOME MEASURES: Number of consultation requests per month, time required to respond, who initiated the request and their geographic origin, and the kind of information requested in the consultation. RESULTS: During the 33-month period studied, we received 1239 requests, an average (SD) of 37.6 (15.9) each month. A total of 1001 consultation requests (81%) were initiated by parents, relatives, or guardians, 126 (10%) by physicians, and 112 (9%) by other health care professionals. Consultation requests were received from 39 states and 37 other countries. In 855 requests (69%), there was a specific question about the cause of a particular child's symptoms, diagnostic tests, and/or therapeutic interventions. In 112 (9%), the requester sought a second opinion about diagnosis or treatment for a particular child, and 272 consultations (22%) requested general information concerning a disorder, treatment, or medication without reference to a particular child. A total of 1078 requests (87%) were answered within 48 hours of the initial request. On average, reading and responding to each e-mail took slightly less than 4 minutes. CONCLUSION: E-mail provides a means for parents, guardians, and health care professionals to obtain patient and disease-specific information from selected medical consultants in a timely manner.     

Peptidyl chemosensors incorporating a FRET mechanism for detection of Ni(II)

Hexapeptides incorporating two fluorophores flanking a tripeptide sequence that binds Ni(II) and Cu(II) with high affinity have been synthesized. While Cu(II) quenches the fluorescence of the resulting peptides, coordination of Ni(II) enables enhanced FRET (fluorescent resonance energy transfer) from one fluorophore to the other.     

Assessing the relationship between maternal opiate use and neonatal mortality

We undertook a number of meta-analyses to estimate more precisely the relationship between neonatal mortality and use of opiates in three groups of women. First, women who continued to use illicit heroin throughout pregnancy; secondly, women stabilized on methadone at the time of conception or shortly after and thirdly, women who use heroin well into pregnancy with late entry into methadone treatment, or who continued to use illicit heroin during pregnancy while receiving methadone. FINDINGS: The pooled estimates of the relative risks of neonatal mortality for separate heroin and methadone use were both near unity: 1.47 (95% CI 0.88-2.33) and 1.75 (95% CI 0.60-4.59), respectively. The result for heroin may be due to the inclusion in the meta-analysis of a particularly large study, which, unlike the two other smaller studies included found a relative risk near unity. When this study was excluded from the meta-analysis the pooled estimate of the relative risk of neonatal mortality for heroin use was 3.27 (95% CI 0.95-9.60). In contrast to the results for use of methadone only, the pooled relative risk associated with heroin and methadone use was 6.37 (95% CI 2.57-14.68). CONCLUSIONS: The increased relative risk for neonatal mortality associated with women using heroin and methadone during pregnancy, compared to those stabilized on methadone, is probably due to the chaotic and high-risk life-style associated with illicit heroin use and not solely to the use of heroin and methadone per se. It is recommended tht women who use heroin well into pregnancy with late entry into methadone treatment, or who continue to use illicit heroin during pregnancy while receiving methadone, receive special attention over and above that provided to women stabilized on methadone.     

Role of nitric oxide in cyclosporine A-induced hypertension

Cyclosporine A (CsA) is an immunosuppressive agent that also causes hypertension. The effect of CsA on vascular responses was determined in Sprague-Dawley rats and isolated rat aortic rings. Male rats weighing 250 to 300 g were given either CsA (25 mg. kg-1. d-1) in olive oil or vehicle by intraperitoneal injection for 7 days. CsA administration produced a 42% increase (P<0.001) in mean arterial pressure (MAP) that reached a plateau after 3 days. Conversely, the levels of both nitrate/nitrite, metabolites of nitric oxide (NO), and cGMP, which mediates NO action, decreased by 50% (P<0.001) and 35% (P<0.001), respectively, in the urine. Thoracic aortic rings from rats treated with CsA and precontracted with endothelin (10(-9) mol/L) showed a 35% increase (P<0.001) in tension, whereas endothelium-dependent relaxation induced by acetylcholine (ACh, 10(-9) mol/L) was inhibited 65% (P<0.001) compared with that in untreated rats. This response was similar to that of endothelium-denuded aortic rings from untreated rats in which ACh-induced relaxation was completely abolished (P<0.001), but relaxation induced by S-nitroso-N-acetylpenicillamine (SNAP, 10(-8) mol/L) was unaffected (P<0.001). ACh-induced formation of both nitrate/nitrite and cGMP by both denuded and CsA-treated aortic rings was inhibited 95% (P<0.001) and 65% (P<0.001), respectively, compared with intact aortic rings. The effects of CsA were reversed both in vivo and in vitro by pretreatment with L-arginine (10 mg. kg-1. d-1 IP), the precursor of NO. There were no changes in MAP and tension in rats treated with L-arginine alone. In summary, CsA inhibits endothelial NO activity, with resulting increases in MAP and tension, and this inhibition can be overcome by parenteral administration of L-arginine.     

Narrow-Angle Beams of Strongly Interacting Phonons

We demonstrate that narrow-angle phonon pulses of low energy phonons in liquid ⁴ He are strongly interacting and rapidly come into equilibrium within a narrow cone in momentum space. The effect of collimation on such a system is to strongly reduce the axial phonon flux. This gives a method of separating high and low energy phonons.     

Eicosanoids and inflammatory cells in frostbitten tissue: prostacyclin, thromboxane, polymorphonuclear leukocytes, and mast cells

The pathophysiology of cold injury is still controversial. An inflammatory process has been implicated as the underlying mechanism and certain anti-inflammatory substances such as ibuprofen and acetylsalicylic acid have been used in the clinical treatment of frostbite injury. It has been postulated that the progressive ischemic necrosis is secondary to excessive thromboxane A2 production, which upsets the normal balance between prostacyclin (prostaglandin I2) and thromboxane A2. It was aimed to clarify the pathophysiology of cold injury in this study. Twenty-one New Zealand White rabbits, each weighing 1.2 to 2.9 kg, were divided into control (n = 10) and frostbitten (n = 11) groups the randomly. The rabbit ears in the frostbitten group were subjected to cold injury, and the levels of thromboxane A2 (as thromboxane B2) and of prostaglandin I2 (as 6-keto-prostaglandin F1alpha) and the number of inflammatory cells (polymorphonuclear leukocytes and mast cells) were measured in normal and frostbitten skin of rabbit ears. The levels of 6-keto prostaglandin F1alpha and thromboxane B2, the stable metabolites of prostaglandin I2 and thromboxane A2, respectively, were increased in a statistically significant way (p < 0.002) by frostbite injury; however, thromboxane B2 increased more than 6-keto prostaglandin F1alpha. Polymorphonuclear leukocytes and mast cells, absent in normal skin, were present in the frostbitten skin. There was a statistically significant (p < 0.01) correlation between the time a rabbit ear was maintained at below -10 degrees C and skin survival and between the weights of rabbits and skin survival (p < 0.024). All these findings suggest that inflammation is involved in frostbite injury; a decrease in prostaglandin I2/thromboxane A2 ratio could be one of the factors leading to necrosis; the bigger the animal, the better its ability to counter frostbite.     

Interaction of the allogeneic state and hypercholesterolemia in arterial lesion formation in experimental cardiac allografts

To learn more about the interaction of allogeneic transplantation and hypercholesterolemia in the formation of arterial lesions, we performed heterotopic cardiac transplantation in rabbits. We analyzed lesions in both the coronary arteries and the proximal ascending aorta 6 weeks after surgery in both transplanted and native hearts of normocholesterolemic rabbits and those with diet-induced hypercholesterolemia (serum cholesterol, 1638 +/- 366 mg/dL, n = 6, 6 weeks after transplantation). All animals received cyclosporin A (5 mg.kg-1.d-1) for immunosuppression. The transplanted aortas of hypercholesterolemic animals had thicker intimal lesions than did the native aortas (intima/media ratio, 0.67 +/- 0.4 versus 0.08 +/- 0.1, P < .05) and contained more T cells (37.4 +/- 12.8 versus 5.7 +/- 6.2 per high-power field, P < .001). In normocholesterolemic animals (n = 5) the coronary arteries had negligible lesions in the native heart and only slight and inconsistent intimal lesions in the transplanted heart. In the hypercholesterolemic animals, more coronary arteries had intimal lesions in the transplanted hearts than in the native hearts (74% versus 43%). Coronary artery lesions in the native hearts consisted mostly of foam cells, while those in transplanted hearts had more abundant smooth muscle cells as determined by alpha-actin staining. Intimal endothelial cells in transplanted aortas expressed increased levels of vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 compared with the native vessels subjected to identical levels of cholesterolemia. Medial smooth muscle cells in transplanted aortas contained much higher levels of immunoreactive tumor necrosis factor-alpha than did medial cells of the native aorta in the same hypercholesterolemic animals. The intima of transplanted aortas contained prominent microvessels compared with the native aorta of the hypercholesterolemic rabbits. We conclude that even during treatment with doses of cyclosporine that control acute myocardial rejection, hypercholesterolemia and the allogeneic state act together to augment allograft atherosclerosis, T-cell accumulation, intimal neovascularization, local cytokine expression, and indices of cell activation in arteries.     

Market influences on internal medicine residents' decisions to subspecialize

BACKGROUND: Managed care reduces the demand for internal medicine subspecialists, but little empirical information is available on how increasing managed care may be affecting residents' training choices. OBJECTIVE: To determine whether increased managed care penetration into an area where residents train was associated with a decreased likelihood that residents who completed general internal medicine training pursued subspecialty training. DESIGN: Secondary logistic regression analysis of data from the 1993 cohort of general internal medicine residents. SETTING: U.S. residency training sites. PARTICIPANTS: 2263 U.S. medical school graduates who completed general internal medicine residency training in 1993. MEASUREMENTS: The outcome variable (enrollment in subspecialty training) was derived from the Graduate Medical Education Tracking Census of the Association of American Medical Colleges (AAMC). Health maintenance organization (HMO) penetration (possible range, 0.0 to 1.0; higher values indicate greater penetration) was taken from the Interstudy Competitive Edge Database. Individual and medical school covariates were taken from the AAMC's Student and Applicant Information Management System database and the National Institutes of Health Information for Management Planning, Analysis, and Coordination system. The U.S. Census division was included as a control covariate. RESULTS: 980 participants (43%) enrolled in subspecialty training. Logistic regression analyses indicated a nonlinear association between managed care penetration into a training area and the odds of subspecialization. Increasing managed care penetration was associated with decreasing odds of subspecialization when penetration exceeded 0.15. The choice of subspecialty training increased as HMO penetration increased from 0 to 0.15. CONCLUSIONS: Local market forces locally influenced the career decisions of internal medicine residents, but the influence was small compared with the effects of age and sex. These results suggest that market forces help to achieve more desirable generalist-to-specialist physician ratios in internal medicine.