Critical appraisal of advance directives given by patients with fatal acute stroke: an observational cohort study.

BACKGROUND: Advance directives (AD) imply the promise of determining future medical treatment in case of decisional incapacity. However, clinical practice increasingly indicates that standardized ADs often fail to support patients' autonomy. To date, little data are available about the quality and impact of ADs on end-of-life decisions for incapacitated acute stroke patients. METHODS: We analyzed the ADs of patients with fatal stroke, focusing on: (a) their availability and type, (b) stated circumstances to which the AD should apply, and (c) stated wishes regarding specific treatment options. RESULTS: Between 2011 and 2014, 143 patients died during their hospitalization on our stroke unit. Forty-two of them (29.4%) had a completed and signed, written AD, as reported by their family, but only 35 ADs (24.5%) were available. The circumstances in which the AD should apply were stated by 21/35 (60%) as a "terminal condition that will cause death within a relatively short time" or an ongoing "dying process." A retrospective review found only 16 of 35 ADs (45.7%) described circumstances that, according to the medical file, could have been considered applicable by the treating physicians. A majority of patients objected to cardiopulmonary resuscitation (22/35, 62.9%), mechanical ventilation (19/35, 54.3%), and artificial nutrition (26/35, 74.3%), while almost all (33/35, 94.3%) directed that treatment for alleviation of pain or discomfort should be provided at all times even if it could hasten death. CONCLUSIONS: The prevalence of ADs among patients who die from acute stroke is still low. A major flaw of the ADs in our cohort was their attempt to determine single medical procedures without focusing on a precise description of applicable scenarios. Therefore, less than half of the ADs were considered applicable for severe acute stroke. These findings stress the need to foster educational programs for the general public about advance care planning to facilitate the processing of timely, comprehensive, and individualized end-of-life decision-making.

Improving access to longitudinal patient health information within an emergency department.

We designed and implemented an electronic patient tracking system with improved user authentication and patient selection. We then measured access to clinical information from previous clinical encounters before and after implementation of the system. Clinicians accessed longitudinal information for 16% of patient encounters before, and 40% of patient encounters after the intervention, indicating such a system can improve clinician access to information. We also attempted to evaluate the impact of providing this access on inpatient admissions from the emergency department, by comparing the odds of inpatient admission from an emergency department before and after the improved access was made available. Patients were 24% less likely to be admitted after the implementation of improved access. However, there were many potential confounders, based on the inherent pre-post design of the evaluation. Our experience has strong implications for current health information exchange initiatives.

Effective surface-based cryopreservation of human embryonic stem cells by vitrification.

Human embryonic stem cells (hESCs) are candidates for many applications in the areas of regenerative medicine, tissue engineering, basic scientific research as well as pharmacology and toxicology. However, use of hESCs is limited by their sensitivity to freezing and thawing procedures. Hence, this emerging science needs new, reliable preservation methods for the long-term storage of large quantities of functional hESCs remaining pluripotent after post-thawing and culturing. Here, we present a highly efficient, surface based vitrification method for the cryopreservation of large numbers of adherent hESC colonies, using modified cell culture substrates. This technique results in much better post-thaw survival rate compared to cryopreservation in suspension and allows a quick and precise handling and storage of the cells, indicating low differentiation rates.

Large-area, uniform, high-spatial-frequency ripples generated on silicon using a nanojoule-femtosecond laser at high repetition rate.

Large-area high-spatial-frequency patterns (HSFLs) of λ/6 periodicity have been generated by a nanojoule-femtosecond laser scanning technique (80 MHz, 170 fs, 700-950 nm) at the silicon-air interface. The excellent large-area uniformity allowed reproducible and accurate measurements of the periodicity. Variation of experimental parameters as illumination geometry, and pulse energy and number showed no influence on the ripple spacing. A wavelength dependence was observed and compared to current models of HSFL formation. A particular second-harmonic model was found to match the results best but needs to take into account transient changes in the refractive index under laser exposure. A second-harmonic mechanism is further supported by direct spectroscopic observation.

Assessing the difficulty and time cost of de-identification in clinical narratives.

OBJECTIVE: To characterize the difficulty confronting investigators in removing protected health information (PHI) from cross-discipline, free-text clinical notes, an important challenge to clinical informatics research as recalibrated by the introduction of the US Health Insurance Portability and Accountability Act (HIPAA) and similar regulations. METHODS: Randomized selection of clinical narratives from complete admissions written by diverse providers, reviewed using a two-tiered rater system and simple automated regular expression tools. For manual review, two independent reviewers used simple search and replace algorithms and visual scanning to find PHI as defined by HIPAA, followed by an independent second review to detect any missed PHI. Simple automated review was also performed for the "easy" PHI that are number- or date-based. RESULTS: From 262 notes, 2074 PHI, or 7.9 +/- 6.1 per note, were found. The average recall (or sensitivity) was 95.9% while precision was 99.6% for single reviewers. Agreement between individual reviewers was strong (ICC = 0.99), although some asymmetry in errors was seen between reviewers (p = 0.001). The automated technique had better recall (98.5%) but worse precision (88.4%) for its subset of identifiers. Manually de-identifying a note took 87.3 +/- 61 seconds on average. CONCLUSIONS: Manual de-identification of free-text notes is tedious and time-consuming, but even simple PHI is difficult to automatically identify with the exactitude required under HIPAA.

Durable treatment-free remission after high-dose cyclophosphamide therapy for previously untreated severe aplastic anemia.

BACKGROUND: Severe aplastic anemia is a life-threatening bone marrow failure disorder. High-dose cyclophosphamide therapy followed by allogeneic bone marrow transplantation cures the disease. However, it requires a suitable donor and carries the risk for graft-versus-host disease. A small pilot study demonstrated that high-dose cyclophosphamide therapy without bone marrow transplantation leads to durable, treatment-free complete remission. OBJECTIVE: To confirm the safety and efficacy of high-dose cyclophosphamide therapy alone in patients with severe aplastic anemia. DESIGN: Uncontrolled clinical trial. SETTING: Three tertiary care hospitals. PATIENTS: 19 patients with untreated severe aplastic anemia. INTERVENTION: Cyclophosphamide, 50 mg/kg of body weight per day for 4 consecutive days. MEASUREMENTS: Probability of response and overall survival were measured. Complete remission was defined as normal blood count for age and sex. Partial remission was defined as independence from transfusion and an absolute neutrophil count greater than 0.5 x 10(9) cells/L without growth factor support. Nonresponders were patients who remained transfusion dependent or died. Relapse was defined as no longer meeting criteria for partial or complete remission. RESULTS: The median time to an absolute neutrophil count of 0.5 x 10(9) cells/L was 49 days. The probability of survival was 84% (95% CI, 59% to 95%) at 24 months. The probability of achieving treatment-free remission was 73% (CI, 51% to 91%) at 24 months, and the probability of achieving complete remission was 65% (CI, 39% to 89%) at 50 months. No responding patients have had relapse or have developed secondary clonal disorders. CONCLUSIONS: High-dose cyclophosphamide therapy without bone marrow transplantation produces durable treatment-free remission in severe aplastic anemia. This approach deserves further study in patients with severe aplastic anemia who are not suitable candidates for allogeneic bone marrow transplantation.

Contralateral effect of topical beta-adrenergic antagonists in initial one-eyed trials in the ocular hypertension treatment study.

PURPOSE: To evaluate the magnitude of the contralateral effect of topically administered beta-blockers on intraocular pressure. METHODS: The Ocular Hypertension Treatment Study enrolled 1,636 subjects. Of these, 817 subjects were randomized to receive topical ocular hypotensive medication and 819 subjects were randomized to close observation (i.e., no topical medication). We compared the intraocular pressure of the contralateral eye of subjects at the baseline visit and after an initial one-eyed therapeutic trial of topical beta-blockers. We examined differences between baseline and follow-up intraocular pressure in untreated eyes of subjects randomized to close observation. RESULTS: The mean reduction in intraocular pressure in the beta-blocker-treated eyes was -5.9 +/- 3. 4 mm Hg (-22% +/- 12%; Student t test, P <.0001). In the contralateral eyes, mean intraocular pressure reduction was -1.5 +/- 3.0 mm Hg (-5.8% +/- 12%; P <.0001). Of the contralateral eyes, 35% showed a reduction of 3 mm Hg or more, and 10% showed a reduction of 6 mm Hg or more. The contralateral effect of the relatively selective beta-blocker betaxolol did not differ from that of any of the nonselective beta-blockers. Factors associated with the magnitude of the contralateral effect were the degree of intraocular pressure reduction in the treated eye and baseline intraocular pressure of the contralateral eye. In the close observation group, no significant reduction in intraocular pressure was noted between the baseline and follow-up visit. CONCLUSIONS: The contralateral effect is important in clinical practice and in clinical trials when the hypotensive effect of a topical beta-blocker is evaluated by means of a one-eyed therapeutic trial.

Concordance of parapapillary chorioretinal atrophy in ocular hypertension with visual field defects that accompany glaucoma development.

OBJECTIVE: To determine whether the extent and location of progressive parapapillary chorioretinal atrophy noted in some patients with ocular hypertension are correlated with the extent and location of visual field defects that occur with progression to glaucoma. STUDY DESIGN: Retrospective cohort study. PARTICIPANTS: Thirty patients with ocular hypertension who had progressive changes of parapapillary atrophy develop before clinically detectable optic disc or visual field damage. MAIN OUTCOME MEASURES: Assessment of changes in the parapapillary atrophy and visual field parameters. METHODS: Baseline and follow-up optic disc photographs and visual field test results were retrospectively analyzed. The relationship between the extent of parapapillary atrophy observed during the ocular hypertension period and initial visual field abnormalities detected after glaucoma development, as well as their spatial relationship, was statistically analyzed. RESULTS: The extent of progressive changes of the parapapillary atrophy detected during the ocular hypertension period was correlated with the extent of changes in the visual field parameters, including corrected pattern standard deviation and mean deviation measured after glaucoma development (Mantel-Haenszel chi-square test, P = 0.026, P = 0.037, respectively). In addition, the visual field abnormalities occurred in the corresponding quadrants of the progressive parapapillary atrophy. Analysis of the spatial relationship revealed that the location of progressive changes of the parapapillary atrophy was concordant with the location of visual field abnormalities in 78% of the quadrants (94 of 120 quadrants) (chi-square test, P = 0.001). CONCLUSIONS: The extent and location of visual field abnormalities that develop in ocular hypertensive eyes with progression to glaucoma exhibit a concordance with the extent and location of progressive parapapillary atrophy noted in the ocular hypertension period. This suggests the importance of detailed examination of the parapapillary area in ocular hypertensive eyes.

Approaching psychotherapy of the personality disorders from the Millon perspective.

Millon's integrative model for a clinical science begins with a theory that is consistent with current knowledge, establishes a taxonomy for classification, develops a coordinated assessment system, and develops and implements interventions with the guidance of the preceding elements of the model. In recent years, work on the last step of the model, clinical interventions, has accelerated rapidly, and the model now permits the therapist to directly extrapolate specific treatment goals, objective, and techniques to the practice of therapy with the individual patient. This article summarizes how treatment planning and implementation flows logically from the Millon model.

Elastosis of the lamina cribrosa in glaucomatous optic neuropathy.

The purpose of this study was to determine whether elastotic degeneration of the elastin component of the lamina cribrosa occurs in optic neuropathy associated with different types of glaucoma. Human optic nerve heads with primary open-angle, neovascular, chronic angle closure and pseudoexfoliation glaucoma, and with varying duration of disease were compared with age-matched normal eyes, using electron microscopy and immunogold labeling of elastin. The percent area occupied by immunogold-labeled elastin material was determined using a digital image analysis system. In all eyes with a history of glaucoma, elastosis was found in the lamina cribrosa and there was a significantly greater percentage of area occupied by elastin compared with age-matched control eyes (P<0.0001). Among the glaucomatous eyes, pseudoexfoliation glaucoma had the largest area of elastosis, followed by primary open-angle and secondary glaucoma (neovascular and chronic angle closure). In all glaucoma samples, large, confluent elastin aggregates of irregular and varied shapes (elastosis) were observed in the lamina cribrosa and insertion region. These results demonstrate that glaucomatous optic neuropathy is associated with elastosis of the lamina cribrosa, which may contribute to the changes in compliance of the optic nerve heads of glaucomatous eyes.

Initial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 1, 6, 8, 10, and 12.

A report on an initial genome screen on 540 individuals in 97 families was collected as part of the NIMH Genetics Initiative on Bipolar Disorder. Families were ascertained to be informative for genetic linkage and underwent a common ascertainment and assessment protocol at four clinical sites. The sample was genotyped for 65 highly polymorphic markers from chromosomes 1, 6, 8, 10, and 12. The average intermarker interval was 16 cM. Genotypic data was analyzed using affected sib pair, multipoint affected sib pair, and pedigree analysis methods. Multipoint methods gave lod scores of approximately two on chromosomes 1, 6, and 10. The peak lod score on chromosome 6 occurred at the end of the q-arm, at some distance from the 6p24-22 area previously implicated for schizophrenia. We are currently genotyping additional markers to reduce the intermarker interval around the signals. The interpretation of results from a genome screen of a complex disorder and the problem of achieving a balance between detecting false positive results and the ability to detect genes of modest effect are discussed.

Lack of diurnal variation in vision, refraction, or keratometry after excimer laser photorefractive keratectomy.

PURPOSE: To examine whether diurnal variation in visual acuity, spherical equivalent, keratometry, or intraocular pressure occurs in patients who have undergone photorefractive keratectomy. METHODS: Twenty-nine post-photorefractive keratectomy patients underwent morning and evening measurements of visual acuity, spherical equivalent, keratometry, and intraocular pressure at intervals between 5 and 13 months after photorefractive keratectomy. RESULTS: There was no statistically significant post-photorefractive keratectomy diurnal variation in visual acuity, spherical equivalent, or keratometry in the group studied. Diurnal variation in post-photorefractive keratectomy intraocular pressure was not significantly different between patients' treated and untreated eyes. CONCLUSION: Photorefractive keratectomy does not appear to result in diurnal variation in visual acuity, spherical equivalent, or keratometry post-operatively, nor does it seem to effect normal diurnal variation in intraocular pressure.

A meta-analysis of chromosome 18 linkage data for bipolar illness.

We find a meta-data set (715 families, up to 1,124 sib pairs) for bipolar illness to have a strong signal in a 10 cM region around D18S40, and excess paternal sharing on the q arm near marker D18S64. We describe a method for meta-analysis of microsatellite marker data using affected sib-pair (ASP) methodology. Inherent difficulties in such analysis include heterogeneity of allele frequencies and protocol design, measurement errors in genotyping, and map construction. Using identity-by-descent (IBD) allele sharing as the dependent variable, a logistic regression to test for heterogeneity finds only mild heterogeneity, and a limited parent-of-origin effect.

[MR tomography and bone marrow scintigraphy in the screening of skeletal metastases in patients with breast carcinoma]. / MRT und Knochenmarkszintigraphie im Screening von Skelettmetastasen bei Patientinnen mit Mammakarzinom.

46 patients with recently diagnosed carcinoma of the breast were included in a prospective comparative study of MRI and bone marrow scintigraphy. The aim of the study was to compare these procedures within a histologically unified patient collective. It was shown that MRI was superior to bone marrow scintigraphy in respect of sensitivity (92% vs 58%) and specificity (97% vs. 85%), although only about three quarters of the marrow spaces are examined by MRI screening. Bone marrow scintigraphy suffered particularly from a relatively high number of false positive findings (haemangiomas, degenerative changes). MRI remains the method of choice for investigating the bone marrow.

The Rorschach Comprehensive System Egocentricity Index in psychiatric inpatients.

This paper reports an exploratory study of potential correlates of Exner's Rorschach Egocentricity Index, a measure of self-focusing, in a sample of 70 psychiatric inpatients. We examined the relationship of the Index of the MMPI Ego Strength scale and to other MMPI and Exner Comprehensive System Rorschach variables, using Pearson Product-Moment correlations with partialling of the number of Rorschach responses. There were seven meaningful significant correlations between the Index and Rorschach variables: M, FM, X +%, F +%, Lambda, D, and A%. The Index-MMPI correlations were not significant. Sex differences and differences between these intercorrelations and some reported by Exner (1983) are discussed.

Follow-up of sixty-one physicians after psychiatric treatment.

Reported the results of a direct follow-up of 61 physicians who had been hospitalized for emotional impairment during 1969-1978. As of the fall-winter of 1979-1980, 35 physicians were in productive practice; 8 had died of purely medical causes; 5 had committed suicide; 2 were over age 65 and retired; 6 were not practicing for other reasons; 2 were physically disabled; and 3 could not be located. Recovery rate varied from 57% to 71% depending on the criteria used in calculating the ratio. Our outcome rate accords with those reported previously. Interviews with surviving physicians revealed that some important factors in recovery were rest and recuperation; spirituality, AA, and NA; modification in workload; support of colleagues; and constructive use of threat of loss of licensure.

Love and the addicted physician.

This paper reviews the cases of two addicted physicians. One is dead and the other alive and well as a result of the heroic and compassionate effort of his friends. We offer speculations regarding the physicians' special vulnerabilities and the role of a tough love in transcending these vulnerabilities.

MMPI profiles of emotionally impaired physicians.

Compared MMPI profiles of 36 male physicians hospitalized in a psychiatric institution to MMPI profiles of physicians hospitalized in a drug treatment center and to profiles of health physicians. The sample of 36 physicians manifested more emotional distress than M.D.s in these two comparison groups. Within our sample, physicians nt addicted to drugs or alcohol had significantly higher Male-Female scores than those M.D.s addicted to drugs.