Complexity science and leadership in healthcare.

The emerging field of complexity science offers an alternative leadership strategy for the chaotic, complex healthcare environment. A survey revealed that healthcare leaders intuitively support principles of complexity science. Leadership that uses complexity principles offers opportunities in the chaotic healthcare environment to focus less on prediction and control and more on fostering relationships and creating conditions in which complex adaptive systems can evolve to produce creative outcomes.

End-of-life care in the pediatric intensive care unit: attitudes and practices of pediatric critical care physicians and nurses.

OBJECTIVE: To determine the attitudes and practices of pediatric critical care attending physicians and pediatric critical care nurses on end-of-life care. DESIGN: Cross-sectional survey. SETTING: A random sample of clinicians at 31 pediatric hospitals in the United States. MEASUREMENTS AND MAIN RESULTS: The survey was completed by 110/130 (85%) physicians and 92/130 (71%) nurses. The statement that withholding and withdrawing life support is unethical was not endorsed by any of the physicians or nurses. More physicians (78%) than nurses (57%) agreed or strongly agreed that withholding and withdrawing are ethically the same (p < .001). Physicians were more likely than nurses to report that families are well informed about the advantages and limitations of further therapy (99% vs. 89%; p < .003); that ethical issues are discussed well within the team (92% vs. 59%; p < .0003), and that ethical issues are discussed well with the family (91% vs. 79%; p < .0002). On multivariable analyses, fewer years of practice in pediatric critical care was the only clinician characteristic associated with attitudes on end-of-life care dissimilar to the consensus positions reached by national medical and nursing organizations on these issues. There was no association between clinician characteristics such as their political or religious affiliation, practice-related variables such as the size of their intensive care unit or the presence of residents and fellows, and particular attitudes about end-of-life care. CONCLUSIONS: Nearly two-thirds of pediatric critical care physicians and nurses express views on end-of-life care in strong agreement with consensus positions on these issues adopted by national professional organizations. Clinicians with fewer years of pediatric critical care practice are less likely to agree with this consensus. Compared with physicians, nurses are significantly less likely to agree that families are well informed and ethical issues are well discussed when assessing actual practice in their intensive care unit. More collaborative education and regular case review on bioethical issues are needed as part of standard practice in the intensive care unit.

End-of-life care in the pediatric intensive care unit after the forgoing of life-sustaining treatment.

OBJECTIVE: To describe the attitudes and practice of clinicians in providing sedation and analgesia to dying patients as life-sustaining treatment is withdrawn. STUDY DESIGN: Prospective case series of 53 consecutive patients who died after the withdrawal of life-sustaining treatment in the pediatric intensive care unit at three teaching hospitals in Boston. Data on the reasons why medications were given were obtained from a self-administered anonymous questionnaire completed by the critical care physician and nurse for each case. Data on what medications were given were obtained from a review of the medical record. RESULTS: Sedatives and/or analgesics were administered to 47 (89%) patients who died after the withdrawal of life-sustaining treatment. Patients who were comatose were less likely to receive these medications. Physicians and nurses cited treatment of pain, anxiety, and air hunger as the most common reasons, and hastening death as the least common reason, for administration of these medications. Hastening death was viewed as an "acceptable, unintended side effect" of terminal care by 91% of physician-nurse matched pairs. The mean dose of sedatives and analgesics administered nearly doubled as life-support was withdrawn, and the degree of escalation in dose did not correlate with clinician's views on hastening death. CONCLUSION: Clinicians frequently escalate the dose of sedatives or analgesics to dying patients as life-sustaining treatment is withdrawn, citing patient-centered reasons as their principle justification. Hastening death is seen as an unintended consequence of appropriate care. A large majority of physicians and nurses agreed with patient management and were satisfied with the care provided. Care of the dying patient after the forgoing of life-sustaining treatment remains underanalyzed and needs more rigorous examination by the critical care community.

Cardiac toxicity of intravenous terbutaline for the treatment of severe asthma in children: a prospective assessment.

OBJECTIVE: To examine the cardiac toxicity as measured by elevations in serum cardiac troponin T (cTnT) and to compare creatine kinase (CK) and creatine kinase MB (CK-MB) and findings on electrocardiography (ECG) as markers of cardiac toxicity with cTnT during the infusion of intravenous terbutaline for the treatment of severe asthma in children. STUDY DESIGN: Prospective cohort study of patients receiving intravenous terbutaline for severe asthma. RESULTS: Only 3 (10%) of the 29 patients had elevations in cTnT. Each underwent mechanical ventilation for >72 hours, which was the earliest point at which cTnT elevations were identified. Eighteen (62%) patients had an elevation in CK, and 3 had an elevation in CK-MB fraction without an elevated cTnT. Twenty (69%) patients had ECG findings consistent with ischemia, and 19 of these patients had the ischemic findings on their preterbutaline ECG. Elevations in CK and CK-MB and ischemic changes on ECG did not correlate with elevations in cTnT. Both mechanical ventilation (P =.02) and prolonged administration (>72 hours) of intravenous terbutaline (P =. 02) were significantly associated with elevations in cTnT. CONCLUSIONS: We found no clinically significant cardiac toxicity from the use of intravenous terbutaline for severe asthma as measured by serum cTnT elevations.

Performance improvement with patient service partners.

Once the decision is made to use a patient-focused care delivery system, a variety of methods can be used to successfully design the model. The author describes the process used by a multilevel, multidisciplinary team at a community hospital to design and implement a Service Partner role that would meet and exceed customer expectations. Demonstrated performance improvements included increased patient satisfaction, productive labor dollar savings, and improvements in the work environment for staff members.

Ethical controversies in pediatric critical care.

Ethical dilemmas in clinical practice frequently center around who should make decisions for the patient, and what common principles can be used in making those decisions. In pediatrics, these dilemmas are complicated by balancing the interests of the child with the rights of parents and the responsibilities of clinicians. Other sources of controversy in caring for the pediatric population concern the confusion that continues around such issues as informed assent, the present standing of the "Baby Doe" regulations, and the forgoing of life-sustaining treatments. This article discusses the framework for decision-making in children that has evolved in ethics and the law over the last several decades.

Mosaic dup (9p) diagnosed by fluorescence in situ hybridization (FISH).

We describe a girl with some manifestations of the dup (9p) syndrome. High-resolution Giemsa-banded karyotype of her lymphocytes documented that she was mosaic with 80% of cells being 46,XX, and 20% 46,XX,-20, + der(20;?) (p13;?). The additional material on 20p could not be defined clearly by high-resolution Giemsa banding, as the banding pattern appeared consistent with either distal 9p or distal 13q. In order to make a definitive cytogenetic diagnosis, we used fluorescence in situ hybridization (FISH) with a chromosome 9 specific DNA library to establish that the origin of the additional chromosomal material on chromosome 20 was from 9p. FISH used in this situation enabled us to counsel the family specifically regarding the prognosis and manifestations of distal 9p duplication.

Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation.

Serial cytogenetic studies were performed on 64 patients with chronic myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow transplantation (BMT). Forty patients with CML in chronic phase (CP) received cytoreduction followed by BMT with HLA-matched T cell-depleted allogeneic marrow. The remaining 24 patients were transplanted in second chronic, accelerated, or blastic phase, or received T cell-depleted grafts with a dose of T cells added back. The Y chromosome and autosomal heteromorphisms were used to distinguish between donor and host cells. Mixed hematopoietic chimerism (presence of donor and host cells) was identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome reappeared in 16 of the 40 first CP CML patients. As expected, patients who had detectable Ph chromosome positive cells at any time during the posttransplant period had a high likelihood of subsequent clinical relapse. Transient disappearance of the Ph positive clone was rarely observed, and was followed by reappearance of the Ph chromosome or clinical relapse. A subset of engrafted patients with greater than 25% host cells within 3 months post-BMT had a significantly shorter survival time free of cytogenetic or clinical relapse compared with other patients. In patients who had received donor T cells added to the T cell-depleted graft, there was a higher proportion of complete chimerism. Clonal progression of Ph positive as well as negative cells was observed and may be the result of radiation induced breakage. Serial cytogenetic studies of patients post-BMT can provide useful information regarding the biologic and clinical behavior of CML.

Clinical evaluation of a DNA probe assay for the Philadelphia (Ph1) translocation in chronic myelogenous leukemia.

We report the clinical evaluation of an improved DNA probe assay for the characteristic genetic marker of human CML, observed by cytogenetics and designated the Philadelphia chromosome (Ph1). The Ph1 chromosome results from the fusion of c-abl proto-oncogene sequences from chromosome 9 to phl gene sequence on chromosome 22. (The phl gene is often referred to as bcr. However, for clarity we prefer to reserve the designation "bcr" for the region within the phl gene in which translocation breakpoints have been found to occur. We also find it useful to distinguish between two such regions in phl, bcr-210 and bcr-190, named after the 210- and 190-kDa phl/abl fusion proteins resulting from translocations with breakpoints in the respective regions. We refer to the corresponding chromosomal translocations as Ph1(bcr-210) and Ph1(bcr-190).) DNA, extracted from peripheral blood (PB) or bone marrow (BM) and digested with restriction endonuclease BglII, is hybridized with a probe (phl/bcr-3) spanning a breakpoint cluster region within phl. Rearrangements are revealed by the presence of one or two novel junction fragments. Clinical specimens from leukemic patients with active disease were compared by cytogenetic and DNA probe analysis at seven centers in the United States and Europe. The probe assay identified the phl rearrangement in 190 of 191 cases of Ph1-positive CML, as well as in 12 of 27 clinically diagnosed CML specimens lacking a typical Ph1 chromosome. DNA rearrangements also were seen in two of six cases of Ph1-positive ALL. No false positive results were obtained among 93 non-leukemic controls. Mixing experiments showed that the DNA probe assay can detect as few as 1% leukemic cells in a specimen. A preliminary study of CML patients in remission after allogeneic BM transplantation revealed a small fraction of residual Ph1-positive leukemic cells in a significant number of such patients.

Analysis of meiotic segregation in a man heterozygous for two reciprocal translocations using the hamster in vitro penetration system.

Sperm chromosomal complements of a man heterozygous for two reciprocal translocations and exhibiting the karyotype 46,XY,t(5;11) (p13;q23.2),t(7;14)(q11;q24.1) were analyzed following in vitro fusion with golden hamster zona-free eggs (the hamster in vitro penetration [HIP] system). Products of alternate, adjacent 1, and 3:1 segregation at meiosis I of both translocation quadrivalents were recovered, and the analysis of their output, which was dissimilar between the two translocations, permitted prediction of probable sites of chiasma formation in the chromosomes involved in the translocation. These data, which comprise the first reported analysis of the products of two translocations in a single individual (hence, in a common genetic background), emphasize the uniqueness in genetic behavior of individual translocations; they further demonstrate the usefulness of the HIP system to carry out such studies.

Morphology and transcriptional activity of mouse oocyte chromosomes.

Lampbrush chromosomes of growing amphibian oocytes carry thousands of lateral loops each of which consists of a chromatin fiber heavily encrusted with nascent ribonucleoprotein fibrils. These are believed to be responsible for the accumulation and maintenance of RNA transcripts found stored in the egg. In the case of mammalian oocytes, lampbrush chromosomes are most likely to occur during the major growth phase and also possibly during pachytene-early diplotene stages of meiosis. We have examined pachytene and early diplotene mouse oocyte chromosomes through the light microscope using sections of plastic-embedded material and air dried spreads stained with either silver nitrate or methyl green pyronin. Our results indicates that the projections radiating from the chromosomal axis are bundles of chromatin fibers rather than single fibers covered with an ribonucleoprotein matrix. These bundles may represent partially unfolded chromomeres. The axis itself could be partially dispersed revealing threads surrounding a fine linear element. -- Little is known about chromosome structure in growing mammalian oocytes, the stage when transcriptional activity is likely to be most rapid. In our preparations chromosomes at this stage appear as partially condensed fuzzy threads of relatively uniform width. In some cases, the fuzzy thread is seen to contain a dense linear core in the center. Thus, during the growth phase, the chromosomes retain a relatively condensed axis, a characteristic of meiotic chromosomes in general. RNA-containing material is found diffusely spread within the nucleus but not specifically associated with the chromosomes. Electron microscopic analysis of spread chromatin from growing oocytes demonstrates that most transcription units possess only one or two nascent ribonucleoprotein fibrils while a few have more. These and other published data indicate that mouse oocytes do not have true lampbrush chromosomes at any stage of their development.

Mid-pachytene chromomere maps of human autosomes.

Using a method of chromosome preparation which yielded pachytene spermatocytes with exceptionally well spread bivalents, we undertook detailed chromomere analysis of each of the 22 autosomal bivalents stained with orcein or quinacrine. A maximum of 442 chromomeres were recognized and mapped at mid-pachytene. The chromomere maps of pachytene chromosomes presented here corresponded well with the high resolution banding maps of somatic chromosomes at the 850 band stage described in the International System for Human Cytogenetic Nomenclature (ISCN, 1981). Our observations of other features of the pachytene chromosomes, such as the parameters, also agree well with previous reports.