Code Status Discussions Between Attending Hospitalist Physicians and Medical Patients at Hospital Admission

BackgroundBioethicists and professional associations give specific recommendations for discussing cardiopulmonary resuscitation (CPR).ObjectiveTo determine whether attending hospitalist physicians' discussions meet these recommendations.DesignCross-sectional observational study on the medical services at two hospitals within a university system between August 2008 and March 2009.ParticipantsAttending hospitalist physicians and patients who were able to communicate verbally about their medical care.Main measuresWe identified code status discussions in audio-recorded admission encounters via physician survey and review of encounter transcripts. A quantitative content analysis was performed to determine whether discussions included elements recommended by bioethicists and professional associations. Two coders independently coded all discussions; Cohen's kappa was 0.64-1 for all reported elements.Key resultsAudio-recordings of 80 patients' admission encounters with 27 physicians were obtained. Eleven physicians discussed code status in 19 encounters. Discussions were more frequent in seriously ill patients (OR 4, 95% CI 1.2-14.6), yet 66% of seriously ill patients had no discussion. The median length of the code status discussions was 1 min (range 0.2-8.2). Prognosis was discussed with code status in only one of the encounters. Discussions of patients' preferences focused on the use of life-sustaining interventions as opposed to larger life goals. Descriptions of CPR as an intervention used medical jargon, and the indication for CPR was framed in general, as opposed to patient-specific scenarios. No physician quantitatively estimated the outcome of or provided a recommendation about the use of CPR.ConclusionsCode status was not discussed with many seriously ill patients. Discussions were brief, and did not include elements that bioethicists and professional associations recommend to promote patient autonomy. Local and national guidelines, research, and clinical practice changes are needed to clarify and systematize with whom and how CPR is discussed at hospital admission

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

Extreme genetic fragility of the HIV-1 capsid

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies

An Integrated Approach Providing Scientific and Policy-Relevant Insights for South-West Bangladesh

Bangladesh is identified as an impact hotspot for sea-level rise in multiple studies. However, a range of other factors must be considered including catchment management, socio-economic development and governance quality, as well as delta plain biophysical processes. Taking an integrated assessment approach highlights that to 2050 future changes are more sensitive to human choice/policy intervention than climate change, ecosystem services diminish as a proportion of the economy with time, continuing historic trends and significant poverty persists for some households. Hence under favourable policy decisions, development could transform Bangladesh by 2050 making it less vulnerable to longer-term climate change and subsidence. Beyond 2050, the threats of climate change are much larger, requiring strategic adaptation responses and policy changes that must be initiated now

A Novel, Low-Volume Method for Organ Culture of Embryonic Kidneys That Allows Development of Cortico-Medullary Anatomical Organization

Here, we present a novel method for culturing kidneys in low volumes of medium that offers more organotypic development compared to conventional methods. Organ culture is a powerful technique for studying renal development. It recapitulates many aspects of early development very well, but the established techniques have some disadvantages: in particular, they require relatively large volumes (1–3 mls) of culture medium, which can make high-throughput screens expensive, they require porous (filter) substrates which are difficult to modify chemically, and the organs produced do not achieve good cortico-medullary zonation. Here, we present a technique of growing kidney rudiments in very low volumes of medium–around 85 microliters–using silicone chambers. In this system, kidneys grow directly on glass, grow larger than in conventional culture and develop a clear anatomical cortico-medullary zonation with extended loops of Henle

Display of probability densities for data from a continuous distribution

Based on cumulative distribution functions, Fourier series expansion and Kolmogorov tests, we present a simple method to display probability densities for data drawn from a continuous distribution. It is often more efficient than using histograms.Comment: 5 pages, 4 figures, presented at Computer Simulation Studies XXIV, Athens, GA, 201

Alveolar soft part sarcoma: clinicopathological findings in a series of 11 cases

<p>Abstract</p> <p>Background</p> <p>Alveolar sarcoma of the soft parts (ASPS) represents a very rare entity of soft tissue sarcoma with special features such as young peak age incidence and frequent metastasis to the brain. The aim of this study was a clinicopathological analysis with special reference to treatment and outcome.</p> <p>Methods</p> <p>From the database of the BG-University Hospital Bergmannsheil, 1597 soft tissue sarcoma (STS) cases were reviewed and 11 consecutive patients with ASPS were isolated. Data was acquired from patients' charts and contact to patients, their relatives or general practitioners, with special reference to treatment and clinical course. The average follow up time from the time of the definite operation for the primary tumor was 6.5 years. Kaplan-Meier method was used to calculate survival.</p> <p>Results</p> <p>Patients with localized disease who received complete resection and adjuvant radiation and who did not develop recurrence or metastatic disease within 2 years after surgery had a positive outcome. The size of the tumor, its localization, and the time of untreated growth before treatment did not influence the long-term results. All patients who developed recurrent disease also suffered from distant metastasis, reflecting the aggressive biology of the tumor. All patients with distant metastasis had the lungs and the brain affected.</p> <p>Conclusion</p> <p>Due to the limited number of patients with ASPS, prospective studies would have to span decades to gather a significant collective of patients; therefore, it is not possible to comment meaningfully on a possible benefit of neoadjuvant or adjuvant therapy.</p> <p>We recommend wide surgical excision and, in the absence of data telling otherwise, adjuvant radiation. In cases with recurrent disease or metastasis, the prognosis is bad and further treatment will be restricted to palliation in most cases.</p

Understanding Variation in Sets of N-of-1 Trials.

A recent paper in this journal by Chen and Chen has used computer simulations to examine a number of approaches to analysing sets of n-of-1 trials. We have examined such designs using a more theoretical approach based on considering the purpose of analysis and the structure as regards randomisation that the design uses. We show that different purposes require different analyses and that these in turn may produce quite different results. Our approach to incorporating the randomisation employed when the purpose is to test a null hypothesis of strict equality of the treatment makes use of Nelder's theory of general balance. However, where the purpose is to make inferences about the effects for individual patients, we show that a mixed model is needed. There are strong parallels to the difference between fixed and random effects meta-analyses and these are discussed

Hospital Readmission in General Medicine Patients: A Prediction Model

Background: Previous studies of hospital readmission have focused on specific conditions or populations and generated complex prediction models. Objective: To identify predictors of early hospital readmission in a diverse patient population and derive and validate a simple model for identifying patients at high readmission risk. Design: Prospective observational cohort study. Patients: Participants encompassed 10,946 patients discharged home from general medicine services at six academic medical centers and were randomly divided into derivation (n = 7,287) and validation (n = 3,659) cohorts. Measurements: We identified readmissions from administrative data and 30-day post-discharge telephone follow-up. Patient-level factors were grouped into four categories: sociodemographic factors, social support, health condition, and healthcare utilization. We performed logistic regression analysis to identify significant predictors of unplanned readmission within 30 days of discharge and developed a scoring system for estimating readmission risk. Results: Approximately 17.5% of patients were readmitted in each cohort. Among patients in the derivation cohort, seven factors emerged as significant predictors of early readmission: insurance status, marital status, having a regular physician, Charlson comorbidity index, SF12 physical component score, ≥1 admission(s) within the last year, and current length of stay >2 days. A cumulative risk score of ≥25 points identified 5% of patients with a readmission risk of approximately 30% in each cohort. Model discrimination was fair with a c-statistic of 0.65 and 0.61 for the derivation and validation cohorts, respectively. Conclusions: Select patient characteristics easily available shortly after admission can be used to identify a subset of patients at elevated risk of early readmission. This information may guide the efficient use of interventions to prevent readmission