Publications

INTRODUCTION

Delirium has a high mortality rate. Understanding predictors of prognosis in patients with delirium will aid treatment decisions and communication. This study aimed to explore variables associated with death during an established episode of delirium in palliative care when haloperidol treatment had been commenced.

METHODS

A consecutive cohort of palliative care patients, from 14 centers across four countries, is reported. The outcome of interest was death within 14 days from commencement of haloperidol treatment for delirium. Clinicodemographic variables explored were delirium severity, age, gender, primary life limiting illness, body mass index (BMI), total daily haloperidol dose at baseline (mg), functional status, and comorbidities.

RESULTS

One hundred and sixteen palliative care patients where vital status was known were included in the analysis; 45% (n = 52) died within 10 days, and 56% (n = 65) died within 14 days. In multivariate analyses no clinical or demographic variables predicted death, apart from lower BMI in noncancer patients.

CONCLUSION

This study has shown a very high mortality rate within two weeks of commencing haloperidol for delirium in palliative care, with no clear clinical predictors for those with a higher chance of dying. Having a higher BMI offered some benefit in survival, but only in noncancer patients. When delirium occurs in advanced illness, discussion should be initiated about the gravity of the clinical situation.

Hospice developed in the United States in the 1970s as a way to address unmet needs for end-of-life care: support for pain and symptom management provided in the location and manner that the patient and family prefer. In Europe and Australia, hospice is available from the time of diagnosis of an advanced life-limiting illness onward, but in the United States, the Medicare hospice benefit restricts eligibility for these services to patients who no longer receive curative treatment. We provide background and analysis of the first Medicare hospice demonstration in 35 years that will test the concurrent provision of curative and hospice services for terminally ill individuals with a life expectancy of six months or less. This demonstration is a harbinger of potential policy changes to hospice and palliative care in the United States that could reduce barriers to end-of-life care that aligns with patient and family preferences as the demand for care increases with an aging population.

During mitosis, RNA polymerase II (Pol II) and many transcription factors dissociate from chromatin, and transcription ceases globally. Transcription is known to restart in bulk by telophase, but whether de novo transcription at the mitosis-G1 transition is in any way distinct from later in interphase remains unknown. We tracked Pol II occupancy genome-wide in mammalian cells progressing from mitosis through late G1. Unexpectedly, during the earliest rounds of transcription at the mitosis-G1 transition, ∼50% of active genes and distal enhancers exhibit a spike in transcription, exceeding levels observed later in G1 phase. Enhancer-promoter chromatin contacts are depleted during mitosis and restored rapidly upon G1 entry but do not spike. Of the chromatin-associated features examined, histone H3 Lys27 acetylation levels at individual loci in mitosis best predict the mitosis-G1 transcriptional spike. Single-molecule RNA imaging supports that the mitosis-G1 transcriptional spike can constitute the maximum transcriptional activity per DNA copy throughout the cell division cycle. The transcriptional spike occurs heterogeneously and propagates to cell-to-cell differences in mature mRNA expression. Our results raise the possibility that passage through the mitosis-G1 transition might predispose cells to diverge in gene expression states.

We describe a phenomenon viewed through the conceptual lens of a naturalistic decision making perspective: a loss of system resilience, due to increased difficulty in performing macrocognition functions, associated with the implementation of new information technology. Examples of the phenomenon collected in a targeted literature review are characterized by stakeholder groups, technology, typical changes in workflow before and after implementation, and potential impacts on macrocognition and patient outcomes for four clinical care environments. The loss of system resilience is due to increased difficulty in performing macrocognition functions: 1) sensemaking due to less effective cognitive warm-up and collaborative framing strategies, 2) detecting events due to missing trends in data and changes to orders, and 3) coordinating due to less clinical knowledge during scheduling and updating information, and less effective cross-checks. Potential impacts to patient safety include an increase in unnecessary care, missed care, delays in diagnoses and treatment, redundant care, inaccurate diagnoses, medication errors, and adverse events. We recommended future conceptually-driven research in other complex, sociotechnical settings order to develop useful metrics and reduce the risk of incurring undesirable and unnecessary impacts on cognitive work associated with new technology.