Publications

Unlike other human biological fluids, semen contains multiple types of amyloid fibrils in the absence of disease. These fibrils enhance HIV infection by promoting viral fusion to cellular targets, but their natural function remained unknown. The similarities shared between HIV fusion to host cell and sperm fusion to oocyte led us to examine whether these fibrils promote fertilization. Surprisingly, the fibrils inhibited fertilization by immobilizing sperm. Interestingly, however, this immobilization facilitated uptake and clearance of sperm by macrophages, which are known to infiltrate the female reproductive tract (FRT) following semen exposure. In the presence of semen fibrils, damaged and apoptotic sperm were more rapidly phagocytosed than healthy ones, suggesting that deposition of semen fibrils in the lower FRT facilitates clearance of poor-quality sperm. Our findings suggest that amyloid fibrils in semen may play a role in reproduction by participating in sperm selection and facilitating the rapid removal of sperm antigens.

BACKGROUND AND OBJECTIVES

Despite significant morbidity and mortality associated with ESRD, these patients receive palliative care services much less often than patients with other serious illnesses, perhaps because they are perceived as having less need for such services. We compared characteristics and outcomes of hospitalized patients in the United States who had a palliative care consultation for renal disease versus other serious illnesses.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

In this observational study, we used data collected by the Palliative Care Quality Network, a national palliative care quality improvement collaborative. The 23-item Palliative Care Quality Network core dataset includes demographics, processes of care, and clinical outcomes of all hospitalized patients who received a palliative care consultation between December of 2012 and March of 2016.

RESULTS

The cohort included 33,183 patients, of whom 1057 (3.2%) had renal disease as the primary reason for palliative care consultation. Mean age was 71.9 (SD=16.8) or 72.8 (SD=15.2) years old for those with renal disease or other illnesses, respectively. At the time of consultation, patients with renal disease or other illnesses had similarly low mean Palliative Performance Scale scores (36.0% versus 34.9%, respectively; =0.08) and reported similar moderate to severe anxiety (14.9% versus 15.3%, respectively; =0.90) and nausea (5.9% versus 5.9%, respectively; >0.99). Symptoms improved similarly after consultation regardless of diagnosis (≥0.50), except anxiety, which improved more often among those with renal disease (92.0% versus 66.0%, respectively; =0.002). Although change in code status was similar among patients with renal disease versus other illnesses, from over 60% full code initially to 30% full code after palliative care consultation, fewer patients with renal disease were referred to hospice than those with other illnesses (30.7% versus 37.6%, respectively; <0.001).

CONCLUSIONS

Hospitalized patients with renal disease referred for palliative care consultation had similar palliative care needs, improved symptom management, and clarification of goals of care as those with other serious illnesses.

BACKGROUND

Respiratory rate (RR) is an independent predictor of adverse outcomes and an integral component of many risk prediction scores for hospitalised adults. Yet, it is unclear if RR is recorded accurately. We sought to assess the potential accuracy of RR by analysing the distribution and variation as a proxy, since RR should be normally distributed if recorded accurately.

METHODS

We conducted a descriptive observational study of electronic health record data from consecutive hospitalisations from 2009 to 2010 from six diverse hospitals. We assessed the distribution of the maximum RR on admission, using heart rate (HR) as a comparison since this is objectively measured. We assessed RR patterns among selected subgroups expected to have greater physiological variation using the coefficient of variation (CV=SD/mean).

RESULTS

Among 36 966 hospitalisations, recorded RR was not normally distributed (p<0.001), but right skewed (skewness=3.99) with values clustered at 18 and 20 (kurtosis=23.9). In contrast, HR was relatively normally distributed. Patients with a cardiopulmonary diagnosis or hypoxia only had modestly greater variation (CV increase of 2%-6%). Among 1318 patients transferred from the ward to the intensive care unit (n=1318), RR variation the day preceding transfer was similar to that observed on admission (CV 0.24 vs 0.26), even for those transferred with respiratory failure (CV 0.25).

CONCLUSIONS

The observed patterns suggest that RR is inaccurately recorded, even among those with cardiopulmonary compromise, and represents a 'spot' estimate with values of 18 and 20 breaths per minute representing 'normal.' While spot estimates may potentially be adequate to indicate clinical stability, inaccurate RR may alternatively lead to misclassification of disease severity, potentially jeopardising patient safety. Thus, we recommend greater training for hospital personnel to accurately record RR.

The National Heart, Lung, and Blood Institute (NHLBI) AIDS Program's goal is to provide direction and support for research and training programs in areas of HIV-related heart, lung, blood, and sleep (HLBS) diseases. To better define NHLBI current HIV-related scientific priorities and with the goal of identifying new scientific priorities and gaps in HIV-related HLBS research, a wide group of investigators gathered for a scientific NHLBI HIV Working Group on December 14-15, 2015, in Bethesda, MD. The core objectives of the Working Group included discussions on: (1) HIV-related HLBS comorbidities in the antiretroviral era; (2) HIV cure; (3) HIV prevention; and (4) mechanisms to implement new scientific discoveries in an efficient and timely manner so as to have the most impact on people living with HIV. The 2015 Working Group represented an opportunity for the NHLBI to obtain expert advice on HIV/AIDS scientific priorities and approaches over the next decade.

BACKGROUND

Missed evidence-based monitoring in high-risk conditions (e.g., cancer) leads to delayed diagnosis. Current technological solutions fail to close this safety gap. In response, we aim to demonstrate a novel method to identify common vulnerabilities across clinics and generate attributes for context-flexible population-level monitoring solutions for widespread implementation to improve quality.

METHODS

Based on interviews with staff in otolaryngology, pulmonary, urology, breast, and gastroenterology clinics at a large urban publicly funded health system, we applied journey mapping to co-develop a visual representation of how patients are monitored for high-risk conditions. Using a National Academies framework and context-sensitivity theory, we identified common systems vulnerabilities and developed preliminary concepts for improving the robustness for monitoring patients with high-risk conditions ("design seeds" for potential solutions). Finally, we conducted a face validity and prioritization assessment of the design seeds with the original interviewees.

RESULTS

We identified five high-risk situations for potentially consequential diagnostic delays arising from suboptimal patient monitoring. All situations related to detection of cancer (head and neck, lung, prostate, breast, and colorectal). With clinic participants we created 5 journey maps, each representing specialty clinic workflow directed at evidence-based monitoring. System vulnerabilities common to the different clinics included challenges with: data systems, communications handoffs, population-level tracking, and patient activities. Clinic staff ranked 13 design seeds (e.g., keep patient list up to date, use triggered notifications) addressing these vulnerabilities. Each design seed has unique evaluation criteria for the usefulness of potential solutions developed from the seed.

CONCLUSIONS

We identified and ranked 13 design seeds that characterize situations that clinicians described 'wake them up at night', and thus could reduce their anxiety, save time, and improve monitoring of high-risk patients. We anticipate that the design seed approach promotes robust and context-sensitive solutions to safety and quality problems because it provides a human-centered link between the experienced problem and various solutions that can be tested for viability. The study also demonstrates a novel integration of industrial and human factors methods (journey mapping, process tracing and design seeds) linked to implementation theory for use in designing interventions that anticipate and reduce implementation challenges.