Prognosis-Based Futility Guidelines: Does Anyone Win?

OBJECTIVE : Advocates for health care reform and others claim that significant savings could be achieved if “futile” care were eliminated. Our objective was to provide an initial estimate of the effects of a public policy that would preclude futile life-sustaining treatments, defined as those employed despite ≤1% chance of surviving for 2 months. DESIGN : Simulation using data from an observational cohort study. SETTING : Five academic medical centers. PATIENTS : Seriously ill hospitalized adults enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT). METHODS : We examined the impact of prognosis-based futility guidelines on survival and hospital length of stay on a cohort of seriously ill adults. We calculated the number of days of hospitalization that would not be used if, on the third study day, life-sustaining treatment had been stopped or not initiated for subjects with estimated 2-month survival probability of ≤1%. RESULTS : Of the 4301 patients, 115 (2.7%) had an estimated chance of 2-month survival of ≤1%. All but one of these 115 subjects died within 6 months. Almost 86% died within 5 days of prognosis. At the time of death, 92 subjects (80.0%) had had no attempt at resuscitation; 35 (30.4%) had had a life-sustaining mechanical ventilator withdrawn. A Do-Not-Resuscitate order was written either before (n = 61) or within 5 days (n = 18) of reaching this prognosis for 68.6% of the patients. These 115 subjects had total hospital charges of $8.8 million. By forgoing or withdrawing life sustaining treatment in accord with a strict 1% futility guideline, 199 of 1,688 hospital days (10.8%) would be forgone, with estimated savings of $1.2 million in hospital charges. Nearly 75% of the savings in hospital days would have resulted from stopping treatment for 12 patients, six of whom were under 51 years old, and one of whom lived 10 months. CONCLUSIONS : Patients at a high risk of dying can be identified prospectively. Implementation of a strict, prognosis-based futility guideline on the third day of a serious illness would result in modest savings.     

Hip fracture risk in older US adults by treatment eligibility status based on new National Osteoporosis Foundation guidance

Summary

This analysis of National Health and Nutrition Examination Survey III data found a significant risk of incident hip fracture in adults aged 65?years and older who are candidates for treatment to lower fracture risk, according to the new National Osteoporosis Foundation Clinician's Guide.

Introduction

The relationship between treatment eligibility by the new National Osteoporosis Foundation (NOF) Guide to the Prevention and Treatment of Osteoporosis and the risk of subsequent hip fracture is unknown.

Methods

The study sample consisted of 3,208 men and women ages 65?years and older who were examined in the third National Health and Nutrition Examination Survey (NHANES III, 1988?C1994), a nationally representative survey. Risk factors used to define treatment eligibility at baseline were measured in NHANES III or were simulated using World Health Organization study cohorts. Incident hip fractures were ascertained using linked mortality and Medicare records that were obtained for NHANES III participants through December 31, 2000. Cox proportional hazards models were used to estimate the relative risk (RR) of hip fracture by treatment eligibility status.

Results

The RR for subsequent hip fracture was 4.9 (95% CI 3.30, 7.94) in treatment-eligible vs treatment-ineligible persons. The increased risk for treatment-eligible persons remained statistically significant when examined by sex or age: RR_men?=?5.5 (2.6, 11.4) and RR_women?=?4.3 (2.2, 8.4); RR_{65-79 y}?=?4.8 (2.6, 8.7) and RR_{80+ y}?=?4.6 (2.1, 10.1).

Conclusions

Treatment-eligible persons were about five times more likely to experience a subsequent hip fracture than the non-eligible persons. The new NOF guidelines appear to predict future hip fracture risk equally in men as in women, and fracture risk prediction did not appear to diminish with age.     

Heart rate reduces when stroke patients are touched . . . And??

McFadden KL, Hernández TD. Cardiovascular benefits of acupressure (Jin Shin) following stroke. Complement Ther Med 2010; 18: 42–8.     

Nucleotide oligomerization domain 1 is a dominant pathway for NOS2 induction in vascular smooth muscle cells: comparison with Toll-like receptor 4 responses in macrophages

Background and purpose:

Gram-negative bacteria contain ligands for Toll-like receptor (TLR) 4 and nucleotide oligomerization domain (NOD) 1 receptors. Lipopolysaccharide (LPS) activates TLR4, while peptidoglycan products activate NOD1. Activation of NOD1 by the specific agonist FK565 results in a profound vascular dysfunction and experimental shock in vivo.

Experimental approach:

Here, we have analysed a number of pharmacological inhibitors to characterize the role of key signalling pathways in the induction of NOS2 following TLR4 or NOD1 activation.

Key results:

Vascular smooth muscle (VSM) cells expressed NOD1 mRNA and protein, and, after challenge with Escherichia coli or FK565, NOS2 protein and activity were induced. Macrophages had negligible levels of NOD1 and were unaffected by FK565, but responded to E. coli and LPS by releasing increased NO and expression of NOS2 protein. Classic pharmacological inhibitors for NF-κB (SC-514) and mitogen-activated protein kinase (SB203580, PD98059) signalling pathways inhibited responses in both cell types regardless of agonist. While TLR4-mediated responses in macrophages were specifically inhibited by the pan-caspase inhibitor z-VAD-fmk and the PKC inhibitor Gö6976, NOD1-mediated responses in VSM cells were inhibited by the Rip2 inhibitor PP2.

Conclusions and implications:

Our findings suggest a selective role for NOD1 in VSM cells, and highlight NOD1 as a potential novel therapeutic target for the treatment of vascular inflammation.     

Imaging breast adipose and fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared spectral tomography

Magnetic resonance (MR)-guided near-infrared spectral tomography was developed and used to image adipose and fibroglandular breast tissue of 11 normal female subjects, recruited under an institutional review board-approved protocol. Images of hemoglobin, oxygen saturation, water fraction, and subcellular scattering were reconstructed and show that fibroglandular fractions of both blood and water are higher than in adipose tissue. Variation in adipose and fibroglandular tissue composition between individuals was not significantly different across the scattered and dense breast categories. Combined MR and near-infrared tomography provides fundamental molecular information about these tissue types with resolution governed by MR T1 images.     

Preoperative breast MRI and mortality in older women with breast cancer

Purpose

The survival benefit from detecting additional breast cancers by preoperative magnetic resonance imaging (MRI) continues to be controversial.

Methods

We followed a cohort of 4454 women diagnosed with non-metastatic breast cancer (stage I–III) from 2/2005–6/2010 in five registries of the breast cancer surveillance consortium (BCSC). BCSC clinical and registry data were linked to Medicare claims and enrollment data. We estimated the cumulative probability of breast cancer-specific and all-cause mortality. We tested the association of preoperative MRI with all-cause mortality using a Cox proportional hazards model.

Results

917 (20.6%) women underwent preoperative MRI. No significant difference in the cumulative probability of breast cancer-specific mortality was found. We observed no significant difference in the hazard of all-cause mortality during the follow-up period after adjusting for sociodemographic and clinical factors among women with MRI (HR 0.90; 95% CI 0.72–1.12) compared to those without MRI.

Conclusion

Our findings of no breast cancer-specific or all-cause mortality benefit supplement prior results that indicate a lack of improvement in surgical outcomes associated with use of preoperative MRI. In combination with other reports, the results of this analysis highlight the importance of exploring the benefit of preoperative MRI in patient-reported outcomes such as women’s decision quality and confidence levels with decisions involving treatment choices.